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J Am Coll Cardiol, 2008; 52:1769-1781, doi:10.1016/j.jacc.2008.08.039
© 2008 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: PREVENTIVE CARDIOLOGY

Primary Prevention of Cardiovascular Mortality and Events With Statin Treatments

A Network Meta-Analysis Involving More Than 65,000 Patients

Edward J. Mills, MSc, PhD, LLM*,*, Beth Rachlis, MSc§, Ping Wu, MBBS, MSc||, Philip J. Devereaux, MD, PhD*,{dagger}, Paul Arora, MSc and Dan Perri, BScPharm, MD, FRCP(C){dagger},{ddagger}

* Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
{dagger} Department of Medicine, McMaster University, Hamilton, Ontario, Canada
{ddagger} Centre for Evaluation of Medicines, McMaster University, Hamilton, Ontario, Canada
§ Department of Healthcare and Epidemiology, University of British Columbia, Vancouver, British Columbia, Canada
|| Department of Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
Centre for Global Health, University of Toronto, Toronto, Ontario, Canada

Manuscript received July 1, 2008; revised manuscript received August 20, 2008, accepted August 25, 2008.

* Reprint requests and correspondence: Dr. Edward J. Mills, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada (Email: millsej{at}mcmaster.ca).

Objectives: 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 [I2 = 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 [I2 = 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 [I2 = 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 [I2 = 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 [I2 = 0%, 95% CI: 0% to 46%]), nor was rhabdomyolysis (RR: 0.97, 95% CI: 0.25 to 3.83, p = 0.96 [I2 = 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.

Key Words: statins • meta-analysis • primary prevention

Abbreviations and Acronyms
  CHD = coronary heart disease
  CI = confidence interval
  CrI = credibility interval
  CVD = cardiovascular disease
  HDL = high-density lipoprotein
  IQR = interquartile range
  LDL = low-density lipoprotein
  MI = myocardial infarction
  OIS = optimal information size
  RR = relative risk


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