Impediments to clinical application of exercise interventions in the treatment of cardiometabolic disease

Statins have become a pharmacologic cornerstone for the prevention and treatment of cardiovascular disease (CVD). However, it is clear from the large statin trials that maximal lowering of low-density lipoprotein cholesterol (LDL-C) levels still allows 2 out of 3 cardiovascular events to occur. These events represent the so-called residual risk that remains after optimized statin therapy. Attempts to further lower LDL-C levels in patients with established CVD using high-dose statins, adding ezetimibe, or adding proprotein convertase subtilisin-kexin type 9 inhibitors have each resulted in a further modest absolute event reduction of 1% to 2% over 2 to 6 years. None of these augmentation trials has shown a reduction in all-cause mortality.