Abbreviated or Standard Dual Antiplatelet Therapy by Sex in Patients at High Bleeding Risk: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: Abbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI). Objectives: To evaluate the association of sex with the comparative effectiveness of abbreviated vs standard DAPT in patients with HBR. Design, Setting, and Patients: This prespecified subgroup comparative effectiveness analysis followed the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated vs Standard DAPT Regimen (MASTER DAPT) trial, a multicenter, randomized, open-label clinical trial conducted at 140 sites in 30 countries and performed from February 28, 2017, to December 5, 2019. A total of 4579 patients with HBR were randomized at 1 month after PCI to abbreviated or standard DAPT. Data were analyzed from July 1 to October 31, 2022. Interventions: Abbreviated (immediate DAPT discontinuation, followed by single APT for ≥6 months) or standard (DAPT for ≥2 additional months, followed by single APT for 11 months) treatment groups. Main Outcomes and Measures: One-year net adverse clinical events (NACEs) (a composite of death due to any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCEs) (a composite of death due to any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding (MCB). Results: Of the 4579 patients included in the analysis, 1408 (30.7%) were women and 3171 (69.3%) were men (mean [SD] age, 76.0 [8.7] years). Ischemic and bleeding events were similar between sexes. Abbreviated DAPT was associated with comparable NACE rates in men (hazard ratio [HR], 0.97 [95% CI, 0.75-1.24]) and women (HR, 0.87 [95% CI, 0.60-1.26]; P = .65 for interaction). There was evidence of heterogeneity of treatment effect by sex for MACCEs, with a trend toward benefit in women (HR, 0.68 [95% CI, 0.44-1.05]) but not in men (HR, 1.17 [95% CI, 0.88-1.55]; P = .04 for interaction). There was no significant interaction for MCB across sex, although the benefit with abbreviated DAPT was relatively greater in men (HR, 0.65 [95% CI, 0.50-0.84]) than in women (HR, 0.77 [95% CI, 0.53-1.12]; P = .46 for interaction). Results remained consistent in patients with acute coronary syndrome and/or complex PCI. Conclusions and Relevance: These findings suggest that women with HBR did not experience higher rates of ischemic or bleeding events compared with men and may derive particular benefit from abbreviated compared with standard DAPT owing to these numerically lower rates of events. Trial Registration: ClinicalTrials.gov Identifier: NCT03023020.

Abbreviated or Standard Antiplatelet Therapy in HBR Patients: Final 15-Month Results of the MASTER-DAPT Trial.

BACKGROUND: Clinical outcomes and treatment selection after completing the randomized phase of modern trials, investigating antiplatelet therapy (APT) after percutaneous coronary intervention (PCI), are unknown. OBJECTIVES: The authors sought to investigate cumulative 15-month and 12-to-15-month outcomes after PCI during routine care in the MASTER DAPT trial. METHODS: The MASTER DAPT trial randomized 4,579 high bleeding risk patients to abbreviated (n = 2,295) or standard (n = 2,284) APT regimens. Coprimary outcomes were net adverse clinical outcomes (NACE) (all-cause death, myocardial infarction, stroke, and BARC 3 or 5 bleeding); major adverse cardiac and cerebral events (MACCE) (all-cause death, myocardial infarction, and stroke); and BARC type 2, 3, or 5 bleeding. RESULTS: At 15 months, prior allocation to a standard APT regimen was associated with greater use of intensified APT; NACE and MACCE did not differ between abbreviated vs standard APT (HR: 0.92 [95% CI: 0.76-1.12]; P = 0.399 and HR: 0.94 [95% CI: 0.76-1.17]; P = 0.579; respectively), as during the routine care period (HR: 0.81 [95% CI: 0.50-1.30]; P = 0.387 and HR: 0.74 [95% CI: 0.43-1.26]; P = 0.268; respectively). BARC 2, 3, or 5 was lower with abbreviated APT at 15 months (HR: 0.68 [95% CI: 0.56-0.83]; P = 0.0001) and did not differ during the routine care period. The treatment effects during routine care were consistent with those observed within 12 months after PCI. CONCLUSIONS: At 15 months, NACE and MACCE did not differ in the 2 study groups, whereas the risk of major or clinically relevant nonmajor bleeding remained lower with abbreviated compared with standard APT. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

