n-3 Fatty Acids in Patients With Multiple Cardiovascular Risk Factors - Risk and Prevention Study

May 08, 2013
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Societa Prodotti Antibiotici, Pfizer, and Sigma-Tau.
Date Published:
01/01/2013
Date Updated:
05/08/2013
Original Posted Date:
05/08/2013
References

Description:

The goal of the trial was to evaluate treatment with n-3 polyunsaturated fatty acids compared with placebo among participants with multiple cardiovascular risk factors or atherosclerotic vascular disease, but no prior myocardial infarction.

Hypothesis:

n-3 polyunsaturated fatty acids will reduce adverse cardiovascular events among high-risk individuals.

Study Design

  • Blinded
  • Randomized
  • Placebo Controlled
  • Stratified
  • Parallel

Patient Populations:

  • Participants with multiple cardiovascular risk factors or atherosclerotic vascular disease, but no prior myocardial infarction

    Number of enrollees: 12,513
    Duration of follow-up: median 5 years
    Mean patient age: 64 years
    Percentage female: 38%

Exclusions:

  • Prior myocardial infarction
  • Hypersensitivity to n-3 fatty acids
  • Pregnancy
  • Limited short-term prognosis

Primary Endpoints:

  • Cardiovascular death or hospitalization for cardiovascular cause

Drug/Procedures Used:

Participants with multiple cardiovascular risk factors or atherosclerotic vascular disease, but no prior myocardial infarction were randomized to n-3 polyunsaturated fatty acids (1 g daily; n = 6,244) versus placebo (olive oil; n = 6,269).

Concomitant Medications:

Angiotension-converting enzyme (ACE) inhibitor: 45%, angiotension-receptor blocker: 22%, beta-blocker: 21%, statin: 41%, antiplatelet agent: 41%

Principal Findings:

Overall, 12,513 participants were randomized. The mean age was 64 years, 62% were men, 85% had hypertension, 71% had hypercholesterolemia, 60% had diabetes, 49% were obese, 32% had history of premature cardiovascular disease, 22% were current smokers, 13% had angina, 9% had prior revascularization, 5% had prior stroke, 8% had prior transient ischemic attack, 8% had peripheral arterial disease, and 3% had heart failure. Never or very seldom, fish consumption was observed in 24% of participants.

At baseline, triglyceride level was 150 mg/dl in both groups. At follow-up, triglyceride level fell 28 mg/dl in the n-3 fatty acid group versus 20 mg/dl in the placebo group (p < 0.001). There was also a slight increase in high-density lipoprotein cholesterol in the n-3 fatty acid group; however, there was no change in blood pressure, heart rate, low-density lipoprotein cholesterol, or blood glucose.

At a median of 5 years of follow-up, the primary outcome of cardiovascular death or hospitalization for cardiovascular cause occurred in 11.7% of the n-3 fatty acid group versus 11.9% of the placebo group (p = 0.58). There was no evidence for effect modification except possibly among women, in whom an enhanced benefit of fatty acids was observed.

- Cardiovascular death: 2.3% vs. 2.2%
- Hospitalization for cardiovascular cause: 9.9% vs. 10.1%
- Cardiovascular death, myocardial infarction, or stroke: 4.6% vs. 4.4%
- Sudden cardiac death: 0.8% vs. 0.6%
- Adverse drug reaction: 3.8% vs. 3.5%, respectively, for n-3 fatty acids vs. placebo

Interpretation:

Among patients with multiple cardiovascular risk factors or atherosclerotic vascular disease, but no prior myocardial infarction, the use of n-3 fatty acids was not beneficial. This therapy did not reduce the incidence of cardiovascular death or hospitalization for cardiovascular causes. The observed cardiovascular event rate was lower than anticipated, which may have reflected healthy dietary patterns or use of preventive medications (e.g., aspirin, statin, ACE inhibitors). At the present time, potential benefit with n-3 fatty acids appears confined to patients with prior myocardial infarction or heart failure.

References:

The Risk and Prevention Study Collaborative Group. n-3 Fatty Acids in Patients With Multiple Cardiovascular Risk Factors. N Engl J Med 2013;368:1800-1808.

Keywords: Ischemic Attack, Transient, Follow-Up Studies, Peripheral Arterial Disease, Blood Pressure, Risk Factors, Plant Oils, Cholesterol, HDL, Hypertension, Death, Sudden, Cardiac, Myocardial Infarction, Stroke, Atherosclerosis, Cholesterol, LDL, Drug-Related Side Effects and Adverse Reactions, Hypercholesterolemia, Heart Rate, Lipoproteins, LDL, Fatty Acids, Omega-3, Blood Glucose, Heart Failure, Triglycerides, Lipoproteins, HDL, Hospitalization, Diabetes Mellitus


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