Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Open accessAbstract
BACKGROUND: Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS: At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS: In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. (Funded by Amgen; FOURIER ClinicalTrials.gov number, NCT01764633 .).
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Claims the paper makes
15 of 26 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured
- Premisecitation
There were little more than 100 events in the phase 2 and phase 3 trials of PCSK9 inhibitors combined.
“However, there were little more than 100 events in these studies combined.”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [9] source
The Results passage reproduced in the Discussion reports 29 cardiovascular events in the evolocumab group and 31 in the standard-therapy group—60 in the combined OSLER trials. The paper identifies these as follow-up trials for participants from phase 2 and phase 3 studies, but it does not establish the claimed total of little more than 100 events across the studies referred to by the citing sentence. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [10] source
- Premisecitation
Exploratory data from longer-term follow-up in phase 2 and phase 3 trials of PCSK9 inhibitors showed significant reductions in cardiovascular outcomes.
“Moreover, exploratory data from longer-term follow-up in phase 2 and phase 3 trials of PCSK9 inhibitors showed significant reductions in cardiovascular outcomes.9,10”
Quote in the paperSubstantial claim1 of 2 sources checked - Premisecitation
A recent mendelian randomization study found that variants in PCSK9 and variants in HMGCR were associated with nearly identical lower risks of cardiovascular events per unit reduction in LDL cholesterol.
“Likewise, these observations are supported by data from a recent mendelian randomization study in which variants in PCSK9 and variants in HMGCR were associated with nearly identical lower risks of cardiovascular events per unit reduction in LDL cholesterol.29”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [29] source
- Interpretationcitation
The rate of discontinuation of evolocumab injections because of adverse events ascribed to the drug compares favorably to rates with atorvastatin 80 mg daily (1.5% per year) and ezetimibe (1.1% per year) in other trials.
“and compares favorably to the rates that have been found with atorvastatin at a dose of 80 mg daily (1.5% per year) and with ezetimibe (1.1% per year) in other trials.14,15”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [14] source
- cites [15] source
The Safety section reports discontinuation owing to an adverse event in 10.6% of patients receiving simvastatin–ezetimibe, versus 10.1% receiving simvastatin alone. It does not report the cited 1.1% per-year rate or identify those adverse events as caused by ezetimibe. The atorvastatin comparison is not a finding of this trial. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Findingown data
In FOURIER, additional lowering of LDL cholesterol levels had no effect on cardiovascular mortality.
“In an observation consistent with previous trials of more intensive LDL cholesterol-lowering therapy as compared with moderate-intensity statin therapy, 15,25 we found no effect of additional lowering of LDL cholesterol levels on cardiovascular mortality.”
Quote in the paperSubstantial claim2 of 2 sources checked
- Premisecitation
Meta-analyses of data from clinical trials of different lipid-lowering interventions show consistent clinical benefits per unit reduction in LDL cholesterol.
“These observations are in accord with meta-analyses of data from clinical trials of different lipid-lowering interventions, which show consistent clinical benefits per unit reduction in LDL cholesterol.28”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] source
- Interpretationcitation
The advent of increasingly sensitive cardiac troponin assays probably makes cardiac ischemia increasingly questionable as the true cause of a hospitalization for chest-pain symptoms without biochemical evidence of myocyte injury.
“The advent of increasingly sensitive cardiac troponin assays probably makes cardiac ischemia increasingly questionable as the true cause of a hospitalization for chestpain symptoms without biochemical evidence of myocyte injury.27”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [27] source
The Conclusions (page unavailable) say that more sensitive troponin assays have reduced the proportion of patients classified as having unstable angina and that it is unclear whether acute coronary syndrome events occur without some troponin increase. That supports questioning an acute coronary syndrome diagnosis when sensitive testing shows no increase, but the paper does not extend that inference to cardiac ischemia as the cause of every chest-pain hospitalization; it also discusses angina without myocardial infarction. (LLM, conf=0.79)
Experimental — accuracy not yet measured
- Premisecitation
A delay between the onset of LDL cholesterol lowering and the emergence of the full clinical benefit has been well documented in trials of statins, ezetimibe, and other LDL cholesterol-lowering therapies.
“A delay between the onset of LDL cholesterol lowering and the emergence of the full clinical benefit of the intervention in terms of clinical risk reduction has been well documented in trials of statins, ezetimibe, and other LDL cholesterollowering therapies.15,[21][22][23][24]”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [15] source
The Efficacy End Points and Discussion sections report that the clinical benefit of adding ezetimibe to simvastatin appeared after about one year, while the Lipid Data section documents LDL lowering. This supports a delayed clinical benefit in this trial, but the paper does not establish that the same delay is well documented across trials of statins and other LDL-lowering therapies. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [21][22][23][24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Study design and conductcitation
A major limitation of FOURIER was a relatively short duration of follow-up as compared with other lipid-lowering trials, in which follow-up periods have averaged approximately 5 years.
“The major limitation of this trial was a relatively short duration of follow-up as compared with that in other lipid-lowering trials, in which follow-up periods have averaged approximately 5 years.28”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [28] source
The Results report a mean follow-up of 4.3 years across 49 lipid-lowering trials, supporting the comparison to approximately five years. The paper does not assess FOURIER or identify its follow-up duration as a limitation, so it supports only the comparison, not the claim about FOURIER. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Findingown data
The median LDL cholesterol level at baseline was 92 mg per deciliter (interquartile range, 80 to 109).
“The median LDL cholesterol level at baseline was 92 mg per deciliter (interquartile range, 80 to 109) (2.4 mmol per liter [interquartile range, 2.1 to 2.8]).”
Quote in the paperNot a substantial claim - Findingown data
The key secondary end point occurred in 816 patients (5.9%) in the evolocumab group and 1013 patients (7.4%) in the placebo group (hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001).
“The key second-ary end point occurred in 816 patients (5.9%) in the evolocumab group and in 1013 patients (7.4%) in the placebo group (hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001) (Table 2 and Fig. 2B).”
Quote in the paperSubstantial claim - Findingown data
Among patients in the top quartile for baseline LDL cholesterol level, evolocumab reduced the risk of the key secondary end point by 17%.
“Specifically, there was a 17% reduction in the risk of the key secondary end point among patients in the top quartile for baseline LDL cholesterol level”
Quote in the paperNot a substantial claim - Findingown data
During a median of 26 months of follow-up, the only adverse events noted to be nominally significantly more common with evolocumab were injection-site reactions.
“During a median of 26 months of follow-up, the only adverse events that were noted to be nominally significantly more common in association with evolocumab were injection-site reactions, but these were rare”
Quote in the paperNot a substantial claim - Findingown data
Injection-site reactions were more common with evolocumab (2.1% vs. 1.6%).
“with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%).”
Quote in the paperNot a substantial claim - Findingown data
In FOURIER, there were consistent reductions in rates of cardiovascular events across the range of baseline LDL cholesterol levels.
“In extending this concept further in FOURIER, we found consistent reductions in rates of cardiovascular events across the range of baseline LDL cholesterol levels.”
Quote in the paperSubstantial claim - Findingown data
The reduction in LDL cholesterol levels was maintained over time.
“The reduction in LDL cholesterol levels was maintained over time (Fig. 1, and Fig. S2 in the Supplementary Appendix).”
Quote in the paperNot a substantial claim - Findingown data
At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter to 30 mg per deciliter (P<0.001).
“At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001).”
- Also stated in: § CONCLUSIONS · plain
“In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events.”
Quote in the paperSubstantial claim - Also stated in: § CONCLUSIONS · plain
- Findingown data
The LDL cholesterol-lowering effect of evolocumab was sustained without evidence of attenuation.
“This effect was sustained without evidence of attenuation.”
Quote in the paperNot a substantial claim - Findingown data
The magnitude of the risk reduction with regard to the primary end point tended to increase over time, from 12% (95% CI, 3 to 20) in the first year to 19% (95% CI, 11 to 27) beyond the first year.
“The magnitude of the risk reduction with regard to the primary end point tended to increase over time, from 12% (95% CI, 3 to 20) in the first year to 19% (95% CI, 11 to 27) beyond the first year.”
Quote in the paperNot a substantial claim - Findingown data
There were reductions of 21 to 27% in the risk of myocardial infarction, stroke, and coronary revascularization with evolocumab.
“There were reductions of 21 to 27% in the risk of myocardial infarction, stroke, and coronary revascularization but no observed effect on the rates of hospitalization”
Quote in the paperSubstantial claim - Findingown data
Evolocumab significantly reduced the risk of the key secondary composite end point of cardiovascular death, myocardial infarction, or stroke.
“Likewise, evolocumab significantly reduced the risk of the key secondary composite end point of cardiovascular death, myocardial infarction, or stroke.”
Quote in the paperSubstantial claim - Findingown data
In FOURIER, the addition of evolocumab to statin therapy significantly reduced the risk of the key secondary end point of cardiovascular death, myocardial infarction, or stroke by 20%.
“and a 20% reduction in the risk of the more clinically serious key secondary end point of cardiovascular death, myocardial infarction, or stroke.”
Quote in the paperSubstantial claim - Findingown data
Among patients in the lowest quartile for baseline LDL cholesterol level, evolocumab reduced the risk of the key secondary end point by 22%.
“and there was a 22% reduction in the risk of the key secondary end point among the patients in the lowest quartile for baseline LDL cholesterol level”
Quote in the paperNot a substantial claim - Findingown data
The rate of discontinuation of the study regimen was no higher with evolocumab than with placebo.
“and the rate of discontinuation of the study regimen was no higher with evolocumab than with placebo.”
Quote in the paperNot a substantial claim - Findingown data
Overall, 74 patients would need to be treated over a period of 2 years to prevent a cardiovascular death, myocardial infarction, or stroke.
“Overall, 74 patients would need to be treated over a period of 2 years to prevent a cardiovascular death, myocardial infarction, or stroke.”
Quote in the paperNot a substantial claim - Findingown data
The rates of adjudicated new-onset diabetes did not differ significantly between the evolocumab and placebo groups (hazard ratio, 1.05; 95% CI, 0.94 to 1.17).
“The rates of adjudicated cases of new-onset diabetes did not differ significantly between the two groups (hazard ratio, 1.05; 95% CI, 0.94 to 1.17).”