Effect of Routine Invasive vs Conservative Strategy in Older Adults With Frailty and Non-ST-Segment Elevation Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance: To our knowledge, no randomized clinical trial has compared the invasive and conservative strategies in frail, older patients with non-ST-segment elevation acute myocardial infarction (NSTEMI). Objective: To compare outcomes of invasive and conservative strategies in frail, older patients with NSTEMI at 1 year. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted at 13 Spanish hospitals between July 7, 2017, and January 9, 2021, and included 167 older adult (≥70 years) patients with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. Data analysis was performed from April 2022 to June 2022. Interventions: Patients were randomized to routine invasive (coronary angiography and revascularization if feasible; n = 84) or conservative (medical treatment with coronary angiography for recurrent ischemia; n = 83) strategy. Main Outcomes and Measures: The primary end point was the number of days alive and out of the hospital (DAOH) from discharge to 1 year. The coprimary end point was the composite of cardiac death, reinfarction, or postdischarge revascularization. Results: The study was prematurely stopped due to the COVID-19 pandemic when 95% of the calculated sample size had been enrolled. Among the 167 patients included, the mean (SD) age was 86 (5) years, and mean (SD) Clinical Frailty Scale score was 5 (1). While not statistically different, DAOH were about 1 month (28 days; 95% CI, -7 to 62) greater for patients managed conservatively (312 days; 95% CI, 289 to 335) vs patients managed invasively (284 days; 95% CI, 255 to 311; P = .12). A sensitivity analysis stratified by sex did not show differences. In addition, we found no differences in all-cause mortality (hazard ratio, 1.45; 95% CI, 0.74-2.85; P = .28). There was a 28-day shorter survival in the invasive vs conservatively managed group (95% CI, -63 to 7 days; restricted mean survival time analysis). Noncardiac reasons accounted for 56% of the readmissions. There were no differences in the number of readmissions or days spent in the hospital after discharge between groups. Neither were there differences in the coprimary end point of ischemic cardiac events (subdistribution hazard ratio, 0.92; 95% CI, 0.54-1.57; P = .78). Conclusions and Relevance: In this randomized clinical trial of NSTEMI in frail older patients, there was no benefit to a routine invasive strategy in DAOH during the first year. Based on these findings, a policy of medical management and watchful observation is recommended for older patients with frailty and NSTEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03208153.

Impact of operators experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry.

BACKGROUND: The Watchman FLX is a device upgrade of the Watchman 2.5 that incorporates several design enhancements intended to simplify left atrial appendage occlusion (LAAO) and improve procedural outcomes. This study compares peri-procedural results of LAAO with Watchman FLX (Boston Scientific, Marlborough, Massachusetts) in centers with varying degrees of experience with the Watchman 2.5 and Watchman FLX. METHODS: Prospective, multicenter, "real-world" registry including consecutive patients undergoing LAAO with the Watchman FLX at 26 Spanish sites (FLX-SPA registry). Implanting centers were classified according to the center's prior experience with the Watchman 2.5. A further division of centers according to whether or not they had performed ≤ 10 or > 10Watchman FLX implants was prespecified at the beginning of the study. Procedural outcomes of institutions stratified according to their experience with the Watchman 2.5 and FLX devices were compared. RESULTS: 359 patients [mean age 75.5 (SD8.1), CHA2DS2-VASc 4.4 (SD1.4), HAS-BLED 3.8(SD0.9)] were included. Global success rate was 98.6%, successful LAAO with the first selected device size was achieved in 95.5% patients and the device was implanted at first attempt in 78.6% cases. There were only 9(2.5%) major peri-procedural complications. No differences in efficacy or safety results according to the centers previous experience with Watchman 2.5 and procedural volume with Watchman FLX existed. CONCLUSIONS: The Watchman FLX attains high procedural success rates with complete LAA sealing in unselected, real-world patients, along with a low incidence of peri-procedural complications, regardless of operators experience with its previous device iteration or the number of Watchman FLX devices implanted.

