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BACKGROUND: Dual antiplatelet therapy with a potent P2Y12 inhibitor coupled with aspirin for 1 year is the recommended treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). As an alternative, monotherapy with a P2Y12 inhibitor after a short period of dual antiplatelet therapy has emerged as a bleeding reduction strategy. METHODS: We pooled individual patient data from randomized trials that included patients with ACS undergoing PCI treated with an initial 3-month course of dual antiplatelet therapy followed by ticagrelor monotherapy versus continued ticagrelor plus aspirin. Patients sustaining a major ischemic or bleeding event in the first 3 months after PCI were excluded from analysis. The primary outcome was Bleeding Academic Research Consortium type 3 or 5 bleeding occurring between 3 and 12 months after index PCI. The key secondary end point was the composite of death, myocardial infarction, or stroke. Hazard ratios and 95% CIs were generated using Cox regression with a one-stage approach in the intention-to-treat population. RESULTS: The pooled cohort (n=7529) had a mean age of 62.8 years, 23.2% were female, and 55% presented with biomarker-positive ACS. Between 3 and 12 months, ticagrelor monotherapy significantly reduced Bleeding Academic Research Consortium 3 or 5 bleeding compared with ticagrelor plus aspirin (0.8% versus 2.1%; hazard ratio, 0.37 [95% CI, 0.24-0.56]; P<0.001). Rates of all-cause death, myocardial infarction, or stroke were not significantly different between groups (2.4% versus 2.7%; hazard ratio, 0.91 [95% CI, 0.68-1.21]; P=0.515). Findings were unchanged among patients presenting with biomarker-positive ACS. CONCLUSIONS: Among patients with ACS undergoing PCI who have completed a 3-month course of dual antiplatelet therapy, discontinuation of aspirin followed by ticagrelor monotherapy significantly reduced major bleeding without incremental ischemic risk compared with ticagrelor plus aspirin. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42023449646.
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Síndrome Coronario Agudo , Infarto del Miocardio , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Humanos , Femenino , Persona de Mediana Edad , Masculino , Ticagrelor/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Intervención Coronaria Percutánea/efectos adversos , Quimioterapia Combinada , Ensayos Clínicos Controlados Aleatorios como Asunto , Aspirina/efectos adversos , Infarto del Miocardio/terapia , Hemorragia/epidemiología , Accidente Cerebrovascular/epidemiología , Biomarcadores , Resultado del TratamientoRESUMEN
BACKGROUND: Diabetes mellitus (DM) is a modifiable risk factor for patients with coronary artery disease (CAD). Treatment with insulin correlates with advanced disease and has been associated with excess cardiovascular risk, but evidence on outcomes of patients with insulin-treated DM (ITDM) undergoing left main percutaneous coronary intervention (LMPCI) remains scarce. AIMS: The aim of the presented study is to evluate the risk attributable to DM and ITDM in patients undergoing LMPCI. METHODS: We included 869 patients undergoing PCI for unprotected LMCAD. The cohort was divided into three subgroups based on diabetic status: No DM, ITDM, and Non-ITDM. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of death, spontaneous myocardial infarction (MI), or stroke at 1 year. Results were adjusted for clinically relevant baseline characteristics. RESULTS: Amongst participants, 58.7% had no DM, 25.9% non-ITDM, and 15.4% ITDM. Diabetics were younger and more likely to be female. They also exhibited higher body mass index as well as prevalence of comorbidities, including hypertension, anemia, and chronic kidney disease. The number of bifurcation lesions and stents used was similar between groups. At 1 year, when compared to no DM, ITDM (25.4% vs. 10.0%, p < 0.01) but not non-ITDM (10.8% vs. 10.0%, p = 0.94) demonstrated higher MACCE. This finding was driven by increased risk of MI. Mortality was 8.4%, 7.8%, and 17.2% for no DM, Non-ITDM, and ITDM, respectively. Results remained unchanged after adjustment. CONCLUSIONS: In a rather contemporary patient population undergoing PCI for LMCAD, ITDM but not non-ITDM was associated with higher risk of 1-year MACCE, primarily driven by MI.
