Icosapent ethyl reduces CVD risk in cardiovascular-kidney-metabolic syndrome: REDUCE-IT CKM
Open accessAbstract
Background/Introduction: Cardiovascular-kidney-metabolic (CKM) syndrome was recently identified as a cardiometabolic disorder that incorporates chronic kidney disease with the metabolic syndrome (MetS). REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was an international, double-blind, placebo-controlled trial that randomized hypertriglyceridemic (TG, 150-499 mg/dL) statin-treated patients with established cardiovascular disease (CVD) or diabetes and multiple CVD risk factors to icosapent ethyl (IPE) or placebo (4 grams/day). It is unknown if renal insufficiency added to MetS confers incremental CVD risk in secondary prevention patients without diabetes and if IPE lowers that risk. Methods: (n=609). Event rates of the primary and secondary trial endpoints were compared in placebo subjects with higher vs lower baseline eGFR, and the effect of IPE on these endpoints was also compared within each of the three subgroups. Results: ). Treatment with IPE was associated with an absolute risk reduction of 11.2% and number needed to treat of 9 patients to prevent an initial primary composite endpoint event over the study period. Conclusions: In this REDUCE-IT analysis of secondary prevention patients without diabetes at baseline, the recently defined CKM syndrome was associated with incremental CVD risk compared with MetS and normal renal function. Treatment with IPE substantially reduced CVD risk in MetS patients with renal insufficiency (i.e., CKM) and CVD.
AI snapshot
Written from the paper’s full text.
TL;DR
In a post hoc REDUCE-IT analysis of secondary prevention patients with metabolic syndrome but without diabetes, adding renal insufficiency (CKM syndrome) was associated with higher cardiovascular risk than metabolic syndrome with normal kidney function. Icosapent ethyl substantially reduced primary and key secondary composite endpoints, especially in patients with eGFR <60 mL/min/1.73 m².
Key findings
- Among placebo-treated patients, CKM was associated with increased primary composite endpoint risk at eGFR <90 mL/min/1.73 m² (HR 1.44 [95% CI 1.05–1.96]; P=0.02) and at eGFR <60 mL/min/1.73 m² (HR 1.87 [95% CI 1.31–2.69]; P=0.0005) versus eGFR ≥90 mL/min/1.73 m².
- In patients with eGFR <60 mL/min/1.73 m², icosapent ethyl versus placebo reduced the primary composite endpoint (HR 0.55 [95% CI 0.38–0.78]; P=0.0009) and key secondary composite endpoint (HR 0.52 [95% CI 0.35–0.79]; P=0.002).
- In that eGFR <60 subgroup, icosapent ethyl was associated with an absolute risk reduction of 11.2% and number needed to treat of 9 to prevent an initial primary composite endpoint event over the study period.
- Icosapent ethyl also reduced the primary endpoint at eGFR ≥60 to <90 mL/min/1.73 m² (HR 0.79 [95% CI 0.63–0.98]; P=0.02), with a non-significant interaction P=0.22 across eGFR groups.
Methods
- Post hoc analysis of REDUCE-IT, an international, double-blind, placebo-controlled trial of statin-treated hypertriglyceridemic patients randomized to icosapent ethyl 4 g/day or mineral oil placebo; this analysis included secondary prevention patients with metabolic syndrome but without diabetes at baseline (n=2860).
- Patients were stratified by baseline eGFR: <60 (n=565), ≥60 to <90 (n=1686), and ≥90 mL/min/1.73 m² (n=609).
- Outcomes used Kaplan–Meier analysis and stratified Cox proportional hazards models, with total events analyzed by negative binomial regression; P-values were nominal and exploratory with no adjustment for multiple comparisons.
Limitations
- The paper states this was a post hoc analysis because CKM was not defined until 2023, after REDUCE-IT was completed and published; the reductions and favorable NNT are therefore hypothesis generating and require confirmation.
- The paper states statistical limitations from using multiple exploratory post hoc data cuts to define reduced kidney function, with analyses intended as exploratory and hypothesis generating across eGFR values.
- Evident from the text: the work was supported by Amarin Corporation, and multiple authors report financial relationships with Amarin and other industry entities; adverse event signals such as bleeding TEAEs trending higher with icosapent ethyl in lower eGFR subgroups and numerically higher atrial fibrillation/flutter were reported but not framed as limitations.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
8 of 12 cited sources checked · 5 supported · 1 flagged · accuracy not yet measured
- Interpretationown data
The current study supports IPE as a potential therapeutic strategy for CKM patients beyond traditional standard of care measures.
