Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients.
OBJECTIVE
This study aimed to evaluate the effectiveness of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) in primary prevention of cardiovascular events.


BACKGROUND
The role of statins is well established for secondary prevention of cardiovascular disease (CVD) clinical events and mortality. Little is known of their role in primary cardiovascular event prevention.


METHODS
We conducted comprehensive searches of 10 electronic databases from inception to May 2008. We contacted study investigators and maintained a comprehensive bibliography of statin studies. We included randomized trials of at least 12-month duration in predominantly primary prevention populations. Two reviewers independently extracted data in duplicate. We performed random-effects meta-analysis and meta-regression, calculated optimal information size, and conducted a mixed-treatment comparison analysis.


RESULTS
We included 20 randomized clinical trials. We pooled 19 trials (n = 63,899) for all-cause mortality and found a relative risk (RR) of 0.93 (95% confidence interval [CI]: 0.87 to 0.99, p = 0.03 [I(2) = 5%, 95% CI: 0% to 51%]). Eighteen trials (n = 59,469) assessed cardiovascular deaths (RR: 0.89, 95% CI: 0.81 to 0.98, p = 0.01 [I(2) = 0%, 95% CI: 0% to 41%]). Seventeen trials (n = 53,371) found an RR of 0.85 (95% CI: 0.77 to 0.95, p = 0.004 [I(2) = 61%, 95% CI: 38% to 77%]) for major cardiovascular events, and 17 trials (n = 52,976) assessed myocardial infarctions (RR: 0.77, 95% CI: 0.63 to 0.95, p = 0.01 [I(2) = 59%, 95% CI: 24% to 74%]). Incidence of cancer was not elevated in 10 trials (n = 45,469) (RR: 1.02, 95% CI: 0.94 to 1.11, p = 0.59 [I(2) = 0%, 95% CI: 0% to 46%]), nor was rhabdomyolysis (RR: 0.97, 95% CI: 0.25 to 3.83, p = 0.96 [I(2) = 0%, 95% CI: 0% to 40%]). Our analysis included a sufficient sample to reliably answer our primary outcome of CVD mortality.


CONCLUSIONS
Statins have a clear role in primary prevention of CVD mortality and major events.
Mills
Edward J
EJ
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. millsej@mcmaster.ca
Rachlis
Beth
B
Wu
Ping
P
Devereaux
Philip J
PJ
Arora
Paul
P
Perri
Dan
D
D006801:Humans; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D016001:Confidence Intervals; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008148:Lovastatin / Q000627:therapeutic use; D017035:Pravastatin / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012306:Risk
D000924:Anticholesteremic Agents; D000069059:Atorvastatin; D005229:Fatty Acids, Monounsaturated; D000077340:Fluvastatin; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008148:Lovastatin; D017035:Pravastatin; D011758:Pyrroles