RESUMO
Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results: Analyses included 6 randomized trials including 25â¯960 patients undergoing PCI, of whom 24â¯394 patients (12â¯403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.
Assuntos
Clopidogrel , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Ticagrelor , Ticagrelor/uso terapêutico , Intervenção Coronária Percutânea/métodos , Humanos , Clopidogrel/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Terapia Antiplaquetária Dupla/métodos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Hemorragia/induzido quimicamenteRESUMO
BACKGROUND: It remains unclear whether P2Y12 inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI). OBJECTIVES: We sought to assess the effects of P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity. METHODS: We pooled patient-level data from randomized controlled trials comparing P2Y12 inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding. RESULTS: Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y12 inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; Pinteraction = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y12 inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; Pinteraction = 0.920). CONCLUSIONS: P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853).
Assuntos
Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Aspirina , Intervenção Coronária Percutânea/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y , Terapia Antiplaquetária Dupla , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Quimioterapia Combinada , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the risks and benefits of P2Y12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients' characteristics. DESIGN: Individual patient level meta-analysis of randomised controlled trials. DATA SOURCES: Searches were conducted in Ovid Medline, Embase, and three websites (www.tctmd.com, www.escardio.org, www.acc.org/cardiosourceplus) from inception to 16 July 2020. The primary authors provided individual participant data. ELIGIBILITY CRITERIA: Randomised controlled trials comparing effects of oral P2Y12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation. MAIN OUTCOME MEASURES: The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding. RESULTS: The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ2=0.00) and in 303 (2.94%) with P2Y12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ2=0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ2=0.03), which was consistent across subgroups, except for type of P2Y12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y12 inhibitor rather than clopidogrel was part of the DAPT regimen. CONCLUSIONS: P2Y12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT. REGISTRATION: PROSPERO CRD42020176853.
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Terapia Antiplaquetária Dupla/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Idoso , Doença da Artéria Coronariana/cirurgia , Terapia Antiplaquetária Dupla/métodos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/mortalidade , Intervenção Coronária Percutânea/normas , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Trombose/tratamento farmacológico , Trombose/prevenção & controleRESUMO
INTRODUCTION: The optimal choice of oral P2Y
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Síndrome Coronariana Aguda , Síndrome Coronariana Aguda/tratamento farmacológico , Humanos , Metanálise em Rede , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: Uric acid has been shown as a predictor and an independent risk factor for coronary heart disease, but little is known regarding the association of uric acid levels with coronary blood flow in STEMI. We hypothesized that elevated uric acid levels would be associated with impaired flow and perfusion in the setting of STEMI treated with primary PCI. METHODS: Two hundred and eighty nine patients with STEMI who treated primary PCI were enrolled to study. Patients were divided into two groups based upon the TIMI flow grade. No-reflow was defined as TIMI Grade 0, 1 and 2 flows (group 1). Angiographic success was defined as TIMI 3 flow (group 2). Uric acid, MPV and high sensitive CRP were measured. Major adverse cardiac events (MACE) were defined as in stent thrombosis, non-fatal myocardial infarction and in-hospital mortality. RESULTS: There were 126 patients (mean age 63±11 and 71% male) in group 1 and 163 patients (mean age 58±12 and 80% male) in group 2. Uric acid, MPV, and hs-CRP levels on admission were higher in group 1 (p=0.0001 for each). A uric acid level ≥5.4 mg/dl measured on admission had a 77% sensitivity and 70% specificity in predicting no-reflow at ROC curve analysis. In-hospital MACE was significantly higher in group 1 (29% vs. 7%, p=0.0001). At multivariate analyses, high plasma uric acid (odds ratio (OR) 2.05, <95% confidence interval(CI) 1.49-2.81; p<0.0001), hs-CRP (OR 1.02, <95% CI 1.01-1.03; p=0.0007) and MPV (OR 3.09, <95% CI 1.95-4.89; p<0.0001) levels were independent predictors of no-reflow post primary PCI and uric acid (OR 2.75, <95% CI 1.93-3.94; p<0.0001), hs-CRP (OR 1.01, <95% CI 1-1.02; p=0.006) levels, but not MPV, were independent predictors of in-hospital MACE. CONCLUSION: Plasma uric acid level on admission is a strong and independent predictor of poor coronary blood flow following primary PCI and in hospital MACE among patients with STEMI. Except for predictive value, uric acid levels may be a useful biomarker for stratification of risk in patients with STEMI and may also lead to carry further therapeutic implications.