The Time-Varying Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes Mellitus: Evidence from Large Multinational Trials

Aims: To evaluate the time-varying cardio-protective effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) using pooled data from eight contemporary cardiovascular outcome trials using the difference in the restricted mean survival time (ΔRMST) as the effect estimate. Material and Methods: Data from eight multinational cardiovascular outcome randomized controlled trials of GLP-1RAs for type 2 diabetes mellitus were pooled. Flexible parametric survival models were fit from published Kaplan-Meier plots. The differences between arms in RMST (ΔRMST) were calculated at 12, 24, 36 and 48 months. ΔRMST values were pooled using an inverse variance-weighted random-effects model; heterogeneity was tested with Cochran\u27s Q statistic. The endpoints studied were: three-point major adverse cardiovascular events (MACE), all-cause mortality, stroke, cardiovascular mortality and myocardial infarction. Results: We included eight large (3183-14 752 participants, total = 60 080; median follow-up range: 1.5 to 5.4 years) GLP-1RA trials. Among GLP-1RA recipients, we observed an average delay in three-point MACE of 0.03, 0.15, 0.37 and 0.63 months at 12, 24, 36 and 48 months, respectively. At 48 months, while cardiovascular mortality was comparable in both arms (pooled ΔRMST 0.163 [−0.112, 0.437]; P = 0.24), overall survival was higher (ΔRMST = 0.261 [0.08-0.43] months) and stroke was delayed (ΔRMST 0.22 [0.15-0.33]) in patients receiving GLP-1RAs. Conclusions: Glucagon-like peptide-1 receptor agonists may delay the occurrence of MACE by an average of 0.6 months at 48 months, with meaningfully larger gains in patients with cardiovascular disease. This metric may be easier for clinicians and patients to interpret than hazard ratios, which assume a knowledge of absolute risk in the absence of treatment

Aortic Root Reconstruction

Aortic root reconstruction represents one of the most complex areas of cardiac surgery as well as one of the most dynamic-major developments in understanding of the aortic root anatomy and physiology, improvements in imaging and surgical technique allowed for development and acceptance into clinical practice of several novel procedures over last couple of decades. From first aortic root replacement reported by Bentall and De Bono in 1968 to aortic root reimplantation (David procedure) and remodeling (Yacoub operation) with multiple contemporary modifications, aortic root reconstruction now is widely used in treatment of chronic aortic aneurysmal disease and acute aortic dissections alike. Basic principles of aortic root structure and function and critical operative strategies for aortic root surgery are reviewed in this chapter

Trends in prescriptions of cardioprotective diabetic agents after coronary artery bypass grafting among U.S. veterans

OBJECTIVE: Patients with type 2 diabetes undergoing coronary artery bypass grafting (CABG) are at risk for cardiovascular events. Sodium–glucose cotransporter 2 receptor inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) are effective cardioprotective agents; however, their prescription among CABG patients is uncertain. The aims of this study were 1) to evaluate the overall use of SGLT2i/GLP-1RA after CABG and explore longitudinal trends and 2) to examine patient-related factors associated with the use of SGLT2i or GLP-1RA. RESEARCH DESIGN AND METHODS: We analyzed the nationwide Veterans Affairs (VA) database (2016–2019) to report trends and factors associated with SGLT2i or GLP-1RA prescription after CABG. RESULTS: Among 5,109 patients operated on at 40 different VA medical centers, 525 of 5,109 (10.4%), 352 of 5,109 (6.8%), and 91 of 5,109 (1.8%) were prescribed SGLT2i, GLP-1RA, and both, respectively. A substantial increase in the quarterly SGLT2i prescription rates (1.6% [first quarter of 2016 (2016Q1)], 33% [2019Q4]) was present but was lower for GLP-1RA (0.8% [2016Q1], 11.2% [2019Q4]). SGLT2i use was less likely with preexisting vascular disease (odd ratio [OR] 0.75, 95% CI 0.75, 0.94) or kidney disease (OR 0.72, 95% CI 0.58, 0.88), while GLP-1RA use was associated with obesity (OR 1.91, 95% CI 1.50, 2.46). CONCLUSIONS: The overall utilization of SGLT2i or GLP-1RA drugs in U.S. veterans with type 2 diabetes undergoing CABG is low, with SGLT2i preferred over GLP-1RA