“As such, the current study supports IPE as a potential therapeutic strategy for CKM patients beyond traditional standard of care measures as outlined in the recent AHA Scientific Statement [3]”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [3] Ndumele, 2023 source
- Premisecitation
IPE reduced TG, a prominent biomarker of CVD risk.
“IPE, a highly purified and prescription form of eicosapentaenoic acid (EPA), reduced TG, a prominent biomarker of CVD risk [13]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [13] Miller, 2011 source
Section 3.4 (page unavailable) describes triglycerides as a biomarker of cardiovascular risk, and Section 13.6 says EPA may reduce triglyceride levels. The paper does not establish that the specific prescription formulation IPE reduced triglycerides; its EPA discussion is broader and more qualified. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Interpretationcitation
The trends observed in the prespecified REDUCE-IT MetS analysis are consistent with results identified for primary and key secondary composite endpoints.
“Overall, the trends observed in the prespecified REDUCE-IT MetS analysis [7] are consistent with results identified for primary and key secondary composite endpoints.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [7] Miller, 2023, Effectiveness of icosapent ethyl on first and total cardiovascular events in patients with metabolic syndrome, but without diabetes: REDUCE-IT MetSyn, Eur Heart J Open source
- Findingown data
In patients with CKM (eGFR <60 mL/min/1.73 m2) adjusted for age and sex, treatment with IPE compared with placebo was associated with significant reduction in the primary composite endpoint, HR 0.55 (95% CI 0.38-0.78), P=0.0009.
“In patients with CKM (eGFR < 60 mL/min/1.73 m2) adjusted for age and sex, treatment with IPE compared with placebo was associated with significant reductions in the primary composite endpoint (HR, 0.55 [95% CI, 0.38, 0.78]; P=0.0009)”
- Also stated in: § Clinical outcomes · plain
“IPE treatment vs placebo was associated with reduction in the primary endpoint at eGFR < 60 mL/min/1.73 m2 (HR, 0.55 [95 % CI, 0.38, 0.78]; P = 0.0009)”
Quote in the paperSubstantial claim - Also stated in: § Clinical outcomes · plain
- Findingown data
In the same population, IPE treatment was associated with a 47% reduction in the key secondary composite endpoint at eGFR <60 mL/min/1.73 m2, HR 0.53 (95% CI 0.35-0.81), P=0.002.
“Use of IPE was also associated with 47 % reduction in the key secondary composite endpoint (HR, 0.53 [95 % CI, 0.35, 0.81]; P = 0.002)”
Quote in the paperSubstantial claim
- Findingown data
In the same population, in the placebo arm, eGFR ≥60 to <90 mL/min/1.73 m2 showed a non-statistically significant trend toward increased risk of the primary composite endpoint compared with normal kidney function (eGFR ≥90 mL/min/1.73 m2), HR 1.30 (95% CI 0.94-1.79), P=0.11.
“A similar trend but without statistical significance was observed for eGFR ≥ 60 to < 90 mL/min/1.73 m² (HR, 1.30 [95% CI, 0.94, 1.79]; P=0.11) compared with MetS patients with normal kidney function.”
Quote in the paperNot a substantial claim - Findingown data
In the same population, there was no statistically significant benefit with IPE for the key secondary composite endpoint at eGFR ≥60 to <90 mL/min/1.73 m2, HR 0.97 (95% CI 0.72-1.30), P=0.81.
“However, there was no statistically significant benefit with IPE at eGFR ≥ 60 to < 90 mL/min/1.73 m2 (HR, 0.97 [95 % CI, 0.72, 1.30]; P = 0.81);”
Quote in the paperNot a substantial claim - Findingown data
In REDUCE-IT secondary prevention patients with MetS but without diabetes at baseline, in the placebo arm, CKM (eGFR <90 mL/min/1.73 m2) was associated with increased risk of the primary composite endpoint compared with normal kidney function (eGFR ≥90 mL/min/1.73 m2), HR 1.44 (95% CI 1.05-1.96), P=0.02.
