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Background: Little is known about the bleeding risk associated with cangrelor use in patients with myocardial infarction (MI) who are exposed to an oral P2Y12 inhibitor before coronary angiography. Methods: Cangrelor in Acute MI: Effectiveness and Outcomes (CAMEO) is an observational registry studying platelet inhibition for patients with MI. Upstream oral P2Y12 inhibition was defined as receipt of an oral P2Y12 inhibitor within 24 hours before hospitalization or in-hospital before angiography. Among cangrelor-treated patients, we compared bleeding after cangrelor use through 7 days postdischarge between patients with and without upstream oral P2Y12 inhibitor exposure. Results: Among 1802 cangrelor-treated patients with MI, 385 (21.4%) received upstream oral P2Y12 inhibitor treatment. Of these, 101 patients (33.8%) started cangrelor within 1 hour, 103 (34.4%) between 1 and 3 hours, and 95 (31.8%), >3 hours after in-hospital oral P2Y12 inhibitor administration; the remaining received an oral P2Y12 inhibitor before hospitalization. There was no statistically significant difference in rates of bleeding among cangrelor-treated patients with and without upstream oral P2Y12 inhibitor exposure (6.5% vs 8.8%; adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.01). Bleeding was observed in 5.0%, 10.7%, and 3.2% of patients treated with cangrelor <1, 1 to 3, and >3 hours after the last oral PY12 inhibitor dose, respectively; bleeding rates were not statistically different between groups (1-3 hours vs <1 hour: adjusted OR, 2.70; 95% CI, 0.87-8.32; >3 hours vs <1 hour: adjusted OR, 0.65; 95% CI, 0.15-2.85). Conclusions: Bleeding risk was not observed to be significantly higher after cangrelor treatment in patients with and without upstream oral P2Y12 inhibitor exposure.
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BACKGROUND: Incomplete revascularization (ICR) after percutaneous coronary intervention (PCI) is associated with mortality and morbidity. AIM: We sought to investigate whether ICR in the left anterior descending artery (LAD) is worse than ICR of the right coronary artery (RCA) or left circumflex artery (LCX); and whether ICR in patients with a chronic total occlusion (CTO) is worse than in those without. METHODS: In the RIVER-PCI trial, 2651 patients with ICR after PCI were randomly assigned to ranolazine or placebo. Angiograms were assessed at an independent core laboratory in 2501 patients (94.3%). The primary endpoint was the composite of ischemia-driven revascularization or hospitalization. RESULTS: A total of 1664 patients (66.5%) had ICR involving the LAD, whereas 837 (33.5%) had ICR limited to the RCA or LCX. At median follow-up of 643 days, the primary endpoint occurred in 26.9% versus 26.5% of patients (adjusted HR [aHR]: 1.03, 95% confidence interval [CI]: 0.88-1.21). A nonrecanalized CTO was present in 854 patients (34.1%) with ICR after PCI. The primary endpoint occurred in 28.6% versus 25.9% of ICR patients with versus without a CTO (aHR: 1.10, 95% CI: 0.94-1.29). However, patients with a CTO had higher rates of ischemia-driven hospitalization without revascularization (aHR: 1.27, 95% CI: 1.04-1.56), heart failure hospitalization (aHR: 2.69, 95% CI: 1.61-4.59) and myocardial infarction (aHR: 1.46, 95% CI: 1.11-1.92) compared with those without. CONCLUSIONS: The 2-year prognosis was similar in post-PCI patients with ICR whether the LAD was versus was not involved. ICR patients with a CTO had more frequent hospitalizations for ischemia and myocardial infarctions compared with those without.
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BACKGROUND: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina. METHODS: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery. RESULTS: There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1-139.5], +84.5 [95% CI, 34.1-134.9], and +115.5 [95% CI, 59.1-171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, -3.1% to 23.5%), 14.3% (95% CI, 2.8%-25.7%), and 10.2% (95% CI, -0.8% to -21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1-11.3), 6.6 (95% CI, 3.5-9.7), and 8.8 (4.6-13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months. CONCLUSIONS: XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04125732.