Estrategia invasiva frente a conservadora en pacientes frágiles con IAMSEST. Diseño del ensayo clínico MOSCA-FRAIL / Invasive versus conservative strategy in frail patients with NSTEMI: the MOSCA-FRAIL clinical trial study design

Introducción y objetivos: Aunque las guías de práctica clínica recomiendan una estrategia invasiva para el infarto agudo de miocardio sin elevación del segmento ST (IAMSEST), en la práctica clínica esta estrategia se infrautiliza en ancianos frágiles. Además estos enfermos habitualmente quedan excluidos de los ensayos clínicos, por lo que la evidencia es escasa. Nuestra hipótesis es que una estrategia invasiva para el anciano con fragilidad y IAMSEST mejorará el pronóstico. Métodos: Se trata de un estudio prospectivo, multicéntrico y aleatorizado que compara una estrategia invasiva frente a una conservadora en ancianos frágiles con IAMSEST. Los criterios de inclusión son: IAMSEST, edad ≥ 70 años y fragilidad definida por al menos 4 criterios de la escala Clinical Frailty Scale. Se aleatorizará a los participantes a una estrategia invasiva (coronariografía y revascularización si se considera anatómicamente indicada) o conservadora (tratamiento médico y coronariografía solo en caso de inestabilidad clínica persistente). El objetivo principal será el número de días vivo fuera del hospital durante el primer año. El objetivo coprincipal será el tiempo hasta la presentación de muerte cardiovascular, reinfarto agudo de miocardio o revascularización tras el alta. El tamaño de la muestra estimado es de 178 pacientes (89 por grupo), asumiendo un incremento del 20% en la proporción de días vivo fuera del hospital con la estrategia invasiva. Resultados: Los resultados del estudio aportarán información novedosa para el tratamiento del anciano frágil con IAMSEST. Conclusiones: Nuestra hipótesis es que una estrategia invasiva mejorará el pronóstico de los pacientes ancianos frágiles con IAMSEST. Si esta hipótesis se confirmara, la situación de fragilidad no debería disuadir al cardiólogo de indicar un tratamiento invasivo. Ensayo registrado en ClinicalTrials.gov (Identificador: NCT03208153)

Introduction and objectives: Although clinical guidelines recommend invasive management in non-ST-segment elevation myocardial infarction (NSTEMI), this strategy is underused in frail elderly patients in the real world. Furthermore, these patients are underrepresented in clinical trials and therefore the evidence is scarce. Our hypothesis is that an invasive strategy will improve prognosis in elderly frail patients with NSTEMI. Methods: This will be a prospective, multicenter, randomized trial, in which the conservative and invasive strategies will be compared in patients meeting all of the following inclusion criteria: NSTEMI diagnosis, age ≥ 70 years, and frailty defined by a category ≥ 4 in the Clinical Frailty Scale. Participants will be randomized to an invasive (coronary angiogram and revascularization if anatomically amenable) or conservative (medical treatment and coronary angiogram only if persistent clinical instability) strategy. The primary endpoint will be the number of days alive out of hospital during the first year. The coprimary endpoint will be the time until the first cardiac event (cardiac death, reinfarction or postdischarge revascularization). We estimate a sample size of 178 patients (89 per arm), considering an increase of 20% in the proportion of days alive out of hospital with the invasive management. Results: The results of this study will add important knowledge to inform the management of frail elderly patients hospitalized with NSTEMI. Conclusions: We hypothesize that the invasive strategy will improve outcomes in frail elderly patients with NSTEMI. If this is confirmed, frailty status should not dissuade physicians from implementing an invasive management strategy. Clinical trial registration: URL: http://www.clinicaltrials.gov .Identifier: NCT03208153

Invasive Versus Conservative Strategy in Frail Patients With NSTEMI: The MOSCA-FRAIL Clinical Trial Study Design.

