RESUMO

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Assuntos

Doença da Artéria Coronariana

RESUMO

OBJECTIVE: This study evaluates the relationship between atherosclerotic plaque characteristics (APCs) and angiographic stenosis severity in patients with and without diabetes. Whether APCs differ based on lesion severity and diabetes status is unknown. RESEARCH DESIGN AND METHODS: We retrospectively evaluated 303 subjects from the Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia (CREDENCE) trial referred for invasive coronary angiography with coronary computed tomographic angiography (CCTA) and classified lesions as obstructive (≥50% stenosed) or nonobstructive using blinded core laboratory analysis of quantitative coronary angiography. CCTA quantified APCs, including plaque volume (PV), calcified plaque (CP), noncalcified plaque (NCP), low-density NCP (LD-NCP), lesion length, positive remodeling (PR), high-risk plaque (HRP), and percentage of atheroma volume (PAV; PV normalized for vessel volume). The relationship between APCs, stenosis severity, and diabetes status was assessed. RESULTS: Among the 303 patients, 95 (31.4%) had diabetes. There were 117 lesions in the cohort with diabetes, 58.1% of which were obstructive. Patients with diabetes had greater plaque burden (P = 0.004). Patients with diabetes and nonobstructive disease had greater PV (P = 0.02), PAV (P = 0.02), NCP (P = 0.03), PAV NCP (P = 0.02), diseased vessels (P = 0.03), and maximum stenosis (P = 0.02) than patients without diabetes with nonobstructive disease. APCs were similar between patients with diabetes with nonobstructive disease and patients without diabetes with obstructive disease. Diabetes status did not affect HRP or PR. Patients with diabetes had similar APCs in obstructive and nonobstructive lesions. CONCLUSIONS: Patients with diabetes and nonobstructive stenosis had an association to similar APCs as patients without diabetes who had obstructive stenosis. Among patients with nonobstructive disease, patients with diabetes had more total PV and NCP.

Assuntos

Aterosclerose , Doença da Artéria Coronariana , Estenose Coronária , Diabetes Mellitus , Placa Aterosclerótica , Humanos , Constrição Patológica/complicações , Estudos Retrospectivos , Doença da Artéria Coronariana/complicações , Placa Aterosclerótica/diagnóstico por imagem , Angiografia Coronária/métodos , Aterosclerose/complicações , Angiografia por Tomografia Computadorizada/métodos , Diabetes Mellitus/epidemiologia , Inteligência Artificial , Estenose Coronária/complicações , Valor Preditivo dos Testes

RESUMO

OBJECTIVES: The aim of this study was to compare aspirin plus clopidogrel with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement (TAVR) for the prevention of ischemic events, bleeding events, and death. BACKGROUND: Few data exist on the optimal antithrombotic therapy following TAVR. METHODS: This was a randomized controlled trial comparing aspirin (80 to 100 mg/day) plus clopidogrel (75 mg/day) (dual antiplatelet therapy [DAPT]) versus aspirin alone (single-antiplatelet therapy [SAPT]) in patients undergoing TAVR with a balloon-expandable valve. The primary endpoint was the occurrence of death, myocardial infarction (MI), stroke or transient ischemic attack, or major or life-threatening bleeding (according to Valve Academic Research Consortium 2 definitions) within the 3 months following the procedure. The trial was prematurely stopped after the inclusion of 74% of the planned study population. RESULTS: A total of 222 patients were included, 111 allocated to DAPT and 111 to SAPT. The composite of death, MI, stroke or transient ischemic attack, or major or life-threatening bleeding tended to occur more frequently in the DAPT group (15.3% vs. 7.2%, p = 0.065). There were no differences between groups in the occurrence of death (DAPT, 6.3%; SAPT, 3.6%; p = 0.37), MI (DAPT, 3.6%; SAT, 0.9%; p = 0.18), or stroke or transient ischemic attack (DAPT, 2.7%; SAPT, 0.9%; p = 0.31) at 3 months. DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6% in the SAPT group, p = 0.038). There were no differences between groups in valve hemodynamic status post-TAVR. CONCLUSIONS: This small trial showed that SAPT (vs. DAPT) tended to reduce the occurrence of major adverse events following TAVR. SAPT reduced the risk for major or life-threatening events while not increasing the risk for MI or stroke. Larger studies are needed to confirm these results. (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation: The ARTE Trial [ARTE], NCT01559298; Aspirin Versus Aspirin+Clopidogrel as Antithrombotic Treatment Following TAVI [ARTE], NCT02640794).

