Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials

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.

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A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes

European Journal of Preventive Cardiology ◽

10.1177/2047487318766612 ◽

2018 ◽

Vol 25 (8) ◽

pp. 844-853 ◽

Cited By ~ 21

Author(s):

Safi U Khan ◽

Swapna Talluri ◽

Haris Riaz ◽

Hammad Rahman ◽

Fahad Nasir ◽

...

Keyword(s):

Myocardial Infarction ◽

Bayesian Network ◽

Cardiovascular Mortality ◽

Cardiovascular Events ◽

Meta Analysis ◽

Credible Interval ◽

Major Adverse Cardiovascular Events ◽

Pcsk9 Inhibitors ◽

Adverse Cardiovascular Event ◽

All Cause Mortality

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.

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Blood Lipid Levels in Patients with Osteopenia and Osteoporosis: A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-26729/v1 ◽

2020 ◽

Author(s):

Hang Zhao ◽

An Song ◽

Yong Li ◽

Licui Qi ◽

Chong Zheng ◽

...

Keyword(s):

Meta Analysis ◽

Density Lipoprotein ◽

Blood Lipid ◽

Relevant Information ◽

Lipid Lowering ◽

Cochrane Library ◽

Lipid Levels ◽

Lipid Lowering Drugs ◽

Blood Lipid Levels

Abstract Background: Considering the controversial relationship between blood lipid levels and osteopenia and osteoporosis (OP), we performed this meta-analysis.Methods: Using specific keywords and related words, we searched PubMed, Embase, and Cochrane Library databases. The Newcastle-Ottawa Scale form was used to evaluate the quality of the literature. According to the inclusion and exclusion criteria, we systematically screened the literature to extract relevant information and data. Revman 5.3 and Stata 13.0 software were used for statistical analysis. Results were expressed as the mean difference and 95% confidence interval. The heterogeneity test was conducted according to I2 and Q tests. Egger’s test was used to quantitatively evaluate publication bias.Results: This analysis involved 12 studies and included 12,395 subjects. The quality of the literature was acceptable. Among subjects who were not taking lipid-lowering drugs, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the osteopenia were not significantly increased/decreased. There were no significant differences in LDL-C in postmenopausal women in osteopenia. TG was unchanged in the OP group in subjects without taking lipid-lowering drugs. HDL-C was elevated in OP group but not in osteopenia group in all subjectsConclusions: HDL-C was elevated in patients with OP.

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Exposure to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the association with neurocognitive side effects: a meta-analysis and meta-regression

European Heart Journal ◽

10.1093/ehjci/ehaa946.3339 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

B Hirsh-Raccah ◽

A Yanovsky ◽

V Rotshild ◽

H Danenberg ◽

R Eliaz ◽

...

Keyword(s):

Side Effects ◽

Adverse Effects ◽

Meta Analysis ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Proprotein Convertase ◽

Pcsk9 Inhibitors ◽

Lowering Therapy ◽

Meta Regression ◽

Meta Analyses

Abstract Background Lipid lowering therapy may be associated with impaired cognitive function. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse effects remains unclear. Purpose To assess the neurocognitive safety of PCSK9 inhibitors using meta-analysis and meta-regression of randomized controlled trials (RCTs). Methods PubMed (MEDLINE), Embase and Cochrane library were searched. RCTs that reported assessments of neurocognitive outcomes of participants using PCSK9 inhibitors, with a duration of follow up of at least six months were included. The results of the search were screened by two independent reviewers. Any disagreements were resolved by consensus. The research was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for meta-analyses. Results were pooled using random-effects models. The primary safety outcome of this analysis was defined as the reported incidence of neurocognitive adverse effects. Results Results of 21 trials were included in the analysis. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. No significant difference in the incidence of neurocognitive side effects between the treatment and control groups was identified (RR=1.01, 95% CI: 0.86–1.19, I2=3%). Same results were seen in separate analysis for each of the medicines (Alirocumab- RR=0.88, 95% CI: 0.72–1.08, I2=0%, Evolocumab- RR=1.42, 95% CI: 0.74–2.73, I2=55%). In a meta-regression analysis there was no statistically significant association between the assessed and the risk for neurocognitive side effects. Conclusions Pooled results of our meta-analysis and meta-regression clearly show that the exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse events. Due to the increasing proportion of patients using lipid-lowering therapy these results are positively reassuring. However, more data from long-term outcomes studies is needed to further evaluate the effect of longer exposure to PCSK9 inhibitors Funding Acknowledgement Type of funding source: None

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Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials

BMC Pharmacology and Toxicology ◽

10.1186/s40360-020-00463-w ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Xiang Zhao ◽

Xubiao Ma ◽

Xing Luo ◽

Zhihua Shi ◽

Ziwen Deng ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Cochrane Library ◽