“In the placebo arm, CKM was associated with increased risk of the primary composite endpoint at eGFR < 90 mL/min/1.73 m2 (Hazard Ratio [HR], 1.44 [95% CI, 1.05, 1.96]; P=0.02)”
- Also stated in: § Clinical outcomes · plain
“Analysis of the incremental effect of CKM on CVD risk in placebo-treated secondary prevention patients with MetS but without diabetes at baseline revealed increased risk of the primary composite endpoint at eGFR < 90 mL/min/1.73 m2 (HR, 1.44 [95 % CI, 1.05, 1.96]; P = 0.02)”
Quote in the paperSubstantial claim - Also stated in: § Clinical outcomes · plain
- Findingown data
In the same population, IPE treatment was associated with a 44% relative risk reduction for time to the primary composite endpoint at eGFR <60 mL/min/1.73 m2, HR 0.56 (95% CI 0.39-0.79), P=0.001, ARR=11.2%, NNT=9.
“Treatment with IPE was associated with a 44 % relative risk reduction for time to the primary composite endpoint (HR, 0.56 [95 % CI, 0.39, 0.79]; P = 0.001, absolute risk reduction [ARR] = 11.2 %; number needed to treat [NNT] = 9)”
Quote in the paperSubstantial claim - Findingown data
In the same population, in the placebo arm, eGFR <60 mL/min/1.73 m2 was associated with increased risk of the primary composite endpoint compared with normal kidney function (eGFR ≥90 mL/min/1.73 m2), HR 1.87 (95% CI 1.31-2.69), P=0.0005.
“and at eGFR < 60 mL/min/1.73 m2 (HR, 1.87 [95% CI, 1.31, 2.69]; P=0.0005) compared with MetS patients with normal kidney function (eGFR ≥ 90 mL/min/1.73 m2).”
- Also stated in: § Clinical outcomes · plain
“and at eGFR < 60 mL/min/1.73 m2 (HR, 1.87 [95 % CI, 1.31, 2.69]; P = 0.0005)”
Quote in the paperSubstantial claim - Also stated in: § Clinical outcomes · plain
- Findingown data
In the same population, IPE treatment was associated with a 46% reduction in total primary composite endpoint events at eGFR <60 mL/min/1.73 m2, rate ratio 0.54 (95% CI 0.36-0.83), P=0.005.
“and 46 % reduction in total events (rate ratio [RR], 0.54 [95 % CI, 0.36, 0.83]; P = 0.005), compared with placebo.”
Quote in the paperSubstantial claim - Findingown data
In the same population, in the placebo arm, eGFR <90 mL/min/1.73 m2 was associated with increased risk of the key secondary composite endpoint compared with normal kidney function (eGFR ≥90 mL/min/1.73 m2), HR 1.55 (95% CI 1.02-2.37), P=0.04.
“increased risk of the key secondary composite endpoint at eGFR < 90 mL/min/1.73 m2 (HR, 1.55 [95 % CI, 1.02, 2.37]; P = 0.04)”
Quote in the paperSubstantial claim - Findingown data
In the same population, in the placebo arm, eGFR ≥60 to <90 mL/min/1.73 m2 showed a non-significant trend of increased risk of the primary and secondary composite endpoints compared with normal kidney function (eGFR ≥90 mL/min/1.73 m2).
“non-significant trend of increased risk of primary and secondary composite endpoint in the eGFR ≥60 to < 90 mL/min/1.73 m2 group compared with patients with normal renal function (eGFR ≥ 90 mL/min/1.73 m2) Supplemental Figure 1.”
Quote in the paperNot a substantial claim - Findingown data
In the same population, IPE vs placebo was associated with reduction in the primary endpoint at eGFR ≥60 to <90 mL/min/1.73 m2, HR 0.79 (95% CI 0.63-0.98), P=0.02.
“IPE treatment vs placebo was associated with reduction in the primary endpoint at eGFR < 60 mL/min/1.73 m2 (HR, 0.55 [95 % CI, 0.38, 0.78]; P = 0.0009), and eGFR ≥ 60 to < 90 mL/min/1.73 m2 (HR, 0.79 [95 % CI, 0.63, 0.98]; P = 0.02).”
Quote in the paperSubstantial claim - Findingown data
In the same population, IPE vs placebo showed a non-statistically significant trend favoring IPE at normal eGFR (≥90 mL/min/1.73 m2) for the primary endpoint, HR 0.67 (95% CI 0.43-1.03), P=0.08.
