The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index; 12 of the 28 sources its claims cite were checked for support.
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
Open accessAbstract
BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).
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Verification
Claims the paper makes
12 of 28 cited sources checked · 7 supported · 1 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The rate of major vascular events as defined by the CTT collaborators 3,4 (a composite of death from coronary heart disease, myocardial infarction, stroke, or coronary revascularization 30 days or more after randomization) was also significantly lower in the simvastatin-ezetimibe group (difference, 2.2 percentage points; hazard ratio, 0.928; P = 0.007).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Efficacy End Points
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Partly supportedcites [4] sourceExperimental — accuracy not yet measured
The Study eligibility and outcomes section (page unavailable) defines a major vascular event as the first major coronary event, coronary revascularisation, or stroke, matching the cited composite. But the sentence makes the 30-day cutoff sound universal: in acute-coronary-syndrome trials, the paper included revascularisation for recurrent ischaemia or procedures more than 30 days after randomisation, depending on the trial. The citation is attached to the CTT definition, not to the simvastatin–ezetimibe results. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“a finding similar to that seen with statin therapy as compared with placebo.3,4”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Supportedcites [4] source
The Discussion reports a nonsignificant excess of haemorrhagic strokes with statin therapy and also describes an excess in an atorvastatin-versus-placebo trial. This supports the cited comparison; the source is not being cited for the simvastatin-ezetimibe finding itself. (LLM, conf=0.90)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“we observed a between-group difference in LDL cholesterol levels (with imputation for missing values) of 12.8 mg per deciliter”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Supportedcites [4] source
The cited CTT paper defines its major vascular-event end point in Study eligibility and outcomes and describes comparing trial results by LDL-cholesterol differences at one year in the Figure 1 caption (pages not provided). The 12.8 mg/dL difference is explicitly presented as the citing authors’ own observation in IMPROVE-IT, not as a result reported by CTT. (LLM, conf=0.86)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“However, the consistency with expectations from the CTT analysis, in which a different class of drug was used, provides further evidence for a relationship between lipid lowering and improved outcomes.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Supportedcites [4] source
The Discussion describes the CTT analysis as comparing statin regimens and reports that greater LDL-cholesterol reductions further reduced major vascular events. The Results likewise report a 22% reduction in major vascular events per 1 mmol/L reduction in LDL cholesterol across all 26 trials. This supports the attributed relationship; the other drug class used by the citing study is not a claim about the CTT paper. (LLM, conf=0.91)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“and a proportional 7.2% lower rate of major vascular events”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Partly supportedcites [4] sourceExperimental — accuracy not yet measured
The Study eligibility and outcomes section defines the CTT major vascular event endpoint, and the Results describe its analysis of first-event rates. Our copy does not report IMPROVE-IT or a 7.2% reduction in that trial; its Results instead report reductions across the trials in this meta-analysis. Page numbers were not available in the supplied passages. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“as compared with 0.78 observed with statins in the CTT meta-analysis.3,4”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Supportedcites [4] source
The Discussion reports a 22% proportional reduction in major vascular events for each 1 mmol/L reduction in LDL cholesterol and explicitly gives the corresponding risk ratio as 0.78. The paper calls this a risk or rate ratio rather than a hazard ratio, but the cited numerical comparison is supported. (LLM, conf=0.92)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesEvery source the paper cites for this claim was checked and supports it.
In the paper
“Although we studied only this regimen, current data indicate that the same relationship between reduction in LDL cholesterol levels and clinical benefit is seen across different statins and statin doses.4”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
What the sources say
- Supportedcites [4] source
The Discussion says the relationship between absolute LDL-cholesterol reduction and proportional risk reduction is consistent across trials of more versus less intensive statin therapy and trials of standard statin regimens versus control. The Introduction describes regimens using different statins and doses, supporting the citing sentence’s paraphrase. (LLM, conf=0.91)
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rate of each of the three secondary end points was significantly lower in the simvastatin-ezetimibe group than in the simvastatinmonotherapy group (Table 2).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Efficacy End Points
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This difference of 16.7 mg per deciliter (0.43 mmol per liter) (P<0.001)represented a 24% further lowering of LDL cholesterol level when ezetimibe was combined with simvastatin than when simvastatin was administered alone.”
