High-Intensity Statins for Secondary Prevention

Whether high-intensity statin therapy is preferable to low- or moderate-intensity statins in patients with established atherosclerotic cardiovascular disease (ASCVD) remains a point of uncertainty. The 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk¹ shifted the secondary prevention strategy from low-density lipoprotein cholesterol targets to a risk-based algorithm, recommending high-intensity statins for all patients age 75 years and younger with documented ASCVD in whom such therapy is tolerated. This recommendation represents an extrapolation of evidence from randomized clinical trials (RCTs) that have examined this specific topic, in which the effect of more intensive statin therapy on overall adverse ASCVD events was variable, but none showed a significant reduction in all-cause mortality.

The data by Rodriguez et al,² derived from more than half a million patients with ASCVD in the Veterans Affairs Health System, are thus of significance. The authors provide compelling evidence that statins reduce mortality even when measured at only 1 year of exposure and that the reduction in mortality is greatest with high-intensity statin therapy. One must interpret these findings with caution because they are derived from a large observational database, with the potential for confounding factors between patients receiving high-intensity and those receiving low-intensity statins, particularly because they run counter to the results of well-designed RCTs. However, it is also possible that this study detected a signal not found in the RCTs because of its very large sample size relative to RCTs and because it involves a broader population, including patients older than 75 years. The evidence base for benefit in patients older than 75 years is limited based on the small number of such patients enrolled in the RCTs, and the American College of Cardiology/American Heart Association guidelines recommend only moderate-intensity statins for secondary prevention in patients with ASCVD in this age group.¹ That patients older than 75 years appear to derive a similar benefit with high-intensity statins to that of younger individuals, with seemingly no excessive untoward risks, is an important observation that should stimulate further RCTs in this age group. Clearly the prescription of statin therapy and its intensity remains highly individualized, but we find these findings confirmatory that high-intensity statin therapy when appropriate is beneficial for secondary prevention, and these benefits are seen even in older persons. These data, along with close adherence to the prevailing guidelines, offer effective strategies to reduce death and disability owing to death and disability from ASCVD.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.