“While there was a non-statistically significant trend favoring IPE at normal eGFR (≥ 90 mL/min/1.73 m2) (HR, 0.67 [95 % CI, 0.43, 1.03]; P = 0.08)”
Quote in the paperNot a substantial claim - Findingown data
In the same population, there was no statistically significant benefit with IPE for the key secondary composite endpoint at eGFR ≥90 mL/min/1.73 m2 (interaction P=0.06).
“or at eGFR ≥ 90 mL/min/1.73 m2 (interaction P = 0.06) (Fig. 1).”
Quote in the paperNot a substantial claim - Findingown data
In the same population, in the placebo arm, eGFR <60 mL/min/1.73 m2 was associated with increased risk of the key secondary composite endpoint compared with normal kidney function (eGFR ≥90 mL/min/1.73 m2), HR 2.65 (95% CI 1.67-4.23), P<0.0001.
“and at eGFR < 60 mL/min/1.73 m2 (HR, 2.65 [95 % CI, 1.67, 4.23]; P < 0.0001)”
Quote in the paperSubstantial claim - Findingown data
In the same population, IPE treatment was associated with a 51% reduction in total key secondary composite endpoint events at eGFR <60 mL/min/1.73 m2, rate ratio 0.49 (95% CI 0.31-0.79), P=0.003.
“and 51 % reduction in total events (RR, 0.49 [95 % CI, 0.31, 0.79]; P = 0.003) (Supplemental Figure 2).”
Quote in the paperSubstantial claim - Findingown data
In patients with CKM (eGFR <60 mL/min/1.73 m2) adjusted for age and sex, treatment with IPE compared with placebo was associated with significant reduction in the key secondary composite endpoint, HR 0.52 (95% CI 0.35-0.79), P=0.002.
“and in the key secondary composite endpoint (HR, 0.52 [95% CI, 0.35,0.79], P= 0.002).”
- Also stated in: § Clinical outcomes · plain
“The key secondary composite endpoint was significantly reduced with IPE treatment vs placebo in secondary prevention patients with MetS but without diabetes at baseline at eGFR < 60 mL/min/1.73 m2 (HR, 0.52 [95 % CI, 0.35, 0.79]; P = 0.002).”
Quote in the paperSubstantial claim - Also stated in: § Clinical outcomes · plain
- Interpretationown data
The current analysis suggests that IPE may help to mitigate the excess risk associated with CKM.
“The current analysis suggests that IPE may help to mitigate the excess risk associated with CKM.”
Quote in the paperSubstantial claim - Interpretationown data
CKM is a bona fide amplifier of CVD risk beyond MetS.
“these data are consistent with CKM as a bona fide amplifier of CVD risk beyond MetS (Graphical Abstract)”
Quote in the paperSubstantial claim - Interpretationown data
In this post hoc analysis, the addition of renal insufficiency provided incremental CVD risk beyond MetS in secondary prevention patients without diabetes at baseline.
“In this post hoc analysis from REDUCE-IT, the addition of renal insufficiency provided incremental CVD risk beyond MetS in secondary prevention patients without diabetes at baseline.”
- Also stated in: § Conclusions · plain
“In a REDUCE-IT post hoc analysis, the CKM syndrome was associated with incremental CVD risk compared with MetS absent diabetes and with normal kidney function in patients with pre-existing CVD.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · plain
- Premisecitation
MetS has been shown to be an independent predictor of CVD events, even when diabetes is not present.
“While MetS has been shown to be an independent predictor of cardiovascular disease (CVD) events, even when diabetes is not present [2]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] Lakka, 2002, The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men, JAMA source
- Interpretationown data
IPE treatment substantially reduced CVD risk in this high-risk secondary prevention cohort.
“IPE treatment substantially reduced CVD risk in this high-risk secondary prevention cohort.”
Quote in the paperSubstantial claim - Premisecitation
The TG reduction with IPE in REDUCE-IT was relatively modest (~20%).
“the effects were relatively modest (∼20 %) in REDUCE-IT”
Quote in the paperNot a substantial claim - Interpretationown data
The non-significant interaction P-value (P=0.22) suggests that the benefit of IPE was consistent across eGFR groups.
