An Update on Statin Alternatives and Adjuncts

Matthew J Sorrentino


Clin Lipidology. 2012;7(6):721-730. 

In This Article

Fish Oils

Treatment with fish oils for the prevention of cardiovascular events has been supported by a number of clinical trials. The GISSI-Prevenzione trial randomly assigned over 11,000 postmyocardial infarction patients to receive 1 g/day of marine fish oils and showed a 15% reduction in the composite primary end point of death, nonfatal myocardial infarction or nonfatal stroke.[31] In addition, there was a 45% reduction in the rate of sudden death suggesting that marine fish oils may have an anti-arrhythmic effect in ischemic heart disease patients. Since the publication of GISSI-Prevenzione, additional studies have shown conflicting results. A recent meta-analysis of 20 studies showed no statistically significant association with fish oils and cardiovascular outcomes.[32] The authors pointed out, however, that strong significant effects of fish oils were seen in earlier studies, but these results were not reproduced in studies reported over the last 5 years. One potential explanation for this finding is the difference in cointerventions in the more recent studies. Current studies have a higher percentage of individuals taking optimal medical management, including statin therapy, which may have brought about significant risk reduction that cannot be further modified by the addition of fish oils. In patients that cannot take statins, however, the benefit of fish oils may approach what was observed in the earlier era studies at a time when patients were not receiving what is now considered optimal medical care.

The addition of ω-3 fish oils to the diet can lower triglyceride levels. Marine-based ω-3 fatty acids (eicosapentenoic acid and docosahexenoic acid) are more effective in lowering triglycerides than plant-derived oils. A meta-analysis of numerous fish oil trials concluded that ω-3 fatty acid consumption can lower triglycerides by 25–30%, raise HDL cholesterol (HDL-C) by 1–3% and raise LDL-C by 5–10% if saturated fat intake remains constant.[33] 2–4 g of eicosapentenoic acid and docosahexenoic acid per day are needed to achieve this triglyceride-lowering effect. Fish oils have also been used in combination with other lipid-lowering agents. In patients with combined hyperlipidemia, the addition of 7.2 g/day of marine oils with simvastatin 10 mg/day brought about a better reduction in triglycerides than with the statin alone.[34] There was no attenuation of the LDL-lowering effect of the statin with the addition of the fish oils. Patients with a sustained hypertriglyceridemia despite adequate treatment of LDL-C with a statin drug achieved a 20–30% reduction in triglycerides over a year of treatment with a concentrated fish oil supplement.[35] Although having no LDL-C-lowering effect, fish oil supplements can be a useful adjunct in individuals with a mixed hyperlipidemia and persistently elevated triglyceride levels.