Formulation-Specific Cardiovascular Outcomes with High-Dose Eicosapentaenoic Acid: A Systematic Review and Meta-analysis
Faheem MA, Azeem B, Ali T, Asim R, Muhammad TS, Dogar ME, Naveed MA
American journal of cardiovascular drugs : drugs, devices, and other interventions · 0 citas
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Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2026-05-02 · Am J Cardiovasc Drugs · vol. 26 · número 4 · págs. 453–465
- Editorial
- Adis, Springer Healthcare
- Citado
- 0 citas · más que el 23% de estudios similares · 0.0× el promedio de su campo
- Referencias
- 0 trabajos
- Acceso
- De pago
- Áreas de investigación
- Fatty Acid Research and Health · Lipoproteins and Cardiovascular Health · Nutritional Studies and Diet
- Palabras clave
- eicosapentaenoic acid, omega-3 fatty acids, icosapent ethyl, atherosclerotic cardiovascular disease, residual cardiovascular risk, myocardial infarction, revascularization, ischemic stroke, cardiovascular mortality, plaque progression, high-sensitivity C-reactive protein
- MeSH
- humans, cardiovascular diseases, docosahexaenoic acids, eicosapentaenoic acid, dietary supplements, randomized controlled trials as topic
7 autores
- Muhammad Anas Faheem🇵🇰 · autor de correspondenciaDow University of Health Sciences
- Bazil Azeem · autor de correspondencia
- Talha Ali · autor de correspondencia
- Rabia Asim · autor de correspondencia
- Tazheen Saleh Muhammad · autor de correspondencia
- Mata‐e‐Alla Dogar · autor de correspondencia
- Muhammad Abdullah Naveed🇵🇰 · autor de correspondenciaDow University of Health Sciences
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background/objective
Residual cardiovascular risk persists despite intensive statin therapy in patients with established atherosclerotic cardiovascular disease (CVD). Omega-3 fatty acids, particularly high-dose eicosapentaenoic acid (EPA), have been proposed as adjunctive therapy, yet trial results conflict, likely due to formulation differences. We conducted a formulation-focused meta-analysis to determine whether high-dose EPA-dominant supplementation reduces cardiovascular events and to quantify the impact of mixed EPA/docosahexaenoic acid (DHA) regimens on efficacy.
Methods
Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched MEDLINE, Embase, CENTRAL, and trial registries through May 2025 for randomized controlled trials, including placebo-controlled and open-label designs, of high-dose EPA-dominant omega-3 (≥ 1.8 g/day; ≥ 50% EPA) in adults with established CVD or other high-risk settings. Six trials (n = 42,738; 31-85% male) were eligible. Random-effects models generated pooled risk ratios (RRs), with I2 assessing heterogeneity; sensitivity analyses excluded mixed EPA/DHA formulations. Imaging surrogate outcomes were summarized narratively when study modalities were not directly comparable.
Results
EPA-based therapy significantly reduced hospitalizations for unstable angina (RR 0.75, 95% CI 0.66-0.87; I2 = 0%). Overall effects on recurrent myocardial infarction and revascularization were not statistically significant, but both became significant after exclusion of STRENGTH, the only mixed EPA/DHA cardiovascular outcomes trial. No significant effect was observed for ischemic stroke, cardiovascular death, or high-sensitivity C-reactive protein (hs-CRP). CHERRY and EVAPORATE both suggested attenuation of plaque progression, but these imaging studies were not pooled because intravascular ultrasound and coronary computed tomography angiography-derived measures were not directly comparable.
Conclusion
High-dose EPA-dominant therapy was associated with fewer unstable angina hospitalizations, and formulation appeared to modify clinical benefit. Among blinded, placebo-controlled, cardiovascular outcomes trials, 4 g/day icosapent ethyl is the only formulation independently associated with reduced cardiovascular events. Larger formulation-specific trials are needed to clarify the roles of purified EPA, mixed EPA/DHA regimens, and patient selection.
Registration
PROSPERO identifier number: CRD420251063069.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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