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AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen.
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Intervenção Coronária Percutânea , Stents , Infarto do MiocárdioRESUMO
BACKGROUND: Although a 1-year duration of dual antiplatelet therapy (DAPT) is used in many patients after drug-eluting stent (DES) implantation, the evidence supporting this duration is uncertain. OBJECTIVES: The authors investigated the risk-benefit profile of 1-year vs ≤6-month DAPT after DES using 2 novel scores to risk stratify bleeding and ischemic events. METHODS: Ischemic and bleeding risk scores were generated from ADAPT-DES (Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents), a multicenter, international, "all-comers" registry that enrolled 8,665 patients treated with DES. The risk-benefit profile of 1-year vs ≤6-month DAPT was then investigated across risk strata from an individual patient data pooled dataset of 7 randomized trials that enrolled 15,083 patients treated with DES. RESULTS: In the derivation cohort, the ischemic score and the bleeding score had c-indexes of 0.76 and 0.66, respectively, and both were well calibrated. In the pooled dataset, no significant difference was apparent in any ischemic endpoint between 1-year and ≤6-month DAPT, regardless of the risk strata. In the overall dataset, there was no significant difference in the risk of clinically relevant bleeding between 1-year and ≤6-month DAPT; however, among 2,508 patients at increased risk of bleeding, 1-year compared with ≤6-month DAPT was associated with greater bleeding (HR: 2.80; 95% CI: 1.12-7.13) without a reduced risk of ischemic events in any risk strata, including those with acute coronary syndromes. These results were consistent in a network meta-analysis. CONCLUSIONS: In the present large-scale study, compared with ≤6-month DAPT, a 1-year duration of DAPT was not associated with reduced adverse ischemic events in any risk strata (including acute coronary syndromes) but was associated with greater bleeding in patients at increased risk of bleeding.
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Síndrome Coronariana Aguda , Stents Farmacológicos , Inibidores da Agregação Plaquetária , Fatores de RiscoRESUMO
Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)
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Humanos , Inibidores da Agregação Plaquetária , Stents , Doença das CoronáriasRESUMO
BACKGROUND: Prolonged dual anti-platelet therapy (DAPT) is intended to reduce ischemic events, at the cost of an increased bleeding risk in patients undergoing percutaneous coronary intervention (PCI). In this study, we evaluated whether race influences the ischemia/bleeding risk trade-off. METHODS: We searched for randomized clinical trials (RCTs) comparing DAPT duration after PCI. To compare the benefit or harm between DAPT duration by race, individual patient-level landmark meta-analysis was performed after discontinuation of the shorter duration DAPT group in each RCT. The primary ischemic endpoint was major adverse cardiac events (MACEs), and the primary bleeding endpoint was major bleeding events (clinicaltrials.gov NCT03338335). RESULTS: Seven RCTs including 16,518 patients (8,605 East Asians, 7,913 non-East Asians) were pooled. MACE occurred more frequently in non-East Asians (0.8% vs. 1.8%, p < 0.001), while major bleeding events occurred more frequently in East Asians (0.6% vs. 0.3%, p = 0.001). In Cox proportional hazards model, prolonged DAPT significantly increased the risk of major bleeding in East Asians (hazard ratio [HR], 2.843, 95% confidence interval [CI], 1.474-5.152, p = 0.002), but not in non-East Asians (HR, 1.375, 95% CI, 0.523-3.616, p = 0.523). East Asians had a higher median probability risk ratio of bleeding to ischemia (0.66 vs. 0.15), and the proportion of patients with higher probability of bleeding than ischemia was significantly higher in East Asians (32.3% vs. 0.4%, p < 0.001). CONCLUSION: We suggest that the ischemia/bleeding trade-off may be different between East Asians and non-East Asians. In East Asians, prolonged DAPT may have no effect in reducing the ischemic risk, while significantly increases the bleeding risk. (AU)
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Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores RaciaisRESUMO
OBJECTIVES: This study sought to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after the implantation of a drug-eluting stent (DES) in elderly patients. BACKGROUND Qualified studies to evaluate the optimal duration of DAPT in elderly patients have been very limited. METHODS: Using 6 randomized trials that compared short-term (#6 months) and long-term (12 months) DAPT, individual participant data meta-analysis was performed in elderly patients ($65 years of age). The primary study outcome was the 12-month risk of a composite of myocardial infarction, definite or probable stent thrombosis, or stroke. The major secondary outcome was the 12-month risk of major bleeding. RESULTS: The primary outcome risk did not significantly differ between patients receiving short-term and long-term DAPT (hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.88 to 1.43; p»0.3581) in the overall group of study participants. In subgroup analysis, a significant interaction between age and DAPT duration was observed for primary outcome risk (p for interaction»0.0384). In the subset of younger patients (<65 years of age, n»6,152), short-term DAPT was associated with higher risk of primary outcome (HR: 1.67; 95% CI: 1.14 to 2.44; p»0.0082). In elderly patients(n»5,319), however, the risk of primary outcome did not significantly differ between patients receiving short-term and long-term DAPT (HR: 0.84; 95% CI: 0.60 to 1.16; p»0.2856). Short-term DAPT was associated with a significant reduction in major bleeding compared with long-term DAPT (HR: 0.50; 95% CI: 0.30 to 0.84; p»0.0081) in the overall group, and particularly in elderly patients (HR: 0.46; 95% CI: 0.24-0.88; p»0.0196). CONCLUSIONS: Short-term DAPT after new-generation DES implantation may be more beneficial in elderly patients than in younger patients.