- Also stated in: § Discussion · plain
“In IMPROVE-IT, the addition to statin therapy of a nonstatin agent, ezetimibe, which reduces the absorption of cholesterol from the gastrointestinal tract, lowered LDL cholesterol by approximately 24%.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Lipid Data
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among patients who had blood samples obtained at 1 year, the mean LDL cholesterol level was 69.9 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group and 53.2 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group (P<0.001)(Table S1 in the Supplementary Appendix).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Lipid Data
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 18
- It may state two separate claims as one. 24
- The quote only partly states this claim. 1
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Randomization was stratified according to prior use of lipid-lowering therapy, type of acute coronary syndrome, and status with respect to enrollment in the concurrent Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial.25”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Study Protocol
What the sources say
- Disputedcites [25] sourceExperimental — accuracy not yet measured
The Study Procedures section (page unavailable) says randomization was blocked by study center and stratified by investigators’ intention to administer early clopidogrel, not by the three factors claimed. The paper identifies itself as the EARLY ACS trial, rather than a separate trial conducted concurrently with it. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Ezetimibe targets the Niemann-Pick C1-like 1 (NPC1L1) protein, thereby reducing absorption of cholesterol from the intestine.15,16”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > CONCLUSIONS
What the sources say
- Not checked — no full text of the sourcecites [15] source
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Introduction says ezetimibe prevents absorption of dietary and biliary cholesterol across the intestinal wall. It does not identify NPC1L1 as ezetimibe’s target; searches for NPC1L1 and the molecular target found no supporting passage in our copy. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Polymorphisms affecting NPC1L1 are associated with both lower levels of LDL cholesterol and a lower risk of cardiovascular events.19”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > CONCLUSIONS
What the sources say
- Partly supportedcites [19] sourceExperimental — accuracy not yet measured
The Abstract Results and Discussion report that carriers of rare, inactivating NPC1L1 mutations had lower LDL cholesterol and a lower risk of coronary heart disease. The claim is broader: the paper does not establish these associations for NPC1L1 polymorphisms generally or for cardiovascular events beyond coronary heart disease. (LLM, conf=0.83)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“According to practice guidelines in place at the time of patient enrollment in IMPROVE-IT, treatment of hypercholesterolemia was based on lowering LDL cholesterol to target levels, 20,21 which were set on the basis of a patient's risk of cardiovascular events.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
What the sources say
- Supportedcites [20] source
The “CHD Risk: Implications for Therapy” section says ATP III prioritized reaching LDL-C goals. Table 2 lists different LDL-C goals for different cardiovascular-risk categories, supporting the claim that treatment targets were set according to risk. The indexed passages do not provide page numbers. (LLM, conf=0.93)
- Supportedcites [21] source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > RESULTS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No significant between-group differences were seen in the percentage of patients who had elevations in alanine aminotransferase levels that exceeded three times the upper limit of the normal range or in the rates of gallbladder-related adverse events, cholecystectomy, muscle-related adverse events, or new, relapsing, or worsening cancer (Table 3).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Safety
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 1 year, levels of total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein were all significantly lower in the simvastatin-ezetimibe group than in the simvastatin-monotherapy group (Table S1 in the Supplementary Appendix).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Lipid Data
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The benefit appeared to be particularly pronounced in patients with diabetes mellitus and in patients 75 years of age or older.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Efficacy End Points
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rates of death from cardiovascular causes and from any cause were similar in the two groups.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Efficacy End Points
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was a nonsignificantly higher risk of hemorrhagic stroke with simvastatin-ezetimibe than with simvastatin monotherapy (difference, 0.2 percentage points; hazard ratio, 1.38; P = 0.11), although the number of hemorrhagic strokes was low.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Efficacy End Points
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Discontinuation of study medication owing to an adverse event occurred in 10.1% of the patients in the simvastatin-monotherapy group and in 10.6% of those in the simvastatin-ezetimibe group.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Safety
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“level of less than 2.0 at 1 month (50.6% vs. 30.5%)(Table S2 in the Supplementary Appendix).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Lipid Data
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No between-group differences in cardiovascular mortality or in the rate of death from any cause were anticipated or observed in IMPROVE-IT”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, significant reductions were observed in the rates of myocardial infarction and ischemic stroke.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“albeit with a higher use of the 80-mg simvastatin dose in the simvastatinmonotherapy group than in the simvastatinezetimibe group.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the treatment period extended for an average of 6 years, and the differences between the two treatment groups emerged after about 1 year, by which time most of the data were from patients in the chronic phase of their disease.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, 42% of the pa-tients discontinued the study medication for any reason prematurely, with an equal proportion in the two groups.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, three interim efficacy analyses were performed, after 45.7%, 76.1%, and 86.9% of the required events had occurred; adjustment of the level of significance to account for the three interim analyses was determined by the Lan-DeMets approximation of the O'Brien-Fleming boundaries for group sequential testing, with a final two-sided P value for significance of 0.0394 or less.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Statistical Analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“The false positive error rate for the three secondary end points was controlled with the use of the Hochberg method.26”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Statistical Analysis
