Additive benefits of pravastatin and aspirin to decrease risks of cardiovascular disease: randomized and observational comparisons of secondary prevention trials and their meta-analyses.
BACKGROUND
In randomized trials of secondary prevention, pravastatin sodium and aspirin reduce risks of cardiovascular disease. Pravastatin has a predominantly delayed antiatherogenic effect, and aspirin has an immediate antiplatelet effect, raising the possibility of additive clinical benefits.


METHODS
In 5 randomized trials of secondary prevention with pravastatin (40 mg/d), comprising 73 900 patient-years of observation, aspirin use was also prescribed in varying frequencies, and data were available on a large number of confounding variables. We tested whether pravastatin and aspirin have additive benefits in the 2 large trials (Long-term Intervention With Pravastatin in Ischaemic Disease trial and the Cholesterol and Recurrent Events trial) that were designed to test clinical benefits. We also performed meta-analyses of these 2 trials and 3 smaller angiographic trials that collected clinical end points. In all analyses, multivariate models were used to adjust for a large number of cardiovascular disease risk factors.


RESULTS
Individual trials and all meta-analyses demonstrated similar additive benefits of pravastatin and aspirin on cardiovascular disease. In meta-analysis, the relative risk reductions for fatal or nonfatal myocardial infarction were 31% for pravastatin plus aspirin vs aspirin alone and 26% for pravastatin plus aspirin vs pravastatin alone. For ischemic stroke, the corresponding relative risk reductions were 29% and 31%. For the composite end point of coronary heart disease death, nonfatal myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or ischemic stroke, the relative risk reductions were 24% and 13%. All relative risk reductions were statistically significant.


CONCLUSIONS
More widespread and appropriate combined use of statins and aspirin in secondary prevention of cardiovascular disease will avoid large numbers of premature deaths.
Hennekens
Charles H
CH
Mount Sinai Medical Center-Miami Heart Institute, Department of Medicine & Epidemiology and Public Health, University of Miami School of Medicine, Boca Raton, FL 33432, USA. PROFCHHMD@prodigy.net
Sacks
Frank M
FM
Tonkin
Andrew
A
Jukema
J Wouter
JW
Byington
Robert P
RP
Pitt
Bertram
B
Berry
Donald A
DA
Berry
Scott M
SM
Ford
Neville F
NF
Walker
Andrew J
AJ
Natarajan
Kannan
K
Sheng-Lin
Chen
C
Fiedorek
Frederick T
FT
Belder
Rene
R
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D017035:Pravastatin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control
D000924:Anticholesteremic Agents; D010975:Platelet Aggregation Inhibitors; D017035:Pravastatin; D001241:Aspirin