scholarly journals Comparative efficacy of pharmacological agents on reducing the risk of major adverse cardiovascular events in the hypertriglyceridemia population: a network meta-analysis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yan-yan Qi ◽  
Li Yan ◽  
Zhong-min Wang ◽  
Xi Wang ◽  
Hua Meng ◽  
...  

Abstract Background Hypertriglyceridemia (HTG) is considered an independent risk factor for major adverse cardiovascular events (MACE). Methods This study analyzed the effects of various agents on MACE risk reduction in HTG (serum triglyceride ≥ 150 mg/dl) populations by performing a network meta-analysis. We performed a frequentist network meta-analysis to conduct direct and indirect comparisons of interventions. PubMed, EMBASE, and the Cochrane library were searched for trials until Jul 6, 2020. Randomized controlled trials that reported MACE associated with agents in entire HTG populations or in subgroups were included. The primary outcome was MACE. Results Of the 2005 articles screened, 21 trials including 56,471 patients were included in the analysis. The network meta-analysis results for MACE risk based on frequency data showed that eicosapentaenoic acid (EPA) (OR: 1.32; 95% CI 1.19–1.46), gemfibrozil (OR: 1.53; 95% CI 1.20–1.95), niacin plus clofibrate (OR: 2.00; 95% CI 1.23–3.25), pravastatin (OR: 1.32; 95% CI 1.15–1.52), simvastatin (OR: 2.38; 95% CI 1.55–3.66), and atorvastatin (OR: 0.55; 95% CI 0.37–0.82) significantly reduced the risk of MACE compared to the control conditions. In the subgroup analysis of HTG patients with triglycerides ≥ 200 mg/dL, bezafibrate (OR: 0.56; 95% CI 0.33–0.94), EPA (OR: 0.72; 95% CI 0.62–0.82), and pravastatin (OR: 1.33; 95% CI 1.01–1.75) significantly reduced the MACE risk. Conclusions Simvastatin had a clear advantage in reducing the risk of MACE in the entire HTG population analyzed in this meta-analysis. EPA, but not omega-3 fatty acid, was considered an effective HTG intervention. Among fibrates, gemfibrozil was most effective, though bezafibrate may significantly reduce the risk of MACE in populations with triglyceride levels of 200–300 mg/dL. Trial registration retrospectively registered in PROSPERO (CRD42020213705).

2021 ◽  
Author(s):  
Yin Jia ◽  
Yafang Huang ◽  
Huili Wang ◽  
Haili Jiang

Abstract Background: Prenatal exposure to omega-3 polyunsaturated fatty acids (n-3 PUFA) present in oily fish may prevent asthma or wheeze in childhood.Objective: By limiting this systematic review to fish oil intervention that commenced in the gestational period, we aim to find more clear evidences about the relationship between supplement with fish oil during pregnancy and the risk of asthma/wheeze in offspring, and to improve the life satisfaction of children who suffered asthma.Methods: A comprehensive literature search was conducted in the following database: PubMed, Medline, Web of Science, the Cochrane library, and Embase up to February 2021. Two reviewers independently selected studies, extracted data of the characteristics, and assessed risk of bias. Eight randomized controlled trials totaling 3,037 mother-infant pairs were analyzed in the end. “Allergic asthma” and “asthma and/or wheeze” were assessed in our meta-analysis. Subgroup analysis and sensitivity analysis were conducted. Dose–response data was examined using the robust-error meta-regression method.Results: This meta-analysis showed that n-3 PUFA during pregnancy did not significantly reduce the risk of asthma/wheeze (RR 0.93; 95% CI 0.82 to1.04, p=0.21) and allergic asthma (RR 0.66, 95% CI 0.24 to 1.86, p=0.44). Subgroup analyses revealed that the risk of childhood asthma/wheeze was significantly decreased: (1) in Europe (RR 0.69; 95% CI 0.53 to 0.89), (2) when the dose was ≥1200 mg/d (RR 0.69; 95% CI 0.55 to 0.88), (3) when supplementation started after gestational age 22 (RR 0.65; 95%CI 0.50 to 0.85), (4) when supplementation was from pregnancy to lactation (RR 0.69; 95% CI 0.51 to 0.95). Furthermore, the linear dose–response analysis showed that when maternal supplementation of n-3 PUFA increased by 100mg/d, the risk of asthma/wheeze was reduced by 2%.Conclusions: Although perinatal replenishment of n-3 PUFA did not prevent allergic disease in offspring, under some conditions, it could reduce the incidence of asthma/wheeze and allergic asthma in children, and the higher the dose, the better the protective effect it has. Additional research is needed to confirm the hypothesis of a link between n-3 PUFA intake and prevention of childhood asthma/wheeze.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yimo Zhou ◽  
Weiqi Chen ◽  
Meng Lu ◽  
Yongjun Wang

