Lowering cholesterol with a statin - when is it worth it?

Although I have never been a big fan of modeling studies, viewing their appropriate role as hypothesis-generating rather than clinical decision-supporting, a study published yesterday in the Annals of Internal Medicine deserves kudos for trying to do what neither the American College of Cardiology/American Heart Association nor the U.S. Preventive Services Task Force did in their respective guidelines on primary prevention of cardiovascular disease for adults aged 40 to 75 years: empirically assess the balance of benefits and harms of statins. (In case you missed it, I recently recorded a Medscape commentary on the 2018 ACC/AHA guideline, which has flaws but overall represents an improvement over the 2013 version.)

In persons at low risk of having a heart attack or stroke, the harms of statins offset (or may be greater than) the benefits, but at what 10-year risk threshold do the benefits begin to outweigh the harms (positive net benefit)? In 2013 and again in 2018, the ACC/AHA proposed an arbitrary threshold of 7.5%, and the USPSTF's slightly higher threshold of 10% is just as arbitrary, even as it compensates for the tendency of the Pooled Equations risk calculator to overestimate true risk and potentially lead to unnecessary therapy. But neither group quantitatively weighed the relatively low probability of preventing a serious cardiovascular event against the higher probability of causing muscle aches, diabetes, and other adverse effects, as this research team did.

The modeling study's results will appeal to patients (including my own) who would prefer that their physicians be conservative in prescribing statins, suggesting that in men the risk threshold where benefits exceed harms ranges from 14% to 21%, while in women it ranges from 17% to 22%. The study's methods are not particularly transparent, relying in part on a network meta-analysis that is not yet published. Even if the model's inputs were clearer, there is no consensus that several of the harms that they attribute to statins (hemorrhagic stroke, renal dysfunction, cancer, and cataracts) are actually medication-related.

Setting the numbers aside, I agree with one general conclusion: although the risk of having a heart attack or stroke rises with age, so, too, does the threshold when it makes sense to take preventive action. Side effects of statins are more common in older persons, and the older you are, the more likely you are to die from something other than cardiovascular disease (so-called "competing causes of death"). Over age 75, it becomes very unlikely that starting or continuing a statin for primary prevention will do more good than harm.