Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke. Meta-analysis of randomized trials.
OBJECTIVE
To estimate the relative risk reduction of the clinical outcomes (coronary events, strokes, cardiovascular, non-cardiovascular and all-cause mortality) associated with statin therapy in primary and secondary prevention.


METHODS
A literature search of the Medline and Cohrane databases for articles published from 1985 to July 2002 was performed. The data on systematic reviews and preliminary reports were also included in this study. Primary and secondary prevention trials and regression trials were eligible. DATA EXTRACTION AND STATISTICAL METHOD: Data were extracted by 2 authors according to the defined inclusion criteria. Disagreements were resolved by consensus or by a third reviewer. Testing for heterogeneity was applied and on the basis of these results a fixed effect model or a random effect model was used for calculation of relative risk values (RR) and 95% confidence intervals (95% CI). Sensitivity analysis tested the impact of the individual study--duration of study, type of statin therapy and study size. The number of patients needed to treat was calculated as an absolute measure of clinical effectiveness of statin therapy when appropriate.


RESULTS
Data from 15 trials with 63,410 participants and mean duration of treatment of 3.6 years, were included in this overview. Tests for heterogeneity showed that the variability between study estimates is sufficiently small to assume that they are estimating the same underlying treatment effect. Statin therapy was associated with a 22% reduction in total cholesterol, 29% reduction in LDL cholesterol, 12% reduction in triglycerides and 6% increase in HDL cholesterol. Overall (primary and secondary studies) statin therapy significantly reduces relative risk of coronary events (RR, 0.73, 95% CI, 0.68, 0.77, *p < 0.0001), relative risk of cardiovascular disease mortality (RR, 0.78, 95% CI, 0.73, 0.84, *p < 0.0001), relative risk of non-fatal stroke (RR, 0.74, 95% CI, 0.67, 0.82, *p < 0.0001), relative risk of total (fatal and non-fatal) stroke (RR, 0.77, 95% CI, 0.70, 0.84, *p < 0.001) and relative risk of all-cause death (RR, 0.85, 95% CI, 0.81, 0.89, *p < 0.0001). There was a slight and insignificant reduction of relative risk in non-cardiovascular mortality (RR, 0.94, 95% CI, 0.86, 1.03, p = 0.1677) and fatal strokes (RR, 0.86, 95% CI, 0.70, 1.07, p = 0.1912). Sensitivity analysis showed the robustness of our results for all outcomes. The results were not altered if an individual study was removed from meta-analysis.


CONCLUSIONS
This overview indicates that statin treatment reduces the relative risk of occurrence of coronary events, cardiovascular disease mortality, non-fatal strokes and all-cause mortality. While secondary prevention with statins provides considerable improvement of cardiovascular morbidity/mortality, primary prevention with statins provides only small and clinically hardly relevant improvement of cardiovascular morbidity/mortality.
Vrecer
M
M
Krka, Novo mesto, University of Ljubljana, Ljubljana, Slovenia.
Turk
S
S
Drinovec
J
J
Mrhar
A
A
D000368:Aged; D003327:Coronary Disease / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors