Statins in Primary Prevention: Uncertainties and Gaps in Randomized Trial Data

Randomized controlled trials (RCTs) have provided evidence of the usefulness of statin primary prevention in lowering cardiovascular morbidity and mortality, yet uncertainties and gaps remain. The objective of this article was to perform a narrative review of RCTs of statins for primary prevention and identify uncertainties and gaps resulting from the design of individual studies. Such knowledge is important for informed physician–patient decisions. A literature search was conducted for RCTs of statins in primary prevention that included >1000 general patients and clinical outcomes as a primary endpoint. A total of 11 RCTs were identified; target population baseline characteristics, outcomes measures, statistical methods, and limitations regarding follow-up were reported. RCTs of statins in primary prevention show consistent overall beneficial effects on cardiovascular morbidity and mortality. Caveats involve the characteristics of individual study populations since target populations often differ from what is currently considered primary prevention. Only middle aged and older populations were adequately represented in these RCTs; women were under-represented. Only one study included total mortality as the primary endpoint; all other RCTs used composite major adverse cardiac events as the primary endpoint, which occasionally included a hard outcome such as death and a soft outcome such as hospitalization for angina. The use of Cox proportional hazard analysis in RCTs poses some challenges, and intention-to-treat analysis may mask adverse events. An understanding of the deficiencies of individual RCTs of statins in primary prevention is important in creating a patient-specific therapeutic clinical decision and in tailoring future research.