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Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II.

ABSTRACT: BACKGROUND:Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking. OBJECTIVES:To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation. METHODS:Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed. RESULTS:Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase. CONCLUSIONS:In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions.

SUBMITTER: Jeger RV

PROVIDER: S-EPMC6333357 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II.

Jeger Raban V RV Pfisterer Matthias M Vogt Deborah R DR Galatius Søren S Abildgaard Ulrik U Naber Christoph C Alber Hannes H Eberli Franz F Kurz David J DJ Pedrazzini Giovanni G Vuilliomenet André A Weilenmann Daniel D Rickli Hans H Hansen Kim Wadt KW Rickenbacher Peter P Conen David D Müller Christian C Osswald Stefan S Gilgen Nicole N Kaiser Christoph C

PloS one 20190115 1

<h4>Background</h4>Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking.<h4>Objectives</h4>To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation.<h4>Methods</h4>Overall, 2,291 patients randomized to drug-eluting or bare met ...[more]

PMID: 30645635

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Project description:ImportancePatients who are candidates for percutaneous coronary intervention (PCI) and are at high bleeding risk constitute a therapeutic challenge because they often also face an increased risk of thrombotic complications.ObjectivesTo develop and validate models to predict the risks of major bleeding (Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and myocardial infarction (MI) and/or stent thrombosis (ST) for individual patients at high bleeding risk and provide assistance in defining procedural strategy and antithrombotic regimens.Design, setting, and participantsThis prognostic study used individual patient data from 6 studies conducted from July 1, 2009, to September 5, 2017, for 6641 patients at more than 200 centers in Europe, the US, and Asia who underwent PCI and were identified as being at high bleeding risk using the Academic Research Consortium criteria. In 1 year of follow-up (excluding periprocedural events), individual patient risks of MI and/or ST and major bleeding were evaluated using 33 baseline variables. To validate these models, a subgroup of 1458 patients at high bleeding risk from the ONYX ONE trial were analyzed. Statistical analysis was performed from February 1, 2019, to April 30, 2020.ExposuresAll patients underwent PCI with bare metal, drug-coated, or drug-eluting stent implants.Main outcomes and measuresForward, stepwise multivariable proportional hazards models were used to identify highly significant predictors of MI and/or ST and BARC types 3 to 5 bleeding.ResultsA total of 6641 patients (4384 men [66.0%]; median age, 77.9 years [interquartile range, 70.0-82.6 years]) were included in this study. Over 365 days, nonperiprocedural MI and/or ST occurred in 350 patients (5.3%), and BARC types 3 to 5 bleeding occurred in 381 patients (5.7%). Eight independent baseline predictors of risk of MI and/or ST and 8 predictors for risk of BARC types 3 to 5 bleeding were identified. Four of these predictors were in both risk models. Both risk models showed moderate discrimination: C statistic = 0.69 for predicting MI and/or ST and 0.68 for predicting BARC types 3 to 5 bleeding. Applying these same models to the validation cohort gave a similar strength of discrimination (C statistic = 0.74 for both MI and/or ST and BARC types 3-5 bleeding). Patients with MI and/or ST had a mortality hazard ratio of 6.1 (95% CI, 4.8-7.7), and those with BARC types 3 to 5 bleeding had a mortality hazard ratio of 3.7 (95% CI, 2.9-4.8) compared with patients free of both events. Taking these data into account, the risk scores facilitate investigation of the individual patient trade-off between these 2 risks: 2931 patients (44.1%) at high bleeding risk in the 6 studies had a greater risk of MI and/or ST than of BARC 3 to 5 bleeding, 1555 patients (23.4%) had a greater risk of BARC 3 to 5 bleeding than of MI and/or ST, and 2155 (32.4%) had a comparable risk of both events.Conclusions and relevanceIn a large cohort of patients at high bleeding risk undergoing PCI, 2 prognostic models have been developed to identify individual patients' risk of major coronary thrombotic and bleeding events. In future clinical practice, using an application on a smartphone to evaluate the trade-off between these 2 quantifiable risks for each patient may help clinicians choose the most appropriate revascularization strategy and tailor the duration and intensity of antithrombotic regimens.

Project description:Preoperative antiplatelet drug use is common in patients undergoing coronary artery bypass grafting (CABG). The impact of these drugs on bleeding and blood transfusion varies. We hypothesize that review of available evidence regarding drug-related bleeding risk, underlying mechanisms of platelet dysfunction, and variations in patient response to antiplatelet drugs will aid surgeons as they assess preoperative risk and attempt to limit perioperative bleeding. The purpose of this review is to (1) examine the role that antiplatelet drugs play in excessive postoperative blood transfusion, (2) identify possible mechanisms to explain patient response to antiplatelet drugs, and (3) formulate a strategy to limit excessive blood product usage in these patients. We reviewed available published evidence regarding bleeding risk in patients taking preoperative antiplatelet drugs. In addition, we summarized our previous research into mechanisms of antiplatelet drug-related platelet dysfunction. Aspirin users have a slight but significant increase in blood product usage after CABG (0.5 U of nonautologous blood per treated patient). Platelet adenosine diphosphate (ADP) receptor inhibitors are more potent antiplatelet drugs than aspirin but have a half-life similar to aspirin, around 5 to 10 days. The American Heart Association/American College of Cardiology and the Society of Thoracic Surgeons guidelines recommend discontinuation, if possible, of ADP inhibitors 5 to 7 days before operation because of excessive bleeding risk, whereas aspirin should be continued during the entire perioperative period in most patients. Individual variability in response to aspirin and other antiplatelet drugs is common with both hyper- and hyporesponsiveness seen in 5 to 25% of patients. Use of preoperative antiplatelet drugs is a risk factor for increased perioperative bleeding and blood transfusion. Point-of-care tests can identify patients at high risk for perioperative bleeding and blood transfusion, although these tests have limitations. Available evidence suggests that multiple blood conservation techniques benefit high-risk patients taking antiplatelet drugs before operation. Guidelines for patients who take aspirin and/or thienopyridines before cardiac procedures include some or all of the following: (1) preoperative identification of high-risk patients using point-of-care testing; (2) withdrawal of aspirin or other antiplatelet drugs for a few days and delay of operation in patients at high risk for bleeding if clinical circumstances permit; (3) selective perioperative use of evidence-based blood conservation interventions (e.g., short-course erythropoietin, off-pump procedures, and use of intraoperative blood conservation techniques), especially in high-risk patients; and (4) platelet transfusions if clinical bleeding occurs.

Project description:BackgroundThere is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. The aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population.MethodsThis study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. The primary ischemic endpoint was 30-month major adverse cardiac and cerebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events.ResultsDAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients' noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236-3.399]; IPTW-adjusted HR: 1.843 [1.250-2.717]). This difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128-2.216]; PS matching-HR: 1.639 [1.075-2.499]; IPTW-adjusted HR: 1.554 [1.110-2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. These findings were consistent across various stent-driven high-ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease.ConclusionsIn patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse cardiovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one.

Dataset Information

Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II.

Publications

Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II.

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