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Angina de Pecho , Terapia Genética , Vectores Genéticos , Neovascularización Fisiológica , Factor A de Crecimiento Endotelial Vascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Angina de Pecho/terapia , Angina de Pecho/fisiopatología , Terapia Genética/efectos adversos , Anciano , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/genética , Factores de Tiempo , Tolerancia al Ejercicio , Adenoviridae/genética , Recuperación de la FunciónRESUMEN
BACKGROUND: Mortality after ST-segment elevation myocardial infarction (STEMI) is increased in patients with hypertension. The mechanisms underlying this association are uncertain. We sought to investigate whether patients with STEMI and prior hypertension have greater microvascular obstruction (MVO) and infarct size (IS) compared with those without hypertension. METHODS: We pooled individual patient data from 7 randomized trials of patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in whom cardiac magnetic resonance imaging was performed within 1 month after reperfusion. The associations between hypertension and MVO, IS, and mortality were assessed in multivariable adjusted models. RESULTS: Among 2174 patients (61.3 ± 12.6 years, 76% male), 1196 (55.0%) had hypertension. Patients with hypertension were older, more frequently diabetic and had more extensive coronary artery disease than those without hypertension. MVO and IS measured as percent LV mass were not significantly different in patients with and without hypertension (adjusted differences 0.1, 95% CI -0.3 to 0.6, P = .61 and -0.2, 95% CI -1.5 to 1.2, P = .80, respectively). Hypertension was associated with a higher unadjusted risk of 1-year death (hazard ratio [HR] 2.28, 95% CI 1.44-3.60, P < .001), but was not independently associated with higher mortality after multivariable adjustment (adjusted HR 1.04, 95% CI 0.60-1.79, P = .90). CONCLUSION: In this large-scale individual patient data pooled analysis, hypertension was not associated with larger IS or MVO after primary PCI for STEMI.
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Hipertensión , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/cirugía , Infarto del Miocardio con Elevación del ST/mortalidad , Intervención Coronaria Percutánea/métodos , Masculino , Femenino , Persona de Mediana Edad , Hipertensión/complicaciones , Imagen por Resonancia Cinemagnética/métodos , Anciano , Microcirculación , Imagen por Resonancia Magnética/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Nearly 20% of patients on ticagrelor experience dyspnea, which may lead to treatment discontinuation in up to one-third of cases. OBJECTIVES: The authors sought to evaluate the incidence, predictors, and outcomes of dyspnea-related ticagrelor discontinuation after percutaneous coronary intervention (PCI). METHODS: In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The occurrence of dyspnea associated with ticagrelor discontinuation was evaluated among all patients enrolled in the trial. A landmark analysis was performed at 3 months after PCI, that is, the time of randomization. Predictors of dyspnea-related ticagrelor discontinuation were obtained from multivariable Cox regression with stepwise selection of candidate variables. RESULTS: The incidence of dyspnea-related ticagrelor discontinuation was 6.4% and 9.1% at 3 and 15 months after PCI, respectively. Independent predictors included Asian race (lower risk), smoking, prior PCI, hypercholesterolemia, prior coronary artery bypass, peripheral artery disease, obesity, and older age. Among 179 patients who discontinued ticagrelor because of dyspnea after randomization, ticagrelor monotherapy was not associated with a higher risk of subsequent ischemic events (composite of all-cause death, myocardial infarction, or stroke) compared with ticagrelor plus aspirin (5.0% vs 7.1%; P = 0.566). CONCLUSIONS: In the TWILIGHT trial, dyspnea-related ticagrelor discontinuation occurred in almost 1 in 10 patients and tended to occur earlier rather than late after PCI. Several demographic and clinical conditions predicted its occurrence, and their assessment may help identify subjects at risk for therapy nonadherence.