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Remarkable progress has been made in the pharmacological management of patients with cardiovascular disease, including the frequent use of antithrombotic agents. Nonetheless, bleeding complications remain frequent and potentially life-threatening. Therapeutic interventions relying on prompt antithrombotic drug reversal or removal have been developed to assist clinicians in treating patients with active bleeding or an imminent threat of major bleeding due to urgent surgery or invasive procedures. Early phase studies on these novel strategies have shown promising results using surrogate pharmacodynamic endpoints. However, the benefit of reversing/removing antiplatelet or anticoagulant drugs should always be weighed against the possible prothrombotic effects associated with withdrawal of antithrombotic protection, bleeding, and surgical trauma. Understanding the ischemic-bleeding risk tradeoff of antithrombotic drug reversal and removal strategies in the context of urgent high-risk settings requires dedicated clinical investigations, but challenges in trial design remain, with relevant practical, financial, and ethical implications.
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Enfermedades Cardiovasculares , Fibrinolíticos , Humanos , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Anticoagulantes/efectos adversos , Enfermedades Cardiovasculares/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversosRESUMEN
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. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Intervención Coronaria Percutánea/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Terapia Antiplaquetaria Doble , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with chronic kidney disease (CKD) are at higher risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). Complex PCI (CPCI) is associated with higher rates of ischemic complications. Whether CPCI confers an additive risk of adverse events in CKD patients is unclear. METHODS: Patients who underwent PCI at a single tertiary-care-center between 2012 and 2019 were stratified by CKD status and CPCI. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target-vessel revascularization (TVR) at 1-year follow-up. Secondary outcomes included the individual components of the primary outcome and major bleeding. RESULTS: Out of 15,071 patients, 4537 (30.1%) had CKD and 10,534 (69.9%) had no CKD. Patients undergoing CPCI were 1151 (25.4%) and 2983 (28.3%) in the two cohorts, respectively. At one year, CPCI compared with no CPCI was associated with higher risk of MACE in both CKD (Adj. HR 1.72, 95% confidence interval [CI] 1.45-2.06, p < 0.001) and no-CKD patients (Adj. hazard ratios [HR] 2.19, 95% CI 1.91-2.51, p < 0.001; p of interaction 0.057), determined by an excess of death, MI and TVR in CKD patients and of TVR and MI only in no-CKD. CPCI was related with a consistent increase of major bleeding in the CKD (Adj. HR 1.49, 95% CI 1.18-1.87, p < 0.001) and no-CKD group (Adj. HR 1.23, 95% CI 0.98-1.54, p = 0.071, p of interaction 0.206). CONCLUSION: At 1-year follow-up, CPCI was associated with higher risk of MACE and major bleeding irrespective of concomitant CKD. CPCI predicted mortality in CKD patients only.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Humanos , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Infarto del Miocardio/etiología , Hemorragia/etiología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapiaRESUMEN
OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.
