Comparative Efficacy And Safety Of Cholesterol Lowering Agents On Hypercholesterolemia

BackgroundWith the development of our country’s economy and society,profound changes have taken place in China’s national lifestyle.Especially with the aging of the population and the acceleration of urbanization process,the prevalence trend of cardiovascular disease risk factors in China is more obvious,and the incidence of cardiovascular diseases in China continues to increase.Hypercholesterolemia is the most important risk factor leading to coronary atherosclerotic cardiovascular diseases.According to the recommendations of the lipid management guidelines,there are three major lipid-lowering drugs,including Statin,Ezetimibe,and PCSK9 inhibitor.ObjectiveThe purpose of this study is to systematically evaluate the current relevant clinical studies from the perspective of evidence-based medicine,and compare the long-term effectiveness and safety of three lipid-lowering drugs with different mechanisms of action on patients with hypercholesterolemia.MethodThis meta-analysis comprehensively searched the randomized controlled clinical trials of PCSK9 inhibitors in Pubmed,Embase,Cochrane Central Register of Controlled Trail(Central)and Clinical Trials.Through reading the title,abstract and full text,the studies were screened according to the inclusion and exclusion criteria of the meta-analysis.Finally,all the original studies that met the inclusion criteria of this meta-analysis received from 2016/01/01 to2020/01/01 were included,and the quality evaluation of the included experiments was conducted,and the evaluation was determined using the evaluation tool CHSRI and evaluation criteria provided by Cochrane Collaboration.The original data in the evaluated RCT study were extracted and analyzed statistically.ContentThe outcome indicators were divided into two categories: efficacy indicators and safety indicators.The efficacy index is the level of LDL-C,and the safety evaluation indicators are the incidence of cardiovascular events and the mortality of cardiovascular events.And the safety evaluation indicators include myocardial infarction,unstable angina,coronary revascularization,and stroke.After the analysis of cardiovascular events with combined statistics,the subgroup analysis method was used to carry out stratified analysis to explore the effectiveness and safety of lipid-lowering drugs to improve a specific cardiovascular disease,combined with the latest version of dyslipidemia management.The recommendation in the guidelines are discussed to provide evidence-based,reference,and guidance for clinicians in making decisions about actual medications and treatment options.ResultAfter literature search and screening,a total of 7 RCT studies including 18,865 patients with hypercholesterolemia were included.7 RCT studies included showed that the probability of research bias was extremely low.Meta-analysis results showed that,comparing with statin drugs or statin drugs combined with ezetimibe treatment group,PCSK9 inhibitor treatment can significantly reduce LDL-C level(MD,-53.27% [95% CI(-59.65%,-47.82%)])and cardiovascular event incidence rate(RR=0.94 [95% CI,0.89-0.98).However,the therapeutic scheme of PCSK9 inhibitor did not show a significant advantage on cardiovascular event mortality(RR=1.00 [95% CI,0.82-1.14).ConclusionAs the first choice of lipid-lowering drugs for hypercholesterolemia,although Statins occupy the cornerstone position in the field of lipid-lowering,PCSK9 inhibitors have significant effects on reducing LDL-C levels and perform better in improving cardiovascular outcomes.Undoubtedly,PCSK9 inhibitors provide a better treatment for those patients who are intolerant to statin drugs or have related adverse reaction symptoms after receiving statin treatment.Due to the difference between the mechanism of PCSK9 inhibitors and Statins,the combination of the two drugs will produce a synergistic lipid-lowering treatment.This conclusion is consistent with the direction of the recommended drug regimen in the latest edition of 2019 ESC guidelines published in September last year,which indicates that the lipidlowering therapy regimen of combined drugs is bound to be the general trend.In future research,researchers in related fields should pay more attention to carrying out high-quality large-scale clinical randomized controlled trials of related drugs to provide higherlevel evidence-based medical evidence support for clinical treatment.