Quote in the paperNot a substantial claim - Findingown data
The rate of discontinuation of evolocumab injections because of adverse events ascribed to the drug was similar to the rate with placebo (0.76% vs. 0.67% per year).
“The rate of discontinuation of evolocumab injections because of adverse events that were ascribed to the drug was similar to the rate with placebo (0.76% vs. 0.67% per year)”
Quote in the paperSubstantial claim - Findingown data
The benefits of evolocumab with regard to the risk of the primary and key secondary composite end points were largely consistent across major subgroups, including those based on age, sex, and type of atherosclerotic vascular disease.
“The benefits of evolocumab with regard to the risk of the primary and key secondary composite end points were largely consistent across major subgroups, including those based on age, sex, and type of atherosclerotic vascular disease (Fig. S5 in the Supplementary Appendix).”
Quote in the paperSubstantial claim - Findingown data
Among patients in the lowest quartile for baseline LDL cholesterol level, evolocumab lowered the median LDL cholesterol level from 73 mg per deciliter to 22 mg per deciliter.
“in whom evolocumab lowered the median LDL cholesterol level from 73 mg per deciliter (1.9 mmol per liter) to 22 mg per deciliter (0.57 mmol per liter).”
Quote in the paperNot a substantial claim - Findingown data
The rates of allergic reactions did not differ significantly between the evolocumab and placebo groups (3.1% vs. 2.9%).
“The rates of allergic reactions also did not differ significantly between the groups (3.1% vs. 2.9%).”
Quote in the paperNot a substantial claim - Findingown data
In FOURIER, the addition of evolocumab to statin therapy significantly reduced the risk of the primary composite end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization by 15%.
“In this dedicated cardiovascular outcomes trial, we found that the addition of evolocumab to statin therapy significantly reduced the risk of cardiovascular events, with a 15% reduction in the risk of the primary composite end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization”
Quote in the paperSubstantial claim - Findingown data
Potential concerns about an increased risk of neurocognitive adverse events were not borne out in FOURIER.
“Potential concerns about an increased risk of neurocognitive adverse events were not borne out in this trial.”
Quote in the paperNot a substantial claim - Findingown data
When added to statin therapy, evolocumab lowered LDL cholesterol levels by 59% from baseline as compared with placebo, from a median of 92 mg per deciliter to 30 mg per deciliter.
“When added to statin therapy, the PCSK9 inhibitor evolocumab lowered LDL cholesterol levels by 59% from baseline levels as compared with placebo, from a median of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter).”
Quote in the paperSubstantial claim - Findingown data
Evolocumab significantly reduced the risk of the primary composite end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.
“Evolocumab significantly reduced the risk of the primary composite end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.”
- Also stated in: § CONCLUSIONS · plain
“In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events.”
Quote in the paperSubstantial claim - Also stated in: § CONCLUSIONS · plain
- Findingown data
The primary end point occurred in 1344 patients (9.8%) in the evolocumab group and 1563 patients (11.3%) in the placebo group (hazard ratio, 0.85; 95% CI, 0.79 to 0.92; P<0.001).
“The primary end point occurred in 1344 patients (9.8%) in the evolocumab group and in 1563 patients (11.3%) in the placebo group (hazard ratio, 0.85; 95% CI, 0.79 to 0.92; P<0.001) (Table 2 and Fig. 2A).”
Quote in the paperSubstantial claim - Findingown data
Evolocumab had no observed effect on cardiovascular mortality.
“In terms of individual outcomes, evolocumab had no observed effect on cardiovascular mortality, and hence P values for other outcomes should be considered exploratory.”
Quote in the paperSubstantial claim - Findingown data
In FOURIER, the magnitude of risk reduction for the key secondary end point appeared to grow over time, from 16% during the first year to 25% beyond 12 months.
“Likewise, in FOURIER, the magnitude of the risk reduction with regard to the key secondary end point appeared to grow over time, from 16% during the first year to 25% beyond 12 months”
Quote in the paperNot a substantial claim - Findingown data
For the key secondary end point, the risk reduction increased from 16% (95% CI, 4 to 26) in the first year to 25% (95% CI, 15 to 34) beyond the first year.
“Likewise, for the key secondary end point, the risk reduction increased from 16% (95% CI, 4 to 26) in the first year to 25% (95% CI, 15 to 34) beyond the first year (Table S1 and Fig. S4 in the Supplementary Appendix).”
Quote in the paperNot a substantial claim - Findingown data
In FOURIER, there was no effect on hospitalization for unstable angina.
“Similar to the findings in the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) and IMPROVE-IT, in our trial we found no effect on hospitalization for unstable angina.”
Quote in the paperNot a substantial claim - Findingnone given
The rate of use of evidence-based cardiovascular pharmacotherapies that lower cardiovascular mortality was very high in FOURIER.
“The rate of use of evidence-based cardiovascular pharmacotherapies that lower cardiovascular mortality was very high in FOURIER”
Quote in the paperNot a substantial claim - Findingown data
Among patients in the top quartile for baseline LDL cholesterol level, evolocumab lowered the median LDL cholesterol level from 126 mg per deciliter to 43 mg per deciliter.
“in whom evolocumab lowered the median LDL cholesterol level from 126 mg per deciliter (3.3 mmol per liter) to 43 mg per deciliter (1.1 mmol per liter)”
Quote in the paperNot a substantial claim - Findingown data
The benefit of evolocumab was consistent regardless of the intensity of statin therapy or ezetimibe use.
“However, the benefit of evolocumab was consistent regardless of the intensity of statin therapy or ezetimibe use.”
Quote in the paperNot a substantial claim - Study design and conductown data
Ascertainment of the primary end point was complete for 99.5% of potential patient-years of follow-up.
“Ascertainment of the primary end point was complete for 99.5% of potential patient-years of follow-up.”
Quote in the paperSubstantial claim - Premisecitation
Evolocumab reduces LDL cholesterol levels by approximately 60%.
“Evolocumab, a member of this class, is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60%.[2][3][4][5][6]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2][3][4][5][6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Study design and conductown data
The baseline characteristics of the patients in the two groups were well matched.
“The baseline characteristics of the patients in the two groups were well matched and are shown in Table 1.”
Quote in the paperSubstantial claim - Interpretationown data
Patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets.
“These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets.”
Quote in the paperSubstantial claim- Rests on an assumption: The reduction in cardiovascular events with evolocumab is mediated by the lowering of LDL cholesterol.
- Interpretationcitation
The FOURIER observations align with the effects of evolocumab on coronary atherosclerotic plaque volume in the GLAGOV trial.
“These observations align well with the effects of evolocumab on coronary atherosclerotic plaque volume in the Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV) trial 17”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] source
- Interpretationown data
The data from FOURIER provide insight into the benefit of decreasing LDL cholesterol levels to median levels lower than those in previous trials.
“The data from our trial provide insight into the benefit of decreasing LDL cholesterol levels to median levels lower than those in previous trials.”
Quote in the paperSubstantial claim - Interpretationown data
The magnitude of benefit of evolocumab in reducing the risk of major coronary events, stroke, and urgent coronary revascularization is largely consistent with the benefit seen with statins on a per-millimole-per-liter basis of LDL cholesterol lowering.
“Given these caveats, the magnitude of benefit of evolocumab in reducing the risk of major coronary events, stroke, and urgent coronary revascularization is largely consistent with the benefit seen with statins on a per-millimole-perliter basis of LDL cholesterol lowering (Fig. S6 in the Supplementary Appendix).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Fig. S6
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation
Continued cardiovascular benefit can be accrued even when LDL cholesterol levels are reduced to 20 to 25 mg per deciliter, a range well below current targets.
“and show that continued cardiovascular benefit can be accrued even when LDL cholesterol levels are reduced to 20 to 25 mg per deciliter (0.52 to 0.65 mmol per liter), a range that is well below current targets.[18][19][20]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18][19][20]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data
Patients with atherosclerotic cardiovascular disease benefit from lowering LDL cholesterol levels below current targets.
“These findings show that patients with atherosclerotic cardiovascular disease benefit from the lowering of LDL cholesterol levels below current targets.”
Quote in the paperSubstantial claim - Premisecitation
Reassuring findings with evolocumab were observed over a period of 4 years in the OSLER-1 trial.
“Furthermore, similarly reassuring findings with evolocumab were observed over a period of 4 years in the Open Label Study of Long-Term Evaluation against LDL-C Trial (OSLER-1).33”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] Koren MJ, JAMA Cardiol
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- May combine two claims. 15
- Classified as probably not a substantial claim. 11
May combine two claims.
Study design and conductcitationThe size of the patient population was based on the key secondary end point, and 1630 such end-point events were required to provide 90% power to detect a 15% relative risk reduction with evolocumab as compared with placebo.
“The size of the patient population in the trial was based on the key secondary end point, and we estimated that 1630 such end-point events were required to provide 90% power to detect a 15% relative risk reduction with evolocumab as compared with placebo.11”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [11] source
May combine two claims.
PremisecitationCarriage of PCSK9 loss-of-function alleles is associated with lower LDL cholesterol levels and a reduced risk of myocardial infarction.
“Genetic studies have shown that carriage of PCSK9 loss-of-function alleles is associated with lower LDL cholesterol levels and a reduced risk of myocardial infarction.7,8”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [7] source
The Discussion (page unavailable) reports that LDL-lowering PCSK9 variants were associated with reduced coronary heart disease. The Methods (page unavailable) define that outcome as a composite including myocardial infarction, CHD death, and coronary revascularization; the paper does not report a separate reduction in myocardial infarction risk. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [8] source
May combine two claims.
PremisecitationIn IMPROVE-IT, the addition of ezetimibe to statin therapy lowered LDL cholesterol levels from 70 mg per deciliter to 54 mg per deciliter and significantly reduced major cardiovascular events.
“More recently, the addition of ezetimibe to statin therapy in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) lowered LDL cholesterol levels from 70 mg per deciliter (1.8 mmol per liter) to 54 mg per deciliter (1.4 mmol per liter) and significantly reduced major cardiovascular events.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [15] source
May combine two claims.