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Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Ticagrelor , Intervención Coronaria Percutánea/efectos adversos , Hemorragia/inducido químicamente , Resultado del Tratamiento , Quimioterapia Combinada , Aspirina , Disnea/inducido químicamente , Disnea/diagnóstico , Disnea/tratamiento farmacológicoRESUMEN
BACKGROUND: In TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention), among high-risk patients undergoing percutaneous coronary intervention (PCI), ticagrelor monotherapy vs continuation of dual antiplatelet therapy (DAPT) with aspirin and ticagrelor after completing a 3-month course of DAPT was associated with reduced bleeding, without an increase in ischemic events. OBJECTIVES: This investigation sought to study the clinical benefit of ticagrelor monotherapy vs DAPT by simultaneously modeling its associated potential bleeding benefits and ischemic harms on an individual patient basis. METHODS: Multivariable Cox regression models for: 1) Bleeding Academic Research Consortium type 2, 3, or 5 (BARC-2/3/5); and 2) cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke (major adverse cardiac and cerebrovascular event [MACCE]) were developed using stepwise forward variable selection. The coefficients in the BARC-2/3/5 and MACCE models were used to calculate bleeding and ischemic risk scores, respectively, for each patient (excluding the coefficient for randomized treatment). RESULTS: In the total study group (N = 7,119), BARC-2/3/5 occurred in 391 (5.5%) patients, and MACCE occurred in 258 (3.6%). There was a consistent reduction in bleeding events associated with ticagrelor monotherapy compared with DAPT across both bleeding and ischemic risk strata (P interaction = 0.54 and 0.11, respectively). Importantly, this benefit associated with ticagrelor monotherapy was not offset by an increase in MACCE at any level of bleeding or ischemic risk. CONCLUSIONS: Three months after PCI, discontinuing aspirin and maintaining ticagrelor monotherapy reduces bleeding in both higher-bleeding risk and lower-bleeding risk patients compared with continued DAPT. This benefit does not appear to be offset by greater ischemic risk. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).
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Intervención Coronaria Percutánea , Humanos , Aspirina/efectos adversos , Corazón , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticagrelor/efectos adversosRESUMEN
BACKGROUND: Heart failure (HF) may complicate acute coronary syndrome (ACS) and is associated with a high burden of short- and long-term morbidity and mortality. Only limited data regarding future ischemic events and rehospitalization are available for patients who suffer HF before or during ACS. METHODS: A secondary analysis of 4 large ACS trials (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) using Cox proportional hazards models was performed to investigate the association of HF status (no HF, chronic HF, de novo HF) at presentation for ACS with all-cause and cardiovascular death, major adverse cardiovascular event (MACE ), myocardial infarction, stroke, and hospitalization for heart failure (HHF) by 1 year. Cumulative incidence plots are presented at 30 days and 1 year. RESULTS: A total of 11.1% of the 47,474 patients presenting with ACS presented with evidence of acute HF, 55.0% of whom presented with de novo HF. Patients with chronic HF presented with evidence of acute HF at a higher rate than those with no previous HF (40.3% vs 6.9%). Compared to those without HF, those with chronic and de novo HF had higher rates of all-cause mortality (adjusted hazard ratio [aHR] 2.01, 95% confidence interval [CI] 1.72-2.34 and aHR 1.47, 95% CI1.15-1.88, respectively), MACE (aHR 1.47, 95% CI1.31-1-.66 and aHR 1.38, 95% CI1.12-1.69), and HHF (aHR 2.29, 95% CI2.02-2.61 and aHR 1.48, 95% CI 1.20-1.82) at 1 year. CONCLUSION: In this large cohort of patients with ACS, both prior and de novo HF complicating ACS were associated with significantly higher risk-adjusted rates of death, ischemic events and HHF at 30 days and 1 year. Further studies examining the association between HF and outcomes in this high-risk population are warranted, especially given the advent of more contemporary HF therapies.
