No free lunch-the price of double versus triple antithrombotic therapy in patients with atrial fibrillation after ACS or PCI.
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ABSTRACT:
SUBMITTER: Valgimigli M
PROVIDER: S-EPMC7210164 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
No free lunch-the price of double versus triple antithrombotic therapy in patients with atrial fibrillation after ACS or PCI.
Valgimigli Marco M Gragnano Felice F
Annals of translational medicine 20200401 7
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Project description:Purpose of reviewThis review aims to discuss the use of antithrombotic therapy in patients with atrial fibrillation who undergo coronary stenting with emphasis on the use of double vs triple therapy.Recent findingsWhen combined with systemic anticoagulation, dual antiplatelet therapy results in an unacceptable increase in bleeding without any improvement in prevention of thrombotic events. Direct oral anticoagulants combined with single antiplatelet therapy have reduced bleeding compared with warfarin plus dual antiplatelet therapy. Triple anticoagulation therapy with warfarin or direct oral anticoagulants leads to an excess of bleeding and is not superior in preventing thrombotic events. Recent randomized, controlled trials have shown a significant reduction in major bleeding events in patients treated with dual antithrombotic therapy compared with triple therapy without any difference in efficacy. These findings call into question whether triple therapy should remain a part of standard practice.
| S-EPMC7347083 | biostudies-literature
Project description:Patients with atrial fibrillation affected by an acute coronary syndrome have indications for oral anticoagulation and dual antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate receptor inhibitor after coronary artery stenting. The concurrent use of all 3 agents, termed triple oral antithrombotic therapy, significantly increases the risk of bleeding. To date, there is a lack of evidence on the proper combination and duration of anticoagulant and antiplatelet agents in patients with indications for both therapies. As such, care has been guided by expert opinion, and there is wide variation in clinician practice. In this review, the latest evidence on the risks and benefits of triple oral antithrombotic therapy in patients with atrial fibrillation after coronary artery stenting is summarized. We discuss the clinical risk scores useful in guiding the prediction of stroke, bleeding, and stent thrombosis. Additionally, we highlight where additional evidence is needed to determine the proper balance of anticoagulant and antiplatelet agents in this patient population.
| S-EPMC6649565 | biostudies-literature
Project description:The coexistence of coronary artery disease and atrial fibrillation (AF) in the same individuals raises great concern about the co-treatment with different antithrombotic agents in the case of percutaneous coronary interventions (PCI). The advent of direct oral anticoagulants (DOACs) revolutionised the therapy of AF; less is known, however, about the safety and efficacy of therapy with DOACs in combination with antiplatelet agents after PCI. We performed a meta-analysis of randomized controlled studies enrolling patients with nonvalvular AF undergoing PCI. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for any bleeding (AB), cardiovascular events (CVE), major bleeding (MB), myocardial infarction (MI), and stent thrombosis (ST) at follow-up: 4849 patients have been included in the analysis. When compared with patients receiving standard triple therapy (vitamin-K antagonists plus double antiplatelet therapy [VKAs plus DAPT]), patients receiving DOACs (rivaroxaban/dabigatran plus either one or two antiplatelet agents) had a statistically significant lower risk of AB (RR, 0.66; 95% CI, 0.59-0.75, p<0.00001), as well as of MB (RR, 0.59; 95% CI, 0.47-0.73, p<0.00001). Equivalent efficacy was found about CVE (RR, 1.03; 95% CI, 0.89-1.19, p=0.69), MI (RR, 1.09; 95% CI, 0.81-1.45, p=0.57), while slight although non-statistically significant increased risk of ST was found (RR, 1.46; 95% CI, 0.86-2.48, p=0.16). In conclusion, DOACs are safer than and as effective as warfarin when used in patients with AF undergoing PCI; dual therapy with DOACs is comparable to triple therapy in terms of safety and efficacy.
| S-EPMC6045730 | biostudies-other
Project description:Atrial fibrillation (AF) is the most common sustained arrhythmia, that substantially increases morbidity and mortality. AF is gaining in clinical and economic importance, with stroke and thromboembolism being major complications. In this article, the evidence for AF treatment trial of antithrombotic therapy is reviewed. Stroke risk stratification of patients with AF is discussed, and practical recommendations for thromboprophylaxis are presented.