FindingcitationThe risk of new-onset diabetes in FOURIER appeared to be similar in the two groups, although the 95% confidence intervals did not exclude the point estimates observed with statins.
“The risk of new-onset diabetes in our trial appeared to be similar in the two groups, although the 95% confidence intervals did not exclude the point estimates observed with statins.30,31”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Findingown dataIn the evolocumab group, new binding antibodies developed in 43 patients (0.3%), and no patient developed neutralizing antibodies.
“In the evolocumab group, new binding antibodies developed in 43 patients (0.3%), and development of neutralizing antibodies did not occur in any patient.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataApproximately 90% of injection-site reactions in each group were classified as mild, and only 0.1% of patients in each group stopped receiving the study agent because of an injection-site reaction.
“The large majority of reactions (approximately 90% in each group) were classified as mild, and only 0.1% of the patients in each group stopped receiving the study agent because of an injection-site reaction.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAt 48 weeks, evolocumab reduced non-HDL cholesterol levels by 52% and apolipoprotein B levels by 49% as compared with placebo (P<0.001 for both).
“as compared with placebo, at 48 weeks, evolocumab had reduced non-HDL cholesterol levels by 52% and apolipoprotein B levels by 49% (P<0.001 for both).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingnone givenThe rate of urgent coronary revascularization appeared to be more modifiable than that of elective revascularization.
“Finally, the rate of urgent coronary revascularization appeared to be more modifiable than that of elective revascularization.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNo significant between-group differences were seen in the overall rates of adverse events, serious adverse events, or adverse events thought to be related to the study agent and leading to discontinuation of the study regimen.
“No significant between-group differences were seen in the overall rates of adverse events, serious adverse events, or adverse events thought to be related to the study agent and leading to discontinuation of the study regimen (Table 3).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe benefit of evolocumab was consistent across levels of intensity of statin therapy, regardless of ezetimibe use, and with both the dosing regimen of 140 mg every 2 weeks and that of 420 mg monthly.
“The benefit of evolocumab was also consistent across levels of intensity of statin therapy, regardless of ezetimibe use, and with both the dosing regimen of 140 mg every 2 weeks and that of 420 mg monthly.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
FindingcitationThe rates of cardiovascular mortality in FOURIER were one third of the rates in the Scandinavian Simvastatin Survival Study (4S).
“in which the rates of cardiovascular mortality were one third of the rates in the Scandinavian Simvastatin Survival Study (4S).26”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] Scandinavian Simvastatin Survival Study Group, 1994, Lancet
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Findingown dataInjection-site reactions were rare but were more frequent with evolocumab than with placebo (2.1% vs. 1.6%).
“Injection-site reactions were rare, but they were more frequent with evolocumab (2.1% vs. 1.6%).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAchievement of very low LDL cholesterol levels with evolocumab did not lead to any significant differences between the two study groups in overall rates of adverse events or in rates of study-regimen discontinuation.
“Achievement of these very low LDL cholesterol levels with evolocumab did not lead to any significant differences between the two study groups in the overall rates of adverse events or in rates of study-regimen discontinuation.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataRandomization was performed in a double-blinded manner with the use of a central computerized system, with stratification according to final screening LDL cholesterol level and region.
“Randomization was performed in a double-blinded manner with the use of a central computerized system, with stratification according to the final screening LDL cholesterol level (<85 or ≥85 mg per deciliter [<2.2 or ≥2.2 mmol per liter]) and region.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductown dataPremature permanent discontinuation of the study regimen occurred in 12.5% of patients (5.7% per year), withdrawal of consent in 0.7% (0.3% per year), and loss to follow-up in less than 0.1% (0.03% per year), with similar rates in the two study groups.
“Premature permanent discontinuation of the study regimen occurred in 12.5% of patients (5.7% per year), withdrawal of consent in 0.7% (0.3% per year), and loss to follow-up in less than 0.1% (0.03% per year), with similar rates in the two study groups”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenA central clinical-events committee whose members were unaware of study-group assignments and lipid levels adjudicated all potential efficacy end-point events and cases of new-onset diabetes.
“A central clinicalevents committee led by the TIMI Study Group, whose members were unaware of study-group assignments and lipid levels, adjudicated all potential efficacy end-point events and cases of new-onset diabetes.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenAll efficacy analyses were conducted on an intention-to-treat basis.
“All efficacy analyses were conducted on an intentionto-treat basis.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataThe FOURIER trial was a randomized, double-blind, placebo-controlled, multinational clinical trial.
“The FOURIER trial was a randomized, doubleblind, placebo-controlled, multinational clinical trial in which patients at 1242 sites in 49 countries underwent randomization”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe raw database was provided to the TIMI Study Group, which conducted data analyses independently of the sponsor.
“The raw database was provided to the Thrombolysis in Myocardial Infarction (TIMI) Study Group, which conducted data analyses independently of the sponsor.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataA total of 27,525 patients (99.9%) received at least one dose of a study agent.
“A total of 27,525 patients (99.9%) received at least one dose of a study agent.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataMost but not all patients in FOURIER received high-intensity statin therapy.
“Most but not all of the patients in the trial received high-intensity statin therapy”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataEzetimibe use was infrequent in FOURIER.
“and ezetimibe use was infrequent.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAlthough the median follow-up period in FOURIER was originally planned to be approximately 4 years, an event rate approximately 50% higher than postulated led to a shorter required duration of follow-up to accrue the prespecified number of events.
“Although the median follow-up period in FOURIER was originally planned to be approximately 4 years, an event rate that was approximately 50% higher than had been postulated led to a shorter required duration of follow-up to accrue the prespecified number of events.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The reduction in cardiovascular events with evolocumab is mediated by the lowering of LDL cholesterol.
“These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The FOURIER open-label extension study reported a 14.0% overall premature discontinuation rate over 5 years among 6,635 patients randomized to evolocumab.
“Regarding the persistence phase, the FOURIER open-label extension study reported a 14.0% overall premature discontinuation rate over 5 years among 6,635 patients randomized to evolocumab.115,116”
From Adherence to PCSK9 Inhibitors in Clinical Practice (2026) · cites this paper as [115]
The Trial Design and Oversight section describes FOURIER as a randomized, double-blind, placebo-controlled trial, not an open-label extension. The Patients section reports 13,784 patients randomized to evolocumab, 12.5% premature permanent discontinuation, and a median follow-up of 26 months—not 6,635 patients, 14.0%, and five years. No page numbers are available in our copy. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe relative and absolute reductions in MACE observed in this analysis are similar in magnitude to those observed for ezetimibe in IMPROVE-IT and evolocumab in FOURIER, with similarly non-significant reductions in all-cause and cardiovascular mortality.
“The relative and absolute reductions in MACE observed in our analysis are similar in magnitude to those observed for the seminal IMPROVE-IT [3] and FOURIER [4] trials for ezetimibe and evolocumab respectively, with similarly non-significant reductions in all-cause and cardiovascular mortality.”
From The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials (2024) · cites this paper as [4]
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredSerious safety concerns were not observed with evolocumab in the FOURIER trial, which had no lower limit for allowable LDL cholesterol levels.
“Serious safety concerns were also not observed with evolocumab in the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial, 11 which had no lower limit for allowable LDL cholesterol levels”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [11]
The Safety results report nearly identical serious-adverse-event rates with evolocumab and placebo (24.8% versus 24.7%), supporting the absence of an observed serious safety signal during the trial. The Lipid Data section reports that many patients reached very low LDL cholesterol levels, but our copy does not state that the trial had no lower limit for allowable LDL levels. (LLM, conf=0.85)
Experimental — accuracy not yet measuredClinically approved PCSK9-targeting antibodies, including evolocumab and alirocumab, systemically reduce LDL-C and have shown acceptable tolerability in large cardiovascular outcome studies.
“This change is not necessarily a toxicity signal, because clinically approved PCSK9-targeting antibodies, including evolocumab and alirocumab, systemically reduce LDL-C and have shown acceptable tolerability in large cardiovascular outcome studies [ 65-67 ].”
From Restores Aβ Clearance by Overcoming PCSK9–LRP1 Dysregulation and TRIB3‐Mediated Autophagy Blockade in Alzheimer's Disease (2026) · cites this paper as [65]
The Methods and Results describe a large cardiovascular outcomes trial in which evolocumab lowered LDL-C, with no significant difference in overall adverse events versus placebo except for more injection-site reactions. This paper did not test alirocumab in that trial; it mentions alirocumab only through a cited earlier study, so it does not establish the claim about both antibodies in large outcomes studies. The passages also do not establish their regulatory approval status. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPCSK9 inhibition safely lowers LDL-C levels (absolute reduction 56 mg/dl, 95% CI 55-57; relative reduction 59%, 95% CI 58-60) and reduces the number of cardiovascular events.
“Both have unequivocally shown that PCSK9 inhibition safely lowers LDL-C levels [56 mg/dl absolute reduction (95% confidence interval 55–57) or 59% relative reduction (95% confidence interval 58–60)] alone or on top of maximally tolerated lipid-lowering therapies (i.e. high-doses statins with or without ezetimibe) and reduces the number of cardiovascular events.”
From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [9]
The Lipid Data section reports a 56 mg/dl absolute LDL-C reduction (95% CI, 55–57) and a 59% relative reduction (95% CI, 58–60). The Discussion reports fewer cardiovascular events and few excess adverse events. However, this trial tested evolocumab on a background of statin therapy in patients with cardiovascular disease; it does not establish the cited effects when PCSK9 inhibition is used alone. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Trials of PCSK9 inhibitors in cardiovascular populations consistently showed substantial reductions in LDL cholesterol without negative cognitive effects.
“Trials of PCSK9 inhibitors in cardiovascular populations consistently showed substantial reductions in LDL cholesterol without negative cognitive effects [11,22].”
From The Roles of PCSK9 in Alzheimer’s Disease: A Systematic Review of Clinical, Genetic, and Preclinical Evidence (2025) · cites this paper as [11]
The Results report a 59% LDL-cholesterol reduction with evolocumab and no significant difference in neurocognitive events versus placebo. The Discussion says concerns about neurocognitive adverse events were not borne out in this trial. This supports the claim for evolocumab in FOURIER, but does not establish that trials of PCSK9 inhibitors generally and consistently found the same cognitive result. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAny protective effects of PCSK9 inhibitors seen in laboratory studies probably occur through an indirect route, likely from improved systemic cholesterol levels and better overall vascular health rather than from direct action within the brain.
