Time to Benefit of Statins for Primary Prevention of Cardiovascular Events
- 100 adults (aged 50-75 years) with low prevalence of cardiovascular disease would need to be treated with a statin for 2.5 years to prevent one MACE.
- Statins are most appropriate for adults with a life-expectancy >2.5 years.
In adults aged 50-75 years, what is the time to benefit (TTB) for statins to prevent a first major adverse cardiovascular event (MACE)?
A meta-analysis was performed of statin trials, with particular focus on large (>1,000 patients) randomized clinical trials, rated as moderate or high quality by Cochrane criteria, patient mean age >55 years, and with <15% of patients having known pre-existing cardiovascular disease. The primary outcome was the time between statin initiation and first major cardiovascular endpoint, a composite of cardiovascular outcomes. The definition of MACE across all trials was broadly similar, including myocardial infarction (MI) and cardiovascular mortality. Survival data from control and intervention groups were independently extracted by two authors and discrepancies resolved by a third author. To obtain the TTB for each study, random-effects survival curves were fit using annual event data and Markov chain Monte Carlo methods were used to estimate time to specific absolute risk reduction (ARR) thresholds (0.2%, 0.5%, and 1%) for each study.
Eight randomized clinical trials were identified, with a total of 65,383 participants of whom 66.3% were men. Trial sizes ranged from 1,129-17,802 subjects. Trial publication dates ranged from 1998-2016. Mean age ranged from 55 (range 45-64) to 69 (range 65-75) years. All studies had a prevalence of prior cardiovascular disease (including prior angina, MI, and/or stroke) of <10% of subjects. The mean length of follow-up ranged from 2-6 years. The ARR of MACE varied from 0.4-3.9%. Only one of the eight studies reported that statins decreased all-cause mortality, while only one other reported that statins decreased cardiovascular mortality. None of the other six studies found a mortality benefit. The authors used advanced statistical techniques to estimate a value, the TTB, which was not included in any of the individual studies, and then performed a meta-analysis based on this estimated value. The result of these calculations showed that 2.5 years (95% confidence interval, 1.7-3.4) were needed to prevent one MACE per 100 adults aged 50-75 years treated with a statin.
This study suggests that for patients aged 50-75 years with a low risk of cardiovascular disease, 100 adults would need to be treated for 2.5 years to avoid one MACE. Only one out of eight randomized trials included in this meta-analysis showed an all-cause mortality benefit from statins.
Based on the results of this survival meta-analysis, the authors suggest that statins may be most appropriate for adults aged 50-75 years with a life-expectancy >2.5 years, assuming that the patients truly have a low risk of cardiovascular disease. It is unclear how applicable these results are to adults over age 75 years, and those with low-to-intermediate or intermediate risk for cardiovascular disease. While the TTB (as opposed to the more commonly measured magnitude of benefit) may be an important consideration for preventive interventions in low-risk populations, the legitimacy of using meta-analysis to estimate TTB, when none of the individual trials directly measured this quantity, is unclear. The authors rightfully suggest that rather than using pooled TTB results, individual patients may be best served by applying the TTB of the individual studies that best fit their patient characteristics.
Keywords: Angina Pectoris, Cardiovascular Diseases, Dyslipidemias, Geriatrics, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myocardial Infarction, Primary Prevention, Stroke, Vascular Diseases
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