The past quarter century has witnessed a series of randomized clinical trials that defined contemporary cholesterol treatment algorithms. The first two of these trials, WOSCOPS and 4S, demonstrated the efficacy of statin therapy vs placebo in persons with very elevated low-density lipoprotein cholesterol (LDL-C) levels ( ≈ 190 mg/dL).1,2 Subsequent studies identified the benefits of statin therapy in populations with progressively lower starting LDL-C levels. As equipoise shifted, trial designs changed from placebo-controlled interventions to evaluating more- vs less-intensive lipid-lowering strategies.
Navar AM, Peterson ED. Challenges in Interpreting the Lipid-Lowering Trials: Biology vs Ecology. JAMA. 2018;319(15):1549–1551. doi:10.1001/jama.2018.4041
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