scholarly journals CETP inhibition and ADCY9 genotype: evidence of a qualitative pharmacogenetic interaction in cardiovascular disease?

2018 ◽  
Author(s):  
Michael V Holmes ◽  
George Davey Smith
Keyword(s):  
Vascular Disease ◽  
Treatment Response ◽  
Meta Analysis ◽  
Hdl Cholesterol ◽  
Major Adverse Cardiac Events ◽  
Phase Iii ◽  
Cardiac Events ◽  
Adverse Cardiac Events ◽  
Cetp Inhibitor ◽  
Cetp Inhibition

AbstractBackgroundCETP inhibitors raise circulating concentrations of HDL-cholesterol, and potent inhibitors also lower non-HDL-cholesterol and risk of vascular disease. Previous genome-wide pharmacogenetic analysis of a phase III randomized controlled trial (RCT) of the CETP inhibitor, dalcetrapib, found variants in ADCY9 to associate with response to treatment. More recently, findings from a pharmacogenetic analysis of the CETP inhibitor evacetrapib reported a lack of such an association.AimsTo clarify the totality of evidence on whether ADCY9 genotype modifies the treatment response to CETP inhibition on risk of major adverse cardiac events through systematic review and meta-analysis.MethodsWe searched PubMed on 22nd May 2018 to identify RCTs of CETP inhibition that reported vascular disease effect estimates stratified by ADCY9 genotype. Stratum-specific estimates were pooled using fixed effect meta-analysis. Tests of heterogeneity between, and trend across, genotypic strata were assessed using Chi2.ResultsNine studies were identified from PubMed, of which two (dal-OUTCOMES and ACCELERATE) were RCTs reporting the treatment response to CETP inhibition by ADCY9 genotype, and fulfilled the inclusion criteria. In meta-analysis of dal-OUTCOMES and ACCELERATE, treatment with a CETP inhibitor was associated with a relative risk (RR) for major adverse cardiac events of RR 0.80 (95%CI, 0.65-0.99) in carriers of ADCY9 rs1967309 AA. For carriers of AG, the corresponding estimate was a RR of 1.01 (95%CI, 0.89-1.13), and for GG carriers, it was RR 1.21 (95%CI, 1.06-1.40). We identified evidence of heterogeneity (P=0.004) and a trend (P=0.0009) across genotypic groups.ConclusionsIn contrast to the interpretation provided by authors of the analysis based in the ACCELERATE trial, the available evidence lends weak support to a potential interaction of CETP treatment by ADCY9 genotype on risk of major adverse cardiac events. Additional data, e.g. from the ongoing dal-GenE trial focused explicitly on this interaction, should provide further clarity regarding the robustness of this pharmacogenetic effect.

scholarly journals Major Adverse Cardiac Events and Mortality Associated with Electroconvulsive Therapy

2019 ◽  
Vol 130 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Andreas Duma ◽  
Mathias Maleczek ◽  
Basil Panjikaran ◽  
Harald Herkner ◽  
Theodore Karrison ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Edema ◽  
Acute Heart Failure ◽  
Electroconvulsive Therapy ◽  
Meta Analysis ◽  
Incidence Rates ◽  
Major Adverse Cardiac Events ◽  
Cardiac Events ◽  
Total N ◽  
Adverse Cardiac Events

Abstract EDITOR’S PERSPECTIVE What We Already Know about This Topic The incidence of major adverse cardiac events after electroconvulsive therapy is not known What This Article Tells Us That Is New Major adverse cardiac events and death after electroconvulsive therapy are infrequent and occur in about 1 of 50 patients and after about 1 of 200 to 500 electroconvulsive therapy treatments Background Cardiac events after electroconvulsive therapy have been reported sporadically, but a systematic assessment of the risk is missing. The goal of this study was to obtain a robust estimate of the incidence of major adverse cardiac events in adult patients undergoing electroconvulsive therapy. Methods Systematic review and meta-analysis of studies that investigated electroconvulsive therapy and reported major adverse cardiac events and/or mortality. Endpoints were incidence rates of major adverse cardiac events, including myocardial infarction, arrhythmia, pulmonary edema, pulmonary embolism, acute heart failure, and cardiac arrest. Additional endpoints were all-cause and cardiac mortality. The pooled estimated incidence rates and 95% CIs of individual major adverse cardiac events and mortality per 1,000 patients and per 1,000 electroconvulsive therapy treatments were calculated. Results After screening of 2,641 publications and full-text assessment of 284 studies, the data of 82 studies were extracted (total n = 106,569 patients; n = 786,995 electroconvulsive therapy treatments). The most commonly reported major adverse cardiac events were acute heart failure, arrhythmia, and acute pulmonary edema with an incidence (95% CI) of 24 (12.48 to 46.13), 25.83 (14.83 to 45.00), and 4.92 (0.85 to 28.60) per 1,000 patients or 2.44 (1.27 to 4.69), 4.66 (2.15 to 10.09), and 1.50 (0.71 to 3.14) per 1,000 electroconvulsive therapy treatments. All-cause mortality was 0.42 (0.11 to 1.52) deaths per 1,000 patients and 0.06 (0.02 to 0.23) deaths per 1,000 electroconvulsive therapy treatments. Cardiac death accounted for 29% (23 of 79) of deaths. Conclusions Major adverse cardiac events and death after electroconvulsive therapy are infrequent and occur in about 1 of 50 patients and after about 1 of 200 to 500 electroconvulsive therapy treatments.

