Acetylsalicylic Acid (Aspirin) for Primary Prevention of Cardiovascular Events in Patients with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Evidence regarding using acetylsalicylic acid (aspirin) for the prevention of cardiovascular (CV) events in patients with diabetes mellitus (DM) is inconsistent. Therefore, we performed a meta-analysis. METHODS: A literature search was performed (January 1990 to February 2022) and publications meeting the inclusion criteria were reviewed, and a meta-analysis was performed using RevMan software. The primary outcome was a composite of CV death, non-fatal myocardial infarction (MI) and stroke. Secondary outcomes included all-cause mortality, individual components of the primary outcome and major bleeding. RESULTS: The study cohort comprised 33525 diabetic patients from 9 randomized controlled trials. The primary outcome was significantly lower for aspirin vs. placebo (7.9 vs. 8.6, RR (risk ratio) 0.92, 95% CI (confidence interval) 0.86-0.99). All-cause mortality (10 vs. 10.3%, RR 0.97, 95% CI 0.90-1.03), CV death (4.4 vs. 4.7%, RR 0.93, 95% CI 0.83-1.04), non-fatal MI (4.6 vs. 4.8% RR 0.97, 95% CI 0.83- 1.15) and stroke (3.2 vs. 3.5%, RR 0.89, 95% CI 0.75-1.06) were similar between the two treatment groups. Major bleeding was significantly higher for aspirin compared with placebo (3.4 vs. 2.8%, RR 1.18, 95% CI 1.01-1.39). CONCLUSION: Aspirin use in patients with DM reduces the composite endpoint of CV death, non-fatal MI and stroke compared with a placebo. However, routine use of aspirin for primary prevention among diabetic patients cannot be advised due to the increased risk of major bleeding. These findings suggest careful risk assessment of individual patients.

Antithrombotic therapy after transcatheter aortic valve replacement: current perspective.

PURPOSE OF REVIEW: Transcatheter aortic valve replacement (TAVR) has expanded as a treatment option for severe aortic stenosis throughout the surgical risk spectrum. Decreasing procedural risk and inclusion of lower risk population has shifted the focus to optimization of postprocedural management and balancing the thrombotic and bleeding complications. In this review, we outline various patient and procedure related factors affecting choice of antithrombotic therapy post TAVR and provide an update of recent development in this area. RECENT FINDINGS: Multiple studies have confirmed the high incidence of both ischemic and bleeding complications in the early to midterm post-TAVR. In addition, new data has emerged for the role of high resolution computed tomography to detect decreased leaflet mobility and leaflet micro thrombi associated with implications for bioprosthetic valve dysfunction and cerebrovascular events post TAVR. Randomized clinical trials have reported increased bleeding with dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC) plus antiplatelet therapy. These findings suggest that aspirin monotherapy or OAC monotherapy likely provides the appropriate balance for antithrombotic protection and risk of bleeding. SUMMARY: Majority of patients undergoing TAVR have multiple comorbidities and are at increased risk of ischemic and bleeding complications. In the absence of robust clinical evidence, there is significant variability among guideline recommendations and antithrombotic therapy post TAVR across institutions. The available evidence confirms a high rate of bleeding with more potent and prolonged antithrombotic regimens without a documented benefit for clinical endpoints. The authors favor a conservative anti thrombotic approach and suggest monotherapy with aspirin or systemic anticoagulation based upon an individual's risk of thromboembolic complications. DAPT is reserved for patients with recent stenting and OAC plus aspirin is prescribed for patients with established CAD in the post TAVR setting.

Natural history of severe tricuspid regurgitation: Outcomes after transcatheter tricuspid valve intervention compared to medical therapy.

AIMS: We aimed to identify the clinical characteristics and examine outcomes in patients with significant tricuspid regurgitation (TR) who received transcatheter tricuspid valve intervention (TTVI) compared with guideline directed medical therapy (GDMT). METHODS AND RESULTS: Between 2015 and 2019, 124 patients with symptomatic severe TR were assessed at St. Michael's Hospital. Seventy-one patients were ineligible and received GDMT only while 53 patients received TTVI and GDMT. During follow-up, TTVI was associated with significant improvements in NYHA functional class and 6-min walk distance (p < .001). GDMT patients had lower survival (46.9% vs 75.1%, p = .047) and lower freedom from heart failure hospitalization (HHF) and mortality (33.2% vs 62.7%, p = .027), higher incidences per 100 person-year of gastrointestinal bleeding [15.58 (95% CI 8.90-25.31) vs 4.24 (95% CI 0.85-12.37), p = .04] and acute kidney injury [36.98 (95% CI 26.17-50.76) vs 14.12 (95% CI 6.76-25.96), p = .001] compared with TTVI patients. CONCLUSION: TTVI in addition to GDMT was effective at improving TR symptoms, functional status, and was associated with lower rates of all-cause mortality, the combined endpoint of HHF and mortality, AKI and GI bleeding. Future randomized controlled trials on TTVI are needed.

Effects of heavy-intensity priming exercise on pulmonary oxygen uptake kinetics and muscle oxygenation in heart failure with preserved ejection fraction.

Exercise intolerance is a hallmark feature in heart failure with preserved ejection fraction (HFpEF). Prior heavy exercise ("priming exercise") speeds pulmonary oxygen uptake (V̇o2p) kinetics in older adults through increased muscle oxygen delivery and/or alterations in mitochondrial metabolic activity. We tested the hypothesis that priming exercise would speed V̇o2p on-kinetics in patients with HFpEF because of acute improvements in muscle oxygen delivery. Seven patients with HFpEF performed three bouts of two exercise transitions: MOD1, rest to 4-min moderate-intensity cycling and MOD2, MOD1 preceded by heavy-intensity cycling. V̇o2p, heart rate (HR), total peripheral resistance (TPR), and vastus lateralis tissue oxygenation index (TOI; near-infrared spectroscopy) were measured, interpolated, time-aligned, and averaged. V̇o2p and HR were monoexponentially curve-fitted. TPR and TOI levels were analyzed as repeated measures between pretransition baseline, minimum value, and steady state. Significance was P < 0.05. Time constant (τ; tau) V̇o2p (MOD1 49 ± 16 s) was significantly faster after priming (41 ± 14 s; P = 0.002), and the effective HR τ was slower following priming (41 ± 27 vs. 51 ± 32 s; P = 0.025). TPR in both conditions decreased from baseline to minimum TPR ( P < 0.001), increased from minimum to steady state ( P = 0.041) but remained below baseline throughout ( P = 0.001). Priming increased baseline ( P = 0.003) and minimum TOI ( P = 0.002) and decreased the TOI muscle deoxygenation overshoot ( P = 0.041). Priming may speed the slow V̇o2p on-kinetics in HFpEF and increase muscle oxygen delivery (TOI) at the onset of and throughout exercise. Microvascular muscle oxygen delivery may limit exercise tolerance in HFpEF.