Impact of Carvedilol and Metoprolol on Inappropriate Implantable Cardioverter-Defibrillator Therapy The MADIT-CRT Trial (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy)

ObjectivesThe goal of this study was to evaluate the effects of carvedilol and metoprolol on the endpoint of inappropriate implantable cardioverter-defibrillator therapy in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy) study.BackgroundThe impact of carvedilol and metoprolol on inappropriate therapy in heart failure patients with devices has not yet been investigated.MethodsAll patients in the MADIT-CRT study who received a device (N = 1,790) were identified. Using time-dependent Cox regression analysis, we compared patients treated with different types of beta-blockers or no beta-blockers on the primary endpoint of inappropriate therapy, delivered as antitachycardia pacing (ATP) or shock therapy. Secondary endpoints were inappropriate therapy due to atrial fibrillation and atrial tachyarrhythmias, also evaluated as ATP or shock therapy.ResultsInappropriate therapy occurred in 253 (14%) of 1,790 patients during a follow-up period of 3.4 ± 1.1 years. Treatment with carvedilol was associated with a significantly decreased risk of inappropriate therapy compared with metoprolol (hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.48 to 0.85]; p = 0.002). The reduction in risk was consistent for inappropriate ATP (HR: 0.66 [95% CI: 0.48 to 0.90]; p = 0.009) and inappropriate shock therapy (HR: 0.54 [95% CI: 0.36 to 0.80]; p = 0.002). The risk of inappropriate therapy caused by atrial fibrillation was also reduced in patients receiving carvedilol compared with metoprolol (HR: 0.50 [95% CI: 0.32 to 0.81]; p = 0.004). General use of beta-blockers (93%) and adherence in this study was high.ConclusionsIn heart failure patients undergoing either cardiac resynchronization therapy with a defibrillator or with an implantable cardioverter-defibrillator device, carvedilol was associated with a 36% lower rate of inappropriate ATP and shock therapy compared with metoprolol. Inappropriate therapy due to atrial fibrillation was associated with a 50% lower rate in patients receiving carvedilol compared with those receiving metoprolol. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271

Impact of socioeconomic position on initiation of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes – a Danish nationwide observational study

BACKGROUND: Low socioeconomic position may affect initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucacon-like-peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D). We examined the association between socioeconomic position and initiation of SGLT-2i or GLP-1RA in patients with T2D at time of first intensification of antidiabetic treatment. METHODS: Through nationwide registers, we identified all Danish patients on metformin who initiated second-line add-on therapy between December 10, 2012, and December 31, 2020. For each time period (2012-2014, 2015-2017, and 2018-2020), we used multivariable multinomial logistic regression to associate disposable income, as proxy for socioeconomic position, with the probability of initiating a specific second-line treatment at time of first intensification. We reported probabilities standardised to the distribution of demographics and comorbidities of patients included in the last period (2018-2020). FINDINGS: We included 48915 patients (median age 62 years; 61·7% men). In each time period, high-income patients were more often men and had less comorbidities as compared with low income-patients. In each time period, the standardised probability of initiating a SGLT-2i or a GLP-1RA was significantly higher in the highest income group compared with the lowest: 11·4% vs. 9·5% (probability ratio [PR] 1·21, 95 % confidence interval [CI] 1·01-1·44) in 2012-2014; 22·6% vs. 19.6% (PR 1·15, CI 1·05-1·27) in 2015-2017; and 65·8% vs. 54·8% (PR 1·20, CI 1·16-1·24) in 2018-2020. The differences by income were consistent across multiple subgroups. INTERPRETATION: Despite a universal healthcare system, low socioeconomic position was consistently associated with a lower probability of initiating a SGLT-2i or a GLP-1RA. These disparities may widen the future socioeconomic gap in cardiovascular outcomes. FUNDING: The work was funded by unrestricted grants from ‘Region Sjaelland Den Sundhedsvidenskabelige Forskningsfond’ and ‘Murermester Lauritz Peter Christensen og hustru Kirsten Sigrid Christensens Fond’

Driving following defibrillator implantation: development and pilot results from a nationwide questionnaire

Abstract Background Implantable cardioverter defibrillator (ICD) implantation is associated with driving restrictions which may have profound effects on the patient’s life. However, there is limited patient-reported data on the information given about driving restrictions, the adherence to the restrictions, the incidence of arrhythmic symptoms while driving, and the driving restrictions’ effect on ICD patients’ daily life and quality of life factors. A specific questionnaire was designed to investigate these objectives, intended for use in a nationwide ICD cohort. Methods The conceptual framework based on literature review and expert opinion was refined in qualitative semi-structured focus group interviews with ten ICD patients. Content validity was pursued through pre-testing, including expert review and 28 cognitive interviews with patients at all ICD implanting centres in Denmark. Finally, the Danish Pacemaker and ICD registry was used to randomly select 50 ICD patients with a first-time implantation between January 1, 2013 and November 30, 2016 for pilot testing, followed by a test-retest on 25 respondents. Test-retest agreement was assessed using kappa statistics or intraclass correlation coefficients. Results The pilot test achieved a response rate of 78%, whereof the majority were web-based (69%). Only 49% stated they had been informed about any driving restrictions after ICD implantation, whereas the number was 75% after appropriate ICD shock. Among respondents, 95% had resumed private driving, ranging from 1 to 90 days after ICD implantation. In those informed of a significant (≥ 1 month) driving ban, 55% stated the driving restrictions had impeded with daily life, especially due to limitations in maintaining employment or getting to/from work and 25% admitted they had knowingly been driving during the restricted period. There were six episodes of dizziness or palpitations not necessitating stopping the vehicle. Test-retest demonstrated good agreement of questionnaire items, with 69% of Kappa coefficients above 0.60. Conclusions We have developed a comprehensive questionnaire on ICD patients’ perspective on driving. Pre-testing and pilot testing demonstrated good content validity, feasible data collection methods, and a robust response rate. Thus, we believe the final questionnaire, distributed to almost 4000 ICD patients, will capture essential evidence to help inform driving guidelines in this population