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Enfermedad de la Arteria Coronaria , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Heparina/efectos adversos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Antitrombinas/efectos adversos , Resultado del Tratamiento , Hirudinas/efectos adversos , Hemorragia/inducido químicamente , Fragmentos de Péptidos/efectos adversos , Proteínas Recombinantes/efectos adversosRESUMEN
BACKGROUND: Percutaneous treatment for ostial left circumflex artery (LCx) lesions is known to be associated with suboptimal results. AIMS: The present study aims to assess the procedural and long-term clinical outcomes of percutaneous coronary intervention (PCI) for de novo ostial LCx lesions overall and according to the coronary revascularization strategy. METHODS: Consecutive patients undergoing PCI with second generation drug eluting stents or drug coated balloons for de novo ostial LCx lesions in three high-volume Italian centers between 2012 and 2021 were retrospectively evaluated. The primary endpoint was target-vessel revascularization (TVR) at 2 years. Secondary endpoints included major adverse cardiovascular and cerebrovascular events (MACCE), target lesion revascularization, myocardial infarction, stroke, all-cause death, and repeat revascularization. RESULTS: A total of 366 patients were included in the analysis with a median follow-up of 901 (IQR: 450-1728) days. 79.5% of the patients were male, 33.6% were diabetic, 49.7% had a previous PCI, and 23.1% a prior surgical revascularization. Very ostial LCx stenting was performed in 34.1%, crossover from left main to LCx in 17.3%, and a two-stent strategy in 48.6% of cases, respectively. In the overall population, the incidence of TVR at 2 years was 19.0% while MACCE rate was 25.7%. No major differences in clinical outcomes were found according to the stenting strategy. Use of intracoronary imaging was associated with fewer MACCE (HR: 0.47, 95% CI: 0.25-1.13, p = 0.01), while the diameter of the stent implanted in the ostial LCx was associated with less TVR (HR: 0.43, 95% CI: 0.25-0.75, p = 0.002). CONCLUSIONS: Percutaneous revascularization of the ostial LCx is associated with a high rate of TVR, regardless of the stenting strategy. Intracoronary imaging and proper stent sizing may reduce the failure rates.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Masculino , Femenino , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/etiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Angiografía Coronaria/métodosRESUMEN
BACKGROUND: Contrast-associated acute kidney injury can occur after percutaneous coronary intervention (PCI). Prediction of the contrast-associated acute kidney injury risk is important for a tailored prevention and mitigation strategy. We sought to develop a simple risk score to estimate contrast-associated acute kidney injury risk based on a large contemporary PCI cohort. METHODS: Consecutive patients undergoing PCI at a large tertiary care centre between Jan 1, 2012, and Dec 31, 2020, with available creatinine measurements both before and within 48 h after the procedure, were included; only patients on chronic dialysis were excluded. Patients treated between 2012 and 2017 comprised the derivation cohort and those treated between 2018 and 2020 formed the validation cohort. The primary endpoint was contrast-associated acute kidney injury, defined according to the Acute Kidney Injury Network. Independent predictors of contrast-associated acute kidney injury were derived from multivariate logistic regression analysis. Model 1 included only pre-procedural variables, whereas Model 2 also included procedural variables. A weighted integer score based on the effect estimate of each independent variable was used to calculate the final risk score for each patient. The impact of contrast-associated acute kidney injury on 1-year deaths was also evaluated. FINDINGS: 32â378 PCI procedures were performed and screened for inclusion in the present analysis. After the exclusion of patients without paired creatinine measurements, patients on chronic dialysis, and multiple procedures, 14â616 patients were included in the derivation cohort (mean age 66·2 years, 29·2% female) and 5606 were included in the validation cohort (mean age 67·0 years, 26·4% female). Contrast-associated acute kidney injury occurred in 860 (4·3%) patients. Independent predictors of contrast-associated acute kidney injury included in Model 1 were: clinical presentation, estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, haemoglobin, basal glucose, congestive heart failure, and age. Additional independent predictors in Model 2 were: contrast volume, peri-procedural bleeding, no flow or slow flow post procedure, and complex PCI anatomy. The occurrence of contrast-associated acute kidney injury in the derivation cohort increased gradually from the lowest to the highest of the four risk score groups in both models (2·3% to 34·9% in Model 1, and 2·0% to 38·8% in Model 2). Inclusion of procedural variables in the model only slightly improved the discrimination of the risk score (C-statistic in the derivation cohort: 0·72 for Model 1 and 0·74 for model 2; in the validation cohort: 0·84 for Model 1 and 0·86 for Model 2). The risk of 1-year deaths significantly increased in patients with contrast-associated acute kidney injury (10·2% vs 2·5%; adjusted hazard ratio 1·76, 95% CI 1·31-2·36; p=0·0002), which was mainly due to excess 30-day deaths. INTERPRETATION: A contemporary simple risk score based on readily available variables from patients undergoing PCI can accurately discriminate the risk of contrast-associated acute kidney injury, the occurrence of which is strongly associated with subsequent death. FUNDING: None.