What the sources say
- Not checked — no full text of the sourcecites [26] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“After a median of 6 years, 42% of the patients in each group had discontinued the study medication without having died or without having had a primary end-point event.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Patients
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In the final protocol, we estimated that 5250 events would be required to give the study 90% power to detect a 9.375% lower relative risk for the primary end point with simvastatin-ezetimibe than with simvastatin monotherapy.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Statistical Analysis
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Intensive statin therapy, as compared with moderate-dose statin therapy, incrementally lowers LDL cholesterol levels and rates of nonfatal cardiovascular events.[5][6][7][8][9]”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > CONCLUSIONS
What the sources say
- Not matchedcites [5][6][7][8][9]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All efficacy and safety analyses were performed in the intention-to-treat population.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Statistical Analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“DCRI managed the database and performed the primary analyses independently using raw data; TIMI and the sponsor verified the analyses.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Study Oversight
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The percentage of potential follow-up that was achieved -calculated as (number of patient-years of follow-up ÷ potential patient-years of follow-up) × 100was 91% for the primary end point and 97% for all-cause mortality.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Patients
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Rules for stopping the study early at interim analyses were prespecified.[22][23][24]”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Statistical Analysis
What the sources say
- Not matchedcites [22][23][24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A data and safety monitoring board oversaw the study.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Study Oversight
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Patients received standard medical and interventional treatment for acute coronary syndrome 22 and were randomly assigned, in a 1:1 ratio and in a double-blind fashion, to receive, once daily, either simvastatin (at a dose of 40 mg) plus ezetimibe (at a dose of 10 mg) (simvastatinezetimibe group) or simvastatin (at a dose of 40 mg) plus placebo (simvastatin-monotherapy group).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Study Protocol
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Independent clinical-events committees, whose members were unaware of the study-group assignments, adjudicated primary end-point events (excluding revascularization), cancer, and muscle-related events (details are provided in the Supplementary Appendix).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > End Points
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Adverse events were assessed in the intention-to-treat population.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The combination of simvastatin and ezetimibe also resulted in a significantly lower risk of cardiovascular events than that with statin monotherapy, with a 2.0-percentage-point lower rate of the primary composite end point of”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All muscle and cancer events were adjudicated by a clinical events committee, whose members were unaware of the study-group assignments.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > CONCLUSIONS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First, we evaluated patients who had had an acute coronary syndrome, and our results are most relevant to that population.”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The extent of benefit afforded by the simvastatin-ezetimibe combination is consistent with that seen in previous statin trials, with a similar reduction in cardiovascular events according to the degree of LDL cholesterol lowering (Fig. 2).”
§ From the Thrombolysis in Myocardial Infarction (TIMI) Study Group > Discussion
What the sources say
- Not matchedcites [1] Scandinavian Simvastatin Survival Study Group, 1994, Lancet
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [2] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
The paper relies on this without support.
Whether additional clinical benefit would be observed with further reductions of LDL cholesterol to levels below 70 mg per deciliter has not been clear.
“Whether additional clinical benefit would be observed with further reductions of LDL cholesterol to levels below 70 mg per deciliter has not been clear.”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Compared with statin monotherapy, a combination of ezetimibe and statins reduces LDL-C by − 24%, ApoB-100 by − 14%, triglycerides by − 12% and high-sensitivity C-reactive protein (hsCRP) by − 13%, whilst maintaining HDL-C levels [59–61].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [59]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“and among patients who receive ezetimibe added to statin therapy than among those who receive a statin alone. 5”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The last factor probably also contributed to the rise in LDL cholesterol observed in the placebo group, in the on-treatment analysis in the alirocumab group, and in previous trials involving patients who had an acute coronary syndrome. 5,21”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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”
From Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (2017) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]”
From Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (2017) · cites this paper as [15]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 [119]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, heterogeneity by age has not been seen in the relative benefit of lipid-lowering therapy in trials that included older participants (100,101,104), and because older age confers higher risk, the absolute benefits are actually greater (104,112).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [112]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The addition of obicetrapib resulted in an incremental LDL-C reduction of approximately 34 %, exceeding the typical benefit achieved with ezetimibe.”