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Síndrome Coronario Agudo , Insuficiencia Cardíaca , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/epidemiología , Insuficiencia Cardíaca/tratamiento farmacológico , Incidencia , Infarto del Miocardio/complicaciones , Accidente Cerebrovascular/etiología , Ensayos Clínicos como AsuntoRESUMEN
BACKGROUND: New therapies are needed for patients with refractory angina. Encoberminogene rezmadenovec (XC001), a novel adenoviral-5 vector coding for all 3 major isoforms of VEGF (vascular endothelial growth factor), demonstrated enhanced local angiogenesis in preclinical models; however, the maximal tolerated dose and safety of direct epicardial administration remain unknown. METHODS: In the phase 1 portion of this multicenter, open-label, single-arm, dose-escalation study, patients with refractory angina received increasing doses of encoberminogene rezmadenovec (1×109, 1×1010, 4×1010, and 1×1011 viral particles) to evaluate its safety, tolerability, and preliminary efficacy. Patients had class II to IV angina on maximally tolerated medical therapy, demonstrable ischemia on stress testing, and were angina-limited on exercise treadmill testing. Patients underwent minithoracotomy with epicardial delivery of 15 0.1-mL injections of encoberminogene rezmadenovec. The primary outcome was safety via adverse event monitoring over 6 months. Efficacy assessments included difference from baseline to months 3, 6 (primary), and 12 in total exercise duration, myocardial perfusion deficit using positron emission tomography, angina class, angina frequency, and quality of life. RESULTS: From June 2, 2020 to June 25, 2021, 12 patients were enrolled into 4 dosing cohorts with 1×1011 viral particle as the highest planned dose. Seventeen serious adverse events were reported in 7 patients; none were related to study drug. Six serious adverse events in 4 patients were related to the thoracotomy, 3 non-serious adverse events were possibly related to study drug. The 2 lowest doses did not demonstrate improvements in total exercise duration, myocardial perfusion deficit, or angina frequency; however, there appeared to be improvements in all parameters with the 2 higher doses. CONCLUSIONS: Epicardial delivery of encoberminogene rezmadenovec via minithoracotomy is feasible, and up to 1×1011 viral particle appears well tolerated. A dose response was observed across 4 dosing cohorts in total exercise duration, myocardial perfusion deficit, and angina class. The highest dose (1×1011 viral particle) was carried forward into phase 2. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04125732.
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Calidad de Vida , Factor A de Crecimiento Endotelial Vascular , Humanos , Resultado del Tratamiento , Angina de Pecho/terapia , Prueba de EsfuerzoRESUMEN
BACKGROUND: Invasive cardiac catheterization (CC) temporarily increases pain, discomfort, and anxiety. Procedural sedation is deployed to mitigate these symptoms, though practice varies. Research evaluating peri-procedural patient-reported outcomes is lacking. METHODS AND RESULTS: We randomized 175 patients undergoing CC to short interval ([SI] group, <6 min) or long interval ([LI] group, ≥6 min) time intervals between initial intravenous sedation and local anesthetic administration. Outcomes included: (1) total pain medication use, (2) patient-reported and behaviorally assessed pain and (3) patient satisfaction during outpatient CC. Generalized linear mixed effect models were used to evaluate the impact of treatment time interval on total medication utilization, pain, and satisfaction. Among enrollees the mean age was 62 (standard deviation [SD] = 13.4), a majority were male (66%), white (74%), and overweight (mean body mass index = 28.5 [SD = 5.6]). Total pain medication use did not vary between treatment groups (p = 0.257), with no difference in total fentanyl (p = 0.288) or midazolam (p = 0.292). Post-treatment pain levels and nurse-observed pain were not statistically significant between groups (p = 0.324 & p = 0.656, respectively. No significant differences with satisfaction with sedation were found between the groups (p = 0.95) Patient-reported pain, satisfaction and nurse-observed measures of pain did not differ, after adjustment for demographic and procedural factors. Analyses of treatment effect modification revealed that postprocedure self-reported pain levels varied systematically between individuals undergoing percutaneous coronary intervention (PCI) (SI = 2.2 [0.8, 3.6] vs. LI = 0.7 [-0.6, 2.0]) compared with participants not undergoing PCI (SI = 0.4 [-0.8, 1.7] vs. LI = 0.7 [-0.3, 1.6]) (p = 0.043 for interaction). CONCLUSION: No consistent treatment differences were found for total medication dose, pain, or satisfaction regardless of timing between sedation and local anesthetic. Treatment moderations were seen for patients undergoing PCI. Further investigation of how procedural and individual factors impact the patient experience during CC is needed.