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Lesión Renal Aguda/inducido químicamente , Medios de Contraste/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Medición de Riesgo/métodos , Lesión Renal Aguda/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Centros de Atención TerciariaRESUMEN
Historically, prevention from ischemic events with dual antiplatelet therapy (DAPT) post percutaneous coronary intervention (PCI) took precedence over protection from bleeding. However, increasing data suggest that major bleeding complications are as detrimental as ischemic events. Awareness about the prognostic impact of bleeding prompted the search for new strategies aimed at maximizing both ischemic and bleeding protection. This is noteworthy because patients at high bleeding risk (HBR) have generally been underrepresented in clinical trials on DAPT and they often are at increased risk of ischemic events as well. The present review discusses the evidence base for new pharmacotherapeutic strategies to decrease bleeding risk without compromising ischemic protection among HBR patients undergoing PCI, including shortening DAPT duration, early aspirin withdrawal, and P2Y 12 inhibitor de-escalation.
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Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) are at increased risk for thrombotic and bleeding complications compared to patients with chronic coronary syndrome (CCS). The academic research consortium (ARC) recently suggested a set of criteria to identify patients at high bleeding risk (HBR). We sought to evaluate the performance of the ARC-HBR criteria among patients undergoing PCI according to clinical presentation. We included all consecutive patients undergoing PCI at a tertiary-care center. Patients were deemed at HBR if they fulfilled ≥ 1 major or ≥ 2 minor ARC-HBR criteria. The primary bleeding endpoint was a composite of in-hospital or post-discharge bleeding at 1-year follow-up. Secondary outcomes included all-cause death and myocardial infarction. Out of 6068 patients, 1391 (22.9 %) presented with AMI and were more often at HBR than those with CCS (46.9 % vs. 43.0 %, p = 0.01). HBR patients had a higher risk for the primary bleeding endpoint than non-HBR, irrespective of the clinical indication for PCI (AMI: 19.5 % vs. 5.5 %; HR 3.86, 95 % CI 2.63-5.69; CCS: 6.8 % vs. 2.6 %; HR 2.65, 95 % CI 1.92-3.68; p-interaction = 0.11). Secondary outcomes followed a similar trend. After multivariable adjustment, AMI presentation remained significantly associated with increased risk for bleeding at 1 year (HR 1.64, 95 % CI 1.13-2.38, p = 0.01). The ARC-HBR criterion associated with the highest bleeding risk was severe/end-stage chronic kidney disease in AMI and moderate/severe anemia in CCS. The ARC-HBR framework successfully identified AMI and CCS patients with increased risk for bleeding complications at 1 year post-PCI. Figure prepared with BioRender.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Cuidados Posteriores , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/cirugía , Alta del Paciente , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Perioperative cardiovascular complications are important causes of morbidity and mortality associated with non-cardiac surgery, especially in patients with recent percutaneous coronary intervention (PCI). We aimed to illustrate the types and timing of different surgeries occurring after PCI, and to evaluate the risk of thrombotic and bleeding events according to the perioperative antiplatelet management. Patients undergoing urgent or elective non-cardiac surgery within 1 year of PCI at a tertiary-care center between 2011 and 2018 were included. The primary outcome was major adverse cardiac events (MACE; composite of death, myocardial infarction, or stent thrombosis) at 30 days. Perioperative bleeding was defined as ≥ 2 units of blood transfusion. A total of 1092 surgeries corresponding to 747 patients were classified by surgical risk (low: 50.9%, intermediate: 38.4%, high: 10.7%) and priority (elective: 88.5%, urgent/emergent: 11.5%). High-risk and urgent/emergent surgeries tended to occur earlier post-PCI compared to low-risk and elective ones, and were associated with an increased risk of both MACE and bleeding. Preoperative interruption of antiplatelet therapy (of any kind) occurred in 44.6% of all NCS and was more likely for procedures occurring later post-PCI and at intermediate risk. There was no significant association between interruption of antiplatelet therapy and adverse cardiac events. Among patients undergoing NCS within 1 year of PCI, perioperative ischemic and bleeding events primarily depend on the estimated surgical risk and urgency of the procedure, which are increased early after PCI. Preoperative antiplatelet interruption was not associated with an increased risk of cardiac events.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Procedimientos Quirúrgicos Electivos/efectos adversos , Hemorragia/inducido químicamente , Humanos , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/efectos adversos , Resultado del TratamientoRESUMEN
Since its introduction in 1977, percutaneous coronary intervention has become one of the most commonly performed therapeutic procedures worldwide. Such widespread diffusion, however, would have not been possible without a concomitant evolution of the pharmacotherapies associated with this intervention. Antithrombotic agents are fundamental throughout the management of patients undergoing coronary stent implantation, starting from the procedure itself to the long-term prevention of cardiovascular events. The last 40 years of interventional cardiology have seen remarkable improvements in both drug therapies and device technologies, which largely reflected a progressive understanding of the pathophysiological mechanisms of coronary artery disease, as well as procedure- and device-related adverse events. The purpose of this article is to provide an overview of the important milestones in antithrombotic pharmacology that have shaped clinical practice of today while also providing insights into knowledge gaps and future directions.