INTRODUCTION AND OBJECTIVES: Although clinical guidelines recommend invasive management in non-ST-segment elevation myocardial infarction (NSTEMI), this strategy is underused in frail elderly patients in the real world. Furthermore, these patients are underrepresented in clinical trials and therefore the evidence is scarce. Our hypothesis is that an invasive strategy will improve prognosis in elderly frail patients with NSTEMI. METHODS: This will be a prospective, multicenter, randomized trial, in which the conservative and invasive strategies will be compared in patients meeting all of the following inclusion criteria: NSTEMI diagnosis, age ≥ 70 years, and frailty defined by a category ≥ 4 in the Clinical Frailty Scale. Participants will be randomized to an invasive (coronary angiogram and revascularization if anatomically amenable) or conservative (medical treatment and coronary angiogram only if persistent clinical instability) strategy. The primary endpoint will be the number of days alive out of hospital during the first year. The coprimary endpoint will be the time until the first cardiac event (cardiac death, reinfarction or postdischarge revascularization). We estimate a sample size of 178 patients (89 per arm), considering an increase of 20% in the proportion of days alive out of hospital with the invasive management. RESULTS: The results of this study will add important knowledge to inform the management of frail elderly patients hospitalized with NSTEMI. CONCLUSIONS: We hypothesize that the invasive strategy will improve outcomes in frail elderly patients with NSTEMI. If this is confirmed, frailty status should not dissuade physicians from implementing an invasive management strategy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.Identifier: NCT03208153.

Systematic isolated post-dilatation of the side branch as part of the provisional stent technique in the percutaneous treatment of coronary bifurcations. CR12 Registry.

AIMS: To analyse systematic isolated post-dilatation of the side branch as a part of provisional stent technique. METHODS: 1960 angioplasties performed in two centres were prospectively registered, of which 382 were coronary bifurcations with a side branch>2mm. In centre A, isolated post-dilatation of the side branch was performed regardless its impairment after main vessel stenting. In centre B, side branch post-dilatation was performed only if it was severely affected after stent implantation. RESULTS: There was no difference between the two centres in the rate of side branch affection after stent implantation (A: 44.6 vs B: 49.3%, p=0.48) nor in the procedural success rate (A: 98.6% vs B: 96.7%, p=0.45). After one-year follow-up, a reduction of cardiovascular events was observed in centre A (A: 4.4% vs B: 10.4%, p=0.043) with a trend towards lower cardiac mortality (A: 2.2% vs B: 6.5%, p=0.093) and stent thrombosis (A: 0% vs B: 2.6%, p=0.077). There were no differences in the rate of myocardial infarction related to the treated artery (A: 1.4% vs B: 3.9%, p=0.29), or target lesion revascularization (A: 1.4% vs. B: 3.2%, p=0.45). CONCLUSIONS: Systematic isolated post-dilatation of the side branch in the provisional stent technique was associated with a high angiographic success rate, and a low rate of cardiovascular events during follow-up. Although the study design does not allow definitive conclusions, this strategy could be considered a valid option in some cases or even as part of the provisional stent technique.

Comparison of iodixanol and ioversol for the prevention of contrast-induced nephropathy in diabetic patients after coronary angiography or angioplasty.

INTRODUCTION AND OBJECTIVES: This study was designed to compare differences in the incidence of contrast-induced nephropathy (CIN) and changes in serum creatinine (SCr) level following iso-osmolar iodixanol or low-osmolar ioversol administration in diabetic patients undergoing coronary angiography, with or without percutaneous coronary intervention (PCI). A number of studies have indicated that iodixanol reduces the risk of CIN in patients with renal impairment, with or without diabetes. Diabetic patients may have some degree of renal dysfunction despite having a normal SCr level. METHODS: The study included 250 consecutive diabetic patients undergoing coronary angiography with or without PCI. Those enrolled during the first 7 months of the study received ioversol and those enrolled during the following 11 months received iodixanol. The primary study endpoint was the incidence of CIN. Secondary objectives were to identify independent predictors of CIN and to determine the mean increase in SCr 72 hours after contrast injection. RESULTS: The overall incidence of CIN was 5.6%. The incidence of CIN was significantly lower with iodixanol than with ioversol (2.5% vs. 8.3%, respectively; odds ratio [OR]=0.255; 95% confidence interval [CI], 0.068-0.952; P=.047). A low estimated glomerular filtration rate (60.8+/-29 mL/min per 1.73 m2 in those with CIN vs. 75.3+/-25 mL/min per 1.73 m2 in those without; OR=0.975; 95% CI, 0.952-0.997; P=.03) and ioversol use were independent predictors of CIN. CONCLUSIONS: In diabetic patients undergoing diagnostic coronary angiography with or without PCI, the iso-osmolar contrast medium iodixanol was associated with a lower incidence of CIN than low-osmolar ioversol.

