This editorial is a follow-up to Redberg’s 2017 editorial: Statins for Primary Prevention: The debate is intense, but the data are weak. It examines the updated USPSTF recommendations on the use of statins for primary prevention.
The authors note that “there is uncertainty regarding the net benefit to risk ratio of using statins to reduce LDL among persons without CVD (primary prevention).”
One trial (PROSPER) only enrolled older individuals between 70 and 82 years of age: new cancer diagnoses were more frequent in patients on pravastatin than on placebo (1.25); stroke risk was unaffected.
The updated evidence synthesis found that statins yielded a smaller (than the 2016 synthesis) reduction in all-cause mortality (0.92 vs 0.86 in 2016); the benefit for CVD mortality was not statistically significant. 19 of the 22 trials included were industry sponsored. The USPSTF no longer recommends the use of low-intensity statins, since the industry trials were mostly-fixed dose, and 12 of 22 used moderate intensity statins. The authors note that “this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases”.
The authors of the editorial dryly note that “The USPSTF recommendations should be considered in the light of a meta-analysis, published in 2010, which included only trials that enrolled patients receiving high-risk primary prevention; this study showed no benefit on all-cause mortality with statins”. (this was a meta-analysis of 11 randomized controlled trials involving 65,229 participants).
Inclusion criteria across studies were heterogeneous and mixed patients with (secondary) and without (primary prevention) heart disease. Since statins have an established role in secondary prevention, this would inflate statins’ benefit.
Individual participant level data of the statin trials is housed at the “cholesterol treatment trialists collaborative” at Oxford University; researchers are not allowed to examine the patient-level data from 24 trials comparing statins to a control group.
The guidelines advise using the American College of Cardiology/American Heart Association pooled cohort equations to stratify risk. The cut points of 5, 7.5, 10, and 20% are arbitrary; the PCE is based on mostly white males enrolled between 1968 and 1990 and does not reflect decreases in rates of CVD due to reduced rates of smoking, shifts in dietary patterns and exercise, and blood pressure control. The risk estimates are inflated. The higher the “risk”, the more the patient will be urged to take a statin.
The USPSTF concluded statins did not have any statistically significant harms, but myalgias are commonly seen, and diabetes risk is increased. The authors note that “it is prudent to keep in mind that although the purported benefits of statins will accrue to a few patients in the future, everyone prescribed a moderate-intensity statin is at risk immediately for the harms. Consideration of adverse effects is especially important for a primary prevention drug, which is prescribed to healthy people who feel perfectly well.”