“the non-significant interaction P-value (P = 0.22) suggests that the benefit of IPE was consistent across eGFR groups.”
Quote in the paperSubstantial claim - Study design and conductreasoning
The analysis used multiple exploratory post hoc data cuts to define reduced kidney function, which is a statistical limitation.
“Similarly, statistical limitations of using multiple exploratory post hoc data cuts to define reduced kidney function is acknowledged”
Quote in the paperNot a substantial claim
- May combine two claims. 6
- Classified as probably not a substantial claim. 9
May combine two claims.
PremisecitationCVD event rates in REDUCE-IT were neither influenced by baseline TG levels nor by on-treatment TG levels <150 mg/dL.
“and CVD event rates were neither influenced by baseline TG levels nor by on-treatment TG levels < 150 mg/dL [14].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [14] Bhatt, 2019, REDUCE-IT investigators. Reduction in first and total ischemic events with icosapent ethyl across baseline triglyceride tertiles, J Am Coll Cardiol source
In the main text (pp. 1159–61), the paper says placebo event rates were highest in the upper baseline triglyceride tertile, contrary to the claim that event rates were not influenced by baseline levels. It reports broadly consistent *relative reductions with icosapent ethyl* across tertiles, which is different from saying event rates did not vary. The paper does not assess event rates by on-treatment triglycerides below 150 mg/dL. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
InterpretationcitationCardioprotective properties of EPA that offset inflammation and oxidative stress while improving endothelial function may have been operative in this high-risk phenotype.
“Although the study was not designed to examine mechanism(s) underlying CVD risk reduction in CKM, cardioprotective properties of EPA that offset inflammation and oxidative stress while improving endothelial function may have been operative in this high-risk phenotype [[15], [16], [17], [18]].”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [15] Mason, 2020, Emerging mechanisms of cardiovascular protection for the omega-3 fatty acid eicosapentaenoic acid, Arter Thromb Vasc Biol source
- cites [16] Lin, 2022, Metabolic syndrome-related kidney injury: a review and update, Front Endocrinol (Lausanne) source
Section 6.6 discusses anti-inflammatory effects and endothelial function, but attributes them to pycnogenol, not EPA. Searches of our copy for EPA, eicosapentaenoic acid, and omega-3 fatty acids found no passage addressing the claimed EPA mechanisms or their possible role in this high-risk phenotype. (LLM, conf=0.75)
Experimental — accuracy not yet measured - cites [17] Scurt, 2024, Association of metabolic syndrome and chronic kidney disease, Obes Rev source
Classified as probably not a substantial claim. May combine two claims.
Study design and conductcitationREDUCE-IT was a randomized, double-blind, placebo-controlled trial.
“REDUCE-IT was a randomized double-blind and placebo-controlled phase 3b trial”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [8] Bhatt, 2019, REDUCE-IT investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia, N Engl J Med source
- cites [9] Bhatt, 2017, REDUCE-IT investigators. Rationale and design of REDUCE-IT: reduction of cardiovascular events with icosapent ethyl-intervention trial, Clin Cardiol source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationElevated TG is associated with an increased likelihood of major adverse CVD events.
“as well as an increased likelihood of major adverse CVD events associated with elevated TG [12]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [12] Ambrosy, 2021, Triglyceride levels and residual risk of atherosclerotic cardiovascular disease events and death in adults receiving statin therapy for primary or secondary prevention: insights from the KP REACH study, J Am Heart Assoc source
May combine two claims.
Findingown dataIn patients with CKM (eGFR <60 mL/min/1.73 m2), IPE treatment was associated with an absolute risk reduction of 11.2% and number needed to treat of 9 to prevent an initial primary composite endpoint event over the study period.
“Treatment with IPE was associated with an absolute risk reduction of 11.2% and number needed to treat of 9 patients to prevent an initial primary composite endpoint event over the study period.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenStudy sites were approved by their respective institutional review board or ethics committee.
“study sites were approved by their respective institutional review board or ethics committee.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningIPE has the potential to redefine secondary preventive strategies in this high-risk cohort.
“In view of the associated reduction in cardiovascular events with CKM, despite standard of care therapies, IPE has the potential to redefine secondary preventive strategies in this high-risk cohort.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPre-existing CVD is associated with a heightened risk of CVD events.