scholarly journals Safety and Efficacy of Double Antithrombotic Therapy With Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta‐Analysis

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Davide Capodanno ◽  
Marco Di Maio ◽  
Antonio Greco ◽  
Deepak L. Bhatt ◽  
C. Michael Gibson ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Vitamin K ◽  
Antithrombotic Therapy ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Vitamin K Antagonist ◽  
Major Adverse Cardiac Events ◽  
Cardiac Events ◽  
Adverse Cardiac Events ◽  
Percutaneous Coronary

Background The optimal antithrombotic therapy for patients with atrial fibrillation undergoing percutaneous coronary intervention is a topic of debate. We aimed at defining the efficacy and safety of double antithrombotic therapy with single antiplatelet therapy (SAPT) plus a non–vitamin K antagonist oral anticoagulant (NOAC) against triple antithrombotic therapy with dual antiplatelet therapy (DAPT) added to a vitamin K antagonist (VKA), illustrating the pooled cumulative distribution of events, the ranking of different NOACs tested in NOAC+SAPT combination strategies, and the state of the current evidence in the field. Methods and Results Randomized controlled trials meeting the inclusion criteria were identified. The primary efficacy end point was the composite of trial‐defined major adverse cardiac events. The primary safety end point was clinically significant bleeding. Secondary end points were the components of primary end points. Trial‐level pairwise and Bayesian network meta‐analyses, reconstructed Kaplan–Meier analyses, and trial sequential analysis were performed. Four randomized controlled trials (10 969 patients) were included. No differences were found in terms of major adverse cardiac events (hazard ratio [HR], 1.07; 95% CI, 0.94–1.22), and the NOAC+SAPT strategy showed a lower rate of clinically significant bleeding compared with VKA + DAPT (HR, 0.56; 95% CI, 0.39–0.80). These results were consistent in reconstructed Kaplan–Meier analyses. In the Bayesian network meta‐analysis, different NOACs displayed diverse risk–benefit profiles. Trial sequential analyses suggest that the evidence for the similarity in major adverse cardiac events compared with VKA + DAPT and the bleeding risk reduction observed with NOAC+SAPT is likely to be conclusive. Conclusions NOAC+SAPT does not increase the risk of major adverse cardiac events and reduces the risk of bleeding compared with VKA + DAPT in AF patients undergoing percutaneous coronary intervention. Various NOACs may have different risk–benefit profiles in combination strategies. Registration URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: CRD42020151089.

The Association of Febuxostat Compared With Allopurinol on Blood Pressure and Major Adverse Cardiac Events Among Adult Patients With Hyperuricemia: A Meta-analysis

2020 ◽  
Vol 76 (4) ◽  
pp. 461-471 ◽  
Author(s):  
Marie Barrientos-Regala ◽  
Renelene A. Macabeo ◽  
Rosemarie Ramirez-Ragasa ◽  
Noemi S. Pestaño ◽  
Felix E. R. Punzalan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Meta Analysis ◽  
Adult Patients ◽  
Major Adverse Cardiac Events ◽  
Cardiac Events ◽  
Adverse Cardiac Events

scholarly journals The HEART score for early rule out of acute coronary syndromes in the emergency department: a systematic review and meta-analysis

2017 ◽  
Vol 7 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Patricia Van Den Berg ◽  
Richard Body
Keyword(s):  
Systematic Review ◽  
Emergency Department ◽  
Diagnostic Accuracy ◽  
Meta Analysis ◽  
Low Risk ◽  
Major Adverse Cardiac Events ◽  
Current Evidence ◽  
Cardiac Events ◽  
Heart Score ◽  
Adverse Cardiac Events

Aims: The objective of this systematic review was to summarise the current evidence on the diagnostic accuracy of the HEART score for predicting major adverse cardiac events in patients presenting with undifferentiated chest pain to the emergency department. Methods and results: Two investigators independently searched Medline, Embase and Cochrane databases between 2008 and May 2016 identifying eligible studies providing diagnostic accuracy data on the HEART score for predicting major adverse cardiac events as the primary outcome. For the 12 studies meeting inclusion criteria, study characteristics and diagnostic accuracy measures were systematically extracted and study quality assessed using the QUADAS-2 tool. After quality assessment, nine studies including data from 11,217 patients were combined in the meta-analysis applying a generalised linear mixed model approach with random effects assumption (Stata 13.1). In total, 15.4% of patients (range 7.3–29.1%) developed major adverse cardiac events after a mean of 6 weeks’ follow-up. Among patients categorised as ‘low risk’ and suitable for early discharge (HEART score 0–3), the pooled incidence of ‘missed’ major adverse cardiac events was 1.6%. The pooled sensitivity and specificity of the HEART score for predicting major adverse cardiac events were 96.7% (95% confidence interval (CI) 94.0–98.2%) and 47.0% (95% CI 41.0–53.5%), respectively. Conclusions: Patients with a HEART score of 0–3 are at low risk of incident major adverse cardiac events. As 3.3% of patients with major adverse cardiac events are ‘missed’ by the HEART score, clinicians must ask whether this risk is acceptably low for clinical implementation.

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