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Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All-Cause Mortality in Clinical Trials of Time-Constrained Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention.

ABSTRACT: Background The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events. A time-constrained approach to DAPT has been recently investigated in 5 multicenter trials including GLOBAL LEADERS, STOPDAPT2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2), SMART-CHOICE, TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention), and TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome). Methods and Results We undertook a pooled analysis of these trials to assess the overall associations between time-constrained P2Y12 inhibitor monotherapy (aspirin-free regimen) for bleeding events, major adverse cardiovascular events, and all-cause mortality as compared to standard care with DAPT for at least 12 months post-percutaneous coronary intervention. We implemented a DerSimonian and Laird random effects meta-analysis using the metafor package in R. 32?361 randomized trial participants, including 16 898 (52.2%) who had a history of acute coronary syndrome, underwent percutaneous coronary intervention, and had outcome data available. P2Y12 inhibitor monotherapy from 1 to 3 months was associated with a reduced risk for bleeding (hazard ratio [HR] 0.60; 95% CI, 0.45-0.81), including in the acute coronary syndrome group in which the magnitude of risk reduction was greatest (HR 0.50; 95% CI, 0.41-0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the HR were also favorable for major adverse cardiovascular events (0.88; 95% CI, 0.77-1.02) and all-cause mortality (0.85; 95% CI, 0.71-1.03). Conclusions Compared with DAPT for 12 months post-percutaneous coronary intervention, P2Y12 inhibitor monotherapy from 1 to 3 months substantially reduces the risk of major and fatal bleeding and, in addition, confers potentially protective effects, for major adverse cardiovascular events and all-cause mortality. Considering patient safety, the results support a strategy of DAPT for 1 to 3 months followed by aspirin-free P2Y12 inhibitor monotherapy.

SUBMITTER: McClure JD

PROVIDER: S-EPMC7660822 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All-Cause Mortality in Clinical Trials of Time-Constrained Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention.

McClure John D JD Ramsay Jennifer C JC Berry Colin C

Journal of the American Heart Association 20200811 16

Background The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events. A time-constrained approach to DAPT has been recently investigated in 5 multicenter trials including GLOBAL LEADERS, STOPDAPT2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2), SMART-CHOICE, TWILIGHT (Ticagrelor With Aspirin or Alone in High-Ris ...[more]

PMID: 32779497

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Project description:Background Dual antiplatelet therapy after percutaneous coronary intervention reduces myocardial infarctions but increases bleeding. The risk of bleeding may be higher among Black patients for unknown reasons. Bleeding risk scores have not been validated among Black patients. We assessed the difference in bleeding risk between Black and White patients along with the performance of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti Platelet Therapy, Patterns of Nonadherence to Antiplatelet Regimens in Stented Patients, and Academic Research Consortium for High Bleeding Risk scores among both groups. Methods and Results This was a single-center prospective study of patients who underwent percutaneous coronary intervention (2014-2019) and were followed for 1 year. The outcome was postdischarge Bleeding Academic Research Consortium 2 to 5 bleeding. Incidence rates were reported. Cox proportional hazards models measured the effect of self-reported Black race on bleeding and determined the predictors of bleeding among 19 a priori variables. The 3 risk scores were assessed among Black and White patients separately using the Harrell concordance index. Of 1529 included patients, 342 (22.4%) self-reported as being Black race. Unadjusted bleeding rates were 22.7 per 100 person-years among Black patients versus 16.3 among White patients (hazard ratio, 1.41 [95% CI, 1.00-2.00], P=0.052). Predictors of bleeding were age, glomerular filtration rate <30 mL/min per 1.73 m2, prior bleeding, ticagrelor or prasugrel use, and anticoagulant use. Among Black and White patients, respectively, the C-indexes were the following: 0.644 versus 0.600 for Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti Platelet Therapy (P<0.001 for both), 0.620 versus 0.612 for Patterns of Nonadherence to Antiplatelet Regimens in Stented Patients (P=0.003 and P<0.001, respectively), and 0.600 versus 0.598 for Academic Research Consortium for High Bleeding Risk (P=0.006 and P<0.001, respectively). Conclusions The risk of dual antiplatelet therapy-associated postdischarge Bleeding Academic Research Consortium 2 to 5 bleeding was not significantly different between self-reported Black and White patients. Bleeding risk scores performed similarly among both groups.

