Does IMPROVE-IT prove it?

•Cholesterol lowering is the foundation of cardiovascular disease prevention guidelines.•Numerous trials of cholesterol lowering have failed to demonstrate consistent benefit.•Failure to acknowledge these negative studies impedes the development of new paradigms.•The benefits of a healthy diet and lifestyle are dramatic and often overlooked.

The recently published IMPROVE-IT trial has been hailed as proof that lowering cholesterol reduces the risk of cardiovascular disease (Cannon et al., 2015). Although this study did demonstrate a modest clinical benefit with incremental low-density lipoprotein cholesterol lowering, many physicians tend to ignore the numerous clinical studies which have failed to demonstrate a benefit of cholesterol lowering. This article challenges the cholesterol hypothesis by reviewing these negative studies and our reluctance to acknowledge them. Paradoxically, cholesterol lowering remains the focus of cardiovascular disease prevention despite the inconsistent benefit demonstrated in dozens of clinical trials. The cholesterol-lowering, statin-centric approach to cardiovascular disease prevention may in fact distract us from other beneficial therapies. Dr. Alexander Leaf, former chief of medicine at Massachusetts General Hospital, commented on this paradox and the Lyon Diet Heart Study nearly 15 years ago by writing, “At a time when health professionals, the pharmaceutical industries, and the research funding and regulatory agencies are almost totally focused on lowering plasma cholesterol levels by drugs, it is heartening to see a well-conducted study finding that relatively simple dietary changes achieved greater reductions in risk of all-cause and coronary heart disease mortality in a secondary prevention trial than any of the cholesterol-lowering studies to date” (Leaf, 1999).