American heart journal最新文献

Background

High to moderate levels of physical activity (PA) are associated with low risk of incident cardiovascular disease. However, it is unclear whether the benefits of PA in midlife extend to cardiovascular health following myocardial infarction (MI) in later life.

Methods

Among 1,111 Atherosclerosis Risk in Communities study participants with incident MI during Atherosclerosis Risk in Communities follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA on average 11.9 (SD 6.9) years prior to incident MI (premorbid PA) was evaluated as the average score of PA between visit 1 (1987-1989) and visit 3 (1993-1995) using a modified Baecke questionnaire. Total and domain-specific PA (sport, nonsport leisure, and work PA) was analyzed for associations with composite and individual outcomes of mortality, recurrent MI, and stroke after index MI using multivariable Cox models.

Results

During a median follow-up of 4.6 (IQI 1.0-10.5) years after incident MI, 823 participants (74%) developed a composite outcome. The 10-year cumulative incidence of the composite outcome was lower in the highest, as compared to the lowest tertile of premorbid total PA (56% vs. 70%, respectively). This association remained statistically significant even after adjusting for potential confounders (adjusted hazard ratio [aHR] 0.80 [0.67-0.96] for the highest vs. lowest tertile). For individual outcomes, high premorbid total PA was associated with a low risk of recurrent MI (corresponding aHR 0.64 [0.44, 0.93]). When domain-specific PA was analyzed, similar results were seen for sport and work PA. The association was strongest in the first year following MI (e.g., aHR of composite outcome 0.66 [95% CI 0.47, 0.91] for the highest vs. lowest tertile of total PA).

Conclusions

Premorbid PA was associated positively with post-MI cardiovascular health. Our results demonstrate the additional prognostic advantages of PA beyond reducing the risk of incident MI.

Background

The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients.

Methods

This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (P-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations.

Results

Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance.

Conclusion

Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin.

Background

Previous studies suggested only the radial artery and the No-touch (NT) technique were effective in reducing graft occlusion after coronary artery bypass grafting (CABG) surgery. However, there is no randomized trial comparing these 2 graft conduits. The optimum second conduit for CABG remains undetermined.

Materials and methods

This study is a prospective, single-center randomized clinical trial, aiming to compare the graft patency between the radial artery and the NT vein graft. All patients undergoing isolated CABG with left internal mammary artery (LIMA) plus at least 2 additional grafts will be considered eligible. About 774 cases (516 in the radial artery group and 258 in the NT vein group) will be enrolled in over 1 to 2 years. Participants will be randomized and allocated to two bypass strategies: the LIMA plus 1 radial artery and 1 conventional vein graft, or the LIMA plus 2 NT vein grafts. The primary outcome is graft occlusion at 1 year after CABG evaluated by CT angiography. The secondary outcomes include graft occlusion at 3 and 5 years and major adverse cardiac or cerebrovascular events at 1, 3, and 5 years follow-ups.

Discussion

This study will define whether or not the NT vein has a lower graft occlusion rate than the radial artery in short and mid-term follow-ups, and provide new evidence for the second conduit choice in CABG surgery.

Trial registration

ClinicalTrials.gov NCT06014047. Registered on October 15th, 2023.

Background

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events.

Methods and results

BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024.

Conclusion

These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.

Clinicians often suspect that a treatment effect can vary across individuals. However, they usually lack “evidence-based” guidance regarding potential heterogeneity of treatment effects (HTE). Potentially actionable HTE is rarely discovered in clinical trials and is widely believed (or rationalized) by researchers to be rare. Conventional statistical methods to test for possible HTE are extremely conservative and tend to reinforce this belief. In truth, though, there is no realistic way to know whether a common, or average, effect estimated from a clinical trial is relevant for all, or even most, patients. This absence of evidence, misinterpreted as evidence of absence, may be resulting in sub-optimal treatment for many individuals. We first summarize the historical context in which current statistical methods for randomized controlled trials (RCTs) were developed, focusing on the conceptual and technical limitations that shaped, and restricted, these methods. In particular, we explain how the common-effect assumption came to be virtually unchallenged. Second, we propose a simple graphical method for exploratory data analysis that can provide useful visual evidence of possible HTE. The basic approach is to display the complete distribution of outcome data rather than relying uncritically on simple summary statistics. Modern graphical methods, unavailable when statistical methods were initially formulated a century ago, now render fine-grained interrogation of the data feasible. We propose comparing observed treatment-group data to “pseudo data” engineered to mimic that which would be expected under a particular HTE model, such as the common-effect model. A clear discrepancy between the distributions of the common-effect pseudo data and the actual treatment-effect data provides prima facie evidence of HTE to motivate additional confirmatory investigation. Artificial data are used to illustrate implications of ignoring heterogeneity in practice and how the graphical method can be useful.

Background

There has not been a consensus on the prothesis sizing strategy in type 0 bicuspid aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). Modifications to standard annular sizing strategies might be required due to the distinct anatomical characteristics. We have devised a downsizing strategy for TAVR using a self-expanding valve specifically for patients with type 0 bicuspid AS. The primary aim of this study is to compare the safety and efficacy of downsizing strategy with the Standard Annulus Sizing Strategy in TAVR for patients with type 0 bicuspid AS.