“Previous studies have demonstrated a heightened risk of CVD events with pre-existing CVD [11]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Bhatt, 2010, Steg PG; REACH Registry Investigators. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis, JAMA source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenP-values presented are nominal and exploratory with no adjustment for multiple comparisons.
“P-values presented are nominal and exploratory with no adjustment for multiple comparisons.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenEfficacy analyses were undertaken using the intention-to-treat (ITT) approach.
“Efficacy analyses were undertaken using the intention-to-treat (ITT) approach”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningThe sizeable reductions in the primary endpoint and favorable NNT associated with IPE use are hypothesis generating and require confirmation with additional testing.
“Consequently, the sizeable reductions in the primary endpoint and favorable NNT associated with IPE use are hypothesis generating that would require confirmation with additional testing.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The incremental effect of CKD on CVD risk beyond MetS is not well studied.
“However, as CKM syndrome inevitably captures a higher risk population than MetS alone, the incremental effect of CKD on CVD risk beyond MetS is not well studied.”
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Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
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“Although the study was not designed to examine mechanism (s) underlying CVD risk reduction in CKM, cardioprotective properties of EPA that offset inflammation and oxidative stress while improving endothelial function may have been operative in this high-risk phenotype [15 – 18].”
Emerging Mechanisms of Cardiovascular Protection for the Omega-3 Fatty Acid Eicosapentaenoic Acid
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Self-citationRomeo, S., Vidal‐Puig, A., Husain, M., Ahima, R. S., Arca, M., Bhatt, D. L., Diehl, A. M., Fontana, L., Foo, R., Frühbeck, G., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf314 · Cited by 91 · cited 1× · see citing works
“…with albuminuria and/or more advanced kidney disease as recently outlined in a consensus statement by the European Athero-sclerosis Society [10] Previous studies have demonstrated a heightened risk of CVD events with pre-existing CVD [11], as well as an increased likelihood of major…”
Self-citationMajithia, A., Bhatt, D. L., Friedman, A. N., Miller, M., Steg, P. G., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Juliano, R. A., Jiao, L., et al. (2021) · Circulation · doi:10.1161/circulationaha.121.055560 · Cited by 74 · cited 2× · see citing works
“…(Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) in a prespecified analysis across the entire range of included GFR [6], and we also examined secondary prevention patients with a history of MetS in a prespecified analysis of REDUCE-IT, irrespective of renal function…”
Self-citationGaba, P., Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Juliano, R. A., Jiao, L., Doyle, R. T., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.02.035 · Cited by 61 · see citing works
Self-citationVerma, S., Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Dhingra, N. K., Ketchum, S. B., Juliano, R. A., Jiao, L., et al. (2021) · Circulation · doi:10.1161/circulationaha.121.056290 · Cited by 60 · see citing works
Self-citationPeterson, B. E., Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Juliano, R. A., Jiao, L., Doyle, R. T., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.050276 · Cited by 57 · see citing works
Self-citationMetabolic Syndrome: The Constellation of Co-morbidities, A Global Threat
Madan, K., Paliwal, S., Sharma, S. K., Kesar, S., Chauhan, N., & Madan, M. (2023) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530323666230309144825 · Cited by 55 · cited 1× · see citing works
“This is a clinically relevant issue because globally, approximately 25 % of adult men and women have MetS [4], and a sizeable percentage (~15”
Peterson, B. E., Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Juliano, R. A., Jiao, L., Doyle, R. T., et al. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.022937 · Cited by 46 · see citing works
Self-citationAmbrosy, A. P., Yang, J., Sung, S. H., Allen, A. R., Fitzpatrick, J. K., Rana, J. S., Wagner, J., Philip, S., Abrahamson, D., Granowitz, C., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.020377 · Cited by 32 · see citing works
Selvaraj, S., Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Juliano, R. A., Jiao, L., Tardif, J., Ballantyne, C. M., et al. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.024999 · Cited by 31 · see citing works
Self-citationIcosapent ethyl following acute coronary syndrome: the REDUCE-IT trial
Sayah, N., Bhatt, D. L., Miller, M. J., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Jiao, L., Pineda, A. L., Doyle, R. T., Tardif, J., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehad889 · Cited by 29 · see citing works
Self-citationREDUCE-IT INTERIM: accumulation of data across prespecified interim analyses to final results
Olshansky, B., Bhatt, D. L., Miller, M., Steg, P. G., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle Jr, R. T., Juliano, R. A., Jiao, L., et al. (2021) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvaa118 · Cited by 25 · cited 1× · see citing works
“As such, the current study supports IPE as a potential therapeutic strategy for CKM patients beyond traditional standard of care measures as outlined in the recent AHA Scientific Statement [3] and extends its potential utility outside other patient groups at high cardiovascular risk ([7,19 – 27]).”
