Statins do not decrease mortality in primary prevention

A systematic review just published in the journal Evidence-Based Medicine adds more clarity to the proper use of statin medications. Clinicians reading this are likely aware of the controversy raised by the  extensive JUPITER trial. The authors note:

"Low-density lipoprotein (LDL) cholesterol (LDL-C) is a risk factor for cardiovascular disease (CVD). Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) lower LDL-C concentrations by about 30–50% and have been shown to reduce mortality in patients with prevalent CVD. However, it is not clear whether statin treatment is beneficial in a primary prevention setting, that is in people without prevalent CVD who are at relatively lower risk. The recent results of the JUPITER trial have fueled an intense debate whether statins should be given for primary prevention of CVD."

They performed a comprehensive analysis of studies published in the MEDLINE and Cochrane Collaboration databases involving trials of statin use whose subjects were without prevalent CVD at baseline. They performed a detailed meta-analysis employing sophisticated statistical methods with all-cause mortality as the primary outcome of interest. In all, 11 studies involving 65,229 patients met their inclusion criteria, comprising 244,000 person-years of observation. An interesting picture emerged when the numbers were crunched:

"...LDL-C concentration was not predictive of mortality. Statin therapy was not associated with a significant survival benefit...The exclusion of the two trials comprising only patients with diabetes did not substantively change these results. Furthermore, the authors did not find a correlation between mortality reduction and baseline LDL-C concentration or with relative LDL-C reduction in the treatment arm."

In other words, in this large cohort of patients without already active cardiovascular disease, statin therapy showed no benefit in mortality reduction. The authors state in their conclusion:

"This investigation is by far the largest analysis of statin therapy in a purely primary prevention setting...the authors observed a consistent null result (for statin benefit) independent of mean baseline LDL concentration and mean LDL-C reduction in the treatment arm and without evidence of relevant heterogeneity across cohorts...This study therefore questions the widespread practice of prescribing statins to middle-aged patients with an average cardiovascular risk profile who do not have overt CVD...The inference can be made that individuals with lower cardiovascular risk are likely to benefit even less from statin therapy."

Statin therapy is not without serious risks and must be pondered carefully for each individual patient. It should not be simply employed as a surrogate for a thorough analysis of the underlying causes promoting dyslipidemia, and most importantly, vascular inflammation—the driving pathological process in cardiovascular disease. The authors further conclude:

"Taken together, the study is the first to meta-analyse statin therapy in a purely primary prevention setting. Its conclusive null result (for statin benefit on all-cause mortality) raises important questions about the current practice of widespread use of statins for primary prevention of CVD in individuals with average cardiovascular risk."