A recent systematic review of statins for primary prevention reports that statins significantly reduced the risk of major cardiovascular events, mortality from cardiovascular disease and total mortality.
This study supports NICE recommendations for primary prevention of cardiovascular (CV) events in its lipid modification guideline. Simvastatin 40mg is recommended as the first-choice statin for primary prevention in people at 20% or greater 10-year CV disease risk. No specific lipid targets are given. Patients need to be given information about their absolute risk of CV disease and the likely absolute benefits and harms of treatment in ways meaningful to them – NICE recommend the patient decision aids on the lipids section of NPC.
What is the background to this?
There is consistent evidence from large randomised controlled trials that statins reduce cholesterol levels and are effective for the secondary prevention of CV events, CV disease death, and all-cause death (see NICE Full Guideline for lipid modification). However, the evidence that statins can reduce some important patient-oriented outcomes for people without existing CV disease is less certain. A recent systematic review and meta-analysis considered the effect of statins in preventing major CV events and death in patients, the majority of whom did not have a history of coronary heart disease.
What does this study claim?
The study, which considered trials of at least 12 months duration, found that statins significantly reduced the risk of all-cause mortality (relative risk [RR] 0.93, 95% confidence interval [CI] 0.87 to 0.99, P=0.03; 19 studies, n=63,899). Significant reductions in risk were also obtained for CV disease mortality (RR 0.89, 95% CI 0.81 to 0.98, P=0.02; 18 studies, n=59,469), major cardiovascular events (RR 0.85, 95% CI 0.77 to 0.95, P=0.004; 17 studies, n=53,371) and myocardial infarction (MI) (RR 0.77, 95% CI 0.63 to 0.95, P=0.01; 17 studies, n=52,976). The benefits for reducing all-cause stroke were less certain (RR=0.88, 95% CI 0.78 to 1.00, P=0.05; 18 studies, n=57,430). There was no significant reduction in risk identified for non-CV mortality. There was no significant increase in the risk of cancers.
How does this relate to other studies?
NICE considered the clinical evidence from meta-analyses and large randomised controlled clinical trials of statins for primary prevention in its Full Guideline for lipid modification. NICE recommended using simvastatin 40 mg as first-choice statin for primary prevention in people at 20% or greater 10-year CV disease risk. No specific lipid targets are given .
Since publication of the NICE guideline and the present meta-analysis, the JUPITER study found that rosuvastatin 20mg daily significantly reduced the risk of all-cause mortality (1.00 vs. 1.25/100 patient years, hazard ratio [HR] 0.80, 95%CI 0.67 to 0.97, P=0.02) compared with placebo in people with few elevated CV risk factors apart from a raised high-sensitivity C-reactive protein. These results are consistent with the present meta-analysis, and provide support to the conclusions and NICE recommendations.
The study supports the NICE recommendations for the use of statins for the primary prevention of people who are at high risk of CV disease. The absolute benefit obtained from statins depends on the patient’s baseline risk, and patients should be fully involved in the decision of whether or not to take statins for the rest of their life, in order to reduce the likelihood of having a cardiovascular event. Patients need to be given information about their absolute risk of CV disease and the likely absolute benefits and harms of treatment in ways meaningful to them – see the patient decision aids on the lipids section of NPC.
The meta-analysis appears comprehensive in terms of its search and appropriate inclusion criteria. No studies with simvastatin were included in this meta-analysis, but there were similar benefits with simvastatin 40mg in patients with and without established CV disease in the large Heart Protection Study.
There was heterogeneity between studies for many of the outcomes, some of which could be explained by a failure to conceal allocation in some studies. Analysis of outcomes from studies in which concealed allocation was reported generally suggested a weaker therapeutic effect for statins. There was no association between reductions in LDL cholesterol and mortality or morbidity.
Design: Literature search (to May 2008), systematic review and random effects meta-analysis of randomised controlled trials of at least 12-month duration.
Patients: Predominantly primary prevention populations (>50% with no history of coronary heart disease).
Intervention: Studies comparing a statin (excluding cerivastatin) with placebo, standard therapy, or no treatment and which reported any of the following clinical CV outcomes: all-cause mortality, CV disease mortality, fatal MI, non-fatal MI, and major coronary events. Studies of high-risk diabetic patients were also excluded (predicted 10-year CVD risk >20%).
Outcomes: All-cause mortality, CV disease mortality (the primary outcome), non-cardiovascular mortality, stroke mortality, major cardiovascular events, MI, stroke, revascularisation, angina, cancer, rhabdomyolysis.
All-cause mortality — RR 0.93, 95% CI 0.87 to 0.99, P=0.03; 19 studies, n=63,899
CV disease mortality — RR 0.89, 95% CI 0.81 to 0.98, P=0.02; 17 studies, n=59,469
Non-CV mortality — RR 0.98, 95% CI 0.90 to 1.07, P=0.62; 18 studies, n=63,333
Major CV events — RR 0.85, 95% CI 0.77 to 0.95, P=0.004; 17 studies, n=53,371
MI — RR 0.77, 95% CI 0.63 to 0.95, P=0.01; 17 studies, n=52,976
All-cause stroke — RR 0.88, 95% CI 0.78 to 1.00, P=0.05; 18 studies, n=57,430
Stroke mortality — RR 1.05, 95%CI 0.79 to 1.39, P=0.72; 11 studies 31,035
Revasularisation — RR 0.84, 95%CI 0.66 to 1.08, P=0.18; 13 studies, n=37,439
Angina — RR 1.01, 95%CI 0.67 to 1.52, P=0.95; 11 studies, n=38,598
Cancer — RR 1.02, 95%CI 0.94 to 1.11, P=0.59; 10 studies, n=45,469
Rhabdomyolysis — RR 0.97, 95%CI 0.25 to 3.83, P=0.96; 9 studies, n=39,383
Sponsorship: no sponsorship reported. The authors are from academic institutions in Canada and the UK.