Abstract

• For patients who have already had a cardiovascular event or who have stable angina or peripheral artery disease, the prevention of cardiovascular events ("secondary prevention") is based on dietary advice, physical activity and cardiovascular risk factor control. Statins are often proposed in this situation.
   
• In 2017, what is the evidence for the efficacy of statins in secondary cardiovascular prevention? In which situations are they effective? What are their harms? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. To analyse efficacy, we searched for randomised trials lasting at least 2 years that included at least 1000 patients and reported all-cause mortality or cardiovascular mortality.
   
• In the two trials of simvastatin versus placebo, simvastatin at a dose of 20 mg to 40 mg per day reduced all-cause mortality: 2 to 3 deaths were prevented per 100 patients treated for 5 years, with a 5-year cardiovascular mortality of about 9% in the placebo groups. In two trials, simvastatin 80 mg daily did not appear to reduce mortality more than 20 mg daily.
   
• In a placebo-controlled trial, pravastatin 40 mg per day prevented about 2 deaths per 100 patients treated for 6 years. Three other trials with lower statistical power neither confirmed nor refuted this result. A meta-analysis of 13 placebo-controlled trials in about 25 000 patients suggests that in patients with coronary heart disease, pravastatin reduces all-cause mortality by about one-fifth.
   
• Trials of atorvastatin versus placebo or usual care have yielded conflicting results. According to a meta-analysis of 5 placebo-controlled trials in about 11 000 patients, atorvastatin does not significantly reduce all-cause mortality in patients with coronary heart disease.
   
• No trials have demonstrated that fluvastatin, lovastatin or rosuvastatin, used in secondary cardiovascular prevention, reduce mortality.
   
• The preventive effects of statins have mainly consisted of a reduction in coronary events. Reduction in cardiovascular or all-cause mortality has only been demonstrated in patients under the age of 80 years with severe coronary heart disease, most of whom had LDL-cholesterol levels above 2.6 mmol/l (1.0 g/l) before treatment initiation.
   
• After an ischaemic stroke or a transient ischaemic attack (TIA), simvastatin and atorvastatin reduce the risk of coronary events, but there is no evidence of an effect on all-cause mortality in this situation.
   
• The most disturbing adverse effects of statins are: dose-dependent muscle effects, a dose-dependent risk of type 2 diabetes and probably a risk of haemorrhagic stroke, especially in patients with low cholesterol levels.
   
• Compared with pravastatin and simvastatin, further lowering LDL-cholesterol levels with atorvastatin (80 mg per day) has no proven effect on cardiovascular mortality, slightly reduces the risk of non-fatal cardiovascular events and increases the incidence of muscular adverse effects.
   
• In practice, as of 2017, the first-choice statins for secondary cardiovascular prevention are pravastatin and simvastatin, at a daily dose of 40 mg. Pravastatin has the advantage of causing fewer drug interactions than simvastatin. In some situations, the harm-benefit balance of statins is uncertain or unfavourable, due to the risk of muscular adverse effects and haemorrhagic stroke.
   

©Prescrire 1 September 2017

"Statins in secondary cardiovascular prevention. Pravastatin is the first choice when statin therapy is justified" Prescrire Int 2017; 26 (185): 213-220. (Pdf, subscribers only)