Assuntos

Valva Aórtica/cirurgia , Aspirina/administração & dosagem , Valvuloplastia com Balão , Fibrinolíticos/administração & dosagem , Próteses Valvulares Cardíacas , Inibidores da Agregação Plaquetária/administração & dosagem , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Substituição da Valva Aórtica Transcateter/instrumentação , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Valvuloplastia com Balão/efeitos adversos , Canadá , Clopidogrel , Quimioterapia Combinada , Término Precoce de Ensaios Clínicos , Europa (Continente) , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/prevenção & controle , Estimativa de Kaplan-Meier , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação Plaquetária/efeitos adversos , Desenho de Prótese , Fatores de Risco , América do Sul , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Trombose/diagnóstico , Trombose/etiologia , Trombose/mortalidade , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do Tratamento

RESUMO

BACKGROUND: A pharmacodynamic comparison between ticagrelor and prasugrel after fibrinolytic therapy has not yet been performed. METHODS: In the single-center SAMPA trial, 50 consecutive STEMI patients previously treated with clopidogrel and undergoing a pharmacoinvasive strategy were randomized to either a ticagrelor (n=25) 180mg loading dose followed by 90mg bid, or a prasugrel (n=25) 60mg loading dose followed by 10mg/day, initiated after fibrinolytic therapy but before angiography. Platelet reactivity was assessed with the VerifyNow P2Y12 assay at 0, 2, 6, and 24h after randomization. RESULTS: Mean times from fibrinolysis to prasugrel or ticagrelor administration were 11.1±6.9 and 13.3±6.3h, respectively (p=0.24). The values of PRU decreased significantly from baseline to 2h (all p<0.001) and from 2h to 6h (all p<0.001) in both groups. There was no difference in PRU values between 6h and 24h. The mean PRU values at 0, 2, 6, and 24h were 234.9, 127.8, 45.4, and 48.0 in the prasugrel group and 233.1, 135.1, 67.7, and 56.9 in the ticagrelor group, respectively. PRU values did not significantly differ between groups at any time period of the study. CONCLUSIONS: In patients with STEMI treated with fibrinolytic therapy, platelet inhibition after clopidogrel is suboptimal and can be further increased with more potent agents. Ticagrelor and prasugrel demonstrated a similar extent of P2Y12 receptor inhibition within 24h, although maximal platelet inhibition after these potent agents was not achieved for 6h.

Assuntos

Adenosina/análogos & derivados , Cloridrato de Prasugrel/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Terapia Trombolítica/métodos , Adenosina/administração & dosagem , Angiografia Coronária , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Ticagrelor , Fatores de Tempo , Resultado do Tratamento

RESUMO

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.

Assuntos

Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hemorragia/induzido quimicamente , Infarto do Miocárdio , Morte Súbita/epidemiologia

RESUMO

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.

Assuntos

Humanos , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Stents Farmacológicos

RESUMO

BACKGROUND: Scoring balloons produce excellent acute results in the treatment of in-stent restenosis (ISR), fibro-calcific and bifurcation lesions but have not been shown to affect the restenosis rate. A novel paclitaxel-coated scoring balloon (SB) was developed and tested to overcome this limitation. METHODS AND RESULTS: SB were coated with paclitaxel admixed with a specific excipient. Patients at four clinical sites in Germany and one in Brazil with ISR of coronary bare metal stent (BMS) were randomized 1:1 to treatment with either a drug-coated or uncoated SB. Baseline and 6-month follow-up quantitative coronary angiography was performed by an independent blinded core lab and all patients will be evaluated clinically for up to one year. The primary endpoint was angiographic in-segment late lumen loss (LLL). Secondary endpoints included the rate of clinically driven target lesion revascularization (TLR), composite of major adverse cardiovascular events (MACE), stent thrombosis and other variables. Sixty-one patients were randomized (28 uncoated and 33 drug-coated SB); mean age 65 years, males 72%, and presence of diabetes 39%. At 6-month angiography, in-segment LLL was 0.48 ± 0.51 mm in the uncoated SB group versus 0.17 ± 0.40 mm in the drug-coated SB group (P = 0.01; ITT analysis). The rate of binary restenosis was 41% in the uncoated SB group versus 7% in the drug-coated SB group (P = 0.004). The MACE rate was 32% with the uncoated SB vs. 6% in the drug-coated SB group (P = 0.016). This difference was primarily due to the reduced need for clinically driven TLR in the coated SB group (3% vs. 32% P = 0.004). CONCLUSIONS: A novel paclitaxel-coated coronary SB has been developed and successfully used in a first-in-human randomized controlled trial [ClinicalTrials.gov Identifier: NCT01495533]. © 2015 Wiley Periodicals, Inc.

