Clinical Question: What methods of lipid lowering decrease overall mortality rates in patients with hyperlipidemia?

Setting: Various (meta-analysis)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: On average, do all lipid-lowering drugs make people live longer? These investigators searched four databases to find randomized trials addressing this question. Two authors then independently determined whether each study was suitable for inclusion, only using studies that were randomized and that were conducted over at least three months. They included studies that involved patients without evidence of heart disease—primary prevention—as well as secondary prevention studies that enrolled patients with known heart disease. They included studies written in any language and ended up with 97 studies that enrolled more than 275,000 patients.

Only statins and omega-3 fatty acids (fish oils or linolenic acid) decreased the overall mortality rate, and the effect of the omega-3 fatty acids was seen only in patients with pre-existing heart disease. In primary prevention trials, fibrates (fenofibrate [Lipidil], clofibrate [Atromid-S], gemfibrozil [Lopid]) increased mortality rates, with one additional death for every 132 patients treated for an average of 4.4 years (number needed to treat to harm [NNH] = 132; 95% confidence interval [CI], 69 to 662). Many patients have to be treated with a statin to prevent one additional death; the number needed to treat for 3.3 years was 228 (95% CI, 123 to 2,958). In patients with known heart disease, 50 patients (95% CI, 38 to 78) would have to be treated with a statin to prevent one additional death, and 44 patients (95% CI, 31 to 84) would need to be treated with fish oil to prevent one additional death, each over an average of 4.4 years (excluding one low-quality study). Treatment with diet, resins (colestipol [Colestid], cholestyramine [Questran]), or niacin did not affect overall mortality rates.

Bottom Line: Only statin lipid-lowering drugs have been shown to decrease overall mortality rates in patients with high cholesterol but without evidence of heart disease. However, most patients treated with one of these drugs will not benefit; 228 have to be treated for 3.3 years to prevent one additional death during this period. In patients with known heart disease, statins and fish oil have been shown to decrease mortality rates, whereas niacin, resins, and diet have not. Fibrates increase overall mortality rates and at the same time decrease cardiac mortality rates. (Level of Evidence: 1a)