Role of Statins in the Primary Prevention of Atherosclerotic Cardiovascular Disease and Mortality in the Population with Mean Cholesterol in the Near-Optimal to Borderline High Range: A Systematic Review and Meta-Analysis

Objective. The objective of this meta-analysis was to analyze the benefits and harms of treating the population with statins in those having mean low-density lipoprotein cholesterol (LDL-C) in the near-optimal (100 to 129 mg/dl) to borderline high (130 to 159 mg/dl) range and free of cardiovascular disease (CVD). Methods. We searched PubMed, PubMed Central, Cochrane Library, and Google Scholar databases for randomized controlled trials (RCTs) published between 1994 and July 2020. We included RCTs with greater than 90% of participants free of CVD. Two reviewers independently screened the articles using the Covidence software, assessed the methodological quality using the risk of bias 2 tool, and analyzed the data using the RevMan 5.4 software. Results. Eleven trials were included. Statin therapy was associated with a decreased risk of myocardial infarction (RR = 0.56, 95% CI: 0.47 to 0.67), major cerebrovascular events (RR = 0.78, 95% CI: 0.63 to 0.96), major coronary events (RR = 0.67, 95% CI: 0.57 to 0.80), composite cardiovascular outcome (RR = 0.71, 95% CI: 0.62 to 0.82), revascularizations (RR = 0.65, 95% CI: 0.57 to 0.74), angina (RR = 0.76, 95% CI: 0.63 to 0.92), and hospitalization for cardiovascular causes (RR = 0.74, 95% CI: 0.64 to 0.86). There was no benefit associated with statin therapy for cardiovascular mortality and coronary heart disease mortality. All-cause mortality benefit with statin therapy was seen in the population with diabetes and increased risk of CVD. Statin therapy was associated with no significant increased risk of myalgia, creatine kinase elevation, rhabdomyolysis, myopathy, incidence of any cancer, incidence of diabetes, withdrawal of the drug due to adverse events, serious adverse events, fatal cancer, and liver enzyme abnormalities. Conclusion. Statin therapy was associated with a reduced risk of cardiovascular disease and procedures without increased risk of harm in populations with mean LDL-C in the near-optimal to the borderline high range and without prior atherosclerotic cardiovascular disease.