| Study |
Population |
Results |
Conclusion |
| Vrecer et al. [9] |
Data from 15 trials with 63,410 participants and mean duration of treatment of 3.6 years, were included in this overview. |
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). |
While secondary prevention with statins provided considerable improvement of cardiovascular morbidity / mortality, primary prevention with statins provides only small and clinically hardly relevant improvement of cardiovascular morbidity/mortality. |
| Thavendiranathan et al. [10] |
Seven trials with 42,848 patients were included. Ninety percent had no history of CV disease. Mean follow-up was 4.3 years. |
Statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = .02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively. Statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). No significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed. |
In patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality. |
| Ward et al. [11] |
Thirty-one randomised studies were identified that compared a statin with placebo or with another statin, and reported clinical outcomes. |
Meta-analysis of the available data from the placebo-controlled studies indicates that, in patients with, or at risk of, CVD, statin therapy is associated with a reduced relative risk of all cause mortality, cardiovascular mortality, CHD mortality and fatal myocardial infarction (MI), but not of fatal stroke. It is also associated with a reduced relative risk of morbidity [non-fatal stroke, non-fatal MI, transient ischaemic attack (TIA), unstable angina] and of coronary revascularisation. |
The cost-effectiveness modelling presented here has shown that statin therapy in secondary prevention is likely to be considered cost-effective while in primary prevention, the cost-effectiveness ratios are dependent on the level of CHD risk and age, |
| Mills et al. [12] |
They included 20 randomized clinical trials. |
They 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%]). |
Statins have a clear role in primary prevention of CVD mortality and major events. |
| Taylor et al. [13] |
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. |
Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.83, 95% CI 0.73 to 0.95) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life. |
Although reductions in all-cause mortality, composite endpoints and revascularisations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk. |
| Ray et al. [14] |
Data were available on 65,229 participants followed for approximately 244,000 person-years, during which 2793 deaths occurred. |
The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction (risk ratio, 0.91; 95% confidence interval, 0.83-1.01) in the risk of all-cause mortality. There was no statistical evidence of heterogeneity among studies (I(2) = 23%; 95% confidence interval, 0%-61% [P = .23]). |
This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up. |
| Brugts et al. [18] |
10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. |
Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to 0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. |
In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events. |
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