Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes - PubMed (original) (raw)

Meta-Analysis

Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes

Bernard M Y Cheung et al. Br J Clin Pharmacol. 2004 May.

Abstract

Aims: Since 2002, there have been five major outcome trials of statins reporting findings from more than 47,000 subjects. As individual trial results differed, we performed a meta-analysis to ascertain the effectiveness and safety of statins overall and in subgroups. The aim of the study was to estimate the effect of statins on major coronary events and strokes, all-cause mortality and noncardiovascular mortality, and in different subgroups.

Methods: PubMed was searched for trials published in English. Randomized placebo-controlled statin trials with an average follow up of at least 3 years and at least 100 major coronary events were included. For each trial, the statin used, number and type of subjects, proportion of women, mean age and follow up, baseline and change in lipid profile, cardiovascular and non-cardiovascular outcomes were recorded.

Results: Ten trials involving 79,494 subjects were included in the meta-analysis. Due to heterogeneity, ALLHAT-LLT was excluded from some analyses. Statin therapy reduced major coronary events by 27% (95%CI 23, 30%), stroke by 18% (95%CI 10, 25%) and all-cause mortality by 15% (95%CI 8, 21%). There was a 4% (95%CI -10, 3%) nonsignificant reduction in noncardiovascular mortality. The reduction in major coronary events is independent of gender and presence of hypertension or diabetes. The risk reduction was greater in smokers (P < 0.05). Coronary events were reduced by 23% (95%CI 18, 29%) in pravastatin trials and 29% (95%CI 25, 33%) in five trials using other statins. Pravastatin reduced strokes by 12% (95%CI 1, 21%) whilst other statins reduced strokes by 24% (95%CI 16, 32%) (P = 0.04).

Conclusions: Statins reduce coronary events, strokes and all-cause mortality without increasing noncoronary mortality. The benefits accrue in men and women, hypertensives and normotensives, diabetics and nondiabetics, and particularly in smokers. Pravastatin appears to have less impact on strokes.

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Figures

Figure 1

Figure 1

Trial flow

Figure 2

Figure 2

Relative risk ratios and 95% confidence intervals for major coronary events (CHD death and nonfatal myocardial infarction) in the major trials. P = 0.57 for heterogeneity

Figure 3

Figure 3

Relative risk ratios for all-cause mortality. P = 0.10 for heterogeneity

Figure 4

Figure 4

Relative risk ratios for non-CHD mortality. P = 0.68 for heterogeneity

Figure 5

Figure 5

Relative risk ratios for strokes (excluding transient ischaemic attacks). P = 0.28 for heterogeneity

Figure 6

Figure 6

Relative risk ratios for major coronary events in females (F) and males (M). P = 0.14 and P = 0.20 for heterogeneity in female and male subgroups, respectively

Figure 7

Figure 7

Relative risk ratios for major coronary events in nonsmokers and smokers. P = 0.74 and P = 0.42 for heterogeneity in subgroups of nonsmokers and smokers, respectively

Figure 8

Figure 8

Relative risk ratios for major coronary events in hypertensive and normotensive subjects. P = 0.14 and P = 0.45 for heterogeneity in hypertensive and normotensive subgroups, respectively

References

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