- Share - [](https://www.facebook.com/sharer.php?u=https://about.ebsco.com/markdownify/node/38141) - []() - []() - []() # EBM Focus: OMG Omega-3? Not Worth the Fish Breath Does addition of omega-3 CA to statin therapy reduce major adverse cardiovascular events in patients at high risk? Find out in this EBM Focus. ![nurse reading blood pressure senior patient blog image template ](/sites/default/files/acquiadam-assets/nurse-reading-blood-pressure-senior-patient-blog-image-template-780.jpg) [Dan Randall, MD, MPH, FACP](/health-notes/bio/dan-randall-md-mph-facp) 6 January 2021 Replicating naturally occurring omega-3 fatty acids, to mirror the dietary benefits for cardiovascular health, suffers from the same problem as many other attempts to copy nature — things don’t always turn out as you might expect. The [**REDUCE-IT**](https://nam10.safelinks.protection.outlook.com/?url=https%3A%2F%2Fgo.ebsco.com%2FSN0Q2T0fH000sLF1O003wVb&data=04%7C01%7Chmarshall%40ebsco.com%7C97bcc6c642ff449b042708d89c543778%7C50fa36ca7dd344f19e3f1bf39a3963a5%7C0%7C0%7C637431232817799918%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=K%2F8J0uGBzSe0MXBuS%2Ba%2FORdTtxbwrPwZSni%2Fbmve3kg%3D&reserved=0) trial published in 2019 suggested that supplementing statins with a proprietary form of eicosapentaenoic acid (EPA) might help secondary prevention of cardiovascular events. Researchers recently conducted a nearly identically designed trial ([**STRENGTH**](https://pubmed.ncbi.nlm.nih.gov/33190147/)) for Astra-Zeneca’s carboxylic acid formulation, called omega-3 CA, which combines EPA and docosahexaenoic acid (DHA). Researchers looked at major adverse cardiovascular events in a multi-site group of 13,078 patients already taking statins, about half of them at high risk of a primary event (due to age, family history, smoking, diabetes, elevated high-sensitivity C-reactive protein \[hsCRP\], or hypertension) and the other half needing secondary prevention after a primary event. Upon randomization, half the group received omega-3 CA and the other half were given corn oil tablets as a comparator. Groups were followed for several years with contact every three months, but the trial was stopped prematurely for futility because the drug didn’t seem to be working. The study was adequately powered to detect a 15 percent difference between groups, and 1,580 of a planned 1,600 events were recorded. There were no significant differences between groups in major adverse cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and admission for unstable angina (hazard ratio \[HR\] 0.99, 95% CI 0.9-1.09), with similar results in subgroup analyses of primary and secondary events. One tertiary outcome stood out, however — the rate of new-onset atrial fibrillation in omega-3 CA patients versus corn oil: 2.2 percent vs. 1.3 percent (HR 1.69, 95% CI 1.29-2.21). This attempt to replicate the benefits of secondary prevention with fish oil found in the REDUCE-IT trial not only didn’t pan out but may have harmed patients by inducing atrial fibrillation (increased incidence of atrial fibrillation was also seen in the REDUCE-IT trial). One criticism of both the STRENGTH and REDUCE-IT trials is the use of corn oil and mineral oil, respectively, as comparators because of possible uncharacterized effects of these oils. Omega-3 CA tablets were associated in this trial with significant reductions in triglycerides, non-HDL cholesterol levels, and hs-CRP, so hypothetically, supplementation should have reduced events in real life. The question remains whether people who consumed an equivalent amount of omega-3 CA in their diet rather than in a pill would have had clinical benefit, as is seen with dietary calcium vs. supplementation. Or perhaps the benefit of statins for secondary prevention is so great that an added benefit from omega-3 CA is too small to realistically measure. This study suggests that the addition of omega-3 CA to a statin does no good and has a risk of harm. For more information, see the topic [**Omega-3 Fatty Acids and Fish Oil**](https://nam10.safelinks.protection.outlook.com/?url=https%3A%2F%2Fgo.ebsco.com%2FO030F0wQ0201sLHc0W0TOfN&data=04%7C01%7Chmarshall%40ebsco.com%7C97bcc6c642ff449b042708d89c543778%7C50fa36ca7dd344f19e3f1bf39a3963a5%7C0%7C0%7C637431232817799918%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=D9hJgkazei6YOEdfp%2BFf5wz%2FtXMCvhgmFl%2F4Rudz3KM%3D&reserved=0) in *DynaMed®*. [ Sign up for EBM Focus ](https://more.ebsco.com/EBM-Focus-Newsletter-Signup.html) Category: [Clinical Practice Perspectives ](/blogs/health-notes/category/clinical-practice-perspectives) Tags: [Evidence–based medicine](/blogs/health-notes/tag/evidence–based-medicine) [EBMFocus](/blogs/health-notes/tag/ebmfocus) - Share - [](https://www.facebook.com/sharer.php?u=https://about.ebsco.com/markdownify/node/38141) - []() - []() - []() ## Related Posts [ ![EBM Focus Low LDL Cholestorol Blog Image ](/sites/default/files/acquiadam-assets/EBM-Focus-Low-LDL-Cholestorol-Blog-Image-780.jpg) ](/blogs/health-notes/ebm-focus-low-ldl-cholesterol-may-be-associated-intracerebral-hemorrhage) [EBM Focus: Low LDL Cholesterol May Be Associated with Intracerebral Hemorrhage](/blogs/health-notes/ebm-focus-low-ldl-cholesterol-may-be-associated-intracerebral-hemorrhage) 30 September 2019 [ ![emb focus cannabis preterm delivery blog image ](/sites/default/files/acquiadam-assets/emb-focus-cannabis-preterm-delivery-blog-image-780.jpg) ](/blogs/health-notes/ebm-focus-antenatal-cannabis-use-may-increase-risk-preterm-delivery) [EBM Focus: Antenatal Cannabis Use May Increase Risk of Preterm Delivery](/blogs/health-notes/ebm-focus-antenatal-cannabis-use-may-increase-risk-preterm-delivery) 6 August 2019 [ ![EBM Focus Dont Overdapt It Blog Image ](/sites/default/files/acquiadam-assets/EBM-Focus-Dont-Overdapt-It-Blog-Image-780.jpg) ](/blogs/health-notes/ebm-focus-dont-overdapt-it-one-month-may-be-enough-after-stent-placement-low) [EBM Focus: Don’t overDAPT it – One Month May Be Enough After Stent Placement for Low-Risk Patients](/blogs/health-notes/ebm-focus-dont-overdapt-it-one-month-may-be-enough-after-stent-placement-low) 29 August 2019