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Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral , Stents Farmacológicos , Infarto do MiocárdioRESUMO
AIM: We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation.METHODS AND RESULTS:We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hemorragia/induzido quimicamente , Infarto do Miocárdio , Morte Súbita/epidemiologiaRESUMO
BACKGROUND:Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear.OBJECTIVES:The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs.METHODS:RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded.
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Humanos , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Stents FarmacológicosRESUMO
OBJECTIVES: The study sought to evaluate the presence of a clinically relevant rebound phenomenon after dual antiplatelet therapy (DAPT) discontinuation in randomized trials. BACKGROUND: It is currently unknown whether clopidogrel discontinuation after short-term DAPT is associated with an early hazard of ischemic events. METHODS: The authors performed an individual participant data analysis and aggregate meta-analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction (MI), or stroke. RESULTS: The study included 11,473 PCI patients with individual participant data from 6 randomized trials comparing short-term DAPT (3 or 6 months) versus long-term DAPT (12 months or more). During the first 90 days following clopidogrel discontinuation, there was no significant increase in the risk of MACCE between patients randomized to short-term DAPT compared with long-term DAPT (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.71 to 1.98; p»0.52; absolute risk difference 0.10%; 95% CI: 0.16% to 0.36%). The risk of MI or stent thrombosis was similar among patients randomized to short-term DAPT versus long-term DAPT (HR: 0.93; 95% CI: 0.46 to 1.90; p»0.85). In the aggregate data meta-analysis of 11 trials including 38,919 patients, a higher risk of early MACCE was observed after long-term ($12 months) DAPT duration (HR: 2.28; 95% CI: 1.69 to 3.09; p<0.001) but not short-term (<12 months) DAPT duration (HR: 1.08; 95% CI: 0.67 to 1.74; p for interaction»0.036).CONCLUSIONS: Among patients undergoing PCI with predominantly new-generation DES, discontinuation of clopidogrel after 3 or 6 months DAPT duration was not associated with an early increase in adverse clinical events. An early increase in MACCE was observed after long-term ($12 months) DAPT exposure.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Reestenose Coronária/etnologia , Trombose Coronária/etiologiaRESUMO
Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods: A total of 14 963 patients treated with DAPT after coronary stentinglargely consisting of aspirin and clopidogrel and without indication to oral anticoagulationwere pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (1224 months) or short (36 months) treatment in relation to baseline bleeding risk...
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Conduta do Tratamento Medicamentoso , Coração , Pacientes , Stents Farmacológicos , TerapêuticaRESUMO
OBJECTIVE: To compare clinical outcomes between short term (up to 6 months) and long term (12 months) dual antiplatelet therapy (DAPT) after placement of a drug eluting stent in patients with and without diabetes.DESIGN: Individual participant data meta-analysis. Cox proportional regression models stratified by trial were used to assess the impact of diabetes on outcomes.DATA SOURCE: Medline, Embase, and Cochrane databases and proceedings of international meetings searched for randomised controlled trials comparing durations of DAPT after placement of a drug eluting stent. Individual patient data pooled from six DAPT trials.PRIMARY OUTCOME: Primary study outcome was one year risk of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, or definite/probable stent thrombosis. All analyses were conducted by intention to treat...