Self-citationLipoprotein(a) Blood Levels and Cardiovascular Risk Reduction With Icosapent Ethyl
Szarek, M. J., Bhatt, D. L., Miller, M. J., Brinton, E. A., Jacobson, T. A., Tardif, J., Ballantyne, C. M., Mason, R. P., Ketchum, S. B., Pineda, A. L., et al. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.02.016 · Cited by 23 · cited 1× · see citing works
“As such, the current study supports IPE as a potential therapeutic strategy for CKM patients beyond traditional standard of care measures as outlined in the recent AHA Scientific Statement [3] and extends its potential utility outside other patient groups at high cardiovascular risk ([7,19 – 27]).”
Self-citationMetabolic syndrome and its components associated with chronic kidney disease
Rashidi, N., Maleki, A., Montazeri, M., et al. (2015) · Journal of Research in Medical Sciences · doi:10.4103/1735-1995.163969 · Cited by 21 · cited 1× · see citing works
“%) also have CKD [5].”
Miller, M. J., Bhatt, D. L., Steg, P. G., Brinton, E. A., Jacobson, T. A., Jiao, L., Tardif, J., Ballantyne, C. M., Budoff, M. J., & Mason, R. P. (2022) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvac045 · Cited by 18 · see citing works
Self-citationMiller, M., Bhatt, D. L., Brinton, E. A., Jacobson, T. A., Steg, P. G., Pineda, A. L., Ketchum, S. B., Doyle, R. T., Tardif, J.-C., & Ballantyne, C. M. (2023) · European Heart Journal Open · doi:10.1093/ehjopen/oead114 · Cited by 11 · cited 5× · see citing works
“…(Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) in a prespecified analysis across the entire range of included GFR [6], and we also examined secondary prevention patients with a history of MetS in a prespecified analysis of REDUCE-IT, irrespective of renal function [7].”
InfluentialSelf-citationRomeo, S., Vidal-Puig, A., Husain, M., et al. (2026) · Yearbook of pediatric endocrinology · doi:10.1530/ey.23.12.8
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Research works printed but not linked: 2
- Ndumele, 2023, 148, 1636
- Miller, 2011, 123, 2292
Cited by
Sorted by citations
Interventions for the prevention and management of cardiometabolic multiple long-term conditions
Valabhji, J., Hope, D. C. D., SAYED, N. A. E., Godia, P., Lawson, C. A., Seidu, S., & Khunti, K. (2026) · The Lancet · doi:10.1016/s0140-6736(26)00608-2 · Cited by 5 · see citing works
- Authors
- Miller, M., Bhatt, D. L., Brinton, E. A., Jacobson, T. A., Steg, P. G., Ketchum, S. B., Pineda, A. L., Tardif, J.-C., & Ballantyne, C. M.
- Affiliations
- Hospital of the University of Pennsylvania (US)
- Icahn School of Medicine at Mount Sinai (US)
- Emory University (US)
- Amarin (United States) (US)
- Montreal Heart Institute (CA)
- Baylor College of Medicine (US)
- ORCID
- Venue
- American Journal of Preventive Cardiology
- Publisher
- Elsevier BV
- Published
- 2026-02
- Volume
- 25
- Pages
- 101387
- ISSN
- 2666-6677 (ISSN-L)
- PMC
- PMC12849052
- OpenAlex
- W4417488461
- Semantic Scholar
- c0f3ef63801e25b6c135e0e9691d13987a3d0bf5
- Cited by
- 0
- References
- 23
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- American Journal of Preventive Cardiology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- Amarin Corporation
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- icosapent ethyl, cardiovascular-kidney-metabolic syndrome, chronic kidney disease, metabolic syndrome, hypertriglyceridemia, secondary prevention, cardiovascular risk reduction, renal failure, EGFR, REDUCE-IT trial, omega-3 fatty acids
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 2026-10-19.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-19.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
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