Trial design

It is a prospective, multi-center, superiority, single-blinded, randomized controlled trial comparing the Down Sizing and Standard Annulus Sizing Strategy in patients with type 0 bicuspid aortic stenosis undergoing transcatheter aortic valve replacement. Eligible participants will include patients with severe type 0 bicuspid AS, as defined by criteria such as mean gradient across aortic valve ≥40 mmHg, peak aortic jet velocity ≥4.0 m/s, aortic valve area (AVA) ≤1.0 cm², or AVA index ≤0.6 cm²/m². These patients will be randomly assigned, in a 1:1 ratio, to either the Down Sizing Strategy group or the Standard Sizing Strategy group. In the Down Sizing Strategy group, a valve one size smaller will be implanted if the “waist sign” manifests along with less than mild regurgitation during balloon pre-dilatation. The primary end point of the study is a composite of VARC-3 defined device success, absence of both permanent pacemaker implantation due to high-degree atrioventricular block and new-onset complete left bundle branch block.

Conclusion

This study will compare the safety and efficacy of Down Sizing Strategy with the Standard Annulus Sizing Strategy and provide valuable insights into the optimal approach for sizing in TAVR patients with type 0 bicuspid AS. We hypothesize that the Down Sizing Strategy will demonstrate superiority when compared to the Standard Annulus Sizing Strategy. (Down Sizing Strategy (HANGZHOU Solution) vs Standard Sizing Strategy TAVR in Bicuspid Aortic Stenosis (Type 0) (TAILOR-TAVR), NCT05511792).

Despite a perceived increase in attention to gender differences in medicine, a comprehensive assessment of gender equality research, particularly in cardiology, remains underexplored. This observational retrospective study, focusing on documents related to “Gender Equality” according to the Sustainable Development Goals, reveals cardiology as a significant area for gender equality research, albeit with a decline in publications post-2018. The analysis highlighted a concentrated effort in the United States and a considerable impact gap between gender-focused and general cardiology research. The global academic community must intensify research into gender disparities, which is essential for achieving professional gender equality and addressing the burden of cardiovascular diseases.

Background

Despite guidelines supporting antithrombotic therapy use in atrial fibrillation (AF), under-prescribing persists. We assessed whether computerized clinical decision support (CDS) would enable guideline-based antithrombotic therapy for AF patients in primary care.

Methods

This cluster randomized trial of CDS versus usual care (UC) recruited participants from primary care practices across Nova Scotia, following them for 12 months. The CDS tool calculated bleeding and stroke risk scores and provided recommendations for using oral anticoagulants (OAC) per Canadian guidelines.

Results

From June 14, 2014 to December 15, 2016, 203 primary care providers (99 UC, 104 CDS) with access to high-speed Internet were recruited, enrolling 1,145 eligible patients (543 UC, 590 CDS) assigned to the same treatment arm as their provider. Patient mean age was 72.3 years; most were male (350, 64.5% UC, 351, 59.5% CDS) and from a rural area (298, 54.9% UC, 315, 53.4% CDS). At baseline, a higher than anticipated proportion of patients were receiving guideline-based OAC therapy (373, 68.7% UC, 442, 74.9% CDS; relative risk [RR] 0.97 (95% confidence interval [CI], 0.87-1.07; P = .511)). At 12 months, prescription data were available for 538 usual care and 570 CDS patients, and significantly more CDS patients were managed according to guidelines (415, 77.1% UC, 479, 84.0% CDS; RR 1.08 (95% CI, 1.01-1.15; P = .024)).

Conclusion

Notwithstanding high baseline rates, primary care provider access to the CDS over 12 months further optimized the prescribing of OAC therapy per national guidelines to AF patients potentially eligible to receive it. This suggests that CDS can be effective in improving clinical process of care.

Trial Registration

Clinical Trials NCT01927367. https://clinicaltrials.gov/ct2/show/NCT01927367?term=NCT01927367&draw=2&rank=1

Background

Atrial fibrillation (AF) is common in patients with heart failure (HF) and is associated with worse clinical outcomes. We evaluated the relationship between AF and longitudinal changes in health-related quality of life (HRQoL) measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) in both HF with preserved (HFpEF) and reduced ejection fraction (HFrEF).

Methods

This is a post-hoc analysis of the TOPCAT and HF-ACTION trials. The effect of AF on KCCQ overall summary scores (OSS), in both trials, was examined using a mixed effects regression model. Patients were divided into 3 groups according to AF status at baseline: patients with a history of AF but no AF detected on ECG at enrollment (Hx AF group), patients with history of AF and AF detected on ECG at enrollment (ECG AF group) and patients with post-randomization new-onset AF (New AF group).

Results

In TOPCAT, among 1,710 patients with KCCQ data available, AF was associated with a significantly lower KCCQ-OSS (-3.98; 95% CI −7.21: −0.74) at 48 months, with a significant AF status by time interaction (P = .03). In HF-ACTION, among 1,814 patients with available KCCQ data, AF was associated with a significantly lower KCCQ-OSS (-3.67; 95% CI −6.21: −1.41) at 24 months but there was no significant AF status by time interaction. In both trials, the type of AF was not associated with significant changes in KCCQ-OSS score.

Conclusion

Ιn patients with both HFpEF and HFrEF, AF was independently associated with worse HRQoL measured by KCCQ.