Observational Study Hints at Real Benefits for Patients Who Take PUFAs After Acute MI

Use of n-3 polyunsaturated fatty acids (PUFAs) following acute MI is associated with reductions in death and recurrent acute MI, even after controlling for other relevant factors related to PUFA use, according to a retrospective study published online November 17, 2015, in the American Journal of Cardiology.

The take home:  Observational Study Hints at Real Benefits for Patients Who Take PUFAs After Acute MI

Questions about the role of PUFAs in heart health date back to the 1970s, when a low risk of heart disease was found among the Inuit population of Greenland, whose diet is very high in PUFAs, William S. Harris, PhD, of the Sanford School of Medicine at the University of South Dakota (Sioux Falls, SD), told TCTMD in a telephone interview. This led to a series of RCTs on PUFA supplements that have produced conflicting results over the decades.  

To gain a better understanding of the role of PUFAs in improving outcomes following acute MI, investigators led by Savina Nodari, MD, of the University of Brescia (Brescia, Italy), conducted a retrospective observational cohort study involving 11,269 patients from 5 Italian local health units who were discharged from the hospital with a primary diagnosis of acute MI between January 1, 2010, and December 31, 2011. The patients were linked across governmental hospital discharge, medication prescription, and mortality databases and followed for 12 months post-index discharge.  

Baseline characteristics and outcomes were compared among patients according to their receipt of prescriptions for n-3 PUFAs postdischarge. Based on the limited availability and reimbursement of PUFAs in Italy, the daily dose of n-3 PUFAs was presumed to be 1 gram per day, consisting of 850-882 mg of eicosapentaenoic acid and docosahexaenoic acid ethyl esters in an average ratio of 1:2. 

Overall, 21.5% of patients were given at least 1 prescription for an n-3 PUFA during follow-up. Adherence rate to PUFA therapy was calculated as the total number of days’ supply of medication dispensed during follow-up divided by total post-discharge days from baseline to 12 months or death, whichever occurred first. Based on this calculation, 25.9% of patients prescribed PUFAs had an adherence rate of 0-40%, 26.4% had an adherence rate of 41-80%, and 47.8% an adherence rate of 81-100%. 

There were a total of 1,198 deaths (10.6%) and 494 repeat acute MIs (4.4%) during follow-up. After adjusting for patient characteristics and concurrent therapies, treatment with n-3 PUFAs was associated with reduced all-cause mortality and recurrent acute MI through 12-month follow-up. 

  Outcomes at 12 Months: With vs Without PUFA Therapy

To our knowledge,” write the authors, “this is the largest study to date specifically investigating the influence of n-3 PUFA use on post-AMI clinical outcomes in a ‘real-world’ non-clinical trial database.” 

These findings contradict those of recent RCTs conducted on PUFA use that did not demonstrate cardiovascular benefits, said Harris. While the observational nature of this study makes it difficult to determine with certainty that the more aggressive treatment of patients who took PUFAs did not contribute to their improved outcomes—despite statistical efforts to eliminate this confounder—its design also means that a the large number of patients were involved, including those who, for any number of reasons, might have failed to meet inclusion criteria for an RCT. “Are we leaving out so many patients in RCTs that we are missing out on what’s happening in the real world?” he speculated. 

While Harris advocates for the use of PUFAs in patients with heart disease, given that some studies show benefits and none have ever identified any risks or disadvantages, he does acknowledge that additional research is needed. In particular, he said, studies should be longer term than the 2 to 3 years typical of research in this area to date, involve doses higher than 1 g per day, include a wider variety of patients (not just those who are very ill), and carefully monitor use of background medical therapy. 

Certain Patients, Contexts May Enable Benefit

It is also important to determine who is likely to benefit most from PUFA supplementation, he said. “It’s possible that advances in cardiovascular care and medications have made fish oil irrelevant,” he said. “But not everyone gets that kind of care. Maybe in the United States everyone gets primary angioplasty when admitted to hospital [for acute MI], but not in Italy and many other places. In those places, fish oil might be more valuable.” 

The study authors make a similar point. “The present analysis,” they write, “carries several notable findings that contextualize the improved clinical outcomes seen with n-3 PUFA treatment.” 

Rates of PCI in this acute MI population were less than 25%, regardless of whether patients went on to receive PUFAs, while dual antiplatelet therapy use also was “low,” they note, adding, “Along these lines, it is notable that the positive findings from GISSI-Prevenzione occurred prior to widespread acceptance of dual antiplatelet therapy and primary and early invasive PCI strategies. Perhaps consistent with underutilization of guideline therapy, the 1-year mortality rate in the present study was markedly higher (10.6%) than that seen in contemporary n-3 PUFA clinical trials.” 


Greene SJ, Temporelli PL, Campia U, et al. Effects of polyunsaturated fatty acid treatment on post-discharge outcomes following acute myocardial infarction. Am J Cardiol. 2015;Epub ahead of print. 

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Observational Study Hints at Real Benefits for Patients Who Take PUFAs After Acute MI