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AIMS: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry. METHODS AND RESULTS: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy. CONCLUSIONS: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.' CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov identifier: NCT01991795.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Infarto del Miocardio , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Humanos , Ticagrelor/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Aspirina/uso terapéutico , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Evaluación de Resultado en la Atención de Salud , Resultado del Tratamiento , Inhibidores de Agregación Plaquetaria/uso terapéuticoRESUMEN
Impella was approved by the Food and Drug Administration in 2015 for use during high-risk percutaneous coronary interventions (PCIs); however, its safety and efficacy compared with intra-aortic balloon pump (IABP) has not been evaluated in contemporary practice and remains debated. We aimed to compare postapproval outcomes and costs of Impella versus IABP support for high-risk PCI in real-world practice across hospitals in the United States. We identified patients from the Premier Healthcare Database undergoing nonemergent Impella- or IABP-supported high-risk PCI. We used propensity adjustment to control baseline, procedure, and post-PCI medical treatment differences between treatment groups. We included patients undergoing nonemergent single-PCI procedures with either Impella or IABP support and excluded patients presenting with acute ST-elevation myocardial infarction or cardiogenic shock or requiring >1 mechanical support devices during index hospitalization. Outcomes included in-hospital survival, myocardial infarction (MI), cardiogenic shock, stroke, bleeding requiring transfusion, acute kidney injury, index hospitalization length of stay, and costs. From April 2016 to June 2019, a total of 48,179 patients were treated with Impella or IABP mechanical circulatory support at 304 hospitals in the United States. Among these, we identified 2,156 patients undergoing nonemergent high-risk PCI treated with Impella (n = 1,447) or IABP (n = 709). After propensity adjustment, Impella use was associated with improved survival (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.02 to 2.36) and less MI (OR 0.29, 95% CI 0.18 to 0.46) and cardiogenic shock (OR 0.54, 95% CI 0.39 to 0.74). Stroke, bleeding requiring transfusion, and acute kidney injury were similar between groups. In conclusion, this Premier Healthcare Database propensity-adjusted analysis, Impella use during nonemergent high-risk PCI was associated with improved survival and reduced in-hospital MI and cardiogenic shock compared with IABP.
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Lesión Renal Aguda , Corazón Auxiliar , Infarto del Miocardio , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Humanos , Estados Unidos/epidemiología , Choque Cardiogénico/epidemiología , Choque Cardiogénico/terapia , Choque Cardiogénico/etiología , Intervención Coronaria Percutánea/métodos , Contrapulsador Intraaórtico , Corazón Auxiliar/efectos adversos , Hemorragia/etiología , Lesión Renal Aguda/etiología , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: There is a paucity of data regarding the safety and efficacy of different antiplatelet regimens according to standardized body mass index (BMI) categories. OBJECTIVES: The aim of this study was to investigate bleeding and ischemic outcomes according to BMI in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial. METHODS: The TWILIGHT trial randomized high-risk patients to ticagrelor plus aspirin or ticagrelor plus placebo at 3 months after percutaneous coronary intervention. In this secondary analysis, patients were stratified by standard BMI categories, as recommended by the European Society of Cardiology Working Group on Thrombosis (normal weight [BMI 18.5-24.99 kg/m2], overweight [BMI 25-29.99 kg/m2], and obese [BMI ≥30 kg/m2]) and by median BMI, as prespecified in the protocol. RESULTS: Among 7,038 patients randomized and with available BMI, 1,807 (25.7%) were normal weight, 2,927 (41.6%) were overweight, and 2,304 (32.7%) were obese. In normal-weight, overweight, and obese patients, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced the primary endpoint of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (normal weight: HR: 0.48 [95% CI: 0.32-0.73]; overweight: HR: 0.57 [95% CI: 0.41-0.78]; obese: HR: 0.63 [95% CI: 0.44-0.91]; P for interaction = 0.627), without any increase in the composite ischemic endpoint of all-cause death, myocardial infarction, or stroke (normal weight: HR: 1.36 [95% CI: 0.84-2.19]; overweight: HR: 0.92 [95% CI: 0.63-1.35]; obese: HR: 0.84 [95% CI: 0.56-1.25]; P for interaction = 0.290). These findings were consistent with the prespecified analysis by median BMI. CONCLUSIONS: Among high-risk patients undergoing percutaneous coronary intervention, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced bleeding events without any increase in ischemic risk across different BMI categories.