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Fibrilación Atrial , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Quimioterapia Combinada , Fibrinolíticos/uso terapéutico , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , StentsRESUMEN
AIMS: Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population. METHODS AND RESULTS: This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status. CONCLUSIONS: Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.
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Intervención Coronaria Percutánea , Quimioterapia Combinada , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticagrelor/efectos adversos , Resultado del TratamientoRESUMEN
AIMS: The aim of this study was to assess the impact of chronic kidney disease (CKD) on the safety and efficacy of ticagrelor monotherapy among patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In this prespecified subanalysis of the TWILIGHT trial, we evaluated the treatment effects of ticagrelor with or without aspirin according to renal function. The trial enrolled patients undergoing drug-eluting stent implantation who fulfilled at least one clinical and one angiographic high-risk criterion. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was a clinical study entry criterion. Following a 3-month period of ticagrelor plus aspirin, event-free patients were randomly assigned to aspirin or placebo on top of ticagrelor for an additional 12 months. Of the 6835 patients randomized and with available eGFR at baseline, 1111 (16.3%) had CKD. Ticagrelor plus placebo reduced the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding as compared with ticagrelor plus aspirin in both patients with [4.6% vs. 9.0%; hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.80] and without (4.0% vs. 6.7%; HR 0.59, 95% CI 0.47-0.75; Pinteraction = 0.508) CKD, but the absolute risk reduction was greater in the former group. Rates of death, myocardial infarction, or stroke were not significantly different between the two randomized groups irrespective of the presence (7.9% vs. 5.7%; HR 1.40, 95% CI 0.88-2.22) or absence of (3.2% vs. 3.6%; HR 0.90, 95% CI 0.68-1.20; Pinteraction = 0.111) CKD. CONCLUSION: Among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events as compared with ticagrelor plus aspirin.
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Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Quimioterapia Combinada , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Ticagrelor/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. METHODS: In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). FINDINGS: A total of nine randomised trials were identified and included in this study, and 42â108 patients randomly allocated to a P2Y12 inhibitor (n=21â043) or aspirin (n=21â065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. INTERPRETATION: Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. FUNDING: Italian Ministry of Education.