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a pivotal protein in low-density lipoprotein cholesterol metabolism, has been validated to be an established target for cardiovascular (CV) risk reduction. Nevertheless, prospective studies concerning the associations between circulating PCSK9 and the risk of CV events and mortality have yielded, so far, inconsistent results. Herein, we conducted a meta-analysis to evaluate the association systemically.Methods: Pertinent studies were identified from PubMed, EMBASE, and Cochrane Library database through July 2020. Longitudinal studies investigating the value of circulating PCSK9 for predicting major adverse cardiovascular events (MACEs) or stroke or all-cause mortally with risk estimates and 95% confidence intervals (CI) were included in the analyses. Dose-response meta-analysis was also applied to evaluate circulating PCSK9 and risk of MACEs in this study.Results: A total of 22 eligible cohorts comprising 28,319 participants from 20 eligible articles were finally included in the study. The pooled relative risk (RR) of MACEs for one standard deviation increase in baseline PCSK9 was 1.120 (95% CI, 1.056–1.189). When categorizing subjects into tertiles, the pooled RR for the highest tertile of baseline PCSK9 was 1.252 (95% CI, 1.104–1.420) compared with the lowest category. This positive association between PCSK9 level and risk of MACEs persisted in sensitivity and most of the subgroup analyses. Twelve studies were included in dose-response meta-analysis, and a linear association between PCSK9 concentration and risk of MACEs was observed (x2 test for non-linearity = 0.31, P non-linearity = 0.575). No significant correlation was found either on stroke or all-cause mortality.Conclusion: This meta-analysis added further evidence that high circulating PCSK9 concentration significantly associated with increased risk of MACEs, and a linear dose-response association was observed. However, available data did not suggest significant association either on stroke or all-cause mortality. Additional well-designed studies are warranted to further investigate the correlations between PCSK9 concentration and stroke and mortality.


2020 ◽  
Vol 48 (12) ◽  
pp. 030006052095368
Author(s):  
Chenyang Wang ◽  
Dong Han ◽  
Xiaojing Feng ◽  
Jing Wu

Objectives The efficacy of omega-3 fatty acids in the treatment of sepsis is controversial. We conducted an updated meta-analysis to clarify the efficacy of omega-3 fatty acids in patients with sepsis. Methods PubMed, EMBASE, and the Cochrane Library were searched for randomized clinical trials (RCTs) on omega-3 fatty acid supplementation in adults with sepsis. Results Twenty eligible RCTs involving 1514 patients were included in the meta-analysis. Omega-3 fatty acid supplementation was linked to reductions of mortality ( I2 = 0, relative risk [RR] = 0.82, 95% confidence interval [CI] = 0.69–0.97), the duration of mechanical ventilation (DMV; I2 = 74%, weighted mean difference [WMD] = −2.20, 95% CI = −4.00 to −0.40), and intensive care unit (ICU) length of stay (LOS; I2 = 91%, WMD = −3.86, 95% CI = −5.72 to −2.01). Subgroup analysis illustrated that mortality was significantly reduced in patients with sepsis and gastrointestinal dysfunction (RR = 0.5, 95% CI = 0.29–0.86, I2 = 0). Conclusion Omega-3 fatty acid supplementation might be associated with reduced mortality in patients with sepsis, especially those with gastrointestinal dysfunction. Furthermore, omega-3 fatty acid administration could shorten DMV and ICU LOS.


2018 ◽  
Vol 24 (17) ◽  
pp. 1873-1878
Author(s):  
Shuqing Chen ◽  
Qian Xiang ◽  
Xia Zhao ◽  
Qiufen Xie ◽  
Shuang Zhou ◽  
...  