Controlled Trials ◽

Efficacy And Safety ◽

Atp Citrate Lyase ◽

Randomized Controlled

Abstract Background Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other lipid-lowering drugs is better than these drugs alone. This study systematically reviewed the efficacy and safety of bempedoic acid monotherapy or combination togethers in hypercholesterolemic patients. Methods Randomized controlled trials were searched across Medline, Embase, Cochrane library, web of science, etc. The net change scores [least squares mean (LSM) percentage change] in LDL-C level were meta-analyzed using weighted mean difference. The reductions in other lipids including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein (ApoB) and high sensitivity C reactive protein (hsCRP) were also assessed. Odds ratio (OR) of the incidence of adverse events (AEs) were calculated to evaluate the safety of bempedoic acid. Results A total of 13 trials (4858 participates) were included. Pooled data showed that the combination togethers resulted in greater reductions in LDL-C level than monotherapies (bempedoic acid + statin vs. statin: LSM difference (%), − 18.37, 95% CI, − 20.16 to − 16.57, I2 = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), − 18.89, 95% CI, − 29.66 to − 8.13, I2 = 87%). But the difference in efficacy between bempedoic acid and ezetimibe was not obvious. Meta-regression analysis showed the treatment duration was a source of heterogeneity (adj R2 = 16.92, 95% CI, 0.04 to 0.72). Furthermore, the background therapy of statin before screening decreased the efficacy of bempedoic acid. In addition, bempedoic acid also resulted in a significant reduction in TC, non-HDL-C, ApoB and hsCRP level. The OR of muscle-related AEs by the combination of bempedoic acid and statin was 1.29 (95% CI, 1.00 to 1.67, I2 = 0) when compared with statin alone. Conclusion This study showed the efficacy of combination togethers were similar but stronger than these drugs alone. Of note, a trend of high risk of muscle-related AEs by the combination of bempedoic acid and statin was observed, though it is not statistically significant, such risk is needed to be confirmed by more trials, because it is important for us to determine which is the better combinative administration for statin-intolerant patients.

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Non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression

European Heart Journal ◽

10.1093/ehjci/ehaa946.2981 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

L.M Lobo ◽

G Molinero ◽

W Masson ◽

D Siniawski ◽

G Masson ◽

...

Keyword(s):

Coronary Atherosclerosis ◽

Meta Analysis ◽

Lipid Lowering ◽

Forest Plot ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitors ◽

Lowering Therapy ◽

Meta Regression ◽

Statin Drugs

Abstract Introduction Several studies have investigated the association between non-statin lipid-lowering therapy and regression of atherosclerosis. However, the studies were mostly small and their results were not always robust. Objectives (1) to define if a dual lipid-lowering therapy (statin ± non-statin drugs) is associated with coronary atherosclerosis regression, estimated by intravascular ultrasound (IVUS); (2) to assess the association between dual lipid-lowering-induced changes in LDL-C and non-HDL-C levels and atherosclerosis regression. Methods We performed a meta-analysis including trials of non-statin lipid-lowering therapy, reporting C-LDL, non-HDL-C and total atheroma volume (TAV) with a minimum of 6 months of follow-up. The primary endpoint was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs. The random-effects model and meta-regression were performed. Results Eight eligible trials of non-statin lipid-lowering drugs (1759 patients) were included. Overall, the dual lipid-lowering therapy was associated with a significant reduction in TAV [−3.5 mm3 (95% CI: −4.5 to −2.6)]; I2=11%]. In the analysis stratified according to the lipid-lowering drug class (ezetimibe or PCSK9 inhibitors), the findings were similar. In a meta-regression, a 10% decrease in LDL-C or non-HDL-C levels, was associated, respectively, with 0.92 mm3 and 1.05 mm3 regressions in TAV. Conclusion Our data suggest the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in significantly increased regression of TAV. When the LDL-C and non-HDL-C levels reached were lower, the observed effect was also greater. Forest Plot by Drugs Group Funding Acknowledgement Type of funding source: None

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Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis

Respiratory Research ◽

10.1186/s12931-020-01540-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Hyun Woo Lee ◽

Jimyung Park ◽

Eun Jin Jang ◽

Chang-Hoon Lee

Keyword(s):