Project description:IntroductionDual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting; however, there is ongoing debate about the optimal duration, especially in specific patient groups. In the proposed systematic review, we intend to assess the optimal duration of DAPT following PCI with stenting, with a focus on clinically relevant patient subgroups.Methods and analysisWe will perform a comprehensive search of the published literature for randomised controlled trials (RCTs) assessing the benefits and harms of extended DAPT (>12 months) compared with short-term DAPT (6-12 months) following PCI with stenting (bare metal or drug eluting). ClinicalTrials.gov and ICTRP will also be searched to identify ongoing and completed clinical trials. Two independent reviewers will select studies for inclusion, and the risk of bias will be assessed by use of Cochrane's Risk of Bias tool. The primary outcome of interest is death (all-cause, cardiovascular, non-cardiovascular). Secondary outcomes are bleeding (major, minor, gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Subgroup data will be sought for patients with prior myocardial infarction, acute coronary syndrome at presentation and diabetes, and based on smoking status and age group. Data will be analysed by random-effects meta-analysis, and separate analyses will be performed for patient subgroups. Bayesian network meta-analysis will be performed to investigate the effect of individual P2Y12 inhibitors at different DAPT durations longer than 6 months.Ethics and disseminationThis review will provide a comprehensive overview of the available evidence of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting and the effects on clinically important subgroups. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration of DAPT following PCI with stenting.Systematic review registrationPROSPERO no. CRD42018082587.

Project description:ObjectiveTo evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients.SettingTertiary care single centre registry.Participants1008 consecutive PCI patients with stent implantation, without exclusion criteria.InterventionPeri-interventional individualisation of DAPT, guided by multiple electrode aggregometry (MEA), to overcome high on-treatment platelet reactivity (HPR) to ADP-induced (≥50 U) and arachidonic acid (AA)-induced aggregation (>35 U).Outcome measuresThe primary efficacy end point was definite stent thrombosis (ST) at 30 days. The primary safety end point was thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Secondary end points were probable ST, myocardial infarction, cardiovascular death and the combined end point: major cardiac adverse event (MACE).Results53% of patients presented with acute coronary syndrome (9% STEMI, 44% non-ST-elevation). HPR to ADP after 600 mg clopidogrel loading occurred in 30% of patients (73±19 U vs 28±11 U; p<0.001) and was treated by prasugrel or ticagrelor (73%), or clopidogrel (27%) reloading (22±12 U; p<0.001). HPR to ADP after prasugrel loading occurred in 2% of patients (82±26 U vs 19±10 U; p<0.001) and was treated with ticagrelor (34±15 U; p=0.02). HPR to AA occurred in 9% of patients with a significant higher proportion in patients with HPR to ADP (22% vs 4%, p<0.001) and was treated with aspirin reloading. Definite ST occurred in 0.09% of patients (n=1); probable ST, myocardial infarction, cardiovascular death and MACE occurred in 0.19% (n=2), 0.09% (n=1) and 1.8% (n=18) of patients. TIMI major and minor bleeding did not differ between patients without HPR and individualised patients (2.6% for both).ConclusionsIndividualisation of DAPT with MEA minimises early thrombotic events in an all-comers PCI population to an unreported degree without increasing bleeding. A randomised multicentre trial utilising MEA seems warranted.Trial registration numberhttp://www.clinicaltrials.gov; NCT01515345.

Dataset Information

Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All-Cause Mortality in Clinical Trials of Time-Constrained Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention.

Publications

Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All-Cause Mortality in Clinical Trials of Time-Constrained Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention.

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