Assuntos

Angioplastia Coronária com Balão/instrumentação , Cateteres Cardíacos , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/terapia , Reestenose Coronária/terapia , Paclitaxel/administração & dosagem , Intervenção Coronária Percutânea/instrumentação , Stents , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Brasil , Fármacos Cardiovasculares/efeitos adversos , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Feminino , Alemanha , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Retratamento , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento

RESUMO

Scoring balloons produce excellent acute results in the treatment of instentrestenosis (ISR), fibro-calcific and bifurcation lesions but have not been shown toaffect the restenosis rate. A novel paclitaxel-coated scoring balloon (SB) was developedand tested to overcome this limitation. Methods and Results: SB were coatedwith paclitaxel admixed with a specific excipient. Patients at four clinical sites inGermany and one in Brazil with ISR of coronary bare metal stent (BMS) were randomized1:1 to treatment with either a drug-coated or uncoated SB. Baseline and 6-monthfollow-up quantitative coronary angiography was performed by an independent blindedcore lab and all patients will be evaluated clinically for up to one year. The primaryendpoint was angiographic in-segment late lumen loss (LLL). Secondary endpoints included the rate of clinically driven target lesion revascularization (TLR), composite ofmajor adverse cardiovascular events (MACE), stent thrombosis and other variables.Sixty-one patients were randomized (28 uncoated and 33 drug-coated SB); mean age65 years, males 72%, and presence of diabetes 39%. At 6-month angiography, insegmentLLL was 0.48 6 0.51 mm in the uncoated SB group versus 0.17 6 0.40 mm inthe drug-coated SB group (P 5 0.01; ITT analysis). The rate of binary restenosis was41% in the uncoated SB group versus 7% in the drug-coated SB group (P 5 0.004). TheMACE rate was 32% with the uncoated SB vs. 6% in the drug-coated SB group(P 5 0.016). This difference was primarily due to the reduced need for clinically drivenTLR in the coated SB group (3% vs. 32% P 5 0.004). Conclusions: A novel paclitaxelcoatedcoronary SB has been developed and successfully used in a first-in-human randomized controlled trial...

Assuntos

Difusão de Inovações , Doença das Coronárias

RESUMO

BACKGROUND: Optimal upfront dual antiplatelet therapy (DAPT) duration after complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear. OBJECTIVES: This study investigated the efficacy and safety of long-term (≥12 months) versus short-term (3 or 6 months) DAPT with aspirin and clopidogrel according to PCI complexity. METHODS: The authors pooled patient-level data from 6 randomized controlled trials investigating DAPT durations after PCI. Complex PCI was defined as having at least 1 of the following features: 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 major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. The primary safety endpoint was major bleeding. Intention-to-treat was the primary analytic approach. RESULTS: Of 9,577 patients included in the pooled dataset for whom procedural variables were available, 1,680 (17.5%) underwent complex PCI. Overall, 85% of patients received new-generation DES. At a median follow-up time of 392 days (interquartile range: 366 to 710 days), patients who underwent complex PCI had a higher risk of MACE (adjusted hazard ratio [HR]: 1.98; 95% confidence interval [CI]: 1.50 to 2.60; p < 0.0001)...

Assuntos

Hemorragia , Infarto do Miocárdio , Stents Farmacológicos , Trombose