Abstract
BackgroundCardiovascular disease is the leading cause of morbidity and mortality with incidence rates of 5–10 per 1000 person-years, according to primary prevention studies. To control hyperlipidemia—a major risk factor of cardiovascular disease—initiation of lipid-lowering therapy with therapeutic lifestyle modification or lipid-lowering agent is recommended. Few systematic reviews and meta-analyses are available on lipid-lowering therapy for the primary prevention of cardiovascular diseases. In addition, the operational definitions of intensive lipid-lowering therapies are heterogeneous. The aim of our study was to investigate whether intensive lipid-lowering therapies reduce greater cardiovascular disease risks in primary prevention settings.MethodsMEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2019 for randomized controlled trials. We used random effects model for overall pooled risk ratio (RR) estimation with cardiovascular events of interest and all-cause mortality rate for the intensive lipid-lowering group using the standard lipid-lowering group as the reference. The Cochrane Risk of Bias Tool was used for quality assessment.ResultsA total of 18 randomized controlled trials were included. The risk reductions in cardiovascular outcomes and all-cause mortality associated with more intensive vs. standard lipid-lowering therapy across all trials were 24 and 10%, respectively (RR 0.76, 95% confidence interval 0.68–0.85; RR 0.90, 95% confidence interval 0.83–0.97); however, the risk reduction varied by baseline LDL-C level in the trial. A greater risk reduction was noted with higher LDL-C level. Intensive lipid-lowering for coronary heart disease protection was more pronounced in the non-diabetic populations than in the diabetic populations.ConclusionsMore intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels than less intensive LDL-C lowering. Intensive lipid-lowering was associated with a significant risk reduction of coronary heart disease and must be considered even in the non-diabetic populations.
Highlights
Cardiovascular disease is the leading cause of morbidity and mortality with incidence rates of 5–10 per 1000 person-years, according to primary prevention studies
18 trials were with coronary event analysis (N = 103,864); trials, total mortality event analysis (N = 93,215); trials, lipid-lowering drug (11 statin trials [16,17,18,19,20,21,22,23,24,25,26], 1 cholestyramine resin trial [18, 27], 1 fibrate trial [28], 1 gemfibrozil trial [29], 1 combination therapy trial [30]) vs. placebo; two trials, lipid-lowering drug vs. usual care; and 1 trial, absolute low-density lipoprotein cholesterol (LDL-C) level
Compared with the cardiovascular risk reduction of 19% in LDL-C level of 130 mg/dL or lesser (RR 0.81, 95% confidence intervals (CI) 0.69–0.97) preferring more intensive lipid-lowering, we found greater cardiovascular risk reduction in higher baseline LDL-C level: 28% in LDL-C level of 160 mg/dL or greater (RR 0.72, 95% CI 0.62–0.84), and 29% in LDL-C level of 130–160 mg/dL (RR 0.71, 95% CI 0.61–0.83)
Summary
Cardiovascular disease is the leading cause of morbidity and mortality with incidence rates of 5–10 per 1000 person-years, according to primary prevention studies. The aim of our study was to investigate whether intensive lipid-lowering therapies reduce greater cardiovascular disease risks in primary prevention settings. For high cardiovascular risk populations, i.e., those with diabetes or several high-risk conditions, a more intensive lipid-lowering strategy is usually recommended, including a combination of lipidlowering agents with therapeutic lifestyle changes to reach a stricter target of atherogenic lipoprotein levels [3,4,5]. The first aim of our study was to investigate whether intensive lipid-lowering therapies reduce greater CHD or all-cause mortality risks in primary prevention settings. The final aim was to evaluate whether factors, including sex, age, and diabetes status, are important effect modifiers between intensive lipid treatment and coronary heart disease prevention
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