Purpose: The purpose of this study was to determine the relationship between Kinesin like protein 6 (KIF6) gene Trp719Arg and major cardiovascular events (MACEs) risk in subjects who received statin therapy. Methods: PubMed, EmBase, and the Cochrane Library were searched from inception through September 2017. The selected studies evaluated the association of Trp719Arg with MACEs in individuals who received statins. Relative risk (RR) and 95% confidence interval (CI) were used to evaluate the effect of statin therapy on MACEs in subjects carrying polymorphisms, and the odds ratio (OR) and 95% CI were used to evaluate the relationship between Trp719Arg and MACE risk in individuals who received statins, using the random-effects model. Results: Seven studies were included (N=48,885). Overall, we found that statin therapy significantly reduced the risk for MACEs in subjects carrying ArgArg (RR: 0.79; 95% CI: 0.69-0.90; P=0.001), ArgTrp (RR: 0.71; 95% CI: 0.60 -0.83; P<0.001), ArgArg+ArgTrp (RR: 0.71; 95% CI: 0.63 -0.81; P<0.001), and TrpTrp (RR: 0.79; 95% CI: 0.73-0.85; P<0.001). Furthermore, there was no significant difference between subjects carrying ArgArg and those carrying TrpTrp (OR: 1.11; 95% CI: 0.92-1.34; P=0.265). However, ArgTrp (OR: 1.29; 95% CI: 1.07-1.55; P=0.007) and ArgArg+ArgTrp (OR: 1.26; 95% CI: 1.05-1.51; P=0.012) were associated with an increased risk for MACEs when compared with TrpTrp. Conclusions: Statin therapy significantly reduced the risk for MACEs in subjects carrier specific KIF6 gene Trp719Arg polymorphisms. Further, subjects carrying ArgTrp or ArgArg+ArgTrp had a greater incidence of MACEs as compared with TrpTrp when they received statins.


2021 ◽  
Vol 8 ◽  
Author(s):  
Hangying Ying ◽  
Hongdi Yuan ◽  
Xiaomei Tang ◽  
Wenpu Guo ◽  
Ruhong Jiang ◽  
...  

Objective: This study aimed to evaluate the potential association between uric acid (UA) lowering and cardiovascular risk reduction among UA-lowering therapies in adults.Methods: A systematic search for randomized controlled trials (RCTs) was conducted according to the protocol pre-registered in PROSPERO (No. CRD42020199259). We search for RCTs in PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov up to July 1, 2020. A meta-analysis was performed using a fixed- or random-effects model.Results: In total, 30 studies involving 18,585 hyperuricaemic patients were included. Xanthine oxidase inhibitor (XOI) therapy produced a 6.0% reduction in relative risk (RR) for major adverse cardiovascular events (MACEs). The use of febuxostat was associated with a higher risk of cardiovascular events (CVEs) (RR: 1.09, 95% CI 0.998–1.19, I2 = 0.0%), but the difference was not statistically significant. Allopurinol treatment was associated with a lower CVE risk (RR: 0.61, 95% CI 0.46–0.80, I2 = 21.0%). Among the UA-lowering therapies, the drug treatments were associated with all-cause mortality (RR: 1.20, 95% CI 1.02–1.41, I2 = 0.0%). The subgroup with a UA endpoint &lt;7 mg/dl was not associated with a higher CVE risk (RR: 0.57, 95% CI 0.35–0.92, I2 = 0.0%), and in the subgroup with a UA endpoint &lt;5 mg/dl group, a lower risk of CVEs was not observed (RR: 0.99, 95% CI 0.69–1.44, I2 = 0.0%).Conclusions: UA reduction caused by XOIs reduced the incidence of MACEs. UA-lowering medicines were associated with changes in all-cause mortality but not cardiovascular outcomes. The lower UA endpoint was not associated with reduced cardiovascular risk.


2019 ◽  
Vol 22 (6) ◽  
pp. E438-E444
Author(s):  
Yu Zhang ◽  
Qingmei Chen ◽  
Guangyin Huang ◽  
Lisha Wang

Introduction: The efficacy of liraglutide to treat heart failure remains controversial. We conducted a systematic review and meta-analysis to explore the influence of liraglutide on heart failure. Methods: We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases through March 2018 for randomized controlled trials (RCTs) assessing the effect of liraglutide on cardiac function of heart failure. Meta-analysis is performed using the random-effect model. Results: Four RCTs involving 629 patients are included in the meta-analysis. Overall, compared with the control group for heart failure, liraglutide treatment significantly can reduce NT-proBNP (Std. MD = -3.06; 95% CI = -5.78 to -0.34; P = .03), and improve 6MWT (Std. MD=1.10; 95% CI = 0.75 to 1.44; P < .00001), but has no remarkable influence on LVEF change (Std. MD=1.10; 95% CI = -1.97 to 3.98; P = 0.51), LVEDV change (Std. MD = 6.26; 95% CI = -1.45 to 13.97; P = .11), LVESV change (Std. MD = -13.47; 95% CI = -31.04 to 4.10; P = .13), hospitalization for heart failure (RR = 1.18; 95% CI = 0.88 to 1.58; P = .27), major adverse cardiovascular events (RR = 1.55; 95% CI = -0.24 to 9.89; P = .64), and cardiac death (RR = 1.11; 95% CI = 0.61 to 2.04; P = .72). Conclusions: Liraglutide treatment has an important ability to reduce NT-proBNP and improve 6MWT for heart failure, but shows no important influence on LVEF, LVEDV, LVESV, hospitalization for heart failure, major adverse cardiovascular events, and cardiac death.