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Aspirina/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ticagrelor/uso terapéutico , Ticlopidina/uso terapéutico , Anciano , Aterosclerosis/complicaciones , Trastornos Cerebrovasculares/tratamiento farmacológico , Enfermedad Coronaria/tratamiento farmacológico , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Enfermedad Arterial Periférica/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Prevención Secundaria/métodos , Accidente Cerebrovascular/prevención & controlRESUMEN
Dual antiplatelet therapy (DAPT) is key for the prevention of recurrent ischemic events after percutaneous coronary intervention (PCI); however, it increases the risk of bleeding complications. While new generation drug-eluting stents have been shown superior to bare-metal stents after a short DAPT course, the optimal DAPT duration in patients at high bleeding risk (HBR) remains to be determined. TRIAL DESIGN: The XIENCE Short DAPT program consists of three prospective, single-arm studies (XIENCE 90, XIENCE 28 Global and XIENCE 28 USA) investigating 3- or 1-month DAPT durations in HBR patients undergoing PCI with the XIENCE stent. The XIENCE 90 study is being conducted in the US and enrolled 2047 subjects who discontinued DAPT at 3 months if they were free from myocardial infarction (MI), repeat coronary revascularization, stroke, or stent thrombosis. The XIENCE 28 program includes the USA study, enrolling 642 patients in US and Canada, and the Global study, enrolling 963 patients in Europe and Asia. In XIENCE 28, patients were to discontinue DAPT at 1 month post-PCI if event-free. The primary hypothesis for both XIENCE 90 and XIENCE 28 is that a short DAPT regimen will be non-inferior to a conventional DAPT duration with respect to the composite of all-cause death or MI. Patients enrolled in the prospective multicenter post-market XIENCE V USA study will be used as historical control group in a stratified propensity-adjusted analysis. CONCLUSIONS: The XIENCE Short DAPT Program will provide insights into the safety and efficacy of 2 abbreviated DAPT regimens of 3- and 1-month duration in a large cohort of HBR patients undergoing PCI with the XIENCE stent.
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Síndrome Coronario Agudo/tratamiento farmacológico , Aspirina/administración & dosificación , Stents Liberadores de Fármacos , Everolimus/administración & dosificación , Inmunosupresores/administración & dosificación , Infarto del Miocardio/prevención & control , Inhibidores de Agregación Plaquetaria/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Aspirina/efectos adversos , Canadá , Causas de Muerte , Esquema de Medicación , Stents Liberadores de Fármacos/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Humanos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Accidente Cerebrovascular , Trombosis , Estados UnidosRESUMEN
OBJECTIVE: It is still debated if benefits associated with radial versus femoral access for coronary angiography and percutaneous coronary interventions (PCI) are due to the access site selection itself, operator expertise or other underlying mechanisms. METHODS: We searched PubMed, Embase, and meeting abstracts for randomized trials comparing radial versus femoral access site for coronary angiography and PCI. Primary safety endpoint was major bleeding. Coprimary efficacy endpoints were stroke and myocardial infarction (MI). This study is registered with PROSPERO. RESULTS: We identified 31 trials (30,096 patients, PCI performed in 21,225 patients). Radial compared to femoral access was associated with a significant risk reduction in major bleeding (OR 0.53, 95%CI 0.42-0.66, I2 = 3.3%). Findings were consistent regardless of clinical characteristics or whether coronary angiography was performed with or without PCI. The benefit of radial access was significantly increased in studies published before 2010 and in patients with chronic coronary syndrome. Risk for stroke (OR 1.11, 95%CI 0.76-1.64, I2 = 0%) and MI (OR 0.90, 95%CI 0.79-1.04, I2 = 0%) were comparable between the groups. Risk for mortality and vascular complications were significantly lower with radial than femoral access. CONCLUSION: In patients undergoing coronary angiography and PCI, radial access is associated with a significant risk reduction in bleeding, vascular complications, and mortality compared to femoral access. The risk of stroke or MI were comparable in patients with radial or femoral access.
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Cateterismo Periférico , Intervención Coronaria Percutánea , Cateterismo Periférico/efectos adversos , Arteria Femoral/diagnóstico por imagen , Humanos , Intervención Coronaria Percutánea/efectos adversos , Arteria Radial/diagnóstico por imagen , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Women with acute coronary syndrome (ACS) generally present with more comorbidities and experience worse clinical outcomes compared with males. However, it is unclear whether this represents genuine sex-related difference or stems from clinical, procedural and socioeconomic factors. METHODS: We analyzed consecutive patients undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), non-STEMI or unstable angina at a single tertiary-care center. Exclusion criteria were unknown sex, age < 18 years and PCI with bare metal stent or without stent placement. The study population was stratified according to sex. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) defined as the composite of death, spontaneous myocardial infarction, or stroke at 1 year. Secondary endpoints were individual components of MACCE, target vessel revascularization (TVR) and clinically significant bleeding. RESULTS: Of the 7362 patients included, 5031 (68.3%) were men and 2331 (31.7%) women. Women were older and presented with a higher burden of comorbidities while men had more complex coronary anatomy. The incidence of 1 year MACCE was significantly higher among women (8.0% versus 5.6%; p < 0.01) compared to men. Women also experienced a higher rate of bleeding (2.3% vs. 1.4%; p = 0.02) while there were no differences between groups in terms of TVR (8.1% vs. 7.8%; p-value = 0.83). Differences in outcomes were attenuated after multivariable adjustment. Findings were consistent across ACS subgroups. CONCLUSIONS: In a contemporary ACS population treated with drug-eluting stents, women experienced a higher crude rate of 1-year MACCE. This was no longer apparent after accounting for baseline imbalances.