Bayesian Network ◽

Meta Analysis ◽

Cochrane Library ◽

Major Adverse Cardiovascular Events ◽

Chronic Obstructive ◽

Level Of Evidence ◽

Obstructive Pulmonary Disease ◽

Beta Agonists ◽

All Cause Mortality ◽

Long Acting

Abstract Background Only few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs). Our study was conducted to compare acute exacerbation and all-cause mortality among different LAMA/LABA regimens using Bayesian network meta-analysis (NMA). Methods We searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallel-group RCTs comparing LAMA/LABA combinations with other inhaled drugs in the stable COPD for ≥ 48 weeks. Two different network geometries were used. The geometry of network (A) had nodes of individual drugs or their combination, while that of network (B) combined all other treatments except LAMA/LABA into each drug class. This study was prospectively registered in PROSPERO; CRD42019126753. Results We included 16 RCTs involving a total of 39,065 patients with stable COPD. Six combinations of LAMA/LABA were identified: tiotropium/salmeterol, glycopyrrolate/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, aclidinium/formoterol, and glycopyrrolate/formoterol. We found that umeclidinium/vilanterol was associated with a lower risk of total exacerbations than other LAMA/LABAs in the NMA using network (A) (level of evidence: low or moderate). However, the significant differences were not present in the NMA of network (B). There were no significant differences among the LAMA/LABA combinations in terms of the number of moderate to severe exacerbations, all-cause mortality, major adverse cardiovascular events, or pneumonia. Conclusions The present NMA including all available RCTs provided that there is no strong evidence suggesting different benefits among LAMA/LABAs in patients with stable COPD who have been followed up for 48 weeks or more. Trial registration: This study was prospectively registered in PROSPERO; CRD42019126753.

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Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 and Major Adverse Cardiovascular Events, Stroke, and All-Cause Mortality: Systemic Review and Meta-Analysis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.617249 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yimo Zhou ◽

Weiqi Chen ◽

Meng Lu ◽

Yongjun Wang

Keyword(s):

Dose Response ◽

Cardiovascular Events ◽

Meta Analysis ◽

Systemic Review ◽

Cochrane Library ◽

Major Adverse Cardiovascular Events ◽

Proprotein Convertase ◽

Standard Deviation Increase ◽

Increased Risk ◽

All Cause Mortality

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.

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

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00626-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Yan-yan Qi ◽

Li Yan ◽

Zhong-min Wang ◽

Xi Wang ◽

Hua Meng ◽

...

Keyword(s):

Cardiovascular Events ◽

Meta Analysis ◽

Serum Triglyceride ◽

Cochrane Library ◽

Major Adverse Cardiovascular Events ◽

Omega 3 ◽

Pharmacological Agents ◽

Omega 3 Fatty Acid ◽

The Cochrane Library ◽

Indirect Comparisons

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).

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P1018LIPID PROFILES AND RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN CKD AND DIABETES: A NATIONWIDE POPULATION-BASED STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1018 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yeonhee Lee ◽

Sehoon Park ◽

Soojin Lee ◽

Min Woo Kang ◽

SangHyun Park ◽

...

Keyword(s):

Cardiovascular Events ◽

Density Lipoprotein ◽

Population Based ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Major Adverse Cardiovascular Events ◽

Linear Association ◽

All Cause Mortality ◽

Patients With Diabetes ◽

The Impact

Abstract Background and Aims The association of lipid parameters with cardiovascular outcomes and the impact of kidney function on this association have not been thoroughly evaluated in chronic kidney disease (CKD) patients with diabetes. Method We reviewed the National Health Insurance Database of Korea, containing the data of 10,505,818 subjects who received routine check-ups in 2009. We analyzed the association of lipid profile parameters with major adverse cardiovascular events (MACEs) risk and all-cause mortality in a nationally representative cohort of 51,757 lipid-lowering medication-naïve patients who had CKD and diabetes. Results Advanced CKD patients with eGFR <30 mL/min/1.73 m2 (n=10,775) had lower serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) but higher non-HDL-c levels and triglyceride (TG) to HDL-c ratios. There was a positive linear association between serum LDL-c and MACE risk in both early and advanced CKD patients (P <0.001 for trend). A U-shaped relationship was observed between serum LDL-c and all-cause mortality (the 4th and 8th octile groups; lowest hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.87-1.05 and highest HR 1.14, 95% CI 1.04-1.26, respectively). A similar pattern remained in both early and advanced CKD patients. The TG/HDL-c ratio categories showed a positive linear association for MACE risk in early CKD (P <0.001 for trend), but this correlation disappeared in advanced CKD patients. There was no correlation between the serum TG/HDL-c ratio and all-cause mortality in the study patients. Conclusion The LDL-c level predicted the risk for MACEs and all-cause mortality in both early and advanced CKD patients with diabetes, although the patterns of the association differed from each other. However, the TG/HDL-c ratio categories could not predict the risk for either MACEs or all-cause mortality in advanced CKD patients with diabetes, except that the TG/HDL-c ratio predicted MACE risk in early CKD patients with diabetes.

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Impact of Serum Uric Acid Lowering and Contemporary Uric Acid-Lowering Therapies on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.641062 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hangying Ying ◽

Hongdi Yuan ◽

Xiaomei Tang ◽

Wenpu Guo ◽

Ruhong Jiang ◽

...

Keyword(s):

Uric Acid ◽

Cardiovascular Risk ◽

Cardiovascular Events ◽

Meta Analysis ◽

Cardiovascular Outcomes ◽

Cochrane Library ◽

Major Adverse Cardiovascular Events ◽

Cardiovascular Risk Reduction ◽

Xanthine Oxidase Inhibitor ◽

All Cause Mortality

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 <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 <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.

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