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Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Aspirina/efectos adversos , Índice de Masa Corporal , Quimioterapia Combinada , Hemorragia/inducido químicamente , Humanos , Obesidad/complicaciones , Obesidad/diagnóstico , Sobrepeso/inducido químicamente , Sobrepeso/complicaciones , Sobrepeso/diagnóstico , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticagrelor/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Prior coronary artery bypass graft surgery (CABG) patients undergoing percutaneous coronary intervention (PCI) are often older and present with multiple comorbidities. Ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) has emerged as an effective bleeding-avoidance strategy among high-risk patients. AIMS: We aimed to examine the effects of ticagrelor with or without aspirin in prior CABG patients undergoing PCI within the TWILIGHT trial. METHODS: After 3 months of ticagrelor plus aspirin, patients were randomised to either aspirin or placebo, in addition to ticagrelor, for 12 months and compared by prior CABG status. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The key secondary endpoint was all-cause death, myocardial infarction (MI), or stroke. RESULTS: Out of 7,119 patients, a total of 703 (10.8%) patients had prior CABG within the randomised cohort. Prior CABG patients had more comorbidities and a higher incidence of BARC type 2, 3, or 5 bleeding and death, MI or stroke at 1 year after randomisation, compared with patients without prior CABG. Ticagrelor monotherapy was associated with significantly less BARC 2, 3, or 5 bleeding among prior CABG patients compared with DAPT (4.9% vs 9.6%, hazard ratio [HR] 0.50, 95% confidence interval [CI]: 0.28 to 0.90; pinteraction=0.676) and similar rates of death, MI or stroke (10.0% vs 8.7%, HR 1.14, 95% CI: 0.70 to 1.87; pinteraction=0.484). When comparing target vessel type, treatment effects were consistent among graft- and native-vessel interventions. CONCLUSIONS: In high-risk patients with prior CABG, ticagrelor monotherapy reduced bleeding without compromising ischaemic outcomes compared with ticagrelor plus aspirin.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Humanos , Ticagrelor , Aspirina , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria , Quimioterapia Combinada , Puente de Arteria Coronaria/efectos adversos , Infarto del Miocardio/etiología , Hemorragia/etiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies.
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Síndrome Coronario Agudo , Diabetes Mellitus , Infarto del Miocardio , Enfermedad Arterial Periférica , Humanos , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
INTRODUCTION: The decision to shorten the duration of DAPT following PCI in patients with ACS remains controversial because of the concern for increased ischemic events. METHODS: We performed a comprehensive literature search in seven databases to explore the efficacy of 1 to 3 months of DAPT in patients who underwent PCI for ACS. Randomized controlled trials that compared 1 to 3 months with 6 to 12 months of DAPT after PCI for ACS were identified. Integrated hazard ratio (HR) and 95% confidence interval (CI) were calculated by random effects model for each prespecified outcome of interest. Meta-regression analyses were performed to examine the association of outcomes with select patient characteristics. RESULTS: A total of 9 randomized controlled trials consisting of 25,907 patients were included. There was no difference in the hazard of NACE (HR 0.92, 95% CI 0.79-1.07) and MACE (HR 0.96, 95% CI 0.78-1.17) between 1 and 3 months of DAPT and 6 to 12 months of DAPT. However, implementing 1 to 3 months of DAPT was associated with lower hazard of both any bleeding (HR 0.55, 95% CI 0.46-0.66) and major bleeding (HR 0.47, 95% CI 0.36-0.62). Meta-regression revealed a nonsignificant but increasing trend of both NACE and MACE with greater proportion of left main and left anterior descending coronary artery lesions and greater proportion of STEMI included in the trials. CONCLUSION: Our findings suggest that 1 to 3 months of DAPT has similar efficacy for preventing ischemic events with reduced bleeding risk compared with 6 to 12 months of DAPT.