| S-EPMC1860779 | biostudies-literature
Project description:BackgroundPrior randomized controlled trials (RCT) evaluating the optimal antithrombotic therapies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been powered to evaluate ischemic outcomes. We compared double therapy with oral anticoagulation (OAC) and a P2Y12 inhibitor to triple therapy with an OAC + dual antiplatelet therapy in patients with AF requiring PCI.MethodsUsing PRISMA guidelines, we searched for RCTs including patients with AF as an indication for OAC and undergoing PCI or medical management of acute coronary syndrome. The results were pooled using fixed-effects and random-effects models to estimate the overall effect of double therapy versus triple therapy on ischemic and bleeding outcomes.ResultsWe identified four RCTs, comprising 10,238 patients (5,498 double therapy, 4,740 triple therapy). Trial-reported major adverse cardiovascular events were similar between double therapy and triple therapy (fixed effect model OR 1.09, 95% CI 0.94-1.26). However, stent thrombosis (61/5,496 double therapy vs. 33/4738 triple therapy; fixed effect model OR 1.57, 95% CI 1.02-2.40; number needed to treat with triple therapy = 242) favored triple therapy. Bleeding outcomes were less frequent with double therapy (746/5470 vs. 950/4710; fixed effect model OR 0.59, 95% CI 0.53-0.65; number needed to harm with triple therapy = 16), but with significant heterogeneity (Q = 8.33, p = .04; I2 = 64%), as were intracranial hemorrhages (19/5470 vs. 30/4710; fixed effect model OR 0.54, 95% CI 0.31-0.96).ConclusionsDouble therapy in patients with AF requiring OAC following PCI or Acute coronary syndrome has a significantly better safety profile than triple therapy but may be associated with a modest increased risk of stent thrombosis.
| S-EPMC7211549 | biostudies-literature
Project description:BackgroundThe RE-DUAL PCI trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), dual therapy with dabigatran and a P2Y12 inhibitor, either clopidogrel or ticagrelor, reduced the risk of bleeding without an increased risk of thromboembolic events as compared to triple therapy with warfarin in addition to a P2Y12 inhibitor and aspirin. What remains unclear is whether this effect is consistent between males and females undergoing PCI.HypothesisThe reduction in risk of bleeding without increased risk of thromboembolic events with dual therapy with dabigatran and a P2Y12 inhibitor in comparison to triple therapy with warfarin, a P2Y12 inhibitor and aspirin is consistent in females and males.MethodsThe primary safety endpoint was the first International Society on Thrombosis and Hemostasis (ISTH) major bleeding event (MBE) or clinically relevant non-major bleeding event (CRNMBE). The efficacy endpoint was the composite of death, thromboembolic event (stroke, myocardial infarction, and systemic embolism) or unplanned revascularization. Cox proportional hazard regression analyses were applied to calculate corresponding hazard ratios and interaction p values for each endpoint.ResultsA total of 655 women and 2070 men were enrolled. The risk of major or CRNM bleeding was lower with both dabigatran 110 mg dual therapy and dabigatran 150 mg dual therapy compared with warfarin triple therapy in female and male patients (for 110 mg: females: HR 0.69, 95% CI 0.47-1.01, males: HR 0.46, 95% CI 0.37-0.59, interaction p value: 0.084 and for 150 mg: females HR 0.74, 95% CI 0.48-1.16, males HR 0.71, 95% CI 0.56-0.90, interaction p value: 0.83). There was also no detectable difference in the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization between dabigatran dual therapy and warfarin triple therapy, with no statistically significant interaction between sex and treatment (interaction p values: 0.73 and 0.72, respectively).ConclusionsConsistent with the overall study results, the risk of bleeding was lower with dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy, and risk of thromboembolic events was comparable with warfarin triple therapy independent of the patient's sex.