From Efficacy and safety of obicetrapib in patients with dyslipidemia: An updated meta-analysis of randomized controlled trials (2025) · cites this paper as [23]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“A limitation of all three trials is the infrequent use of ezetimibe, for which cardiovascular efficacy was established 5 after most of the patients had already been enrolled and the trials were well under way.”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“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.”
From Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (2017) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“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.”
From Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (2017) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“The trial showed the addition of ezetimibe to a moderate-intensity statin led to a 6.4% relative benefit and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of benefit being directly proportional to the change in LDL cholesterol (119).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [119]
The cited source says what the claim attributes to it.
In the citing paper
“The trial showed the addition of ezetimibe to a moderate-intensity statin led to a 6.4% relative benefit and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of benefit being directly proportional to the change in LDL cholesterol (112).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [112]
The cited source says what the claim attributes to it.
In the citing paper
“The trial showed the addition of ezetimibe to a moderate-intensity statin led to a 6.4% relative benefit and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of benefit being directly proportional to the change in LDL cholesterol (112).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [112]
The cited source says what the claim attributes to it.
In the citing paper
“The trial showed the addition of ezetimibe to a moderate-intensity statin led to a 6.4% relative benefit and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of benefit being directly proportional to the change in LDL cholesterol (112).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [112]
The cited source says what the claim attributes to it.
In the citing paper
“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 [3]
The cited source says what the claim attributes to it.
In the citing paper
“NPC1L1 is a target of the drug ezetimibe (EZ) (8–10).”
From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“The combination of EZ and a statin further reduces cardiovascular events compared to statin alone (10), validating the intestine as a therapeutic target for the regulation of cholesterol homeostasis.”
From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [10]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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 [119]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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 [112]
Experimental — accuracy not yet measuredIn the citing paper
“In addition to their initial events, such patients are at substantial risk for recurrent, potentially fatal events.”
From Effects of Icosapent Ethyl on Total Ischemic Events (2019) · cites this paper as [9]
In the citing paper
“The observed annualized primary endpoint event rate for placebo patients in REDUCE-IT was 5.74%, which is consistent with historical cardiovascular outcome studies, including those published since the design of REDUCE-IT, with comparable patient populations and expanded or hard major adverse cardiovascular events (MACE) (4,8,9,30-44).”
From Effects of Icosapent Ethyl on Total Ischemic Events (2019) · cites this paper as [9]
In the citing paper
“randomization, or non-fatal stroke; HR 0.94; 95% CI, 0.89-0.99) in patients post-ACS receiving simvastatin plus ezetimibe, with a stronger benefit in the sub-group of patients with diabetes (HR 0.85; 95% CI, 0.78-0.94;P <0.001).259,260”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [259]
In the citing paper
“In SHARP trial [90], non-statin drug ezetimibe (intestinal cholesterol transporter inhibitor) showed a significant reduction in CV events.”
From Pemafibrate, a new selective PPARα modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases (2020) · cites this paper as [90]
In the citing paper
“Although healthy lifestyle habits remain a cornerstone of T2DM management, trial data have confirmed the additional benefits of statin therapy in the primary and secondary prevention of CAD.13,102–112”
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 [13]
In the citing paper
“IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) was the first study to demonstrate the benefit of a nonstatin add-on to background statin therapy.13”
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 [13]
In the citing paper
“Specifically, the addition of 10 mg ezetimibe to 40 mg simvastatin within 10 days of hospitalization for an acute coronary syndrome lowered LDL-C levels by an additional 17 mg/dL (0.4 mmol/L), which was associated with an overall modest, but significant, 2.0% absolute/6.4% relative reduction in the primary composite end point of cardiovascular death, major coronary event, or stroke after a median”
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 [13]
In the citing paper
“After an acute coronary syndrome, patients with diabetes are at particularly high risk of recurrent ischaemic cardiovascular events, and also derive the greatest absolute benefit from a given degree of lipid lowering with high-intensity statins 15 or statins plus ezetimibe.2,16”
In the citing paper
“This graded approach is based on evidence from multiple meta-analyses and individual randomized controlled trials (RCTs), which show a consistent and graded reduction in ASCVD risk in response to reductions in TC and LDL-C levels (see Recommendations for cardiovascular disease risk estimation below) [31-41].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [32]
In the citing paper