“This suggests that any protective effects seen in laboratory studies probably occur through an indirect route. The benefits likely stem from improved systemic cholesterol levels and better overall vascular health, rather than from the drugs acting directly within the brain [11,27,50].”
From The Roles of PCSK9 in Alzheimer’s Disease: A Systematic Review of Clinical, Genetic, and Preclinical Evidence (2025) · cites this paper as [11]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIntensive therapy is indicated because cardiovascular event rates are increased in people with diabetes and established ASCVD, and it has been shown to be of benefit in multiple large meta-analyses and randomized cardiovascular outcomes trials.
“Intensive therapy is indicated because cardiovascular event rates are increased in people with diabetes and established ASCVD, and it has been shown to be of benefit in multiple large meta-analyses and randomized cardiovascular outcomes trials (99,100,108,119,121).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [121]
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredNo change in cognitive function has been reported in studies with the addition of ezetimibe or PCSK9 inhibitors to statin therapy, including among individuals treated to very low LDL cholesterol levels.
“In addition, no change in cognitive function has been reported in studies with the addition of ezetimibe (119) or PCSK9 inhibitors (121,170) to statin therapy, including among individuals treated to very low LDL cholesterol levels.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [121]
The Results report no significant difference in neurocognitive adverse events between evolocumab and placebo, and the Lipid Data section shows that many evolocumab-treated patients reached very low LDL cholesterol levels. The paper does not report cognitive-function testing or establish the absence of cognitive changes specifically among patients who reached those levels. The ezetimibe finding has a separate citation in the citing sentence and is not attributed to this paper. (LLM, conf=0.83)
Experimental — accuracy not yet measuredWhen added to a maximally tolerated statin, PCSK9 monoclonal antibodies significantly reduced the risk of major adverse cardiovascular events by 15-20% in the FOURIER and ODYSSEY OUTCOMES trials.
“When added to a maximally tolerated statin, these agents reduced LDL cholesterol by ∼60% (115) and significantly reduced the risk of major adverse cardiovascular events by 15–20% in the FOURIER (evolocumab) and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trials (115,117,122).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [115]
The Discussion reports that adding evolocumab to statin therapy in FOURIER significantly reduced the primary composite cardiovascular endpoint by 15% and the key secondary endpoint by 20%. The Trial Population section describes an optimized statin regimen, preferably high-intensity, but does not establish that every participant received a maximally tolerated dose. This paper reports FOURIER, not ODYSSEY OUTCOMES; the citing sentence supplies other citations for its combined trial claim. (LLM, conf=0.85)
Experimental — accuracy not yet measuredWhen added to a maximally tolerated statin, PCSK9 monoclonal antibodies reduced LDL cholesterol by ∼60%.
“When added to a maximally tolerated statin, these agents reduced LDL cholesterol by ∼60% (115) and significantly reduced the risk of major adverse cardiovascular events by 15–20% in the FOURIER (evolocumab) and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trials (115,117,122).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [115]
The Discussion reports that adding evolocumab to statin therapy lowered LDL cholesterol by 59% versus placebo, supporting the approximate 60% figure. The Trial Population section describes an optimized statin regimen, preferably high-intensity but permitting at least atorvastatin 20 mg daily or equivalent; it does not establish that every patient was taking a maximally tolerated dose. The trial directly tested evolocumab, not PCSK9 monoclonal antibodies as a group. Page numbers are not available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNo change in cognitive function has been reported in studies with the addition of ezetimibe or PCSK9 monoclonal antibodies to statin therapy, including among individuals treated to very low LDL cholesterol levels.
“In addition, no change in cognitive function has been reported in studies with the addition of ezetimibe (112) or PCSK9 monoclonal antibodies (115,164) to statin therapy, including among individuals treated to very low LDL cholesterol levels.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [115]
The Results report no significant difference in neurocognitive events between evolocumab and placebo when added to statin therapy; Table 3 gives rates of 1.6% and 1.5%. The paper also reports a median LDL cholesterol level of 30 mg/dL with evolocumab. It does not report a direct measure of cognitive function or a separate cognitive analysis of patients who reached very low LDL levels. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAddition of injectable agents like evolocumab or alirocumab to intensive statin therapy lowers LDL-C by roughly 50-60% and reduces major adverse cardiovascular events in high-risk populations.
“PCSK9 inhibition has emerged as a potent therapeutic modality, with large outcome trials showing that the addition of injectable agents like evolocumab or alirocumab to intensive statin therapy lowers LDL-C by roughly 50–60% and reduces major adverse cardiovascular events in high-risk populations [2,3].”
From Oral PCSK9 inhibitors for elevated LDL-C: A systematic review and meta-analysis of randomized trials (2026) · cites this paper as [2]
The Results and Discussion report that adding evolocumab to statin therapy lowered LDL-C by 59% and reduced cardiovascular events in patients with atherosclerotic cardiovascular disease. The Trial Population section says high-intensity statins were preferred but moderate-intensity therapy was also permitted, so the finding is not limited to intensive statin therapy. This paper's outcome trial tested evolocumab, not alirocumab. (LLM, conf=0.85)
Experimental — accuracy not yet measuredBempedoic acid increased the risk of gout, renal impairment, and cholelithiasis, none of which were significantly increased with ezetimibe or evolocumab.
“However, BA increased the risk of gout, renal impairment, and cholelithiasis, none of which were significantly increased with ezetimibe or evolocumab.”
From The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials (2024) · cites this paper as [4]
The Safety section reports no significant difference in overall adverse events between evolocumab and placebo, supporting the general safety comparison. It does not report separate results for gout, renal impairment, or cholelithiasis; bempedoic acid and ezetimibe were not the treatments compared in this trial. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPCSK9 inhibitory antibodies and siRNA potently reduce LDL cholesterol to unprecedented low levels and are approved for treatment of hypercholesterolemia.
“Accordingly, PCSK9 inhibitory antibodies and siRNA potently reduce LDL cholesterol to unprecedented low levels and are approved for treatment of hypercholesterolemia.”
From PCSK9 deficiency alters brain lipid composition without affecting brain development and function (2023) · cites this paper as Sabatine et al., 2017
The introduction (p. 1714) says PCSK9-inhibiting monoclonal antibodies effectively lower LDL cholesterol, and the Discussion reports that evolocumab lowered it by 59% to a median of 30 mg/dL—below levels in previous trials. The paper does not establish the claim about siRNA or state that both antibodies and siRNA are approved for hypercholesterolemia. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPCSK9 siRNA and monoclonal antibodies blocking the PCSK9/LDLR interaction potently lower LDL cholesterol and reduce the risk of adverse cardiovascular events.
“Accordingly, PCSK9 siRNA and monoclonal antibodies blocking the PCSK9/LDLR interaction potently lower LDL cholesterol and reduce the risk of adverse cardiovascular events (Sabatine et al., 2017; Schwartz et al., 2018; Ray et al., 2020).”
From PCSK9 deficiency alters brain lipid composition without affecting brain development and function (2023) · cites this paper as Sabatine et al., 2017
The introduction (p. 1714) identifies evolocumab as a PCSK9-inhibiting monoclonal antibody, and the Discussion reports that it lowered LDL cholesterol by 59% and reduced cardiovascular events when added to statins. The paper does not establish those effects for PCSK9 siRNA, so it supports the antibody portion of the citing sentence but not the siRNA portion. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTwo PCSK9 antibodies reduce the risk of ischemic cardiovascular events in patients with stable atherosclerotic disease or high cardiovascular risk and elevated atherogenic lipoproteins despite statin treatment.
“Two of these agents were reported to reduce the risk of ischemic cardiovascular events in patients who had stable atherosclerotic disease or high cardiovascular risk and an elevated level of atherogenic lipoproteins despite statin treatment, 11,13”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [11]
Monoclonal antibodies to PCSK9 produce substantial reductions in LDL cholesterol when administered alone or with a statin.
“These findings have led to the development of monoclonal antibodies to PCSK9 that produce substantial reductions in LDL cholesterol when administered alone or with a statin. 8-12”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [11]
The FOURIER trial had a shorter median follow-up, and very few patients were followed for 3 or more years.
“however, that trial had a shorter median follow-up, and very few patients were followed for 3 or more years.”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [11]
Large cardiovascular trials of PCSK9 antibodies such as evolocumab have not demonstrated cognitive harm.
“large cardiovascular trials of PCSK9 antibodies such as evolocumab have not demonstrated cognitive harm10,43”
From Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses microglial inflammation in Alzheimer’s disease models (2026) · cites this paper as [10]
The SIRIUS in silico trial estimated that inclisiran could reduce the risk of 3-point MACE by 25% over 5 years compared to placebo, when added to high-intensity statins with or without ezetimibe.
“This innovative approach, calibrated and validated against major outcome trials such as FOURIER19 and ORION-10, estimated that inclisiran could reduce the risk of 3-point MACE by 25% over 5 years compared to placebo, when added to high-intensity statins with or without ezetimibe.”
From Small Interfering RNA for LDL-Cholesterol Reduction (2026) · cites this paper as [19]
Injectable PCSK9 inhibitors are an established strategy to lower LDL-C and reduce atherosclerotic cardiovascular disease risk.
“Injectable proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an established strategy to lower low-density lipoprotein cholesterol (LDL-C) and reduce atherosclerotic cardiovascular disease risk.”
From Oral PCSK9 inhibitors for elevated LDL-C: A systematic review and meta-analysis of randomized trials (2026) · cites this paper as [2]
Evolocumab reduced LDL-C by ∼59% and alirocumab by ∼60% in the FOURIER and ODYSSEY OUTCOMES trials, respectively.
“In comparison, evolocumab reduced LDL-C by ∼59% and alirocumab by ∼60% in the FOURIER and ODYSSEY OUTCOMES trials, respectively [2,3]”
From Oral PCSK9 inhibitors for elevated LDL-C: A systematic review and meta-analysis of randomized trials (2026) · cites this paper as [2]
Ezetimibe, evolocumab, and alirocumab reduce LDL-C and cardiovascular events, based on the IMPROVE-IT, FOURIER, and ODYSSEY Outcomes trials respectively.