Comparación de iodixanol frente a ioversol en la prevención de la nefropatía por contraste tras coronariografía o angioplastia en pacientes diabéticos / Comparison of iIodixanol and ioversol for the prevention of contrast-induced nephropathy in diabetic patients after coronary angiography or angioplasty

Introducción y objetivos. Este estudio se diseñó para comparar la incidencia de nefropatía por contraste (NC) y los cambios en la creatinina sérica (CrS) tras el uso del contraste isoosmolar iodixanol o el contraste de baja osmolaridad ioversol en pacientes diabéticos sometidos a coronariografía y/o intervención coronaria percutánea (ICP). Algunos estudios indican que el iodixanol reduce el riesgo de NC en pacientes con disfunción renal, con o sin diabetes. Los pacientes diabéticos pueden tener cierto grado de disfunción renal a pesar de tener niveles normales de CrS. Métodos. Se incluyeron 250 pacientes diabéticos consecutivos a los que se realizó coronariografía y/o ICP. Los pacientes incluidos durante los primeros 7 meses del estudio recibieron ioversol, y los incluidos en los siguientes 11 meses recibieron iodixanol. El objetivo primario del estudio fue la incidencia de NC. Los predictores independientes de NC y el incremento medio de CrS 72 h tras el contraste fueron objetivos secundarios. Resultados. La incidencia total de NC fue del 5,6%. La incidencia de NC fue significativamente menor con iodixanol que con ioversol (el 2,5 frente al 8,3%; odds ratio = 0,255; intervalo de confianza del 95%, 0,068-0,952; p = 0,047). Una menor tasa de filtrado glomerular estimada (60,8 ± 29 frente a 75,3 ± 25 ml/min/1,73 m2; odds ratio = 0,975; intervalo de confianza del 95%, 0,952-0,997; p = 0,03) y el uso de ioversol se demostraron predictores independientes de NC. Conclusiones. En pacientes diabéticos sometidos a coronariografía diagnóstica y/o ICP, el contraste isoos-molar iodixanol mostró menor incidencia de NC que el contraste de baja osmolaridad ioversol (AU)

Introduction and objectives. This study was designed to compare differences in the incidence of contrast-induced nephropathy (CIN) and changes in serum creatinine (SCr) level following iso-osmolar iodixanol or low-osmolar ioversol administration in diabetic patients undergoing coronary angiography, with or without percutaneous coronary intervention (PCI). A number of studies have indicated that iodixanol reduces the risk of CIN in patients with renal impairment, with or without diabetes. Diabetic patients may have some degree of renal dysfunction despite having a normal SCr level. Methods. The study included 250 consecutive diabetic patients undergoing coronary angiography with or without PCI. Those enrolled during the first 7 months of the study received ioversol and those enrolled during the following 11 months received iodixanol. The primary study endpoint was the incidence of CIN. Secondary objectives were to identify independent predictors of CIN and to determine the mean increase in SCr 72 hours after contrast injection. Results. The overall incidence of CIN was 5.6%. The incidence of CIN was significantly lower with iodixanol than with ioversol (2.5% vs. 8.3%, respectively; odds ratio [OR]=0.255; 95% confidence interval [CI], 0.068-0.952; P=.047). A low estimated glomerular filtration rate (60.8±29 mL/min per 1.73 m2 in those with CIN vs. 75.3±25 mL/min per 1.73 m2 in those without; OR=0.975; 95% CI, 0.952-0.997; P=.03) and ioversol use were independent predictors of CIN. Conclusions. In diabetic patients undergoing diagnostic coronary angiography with or without PCI, the iso-osmolar contrast medium iodixanol was associated with a lower incidence of CIN than low-osmolar ioversol (AU)