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.

Sanjay S Srivatsa,Sijan Khatiwada,Bikash J Kshetri,Hari K Lamichhane,Gerardo E Guill N Nieto,Prabhat Adhikari,Dhan B Shrestha,Bishnu M Singh

doi:10.1155/2020/6617905

Abstract

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.

Highlights

Atherosclerotic Cardiovascular disease (ASCVD) encompasses four major diseases, including coronary heart disease (CHD), cerebrovascular disease, peripheral artery disease (PAD), and aortic atherosclerosis
We found the estimate of effect size to be homogenous across all these groups except for the outcomes, major cerebrovascular events, and all-cause mortality. e effect size of these outcomes was remarkably significant for the group of trials where the mean low-density lipoprotein cholesterol (LDL-C) of participants was in the near-optimal range (100–129 mg/dl)
We suggest no benefit of statin therapy on reducing cardiovascular mortality in a population with baseline average LDL-C in near-optimal to borderline high range, which is consistent with nine trials that reported the outcome

Summary

Introduction

Atherosclerotic Cardiovascular disease (ASCVD) encompasses four major diseases, including coronary heart disease (CHD), cerebrovascular disease, peripheral artery disease (PAD), and aortic atherosclerosis. Previous prospective observational studies revealed that the relationship between serum cholesterol and CHD is a continuously graded one rather than just a threshold one and the risk gradient to be continuous over the whole range of cholesterol concentrations [3]. A study done in Shanghai, China, suggested that cholesterol is still an important cause of CHD, where the mean baseline serum cholesterol concentration is considered a normal or low concentration by the western standards [4]. A study conducted in India revealed that low serum cholesterol has a strong positive relationship with coronary artery disease. It did not show any evidence of a threshold. It is essential to study the effect of cholesterol-lowering on cardiovascular prevention in populations with low mean cholesterol

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Results

Conclusion