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Síndrome Coronario Agudo , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/cirugía , Adolescente , Femenino , Humanos , Masculino , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the prognostic impact of anemia in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: Whether the periprocedural use of bivalirudin as compared with UFH in anemic patients undergoing TAVR has an impact on outcomes remains unknown. METHODS: The BRAVO-3 trial compared the use of bivalirudin versus UFH in 802 high risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence (defined as hemoglobin levels <13 g/dl in men and <12 g/dl in women) or absence of anemia. The primary outcomes were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or bleeding) and major bleeding (Bleeding Academic Research Consortium ≥3b) at 30 days. RESULTS: Among 798 patients with available baseline hemoglobin levels, 427 (54%) were anemic of whom 221 (52%) received bivalirudin. There were no significant differences in NACE and major bleeding at 30 days between patients with and without anemia, irrespective of the type of anticoagulant used (pinteraction = 0.71 for NACE, pinteraction = 1.0 for major bleeding). However, anemic patients had a higher risk of major vascular complications (adjusted OR 2.43, 95% CI 1.42-4.16, p = 0.001), and acute kidney injury (adjusted OR 1.74, 95% CI 1.16-2.59, p = 0.007) compared to non-anemic patients at 30 days. CONCLUSIONS: Anemia was not associated with a higher risk of NACE or major bleeding at 30 days after TAVR without modification of the treatment effects of periprocedural anticoagulation with bivalirudin versus UFH.
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Anemia , Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Anemia/diagnóstico , Antitrombinas , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Femenino , Heparina , Humanos , Masculino , Nitrilos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the impact of ischemic and bleeding risk factors on long-term clinical outcomes of patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) with everolimus-eluting stents. BACKGROUND: Second-generation drug-eluting stents have substantially improved outcomes after PCI in the general population; however, DM patients continue to experience high rates of ischemic and bleeding complications. METHODS: DM patients from the pooled XIENCE V registry were divided into high or low bleeding and ischemic risk groups (HBR, LBR, HIR, and LIR) based on established bleeding (age ≥ 75 years; chronic kidney disease; anemia; prior stroke; oral anticoagulation; thrombocytopenia; prior major bleeding) and ischemic (acute coronary syndrome; prior myocardial infarction [MI]; ≥3 stents implanted; ≥3 vessels treated; ≥3 lesions treated; stent length > 60 mm; bifurcation treated with ≥2 stents; chronic total occlusion) risk factors. The primary outcomes were major adverse cardiac events (MACE; cardiac death, MI, or stent thrombosis) and major bleeding at 4-year follow-up. RESULTS: A total of 3,704 DM patients were divided into four groups (21.5% LBR/LIR; 39.0% LBR/HIR; 15.6% HBR/LIR; 23.9% HBR/HIR). Compared with LBR/LIR patients, those at HBR/HIR and HBR/LIR had a significantly higher risk of MACE (HR (95% CI) 2.7 (1.9-3.9) and 2.2 (1.5-3.2), respectively) and major bleeding (2.7 (1.6-4.8) and 2.6 (1.4-4.7), respectively), while LBR/HIR patients did not. CONCLUSIONS: Among DM patients undergoing PCI, presence of bleeding risk factors was associated with a higher risk of both ischemic and bleeding events, whereas commonly used features of ischemic risk did not impact long-term clinical outcomes.