“The main alternative treatments indicated to lower LDL-C and cardiovascular risk are ezetimibe, evolocumab, and alirocumab based on the IMPROVE-IT [3], FOURIER [4], and ODYSSEY Outcomes [5] trials respectively, wherein the 3 treatments resulted in significant reductions in LDL-C and cardiovascular events.”
From The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials (2024) · cites this paper as [4]
Evolocumab in FOURIER reduced Lp(a) by a median of 26.9% at 48 weeks, and alirocumab in ODYSSEY OUTCOMES showed a median relative reduction of −23% by 4 months.
“evolocumab in the FOURIER trial reduced Lp(a) by a median of 26.9% at 48 weeks[2,25], and alirocumab in ODYSSEY OUTCOMES showed a median relative reduction of −23% by 4 months[3,26].”
From Oral PCSK9 inhibitors for elevated LDL-C: A systematic review and meta-analysis of randomized trials (2026) · cites this paper as [2]
The Characteristics section reports baseline lipoprotein(a) levels, while Lipid Data reports 48-week reductions in LDL cholesterol and other lipid measures. Our copy does not report a 48-week lipoprotein(a) reduction of 26.9% (searched: lipoprotein(a), Lp(a), and 26.9%). The alirocumab clause has separate citations and is not attributed to this source. (LLM, conf=0.76)
Experimental — accuracy not yet measuredEvolocumab showed a 17% relative risk reduction of a composite primary endpoint of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization in patients with diabetes included in the FOURIER trial (HR 0.83; 95% CI, 0.75-0.93; P = 0.0008).
“In particular, evolocumab showed a 17% RR reduction of a composite primary endpoint of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization in patients with diabetes included in the FOURIER trial (HR 0.83; 95% CI, 0.75-0.93;P = 0.0008).263”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [263]
Cumulative FOURIER and ODYSSEY OUTCOMES data suggest PCSK9 inhibitors lower LDL cholesterol and cardiovascular risk effectively in coronary disease regardless of diabetes status.
“the cumulative data from the FOURIER and ODYSSEY OUTCOMES trials suggest that PCSK9 inhibitors effectively lower LDL-C and cardiovascular risk in individuals with CAD regardless of diabetes mellitus status.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [125]
Neither PCSK9 inhibitor reduced cardiovascular mortality in FOURIER or ODYSSEY OUTCOMES.
“Although neither PCSK9 inhibitor reduced cardiovascular mortality in these trials,125,126”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [125]
The best evidence to support lower LDL cholesterol targets in people with diabetes and established cardiovascular disease derives from multiple large randomized trials investigating the benefits of adding nonstatin agents to statin therapy.
“However, the best evidence to support lower LDL cholesterol targets in people with diabetes and established cardiovascular disease derives from multiple large randomized trials investigating the benefi ts of adding nonstatin agents to statin therapy.”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [108]
Cardiovascular event rates are increased in people with diabetes and established ASCVD, and intensive therapy has been shown to be of benefit in multiple large meta-analyses and randomized cardiovascular outcomes trials.
“Because cardiovascular event rates are increased in people with diabetes and established ASCVD, intensive therapy is indicated and has been shown to be of bene fi t in multiple large meta-analyses and randomized cardiovascular outcomes trials (91,99,105,107,108).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [108]
In FOURIER, during median follow-up of 2.2 years, the composite outcome of cardiovascular death, MI, stroke, hospitalization for angina, or revascularization occurred in 11.3% versus 9.8% of placebo and evolocumab groups, a 15% relative risk reduction.
“During the median follow-up of 2.2 years, the composite outcome of cardiovascular death, MI, stroke, hospitalization for angina, or revascularization occurred in 11.3% vs. 9.8% of the placebo and evolocumab groups, respectively, representing a 15% relative risk reduction (P < 0.001).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [108]
In FOURIER, evolocumab reduced LDL cholesterol by 59% from a median of 92 to 30 mg/dL.
“Evolocumab reduced LDL cholesterol by 59% from a median of 92 to 30 mg/dL in the treatment arm.”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [108]
In FOURIER, the combined endpoint of cardiovascular death, MI, or stroke was reduced by 20%, from 7.4 to 5.9%.
“The combined end point of cardiovascular death, MI, or stroke was reduced by 20%, from 7.4 to 5.9% ( P < 0.001).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [108]
Each of these trials found a significant benefit in reduction of ASCVD events directly related to the degree of further LDL cholesterol lowering.
“Each trial found a signi fi cant bene fi t in the reduction of ASCVD events that was directly related to the degree of further LDL cholesterol lowering.”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [108]
Cites
Stone, N. J., Robinson, J. G., Lichtenstein, A. H., Bairey Merz, C. N., Blum, C. B., Eckel, R. H., Goldberg, A. C., Gordon, D., Levy, D., Lloyd-Jones, D. M., et al. (2014) · Circulation · doi:10.1161/01.cir.0000437738.63853.7a · Cited by 7,081 · see citing works
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550 · see citing works
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Cannon, C. P., Braunwald, E., McCabe, C. H., Rader, D. J., Rouleau, J. L., Belder, R., Joyal, S. V., Hill, K. A., Pfeffer, M. A., & Skene, A. M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040583 · Cited by 4,938 · see citing works
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., Darius, H., Lewis, B. S., Ophuis, T. O., Jukema, J. W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1410489 · Cited by 4,487 · see citing works
Self-citationHelsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle-Aged Men with Dyslipidemia
Frick, M. H., Elo, O., Haapa, K., Heinonen, O. P., Heinsalmi, P., Helo, P., Huttunen, J. K., Kaitaniemi, P., Koskinen, P., Manninen, V., et al. (1987) · New England Journal of Medicine · doi:10.1056/nejm198711123172001 · Cited by 3,881 · see citing works
Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease
LaRosa, J. C., Grundy, S. M., Waters, D. D., Shear, C., Barter, P., Fruchart, J.-C., Gotto, A. M., Greten, H., Kastelein, J. J. P., Shepherd, J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050461 · Cited by 3,489 · see citing works
Sequence Variations in <i>PCSK9,</i> Low LDL, and Protection against Coronary Heart Disease
Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054013 · Cited by 3,181 · see citing works
Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials
Sattar, N., Preiss, D., Murray, H. M., Welsh, P., Buckley, B. M., de Craen, A. J., Seshasai, S. R. K., McMurray, J. J., Freeman, D. J., Jukema, J. W., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61965-6 · Cited by 2,436 · see citing works
Self-citationEfficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
Robinson, J. G., Farnier, M., Krempf, M., Bergeron, J., Luc, G., Averna, M., Stroes, E. S., Langslet, G., Raal, F. J., El Shahawy, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501031 · Cited by 2,296 · see citing works
Interpretation of the evidence for the efficacy and safety of statin therapy
Collins, R., Reith, C., Emberson, J., Armitage, J., Baigent, C., Blackwell, L., Blumenthal, R., Danesh, J., Smith, G. D., DeMets, D., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31357-5 · Cited by 1,857 · see citing works
Self-citationEfficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
Sabatine, M. S., Giugliano, R. P., Wiviott, S. D., Raal, F. J., Blom, D. J., Robinson, J., Ballantyne, C. M., Somaratne, R., Legg, J., Wasserman, S. M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500858 · Cited by 1,509 · see citing works
Self-citationSilverman, M. G., Ference, B. A., Im, K., Wiviott, S. D., Giugliano, R. P., Grundy, S. M., Braunwald, E., & Sabatine, M. S. (2016) · JAMA · doi:10.1001/jama.2016.13985 · Cited by 1,483 · see citing works
Self-citationPreiss, D. (2011) · JAMA · doi:10.1001/jama.2011.860 · Cited by 1,390 · see citing works
Nicholls, S. J., Puri, R., Anderson, T., Ballantyne, C. M., Cho, L., Kastelein, J. J. P., Koenig, W., Somaratne, R., Kassahun, H., Yang, J., et al. (2016) · JAMA · doi:10.1001/jama.2016.16951 · Cited by 1,178 · see citing works
Self-citationBuchwald, H., Varco, R. L., Matts, J. P., Long, J. M., Fitch, L. L., Campbell, G. S., Pearce, M. B., Yellin, A. E., Edmiston, W. A., Smink, R. D., et al. (1990) · New England Journal of Medicine · doi:10.1056/nejm199010043231404 · Cited by 1,001 · see citing works
Raal, F. J., Stein, E. A., Dufour, R., Turner, T., Civeira, F., Burgess, L., Langslet, G., Scott, R., Olsson, A. G., Sullivan, D., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61399-4 · Cited by 756 · see citing works
Self-citationVariation in<i>PCSK9</i>and<i>HMGCR</i>and Risk of Cardiovascular Disease and Diabetes
Ference, B. A., Robinson, J. G., Brook, R. D., Catapano, A. L., Chapman, M. J., Neff, D. R., Voros, S., Giugliano, R. P., Davey Smith, G., Fazio, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1604304 · Cited by 743 · see citing works
Self-citationA 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
Blom, D. J., Hala, T., Bolognese, M., Lillestol, M. J., Toth, P. D., Burgess, L., Ceska, R., Roth, E., Koren, M. J., Ballantyne, C. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1316222 · Cited by 720 · see citing works
Self-citationAnti-PCSK9 Antibody Effectively Lowers Cholesterol in Patients With Statin Intolerance
Stroes, E., Colquhoun, D., Sullivan, D., Civeira, F., Rosenson, R. S., Watts, G. F., Bruckert, E., Cho, L., Dent, R., Knusel, B., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.019 · Cited by 526 · see citing works
Self-citationRobinson, J. G., Nedergaard, B. S., Rogers, W. J., Fialkow, J., Neutel, J. M., Ramstad, D., Somaratne, R., Legg, J. C., Nelson, P., Scott, R., et al. (2014) · JAMA · doi:10.1001/jama.2014.4030 · Cited by 496 · see citing works
Self-citationLloyd-Jones, D. M., Morris, P. B., Ballantyne, C. M., Birtcher, K. K., Daly, D. D., DePalma, S. M., Minissian, M. B., Orringer, C. E., & Smith, S. C. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.03.519 · Cited by 459 · see citing works
Anti-PCSK9 Monotherapy for Hypercholesterolemia
Koren, M. J., Lundqvist, P., Bolognese, M., Neutel, J. M., Monsalvo, M. L., Yang, J., Kim, J. B., Scott, R., Wasserman, S. M., & Bays, H. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.018 · Cited by 411 · see citing works
Self-citationEfficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
Sabatine, M. S., Giugliano, R. P., & Wiviott, S. D. (2015) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2015.08.004 · Cited by 360 · see citing works
Self-citationUnstable Angina: Is It Time for a Requiem?