Off‐pump coronary artery bypass grafting: department of veteran affairs’ use and outcomes

Background: Coronary artery bypass can be performed off pump (OPCAB) without cardiopulmonary bypass. However, trends over time for OPCAB versus on‐pump (ONCAB) use and long‐term outcome has not been reported, nor has their long‐term outcome been compared. Methods and Results: We queried the national Veterans Affairs database (2005–2019) to identify isolated coronary artery bypass procedures. Procedures were classified as OPCAB on ONCAB using the as‐treated basis. Trend analyses were performed to evaluate longitudinal changes in the preference for OPCAB. The median follow‐up period was 6.6 (3.5–10) years. An inverse probability weighted Cox model was used to compare all‐cause mortality between OPCAB and ONCAB. From 47 685 patients, 6759 (age 64±8 years) received OPCAB (14%). OPCAB usage declined from 16% (2005–2009) to 8% (2015–2019). Patients with triple vessel disease who received OPCAB received a lower mean number of grafts (2.8±0.8 versus 3.2±0.8; P<0.01). The ONCAB 5‐, 10‐, and 15‐year survival rates were 82.9% (82.5–83.3), 60.4% (59.8–61.1), and 37.2% (36.1–38.4); correspondingly, OPCAB rates were 80.7% (79.7–81.7), 57.4% (56–58.7), and 34.1% (31.7–36.6) (P<0.01). OPCAB was associated with increased risk‐adjusted all‐cause mortality (hazard ratio, 1.15 [1.13–1.18]; P<0.01) and myocardial infarction (incident rate ratio, 1.16 [1.05–1.28]; P<0.01). Conclusions: Over 15 years, OPCAB use declined considerably in Veterans Affairs medical centers. In Veterans Affairs hospitals, late all‐cause mortality and myocardial infarction rates were higher in the OPCAB cohort

Outcomes of surgical mitral and aortic valve replacements among kidney transplant candidates: implications for valve selection

Background: Limited literature exists that evaluated outcomes of kidney transplant–eligible patients who are having dialysis and who are undergoing valve replacement. Our main objective in this study was to compare mortality, reoperation, and bleeding episodes between bioprosthetic and mechanical valve procedures among kidney transplant–eligible patients who are having dialysis. Methods and Results: We studied 887 and 1925 dialysis patients from the United States Renal Data System, who underwent mitral valve replacement and aortic valve replacement (AVR) after being waitlisted for a kidney transplant (2000–2015), respectively. Time to death, time to reoperation, and time to bleeding requiring hospitalizations were compared separately for AVR and mitral valve replacement. Kaplan–Meier survival curves, Cox proportional hazards model for time to death, accelerated time to event model for time to reoperation, and counting process model for time to recurrent bleeding were used. There were no differences in mortality (hazard ratio [HR], 0.92; 95% CI, 0.77–1.09) or risk of reoperation or risk of significant bleeding events between bioprosthetic and mechanical mitral valve replacement. However, mechanical AVR was associated with a modestly significant less hazard of death (HR, 0.83; 95% CI, 0.74–0.94) compared with bioprosthetic AVR. There were no differences in time to reoperation, or time to significant bleeding events between bioprosthetic and mechanical AVR. Conclusions: For kidney transplant waitlisted patients who are on dialysis and who are undergoing surgical valve replacement, bioprosthetic and mechanical valves have comparable survival, reoperation rates, and bleeding episodes requiring hospitalizations at both mitral and aortic locations. These findings emphasize that an individualized informed decision is recommended when choosing the type of valve for this special group of patients having dialysis

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Survival analysis-part 2: Cox proportional hazards model

Learning objectives: 1. To understand the log-rank test and limitations of the log-rank test in comparing survival between groups. 2. To understand the fundamental concepts of the proportional hazards assumption. 3. To understand basic steps in the development of the Cox proportional hazards model and reported hazard ratios. 4. To understand how results of a Cox model run using STATA© (a commonly used proprietary statistical software) can be understood and interpreted