“These trials are consistent in showing that the higher the initial LDL-C level, the greater the absolute reduction in risk, while the relative risk reduction remains constant at any given baseline LDL-C level.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“This graded approach is based on evidence from multiple meta-analyses and individual RCTs, which show a consistent and graded reduction in CVD risk in response to reductions in TC and LDL-C levels. 61-71”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“The benefits related to LDL-C reduction are not specific for statin therapy. 63”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“However, the study supports the proposition that LDL-C lowering by means other than statins is beneficial and can be performed without adverse effects.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“The average LDL-C during the study was 1.8 mmol/L in the simvastatin group and 1.4 mmol/L in patients taking ezetimibe plus simvastatin.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“Also, ischaemic stroke was reduced by 21% in this trial ( P ¼ 0.008).”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“The rate of the composite endpoint of death from CV causes, MI or stroke was significantly lower, by 1.8 percentage points, in the combination group and the benefit of simvastatin-ezetimibe was consistent for women. 63”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“The IMPROVE-IT study 63 included patients at least 50 years of age who had been hospitalized within the preceding 10 days for an ACS (24% women).”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“Ezetimibe further reduced LDL-C and offered additional benefit (6.4% relative risk reduction in composite clinical endpoint) in association with simvastatin in post-ACS patients. 63”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“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: Standards of Care in Diabetes—2023 (2023) · cites this paper as [105]
In the citing paper
“Overall, the addition of ezetimibe led to a 6.4% relative bene fi t and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of bene fi t being directly proportional to the change in LDL cholesterol, which was 70 mg/dL in the statin group on average and 54 mg/dL in the combination group (105).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [105]
In the citing paper
“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: Standards of Care in Diabetes—2023 (2023) · cites this paper as [105]
In the citing paper
“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: Standards of Care in Diabetes—2023 (2023) · cites this paper as [105]
In the citing paper
“The benefits related to LDL-C reduction are not specific for statin therapy.63”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“Taken together with other studies such as the PRECISE-IVUS study, 246 IMPROVE-IT supports the proposal that ezetimibe should be used as second-line therapy in association with statins when the therapeutic goal is not achieved at the maximal tolerated statin dose or in patients intolerant of statins or with contraindications to these drugs.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“However, the study supports the proposition that LDL-C lowering by means other than statins is beneficial and can be performed without adverse effects.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“Also, ischaemic stroke was reduced by 21% in this trial (P ¼ 0.008).”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“The average LDL-C during the study was 1.8 mmol/L in the simvastatin group and 1.4 mmol/ L in patients taking ezetimibe plus simvastatin.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“A total of 18 144 patients were randomized and 5314 patients over 7 years experienced a CVD event; 170 fewer events (32.7 vs. 34.7%)were recorded in the group taking simvastatin plus ezetimibe (P ¼ 0.016).”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“In this group of patients already treated with statins to reach goals, the absolute benefit from added ezetimibe was small, although significant.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“There was no evidence of harm caused by the further LDL-C reduction.”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“The rate of the composite endpoint of death from CV causes, MI or stroke was significantly lower, by 1.8 percentage points, in the combination group and the benefit of simvastatineezetimibe was consistent for women.63”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“Ezetimibe further reduced LDL-C and offered additional benefit (6.4% relative risk reduction in composite clinical endpoint) in association with simvastatin in post-ACS patients. 63”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“The addition of ezetimibe to simvastatin in post-ACS patients had an incremental beneficial effect for ischaemic stroke or all strokes (marginal statistical significance for the latter).63”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [63]
In the citing paper
“It has been reported that the risk of cardiovascular events increased in patients with the escape phenomenon (i.e., re-elevation in LDL-C level of ≥ 10% after a reduction) following the start of statin treatment634).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [634]
In the citing paper
“In the ACCORD study involving high-risk subjects with DM, the sub-analysis suggested that the risk for cardiovascular events might be significantly suppressed by adding fibrate in patients who have hypertriglyceridemia and low HDL-C after statin administration806).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [806]
In the citing paper
“the addition of ezetimibe may be considered given the improved ASCVD outcomes and demonstrated safety of the combination of ezetimibe with moderate-intensity simvastatin versus simvastatin monotherapy (8).”
In the citing paper
“given the benefits on ASCVD outcomes and demonstrated safety of ezetimibe in patients with ACS treated with ezetimibe-simvastatin versus simvastatin monotherapy (Table 3) (8).”
In the citing paper
“the addition of ezetimibe may be considered based upon the improved ASCVD outcomes and demonstrated safety of the combination of ezetimibe with moderate-intensity simvastatin versus simvastatin monotherapy (8).”