Braunwald, E., & Morrow, D. A. (2013) · Circulation · doi:10.1161/circulationaha.113.001258 · Cited by 226 · see citing works
Are PCSK9 Inhibitors the Next Breakthrough in the Cardiovascular Field?
Giugliano, R. P., & Sabatine, M. S. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.05.001 · Cited by 197 · see citing works
Self-citationA<i>PCSK9</i>Missense Variant Associated with a Reduced Risk of Early-Onset Myocardial Infarction
Kathiresan, S. (2008) · New England Journal of Medicine · doi:10.1056/nejmc0707445 · Cited by 183 · see citing works
Sabatine, M. S., Giugliano, R. P., Keech, A., Honarpour, N., Wang, H., Liu, T., Wasserman, S. M., Scott, R., Sever, P. S., & Pedersen, T. R. (2016) · American Heart Journal · doi:10.1016/j.ahj.2015.11.015 · Cited by 176 · see citing works
Self-citationKoren, M. J., Sabatine, M. S., Giugliano, R. P., Langslet, G., Wiviott, S. D., Kassahun, H., Ruzza, A., Ma, Y., Somaratne, R. M., & Raal, F. J. (2017) · JAMA Cardiology · doi:10.1001/jamacardio.2017.0747 · Cited by 167 · see citing works
Self-citationLandmesser, U., Chapman, M. J., Farnier, M., Gencer, B., Gielen, S., Hovingh, G. K., Lüscher, T. F., Sinning, D., Tokgözoğlu, L. S., Wiklund, O., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw480 · Cited by 161 · see citing works
Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes
Cannon, C. P., D, E. B. M., & al, C. H. M. (2004) · ACC Current Journal Review · doi:10.1016/j.accreview.2004.04.071 · Cited by 18 · see citing works
Raal, F. J., Stein, E. A., & Dufour, R. (2015) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2015.09.006 · Cited by 9 · see citing works
Giugliano, R. P., Cannon, C. P., Blazing, M. A., White, J. A., Murphy, S. A., Tershakovec, A. M., Musliner, T., Califf, R. M., & D, E. B. M. (2015) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(15)60004-3 · Cited by 7 · see citing works
Self-citationIntensive Lipid Lowering With Atorvastatin in Patients With Stable Coronary Disease
LaRosa, J. C., Grundy, S. M., & Waters, D. D. (2005) · ACC Current Journal Review · doi:10.1016/j.accreview.2005.05.022 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Landmesser U, Eur Heart J
- Sabatine MS, Eur Heart J
- Scandinavian Simvastatin Survival Study Group, 1994, Lancet, 344, 1383
- Koren MJ, JAMA Cardiol
Cited by
Sorted by citations
Ibanez, B., James, S., Agewall, S., Antunes, M. J., Bucciarelli-Ducci, C., Bueno, H., Caforio, A. L. P., Crea, F., Goudevenos, J. A., Halvorsen, S., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehx393 · Cited by 9,728 · see citing works
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482 · see citing works
2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes
Knuuti, J., Wijns, W., Saraste, A., Capodanno, D., Barbato, E., Funck-Brentano, C., Prescott, E., Storey, R. F., Deaton, C., Cuisset, T., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz425 · Cited by 7,166 · see citing works
2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Bäck, M., Benetos, A., Biffi, A., Boavida, J.-M., Capodanno, D., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab484 · Cited by 6,485 · see citing works
Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000625 · Cited by 6,185 · see citing works
Collet, J.-P., Thiele, H., Barbato, E., Barthélémy, O., Bauersachs, J., Bhatt, D. L., Dendale, P., Dorobantu, M., Edvardsen, T., Folliguet, T., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehaa575 · Cited by 5,037 · see citing works
2023 ESC Guidelines for the management of acute coronary syndromes
Byrne, R. A., Rossello, X., Coughlan, J. J., Barbato, E., Berry, C., Chieffo, A., Claeys, M. J., Dan, G.-A., Dweck, M. R., Galbraith, M., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad191 · Cited by 5,333 · see citing works
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854 · see citing works
Self-citationReading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians
Davies, N. M., Holmes, M. V., & Davey Smith, G. (2018) · BMJ · doi:10.1136/bmj.k601 · Cited by 4,404 · see citing works
Ference, B. A., Ginsberg, H. N., Graham, I., Ray, K. K., Packard, C. J., Bruckert, E., Hegele, R. A., Krauss, R. M., Raal, F. J., Schunkert, H., et al. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx144 · Cited by 3,962 · see citing works
Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome
Schwartz, G. G., Steg, P. G., Szarek, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Edelberg, J. M., Goodman, S. G., Hanotin, C., Harrington, R. A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1801174 · Cited by 3,634 · see citing works
Aboyans, V., Ricco, J.-B., Bartelink, M.-L. E. L., Björck, M., Brodmann, M., Cohnert, T., Collet, J.-P., Czerny, M., De Carlo, M., Debus, S., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehx095 · Cited by 3,293 · see citing works
Kleindorfer, D. O., Towfighi, A., Chaturvedi, S., Cockroft, K. M., Gutierrez, J., Lombardi-Hill, D., Kamel, H., Kernan, W. N., Kittner, S. J., Leira, E. C., et al. (2021) · Stroke · doi:10.1161/str.0000000000000375 · Cited by 3,237 · see citing works
Libby, P., Buring, J. E., Badimon, L., Hansson, G. K., Deanfield, J., Bittencourt, M. S., Tokgözoğlu, L., & Lewis, E. F. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0106-z · Cited by 3,211 · see citing works
The changing landscape of atherosclerosis
Libby, P. (2021) · Nature · doi:10.1038/s41586-021-03392-8 · Cited by 2,873 · see citing works
2024 ESC Guidelines for the management of chronic coronary syndromes
Vrints, C. J., Andreotti, F., Koskinas, K. C., Rosselló, X., Adamo, M., Ainslie, J., BANNING, A. P., Budaj, A., Buechel, R. R., Chiariello, G. A., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae177 · Cited by 3,314 · see citing works
Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.003 · Cited by 2,691 · see citing works
Colchicine in Patients with Chronic Coronary Disease
Nidorf, S. M., Fiolet, A. T. L., Mosterd, A., Eikelboom, J. W., Schut, A., Opstal, T. S. J., The, S. H. K., Xu, X.-F., Ireland, M. A., Lenderink, T., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2021372 · Cited by 2,299 · see citing works
Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.002 · Cited by 1,751 · see citing works
Immunity and Inflammation in Atherosclerosis
Wolf, D., & Ley, K. F. (2019) · Circulation Research · doi:10.1161/circresaha.118.313591 · Cited by 1,764 · see citing works
The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019)
Umemura, S., Arima, H., Arima, S., Asayama, K., Dohi, Y., Hirooka, Y., Horio, T., Hoshide, S., Ikeda, S., Ishimitsu, T., et al. (2019) · Hypertension Research · doi:10.1038/s41440-019-0284-9 · Cited by 1,880 · see citing works
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Ray, K. K., Wright, R. S., Kallend, D., Koenig, W., Leiter, L. A., Raal, F. J., Bisch, J. A., Richardson, T., Jaros, M., Wijngaard, P. L. J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1912387 · Cited by 1,665 · see citing works
Greenberg, S. M., Ziai, W., Cordonnier, C., Dowlatshahi, D. D., Francis, B. A., Goldstein, J. N., Hemphill, J. C., Johnson, R., Keigher, K. M., Mack, W. J., et al. (2022) · Stroke · doi:10.1161/str.0000000000000407 · Cited by 1,700 · see citing works
2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
Marx, N., Federici, M., Schütt, K., Müller-Wieland, D., Ajjan, R. A., Antunes, M. J., Christodorescu, R. M., Crawford, C., Di Angelantonio, E., Eliasson, B., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad192 · Cited by 1,642 · see citing works
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz962 · Cited by 1,601 · see citing works
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001168 · Cited by 1,598 · see citing works
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“Beta-blocker 1357/4142 (33) 672/2070 (32) 685/2072 (33)”
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Paunovska, K., Loughrey, D., & Dahlman, J. E. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00439-4 · Cited by 1,349 · see citing works
Anderson, T. J., Grégoire, J., Pearson, G. J., Barry, A. R., Couture, P., Dawes, M., Francis, G. A., Genest, J., Grover, S., Gupta, M., et al. (2016) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2016.07.510 · Cited by 1,173 · see citing works
Oikonomou, E. K., Marwan, M., Desai, M. Y., Mâncio, J., Alashi, A., Hutt, E., Thomas, S., Herdman, L., Kotanidis, C. P., Thomas, K. E. H., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31114-0 · Cited by 1,193 · see citing works
Jellinger, P. S., Handelsman, Y., Rosenblit, P. D., Bloomgarden, Z. T., Fonseca, V. A., Garber, A. J., Grunberger, G., Guerin, C. K., Bell, D. S. H., Mechanick, J. I., et al. (2017) · Endocrine Practice · doi:10.4158/ep171764.appgl · Cited by 1,094 · see citing works
Reducing the Global Burden of Cardiovascular Disease, Part 1
Joseph, P. G., Leong, D. P., McKee, M., Anand, S. S., Schwalm, J.-D., Teo, K. K., Mente, A., & Yusuf, S. (2017) · Circulation Research · doi:10.1161/circresaha.117.308903 · Cited by 1,089 · see citing works
Effects of anacetrapib in patients with atherosclerotic vascular disease
The HPS3/TIMI55–REVEAL Collaborative Group (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1706444 · Cited by 1,047 · see citing works
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O’Donoghue, M. L., Fazio, S., Giugliano, R. P., Stroes, E. S. G., Kanevsky, E., Gouni-Berthold, I., Im, K., Lira Pineda, A., Wasserman, S. M., Češka, R., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.037184 · Cited by 984 · see citing works
Self-citation2024 ESC Guidelines for the management of peripheral arterial and aortic diseases
Mazzolai, L., Teixidó‐Turà, G., Lanzi, S., Boc, V., Bossone, E., Brodmann, M., Bura-Rivière, A., Backer, J. F. A. D., Déglise, S., Corte, A. D., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae179 · Cited by 1,222 · see citing works
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Ray, K. K., Landmesser, U., Leiter, L. A., Kallend, D., Dufour, R., Karakas, M., Hall, T., Troquay, R. P. T., Turner, T., Visseren, F. L. J., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615758 · Cited by 992 · see citing works
Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients
Nissen, S. E., Lincoff, A. M., Brennan, D., Ray, K. K., Mason, D., Kastelein, J. J. P., Thompson, P. D., Libby, P., Cho, L., Plutzky, J., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2215024 · Cited by 988 · see citing works
Aboyans, V., Ricco, J., Bartelink, M.-L. E. L., Björck, M., Brodmann, M., Cohnert, T. U., Collet, J., Czerny, M., Carlo, M. D., Debus, S., et al. (2017) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2017.07.018 · Cited by 1,006 · see citing works
NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis
Grebe, A., Hoss, F., & Latz, E. (2018) · Circulation Research · doi:10.1161/circresaha.118.311362 · Cited by 926 · see citing works
Ridker, P. M., MacFadyen, J. G., Everett, B. M., Libby, P., Thuren, T. Y., Glynn, R. J., Ridker, P. M., MacFadyen, J. G., Everett, B. M., Libby, P., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)32814-3 · Cited by 943 · see citing works
Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C. T., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S. D., Faiella-Tommasino, J., Forman, D. E., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000624 · Cited by 920 · see citing works
10. Cardiovascular Disease and Risk Management: <i>Standards of Medical Care in Diabetes—2022</i>
American Diabetes Association Professional Practice Committee (2022) · Diabetes Care · doi:10.2337/dc22-s010 · Cited by 869 · see citing works
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The Global Cardiovascular Risk Consortium (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2206916 · Cited by 909 · see citing works
“Although very low non-HDL cholesterol concentrations are related to reduced CVD events, 25,26 some observations point towards higher all-cause mortality rates in individuals with very low levels at least in longer-term follow-up.”