2019 ◽  
Vol 27 (12) ◽  
pp. 1255-1268 ◽  
Author(s):  
Safi U Khan ◽  
Muhammad U Khan ◽  
Shahul Valavoor ◽  
Muhammad Shahzeb Khan ◽  
Victor Okunrintemi ◽  
...  

Aims The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these potential effects vary by different lipid-lowering strategies. Methods A total of 29 randomized controlled trials were selected using PubMed, Cochrane Library and EMBASE through 2018. We selected trials of therapies which ultimately clear apolipoprotein B particles by upregulating low-density lipoprotein receptor (LDL-R) expression (statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bile acid sequestrants) or therapies which reduce apolipoprotein B independent of LDL-R (cholesteryl ester transfer protein inhibitor, fibrates, niacin, omega-3 fatty acids) with sample size of ≥1000 patients and follow-up of ≥1 year. The meta-regression and meta-analyses were constructed using a random effects model. Results In 332,912 patients, meta-regression analyses showed relative risks of 0.95 for all-cause mortality (95% confidence interval 0.92–0.99) and 0.93 (0.88–0.98) for cardiovascular mortality for every 10 mg/dL decrease in apolipoprotein B by all interventions combined. Reduction in all-cause mortality was limited to statins (0.92 (0.86–0.98)). For MACE, the relative risk per 10 mg/dL reduction in apolipoprotein B was 0.93 (0.90–0.97) for all therapies combined, with both statin (0.88 (0.83–0.93)) and non-statin therapies (0.96 (0.94–0.99)). which clear apolipoprotein B by upregulating LDL-R showing significant reductions; whereas interventions which lower apolipoprotein B independent of LDL-R did not demonstrate this effect (1.02 (0.81–1.30)). Conclusion While both statin and established non-statin therapies (PCSK9 inhibitor and ezetimibe) reduced cardiovascular risk per decrease in apolipoprotein B, interventions which reduce apolipoprotein B independently of LDL-R were not associated with cardiovascular benefit.


Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001616
Author(s):  
Gregory Curfman ◽  
Emile Shehada

Icosapent ethyl (Vascepa) is a purified preparation of the omega-3 fatty acid eicosapentaenoic acid, which is marketed by Amarin Pharma based in Ireland. The product was initially approved by the US Food and Drug Administration for the use of a high dose (4 g/day) in the treatment of hypertriglyceridaemia. On the basis of the results of the REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl Intervention Trial), the agency later granted a label extension to include the additional indication of a reduction in risk of cardiovascular events in persons with serum triglyceride levels of 150 mg/dL or greater and established cardiovascular disease or diabetes. Data supporting the efficacy of omega-3 fatty acids in the prevention of cardiovascular disease have been inconsistent and controversial. The story of the development of icosapent ethyl has been fraught with challenges, including the invalidation of six core patents on the product, and recently, the completion of a new clinical trial, STRENGTH (Long-Term Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia), that directly contradicts REDUCE-IT and calls into question whether icosapent ethyl is actually effective in the secondary prevention of cardiovascular events. This article traces the course of the development of this fascinating product and discusses its complex medical, regulatory and legal history, which is still continuing to unfold.


2021 ◽  
Vol 24 (5) ◽  
pp. E863-E867
Author(s):  
Chenchao Fu ◽  
Xin Wu

Background: The efficacy of colchicine administration for coronary heart disease remains controversial. We conducted a systematic review and meta-analysis to explore the influence of colchicine administration versus placebo on treatment efficacy for coronary heart disease. Methods: We have searched PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through May 2021 for randomized controlled trials (RCTs) assessing the effect of colchicine administration versus placebo in patients with coronary heart disease. This meta-analysis was performed using the random-effects model. Results: Six RCTs involving 6,321 patients were included in the meta-analysis. Overall, compared with control groups for coronary heart disease, colchicine intervention can significantly reduce major adverse cardiovascular events (odds ratio [OR] 0.74; 95% confidence interval [CI] 0.59 to 0.92; P = .006), but revealed no obvious impact on mortality (OR=0.93; 95% CI=0.63 to 1.36; P = .69), serious adverse events (OR 0.71; 95% CI 0.31 to 1.61; P = .41), or restenosis (OR 1.02; 95% CI 0.63 to 1.64; P = .95). Conclusions: Colchicine treatment may be effective to reduce major adverse cardiovascular events in patients with coronary heart disease.


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