N-3 Fatty Acids as Secondary Prevention against Cardiovascular Events in Patients Who Undergo Chronic Hemodialysis

Abstract

Patients who are treated with chronic hemodialysis (HD) experience premature cardiovascular disease and an increased mortality. N-3 polyunsaturated fatty acids (PUFA) may be effective in the secondary prevention of cardiovascular disease, but the effects of n-3 PUFA has not previously been examined in HD patients. It was hypothesized that secondary prevention with n-3 PUFA would reduce the number of cardiovascular events and death in patients who are treated with chronic HD. A randomized, double-blind, placebo-controlled intervention trial compared the effect of n-3 PUFA and a control treatment as secondary prevention of cardiovascular events in HD patients. The primary outcome was a composite of total cardiovascular events and death. A total of 206 patients were randomly assigned to treatment with n-3 PUFA or control treatment and followed for 2 yr or until reaching a predefined end point. During the trial, 121 (59%) of 206 patients reached a primary end point. N-3 PUFA had no significant effect on the primary composite end point of cardiovascular events and death (62 versus 59; NS). In the n-3 PUFA group, a significant reduction was seen in the number of myocardial infarctions (four versus 13; P ‫؍‬ 0.036). This trial was limited by a relatively small number of patients and a large number of withdrawals. However, it is concluded that treatment with n-3 PUFA did not reduce the total number of cardiovascular events and death in this high-risk population. N-3 PUFA significantly reduced the number of myocardial infarctions as a secondary outcome, a finding that might be of clinical interest.Clin J Am Soc Nephrol 1: 780 -786, 2006. doi: 10.2215/CJN.00630206 P atients who are treated with chronic hemodialysis (HD) have a high incidence of cardiovascular disease (CVD) and an increased premature mortality (1,2). Traditional risk factors of CVD are frequent in patients with kidney disease (3); in addition, the uremic milieu results in inflammation (4), specific alterations in lipid metabolism (5), and accumulation of uremic toxins (6), which may contribute to the high risk for CVD. During recent years, there has been focus on the need for intervention trials to prevent CVD and reduce mortality in this high-risk population (7).Evidence exists from both epidemiologic (8) and interventional studies (9) that n-3 polyunsaturated fatty acids (PUFA) might be effective as secondary prevention of CVD and possibly prevent sudden cardiac death (10). However, a recent Cochrane analysis concluded that there is no clear evidence that n-3 PUFA reduce cardiovascular mortality and that there is a need for additional intervention studies in this area of research (11). The possible mechanisms of n-3 PUFA include a lipidlowering effect, with a reduction in plasma triglycerides (12) and a mild antihypertensive effect (13). Several other possible protective mechanisms of n-3 PUFA also have been reported, such as anti-inflammatory (14), antiatherosclerotic (15), antithrombotic (16), and antiarrhythmic (17). The effect of n-3 PUFA on CVD has ...

The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

“…Whether these effects are applicable to RTRs is unclear. In patients who are uremic and treated with hemodialysis, high intake of marine n-3 PUFAs was associated with a lower risk of SCD (17), and an RCT found a lower cumulative incidence of MI after marine n-3 PUFA supplementation (16). In RTRs, there have been reports of improved renal function with marine n-3 PUFA supplementation (29).…”

“…In patients with ESRD, favorable effects of marine n-3 PUFAs on cardiovascular morbidity and mortality have been shown (16,17). Although renal transplantation reduces the risk of CVD in patients with ESRD, CVD remains the leading cause of death in recipients of renal transplants (RTRs) (18).…”

Docosahexaenoic Acid Is an Independent Predictor of All-Cause Mortality in Hemodialysis Patients

“…Kutner et al [5] reported that mortality in patients on HD decreased with fish consumption; however, mortality from cardiac and cardiovascular diseases was similar between patients on HD who consumed fish (60%) and those who did not (61%). Svensson et al [19] conducted a clinical trial with n–3 PUFAs for secondary prevention of CHD in patients on HD and observed no significant effect on the primary composite endpoint of total cardiovascular events and death. However, as a secondary outcome, they found that the incidence of myocardial infarction was significantly reduced in the group treated with n–3 PUFAs.…”

Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A Review

“…Interventional studies of omega-3 PUFAs have investigated the potential effectiveness of PUFA treatment in reducing CV risk in patients on hemodialysis. These include studies of treatment with fish oil dietary supplements containing EPA, DHA, and other ingredients as well as studies of purified products that contain both EPA and DHA or only EPA; results were varied [24,25,26,27,28,29]. Here, we examine the interventional outcomes studies of EPA-only therapy in hemodialysis patients as well as the effects of EPA on factors such as lipids, inflammation, and oxidative stress, which are likely to play a role in the increased CVD risk in this patient population.…”