Garber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S. E., DeFronzo, R. A., EINHORN, D. F., Fonseca, V. A., et al. (2016) · Endocrine Practice · doi:10.4158/ep151126.cs · Cited by 874 · see citing works
Pearson, G. J., Thanassoulis, G., Anderson, T. J., Barry, A. R., Couture, P., Dayan, N., Francis, G. A., Genest, J. J., Grégoire, J. C., Grover, S. A., et al. (2021) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2021.03.016 · Cited by 870 · see citing works
Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia
Raal, F. J., Kallend, D., Ray, K. K., Turner, T., Koenig, W., Wright, R. S., Wijngaard, P. L. J., Curcio, D., Jaros, M. J., Leiter, L. A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1913805 · Cited by 818 · see citing works
Kinoshita, M., Yokote, K., Arai, H., Iida, M., Ishigaki, Y., Ishibashi, S., Umemoto, S., Egusa, G., Ohmura, H., Okamura, T., et al. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2017 · Cited by 813 · see citing works
Evinacumab for Homozygous Familial Hypercholesterolemia
Raal, F. J., Rosenson, R. S., Reeskamp, L. F., Hovingh, G. K., Kastelein, J. J. P., Rubba, P., Ali, S., Banerjee, P., Chan, K.-C., Gipe, D. A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2004215 · Cited by 793 · see citing works
Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options
Taqueti, V. R., & Carli, M. F. D. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.09.042 · Cited by 797 · see citing works
Burgess, S., Ference, B. A., Staley, J. R., Freitag, D. F., Mason, A. M., Nielsen, S. F., Willeit, P., Young, R., Surendran, P., Karthikeyan, S., et al. (2018) · JAMA Cardiology · doi:10.1001/jamacardio.2018.1470 · Cited by 689 · see citing works
Giugliano, R. P., Pedersen, T. R., Park, J.-G., De Ferrari, G. M., Gaciong, Z. A., Ceska, R., Toth, K., Gouni-Berthold, I., Lopez-Miranda, J., Schiele, F., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)32290-0 · Cited by 682 · see citing works
Self-citationMendelian randomization in cardiometabolic disease: challenges in evaluating causality
Holmes, M. V., Ala-Korpela, M., & Smith, G. D. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.78 · Cited by 679 · see citing works
Feinstein, M. J., Hsue, P. Y., Benjamin, L. A., Bloomfield, G. S., Currier, J. S., Freiberg, M. S., Grinspoon, S. K., Levin, J., Longenecker, C. T., & Post, W. S. (2019) · Circulation · doi:10.1161/cir.0000000000000695 · Cited by 666 · see citing works
Halliday, A. W., & Bax, J. J. (2018) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2018.03.004 · Cited by 654 · see citing works
Delgado-Lista, J., Alcala-Diaz, J. F., Torres-Peña, J. D., Quintana-Navarro, G. M., Fuentes, F., Garcia-Rios, A., Ortiz-Morales, A. M., Gonzalez-Requero, A. I., Perez-Caballero, A. I., Yubero-Serrano, E. M., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)00122-2 · Cited by 642 · see citing works
“33,34 The fact that primary endpoint rates were lower than expected might support the hypothesis that the two diets had high efficacy in preventing cardiovascular recurrences and support the previous results of studies with low-fat diet versus control diets, 3–10 or with the Mediterranean diet in…”
Joseph, J. J., Deedwania, P., Acharya, T., Aguilar, D., Bhatt, D. L., Chyun, D. A., Di Palo, K. E., Golden, S. H., Sperling, L. S., & on behalf of the American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, T. A. V. B. C. O. C. C. A. C. O. H. (2022) · Circulation · doi:10.1161/cir.0000000000001040 · Cited by 660 · see citing works
ATUALIZAÇÃO DA DIRETRIZ BRASILEIRA DE DISLIPIDEMIAS E PREVENÇÃO DA ATEROSCLEROSE - 2017
Faludi, A., Izar, M. C. D. O., Saraiva, J., Chacra, A., Bianco, H. T., Neto, A. A., Bertolami, A., Pereira, A., Lottenberg, A., Sposito, A. C., et al. (2017) · Arquivos Brasileiros de Cardiologia · doi:10.5935/abc.20170121 · Cited by 660 · see citing works
Macrophages in Atherosclerosis Regression
Barrett, T. J. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312802 · Cited by 633 · see citing works
Targeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation
Marchio, P., Guerra‐Ojeda, S., Vila, J. M., Aldasoro, M., Víctor, V. M., & Mauricio, M. D. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/8563845 · Cited by 628 · see citing works
“In patients with atherosclerotic CVD and high levels of LDL in treatment with statins, evolocumab further reduced LDL levels (59% compared vs placebo) and the risk of major cardiovascular events by 15-20% [236].”
BackgroundInterleukin-1 Beta as a Target for Atherosclerosis Therapy
Libby, P. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.09.028 · Cited by 629 · see citing works
Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program
Klarin, D. M., Program, T. V. M. V., Damrauer, S. M., Cho, K., Sun, Y. V., Teslovich, T. M., Honerlaw, J. P., GAGNON, D. R., DuVall, S. L., Li, J., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0222-9 · Cited by 594 · see citing works
Räber, L., Ueki, Y., Otsuka, T., Losdat, S., Häner, J. D., Lønborg, J., Fahrni, G., Iglesias, J. F., van Geuns, R., Ondracek, A. S., et al. (2022) · JAMA · doi:10.1001/jama.2022.5218 · Cited by 616 · see citing works
Sabatine, M. S., Leiter, L. A., Wiviott, S. D., Giugliano, R. P., Deedwania, P., De Ferrari, G. M., Murphy, S. A., Kuder, J. F., Gouni-Berthold, I., Lewis, B. S., et al. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30313-3 · Cited by 603 · see citing works
Self-citationStroke genetics informs drug discovery and risk prediction across ancestries
Mishra, A., Malik, R., Hachiya, T., Jürgenson, T., Namba, S., Posner, D. C., Kamanu, F., Koido, M., Grand, Q. L., Shi, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05165-3 · Cited by 593 · see citing works
“…54 (prevention of cardiovascular events in patients with prior heart attack using ticagrelor compared to placebo on a background of aspirin) 112 and FOURIER (further cardiovascular outcomes research with PCSK9 inhibition in patients with elevated risk) 113 trials were included in this analysis.”