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Síndrome Coronario Agudo , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Quimioterapia Combinada , Stents Liberadores de Fármacos/efectos adversos , Humanos , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The author recently reported â¼50% excess early mortality in patients with first-presentation ST-segment elevation myocardial infarction (STEMI) without standard modifiable cardiovascular risk factors (SMuRFs); the cause of this is not clear. OBJECTIVES: The aim of this study was to examine differences in infarct characteristics and clinical outcomes in patients with versus without SMuRFs (dyslipidemia, hypertension, diabetes mellitus, and smoking). METHODS: Individual-level data were pooled from 10 randomized percutaneous intervention (PCI) trials in which infarct size was measured within 1 month by either cardiac magnetic resonance or technetium-99m sestamibi single-photon emission computed tomography imaging. First-presentation STEMI was classified into 2 groups according to the presence or absence of at least 1 SMuRF. RESULTS: Among 2,862 patients, 524 (18.3%) were SMuRF-less. After adjusting for study effect, SMuRF-less patients had more frequent poor pre-PCI flow Thrombolysis In Myocardial Infarction 0/1 compared with patients with at least 1 SMuRF (72.0% vs 64.1%; OR: 1.35; 95% CI: 1.08-1.70). There were no independent associations between the presence or absence of SMuRFs at baseline and infarct size (estimate = -0.35; 95% CI: -1.93 to 1.23), left ventricular ejection fraction (estimate = -0.06; 95% CI: -1.33 to 1.20), or mortality at 30 days (HR: 0.46; 95% CI: 0.19-1.07) and 1 year (HR: 0.74; 95% CI: 0.43-1.29). CONCLUSIONS: First-presentation STEMI patients with no identifiable baseline SMuRFs had a higher risk of Thrombolysis In Myocardial Infarction flow grade 0/1 pre-PCI. However, after adjustment, there were no significant associations between SMuRF-less status and infarct size, left ventricle ejection fraction, or mortality.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
Background In clinical trials, cangrelor has been shown to reduce percutaneous coronary intervention-related ischemic complications without increasing major bleeding. This study was performed to examine cangrelor use and transition to oral P2Y12 inhibitors in routine clinical practice. Methods and Results The CAMEO (Cangrelor in Acute Myocardial Infarction: Effectiveness and Outcomes) registry is a multicenter, retrospective observational study of platelet inhibition strategies for patients with myocardial infarction undergoing percutaneous coronary intervention. In phase 1, data were collected on consecutive patients with myocardial infarction (n=482) treated with any P2Y12 inhibitor to understand cangrelor use by hospital. In phase 2, data were collected in a 2:1 (cangrelor-: non-cangrelor-treated) ratio of patients with myocardial infarction (n=873). In phase 1, cangrelor use varied across hospitals (overall, 50.4% [range, 6.0%-100%]). Of patients receiving cangrelor in both phases (n=819), 3.3% received either the bolus or infusion only. Cangrelor was infused for a median of 121 (76-196) minutes; and 38.3% received an infusion for <2 hours. Most patients transitioned from cangrelor to ticagrelor (ticagrelor, 85.3%; clopidogrel, 9.5%; prasugrel, 5.2%). Many patients (16.4%) had a >1-hour gap between cangrelor cessation and oral P2Y12 inhibitor initiation; this was highest among those transitioned to clopidogrel (56.6% versus 34.5% prasugrel versus 10.8% ticagrelor; P<0.001). Only 27.3% were dosed with cangrelor and transitioned to an oral P2Y12 inhibitor in a fashion consistent with the pivotal trials and US Food and Drug Administration label. Conclusions This multicenter registry demonstrated interhospital variability in how cangrelor was administered and transitioned to an oral P2Y12 inhibitor. These findings highlight opportunities for optimization of cangrelor dosing, infusion duration, and transition of care from the catheterization laboratory to the ward setting.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Adenosina Monofosfato/análogos & derivados , Clopidogrel/uso terapéutico , Humanos , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Sistema de Registros , Ticagrelor/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The risk/benefit tradeoff of dual antiplatelet therapy after percutaneous coronary intervention may vary in East Asian patients as compared with their non-East Asian counterparts. METHODS: The double-blind, placebo-controlled, randomized TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) enrolled patients undergoing high-risk percutaneous coronary intervention. After 3 months of treatment with ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding; the key secondary end point was the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Of 9006 enrolled and 7119 randomized patients in TWILIGHT, 1169 patients (13.0%) were enrolled at 27 Chinese sites in this prespecified substudy, of whom 1028 (14.4%) patients were randomized after 3 months. The incidence of the primary end point was 6.2% in the ticagrelor+aspirin group versus 3.5% in the ticagrelor+placebo group between randomization and 1 year (hazard ratio, 0.56 [95% CI, 0.31-0.99]; P=0.048). The key secondary end point occurred in 3.4% of patients in the ticagrelor+aspirin group versus 2.4% in the ticagrelor+placebo group (hazard ratio, 0.70 [95% CI, 0.33-1.46]; P=0.34). There was no interaction between the region of randomization (China versus the rest of the world) and randomized treatment assignment in terms of the primary or key secondary end points. CONCLUSIONS: Ticagrelor monotherapy significantly reduced clinically relevant bleeding without increasing ischemic events as compared with ticagrelor plus aspirin in Chinese patients undergoing high-risk percutaneous coronary intervention. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02270242.