In the citing paper
“IMPROVE-IT (8) (The addition of ezetimibe to moderate-intensity statin in patients with recent ACS resulted in incremental lowering of LDL-C and reduced primary composite endpoint of CV death, nonfatal MI, UA requiring re-hospitalization, coronary revascularization [$30 days after randomization], or nonfatal stroke.”
In the citing paper
“Combination therapy demonstrated a statistically significant, but clinically modest, reduction in events over 7 years of follow-up, and no safety concerns were observed with the addition of ezetimibe (8).”
In the citing paper
“The IMPROVE-IT trial (published in 2015) (8) in patients with recent acute coronary syndromes (ACSs) demonstrated further reductions in LDL-C with the addition of ezetimibe to a moderate-intensity statin (simvastatin) compared with moderate-intensity statin monotherapy.”
Citations
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Flagged first, then by citations
Research works printed but not linked: 2
- Scandinavian Simvastatin Survival Study Group, 1994, Lancet, 344, 1383
- GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico), 2000, Ital Heart J, 1, 810
Cited by
Sorted by citations
Items 1,001–1,100 of 4,475
Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia
Ferreira, A. M., & da Silva, P. M. (2016) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-016-0205-0 · Cited by 33
Development and Population Results of a Fully Automated Homogeneous Assay for LDL Triglyceride
Ito, Y., Ohta, M., Ikezaki, H., et al. (2018) · The Journal of Applied Laboratory Medicine · doi:10.1373/jalm.2017.024554 · Cited by 30
Yamaguchi, J., Kawada‐Watanabe, E., Koyanagi, R., Arashi, H., Sekiguchi, H., Nakao, K., Tobaru, T., Tanaka, H., Oka, T., Endo, Y., et al. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.04.036 · Cited by 30
Evidence-Based Management of Diabetes in Older Adults
Mooradian, A. D. (2018) · Drugs & Aging · doi:10.1007/s40266-018-0598-3 · Cited by 31
IL-1β and Statin Treatment in Patients with Myocardial Infarction and Diabetic Cardiomyopathy
Liberale, L., Carbone, F., Camici, G. G., & Montecucco, F. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8111764 · Cited by 31
Primary Prevention of Atherosclerosis
Nambi, V., & Bhatt, D. L. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.10.068 · Cited by 30
Causal Effect of Lipids and Lipoproteins on Atherosclerosis
Ference, B. A. (2018) · Cardiology Clinics · doi:10.1016/j.ccl.2017.12.001 · Cited by 28
Jones, J. E., Tang, K. S., Barseghian, A., & Wong, N. D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12237432 · Cited by 34
Drugs for dyslipidaemia: the legacy effect of the Scandinavian Simvastatin Survival Study (4S)
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Metadata
- Authors
- 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., De Ferrari, G. M., Ruzyllo, W., De Lucca, P., Im, K., Bohula, E. A., Reist, C., Wiviott, S. D., Tershakovec, A. M., Musliner, T. A., Braunwald, E., & Califf, R. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Canisius-Wilhelmina Ziekenhuis (NL)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-06-18
- Volume
- 372
- Issue
- 25
- Pages
- 2387-2397
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1520609538
- Semantic Scholar
- 33bafb0063a59a82a1f6e9a7d95c2b882edff0d3
- Cited by
- 4,487
- References
- 43
- Citations by year
- 2026: 320 · 2025: 325 · 2024: 354 · 2023: 355 · 2022: 366 · 2021: 387 · 2020: 415 · 2019: 416 · 2018: 403 · 2017: 486 · 2016: 472 · 2015: 173
- FWCI
- 514.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Intellectum (Universidad de La Sabana) (submittedVersion, other-oa)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- ORBi (University of Liège) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- ezetimibe, simvastatin, statin therapy, acute coronary syndrome, LDL cholesterol lowering, cardiovascular events, lipid-lowering therapy, combination therapy, cardiovascular mortality, myocardial infarction, LDL cholesterol targets, cholesterol absorption inhibition, adverse drug reactions, cancer risk, gallbladder disease, hepatic adverse effects, coronary revascularization, stroke
- MeSH terms
- Ezetimibe, Aged, Anticholesteremic Agents, Azetidines, Cardiovascular Diseases, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Triglycerides, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Kaplan-Meier Estimate, Acute Coronary Syndrome
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.
A language model drew the claims from the paper on 2026-10-16, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-16 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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