Garber, A. J., Handelsman, Y., Grunberger, G., Einhorn, D., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bush, M. A., DeFronzo, R. A., Garber, J. R., et al. (2020) · Endocrine Practice · doi:10.4158/cs-2019-0472 · Cited by 598 · see citing works
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.04.003 · Cited by 596 · see citing works
Cardiovascular and Metabolic Effects of <i>ANGPTL3</i> Antisense Oligonucleotides
Graham, M. J., Lee, R. G., Brandt, T. A., Tai, L.-J., Fu, W., Peralta, R., Yu, R., Hurh, E., Paz, E., McEvoy, B. W., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701329 · Cited by 573 · see citing works
Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
Bittner, V. A., Szarek, M., Aylward, P. E., Bhatt, D. L., Diaz, R., Edelberg, J. M., Fras, Z., Goodman, S. G., Halvorsen, S., Hanotin, C., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.10.057 · Cited by 572 · see citing works
Navarese, E. P., Robinson, J. G., Kowalewski, M., Kolodziejczak, M., Andreotti, F., Bliden, K., Tantry, U., Kubica, J., Raggi, P., & Gurbel, P. A. (2018) · JAMA · doi:10.1001/jama.2018.2525 · Cited by 549 · see citing works
“clonal antibody); and (3) reported cardiovascular andmortal-”
Willeit, P., Ridker, P. M., Nestel, P. J., Simes, J., Tonkin, A. M., Pedersen, T. R., Schwartz, G. G., Olsson, A. G., Colhoun, H. M., Kronenberg, F., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31652-0 · Cited by 564 · see citing works
Self-citationLloyd-Jones, D. M., Morris, P. B., Ballantyne, C. M., Birtcher, K. K., Covington, A. M., DePalma, S. M., Minissian, M. B., Orringer, C. E., Smith, S. C., Waring, A. A., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.07.006 · Cited by 569 · see citing works
Volgman, A. S., Palaniappan, L. S., Aggarwal, N. T., Gupta, M., Khandelwal, A., Krishnan, A. V., Lichtman, J. H., Mehta, L. S., Patel, H. N., Shah, K. S., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000580 · Cited by 552 · see citing works
Japanese clinical practice guideline for diabetes 2019
Araki, E., Goto, A., Kondo, T., Noda, M., Noto, H., Origasa, H., Osawa, H., Taguchi, A., Tanizawa, Y., Tobe, K., et al. (2020) · Diabetology International · doi:10.1007/s13340-020-00439-5 · Cited by 545 · see citing works
2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Bäck, M., Bénétos, A., Biffi, A., Boavida, J.-M., Capodanno, D., et al. (2021) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwab154 · Cited by 565 · see citing works
Zuber, V., Grinberg, N. F., Gill, D., Manipur, I., Slob, E. A. W., Patel, A., Wallace, C., & Burgess, S. (2022) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.04.001 · Cited by 532 · see citing works
“77 For Alzheimer disease, a polygenic Mendelian randomization analysis gives a random-effects IVW estimate of OR 1.27 (95% CI: 1.04, 1.55).”
InfluentialFamilial hypercholesterolaemia
Defesche, J. C., Gidding, S. S., Harada‐Shiba, M., Hegele, R. A., Santos, R. D., & Wierzbicki, A. S. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.93 · Cited by 540 · see citing works
Wilson, D. P., Jacobson, T. A., Jones, P. H., Koschinsky, M. L., McNeal, C. J., Nordestgaard, B. G., & Orringer, C. E. (2019) · Journal of clinical lipidology · doi:10.1016/j.jacl.2019.04.010 · Cited by 515 · see citing works
Nordanstig, J., Behrendt, C., Baumgärtner, I., Belch, J. J. F., Bäck, M., Fitridge, R., Hinchliffe, R. J., Lejay, A., Mills, J. L., Rother, U., et al. (2023) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2023.08.067 · Cited by 545 · see citing works
Aminian, A., Zajichek, A., Arterburn, D. E., Wolski, K. E., Brethauer, S. A., Schauer, P. R., Kattan, M. W., & Nissen, S. E. (2019) · JAMA · doi:10.1001/jama.2019.14231 · Cited by 505 · see citing works
Garber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S. E., DeFronzo, R. A., EINHORN, D. F., Fonseca, V. A., et al. (2018) · Endocrine Practice · doi:10.4158/cs-2017-0153 · Cited by 499 · see citing works
Drug development in the era of precision medicine
Dugger, S. A., Platt, A., & Goldstein, D. B. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.226 · Cited by 493 · see citing works
JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome
Kimura, K., Kimura, T., Ishihara, M., Nakagawa, Y., Nakao, K., Miyauchi, K., Sakamoto, T., Tsujita, K., Hagiwara, N., Miyazaki, S., et al. (2019) · Circulation Journal · doi:10.1253/circj.cj-19-0133 · Cited by 565 · see citing works
Cognitive function in a randomized trial of evolocumab
Giugliano, R. P., Mach, F., Zavitz, K., Kurtz, C., Im, K., Kanevsky, E., Schneider, J., Wang, H., Keech, A., Pedersen, T. R., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701131 · Cited by 492 · see citing works
Self-citation10. Cardiovascular Disease and Risk Management: <i>Standards of Medical Care in Diabetes—2020</i>
American Diabetes Association (2020) · Diabetes Care · doi:10.2337/dc20-s010 · Cited by 487 · see citing works
Bergmark, B. A., Mathenge, N., Merlini, P. A., Lawrence-Wright, M. B., & Giugliano, R. P. (2022) · The Lancet · doi:10.1016/s0140-6736(21)02391-6 · Cited by 518 · see citing works
Self-citation9. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2018
(2017) · Diabetes Care · doi:10.2337/dc18-s009 · Cited by 490 · see citing works
10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i>
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Das, S. R., Hilliard, M. E., Isaacs, D., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s010 · Cited by 465 · see citing works
10. Cardiovascular Disease and Risk Management: <i>Standards of Medical Care in Diabetes—2019</i>
American Diabetes Association (2019) · Diabetes Care · doi:10.2337/dc19-s010 · Cited by 471 · see citing works
Inflammation and cardiovascular disease: From mechanisms to therapeutics
Alfaddagh, A., Martin, S. S., Leucker, T. M., Michos, E. D., Blaha, M. J., Lowenstein, C. J., Jones, S. R., & Toth, P. P. (2020) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2020.100130 · Cited by 473 · see citing works
“The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial showed significant LDL-C lowering and improvement in CVD events with evolocumab in statin treated or statin intolerant patients with ASCVD who had LDL-C 70 mg/dL [192].”
BackgroundPrimary prevention of cardiovascular disease: A review of contemporary guidance and literature
Stewart, J., Manmathan, G. P. R., & Wilkinson, P. (2017) · JRSM Cardiovascular Disease · doi:10.1177/2048004016687211 · Cited by 477 · see citing works
Ibáñez, B., James, S. K., Agewall, S., Antunes, M. J., Bucciarelli‐Ducci, C., Bueno, H., Caforio, A. L. P., Crea, F., Goudevenos, J. A., Halvorsen, S., et al. (2017) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2017.11.010 · Cited by 469 · see citing works
Nicholls, S. J., Kataoka, Y., Nissen, S. E., Prati, F., Windecker, S., Puri, R., Hucko, T., Aradi, D., Herrman, J. R., Hermanides, R. S., et al. (2022) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2022.03.002 · Cited by 469 · see citing works
Self-citationTargeting cardiovascular inflammation: next steps in clinical translation
Lawler, P. R., Bhatt, D. L., Godoy, L. C., Lüscher, T. F., Bonow, R. O., Verma, S., & Ridker, P. M. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa099 · Cited by 454 · see citing works
Updated Cardiovascular Prevention Guideline of the Brazilian Society of Cardiology - 2019
Précoma, D. B., de Oliveira, G. M. M., Simão, A. F. L., Dutra, Ó. P., Coelho-Filho, O. R., Izar, M. C. D. O., Póvoa, R., Giuliano, I. D. C. B., Filho, A. C. D. A., Machado, C. A., et al. (2019) · Arquivos Brasileiros de Cardiologia · doi:10.5935/abc.20190204 · Cited by 469 · see citing works
10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2024</i>
American Diabetes Association Professional Practice Committee, ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Das, S. R., Ekhlaspour, L., Hilliard, M. E., Johnson, E. L., et al. (2024) · Diabetes Care · doi:10.2337/dc24-s010 · Cited by 438 · see citing works
ST-segment elevation myocardial infarction
Vogel, B., Claessen, B. E. P. M., Arnold, S. V., Chan, D., Cohen, D. J., Giannitsis, E., Gibson, C. M., Goto, S., Katus, H. A., Kernéis, M., et al. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0090-3 · Cited by 448 · see citing works
Safety and efficacy of statin therapy
Adhyaru, B. B., & Jacobson, T. A. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0098-5 · Cited by 424 · see citing works
Stent-Related Adverse Events >1 Year After Percutaneous Coronary Intervention
Madhavan, M. V., Kirtane, A. J., Redfors, B., Généreux, P., Ben‐Yehuda, O., Palmerini, T., Benedetto, U., Biondi‐Zoccai, G., Smits, P. C., von Birgelen, C., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.058 · Cited by 433 · see citing works
Reducing the Global Burden of Cardiovascular Disease, Part 2
Leong, D. P., Joseph, P. G., McKee, M., Anand, S. S., Teo, K. K., Schwalm, J.-D., & Yusuf, S. (2017) · Circulation Research · doi:10.1161/circresaha.117.311849 · Cited by 423 · see citing works
O’Sullivan, J. W., Raghavan, S., Márquez‐Luna, C., Luzum, J. A., Damrauer, S. M., Ashley, E. A., O’Donnell, C. J., Willer, C. J., & Natarajan, P. (2022) · Circulation · doi:10.1161/cir.0000000000001077 · Cited by 424 · see citing works
- Authors
- Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., Sever, P. S., & Pedersen, T. R.
- Affiliations
- Oslo University Hospital (NO)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-05-04
- Volume
- 376
- Issue
- 18
- Pages
- 1713-1722
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2596179513
- Semantic Scholar
- 993698ddc1fcdfd3e66edebf1904b360eca3b4a8
- Cited by
- 6,138
- References
- 28
- Citations by year
- 2026: 628 · 2025: 589 · 2024: 608 · 2023: 635 · 2022: 623 · 2021: 632 · 2020: 658 · 2019: 637 · 2018: 669 · 2017: 443 · 2016: 6 · 2013: 1
- FWCI
- 674.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Use Siena air (University of Siena) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institute for Health and Care Research (NF-SI-0513-10059)
- Medical Research Council (MC_EX_MR/M009203/1, MC_PC_14089)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- evolocumab, PCSK9 inhibition, LDL cholesterol lowering, atherosclerotic cardiovascular disease, cardiovascular events, myocardial infarction, stroke, cardiovascular mortality, statin therapy, LDL cholesterol levels, new-onset diabetes, injection site reactions, primary prevention of cardiovascular disease, LDL-C lowering therapy
- MeSH terms
- Proprotein Convertase 9, PCSK9 Inhibitors, Aged, Antibodies, Monoclonal, Anticholesteremic Agents, Cardiovascular Diseases, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Middle Aged, Incidence, Least-Squares Analysis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atherosclerosis, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-16.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-16.
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