| S-EPMC8259156 | biostudies-literature
Project description: Not available
| S-EPMC9912951 | biostudies-literature
Project description:BackgroundIn patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), selecting an antithrombotic regimen requires balancing risks of ischemic cardiac events, stroke, and bleeding.MethodsWe studied 467 patients with AF undergoing PCI in the time period from December 2015 to July 2018 identified via a chart audit by 47 Canadian cardiologists in the CONNECT AF+PCI (the Coordinated National Network to Engage Interventional Cardiologists in the Antithrombotic Treatment of Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) study, to determine patterns of initial antithrombotic therapy selection.ResultsThe median (25th, 75th percentile) CHADS2 score was 2 (1, 3), and PCI was performed in the setting of acute coronary syndrome in 62.1%. Triple antithrombotic therapy (TAT) was the initial treatment in 62.7%, dual-pathway therapy in 25.7%, and dual antiplatelet therapy in 11.6%, with a temporal increase in use of dual-pathway therapy during the course of the study; median intended TAT duration was 1 (1, 3) month. Compared with patients selected for TAT, patients selected for dual-pathway therapy were less likely to have prior myocardial infarction (35.8% vs 25.8%, P = 0.045) and prior PCI (33.8% vs 23.3%, P = 0.03), and they received shorter total length of stents (38 [23, 56] vs 30 [20, 46] mm, P = 0.03). Patients selected for dual-pathway therapy had a higher prevalence of prior stroke/transient ischemic attack (13.0% vs 23.3%, P = 0.01). There was no difference in prevalence of anemia (21.5% vs 25.8%, P = 0.30). Use of dual-pathway therapy was similar among patients with acute coronary syndrome and those with stable disease (24.1% vs 28.2%, P = 0.32).ConclusionsApproximately one-quarter of AF patients undergoing PCI are treated with dual-pathway therapy in Canadian practice, with its use increasing during the studied period. Patients selected for dual-pathway therapy have less-complex coronary disease history and intervention.
| S-EPMC8712598 | biostudies-literature
Project description:ObjectiveCreating an appropriate antithrombotic therapy for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) remains a dilemma. Several clinical trials compared the use of a dual antithrombotic therapy (DAT) regimen with a direct oral anticoagulants including (apixaban, dabigatran, edoxaban or rivaroxaban) and a P2Y12 inhibitor versus a triple antithrombotic therapy (TAT) that includes a vitamin K antagonist plus aspirin and a P2Y12 inhibitor in patients with AF who have undergone PCI. However, there are no head-to-head trials comparing the DAT regimens to each other. We aimed to compare the efficacy and safety of DAT regimens using a network meta-analysis (NMA) approach.DesignA systematic review and NMA of randomised clinical trials.MethodsWe conducted a systematic literature review to identify relevant randomised clinical trials and performed a Bayesian NMA for International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding, all-cause mortality, stroke, myocardial infarction (MI) and stent thrombosis outcomes. We used NetMetaXL V.1.6.1 and WinBUGS V.1.4.3 for the NMA and estimated the probability of ranking the treatments based on the surface under the cumulative ranking curve.ResultsThe comparison between DAT regimens showed no significant difference in the safety or efficacy outcomes. Apixaban regimen was ranked first as the preferred therapy in terms of ISTH major or CRNM bleeding and stroke, with a probability of 52% and 54%, respectively. Rivaroxaban regimen was the preferred therapy in terms of MI and stent thrombosis, with a probability of 34% and 27%, respectively. Dabigatran regimen was ranked first in terms of all-cause mortality, with a probability of 28%.ConclusionThe DAT regimens are as safe and effective as TAT regimens. However, ranking probabilities for the best option in the selected outcomes can be used to guide the selection among these agents based on different patients' conditions.
| S-EPMC7526290 | biostudies-literature
Project description:BackgroundTriple antithrombotic therapy (TAT) with aspirin, a P2Y12 inhibitor, and oral anticoagulation in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raises concerns about increased bleeding. Regimens incorporating more potent P2Y12 inhibitors over clopidogrel have not been investigated adequately.Research design and methodsA retrospective observational study was performed on 387 patients with AF receiving TAT for 1 month (n = 236) or ≤1 week (n = 151) after PCI. Major and clinically relevant non-major bleeding and major adverse cardiac and cerebrovascular events (MACCE) were assessed up to 30 days post-procedure.ResultsBleeding was less frequent with ≤1 week versus 1 month of TAT (3.3 vs 9.3%; p = 0.025) while MACCE were similar (4.6 vs 4.7%; p = 0.998). No differences in bleeding or MACCE were observed between ticagrelor/prasugrel and clopidogrel regimens. For patients receiving ≤1 week of TAT, no excess of MACCE was seen in the subgroup given no further aspirin post-PCI compared with those given aspirin for up to 1 week (3.6 vs 5.2%).ConclusionsTAT post-PCI for ≤1 week was associated with less bleeding despite greater use of ticagrelor/prasugrel but similar MACCE versus 1-month TAT. These findings support further studies on safety and efficacy of dual therapy with ticagrelor/prasugrel immediately after PCI.
| S-EPMC11262428 | biostudies-literature