Coronary Artery Disease Trial Research Articles

Insights into the reporting of major adverse cardiovascular events in coronary artery disease trials

Abstract Background and Purpose Major adverse cardiovascular event (MACE) is one of the most used composite outcomes in coronary artery disease (CAD) trials, though its lack of a standardised definition has led to ambiguity and challenges in its interpretation. This study aims to elucidate the definition of MACE and guide future interpretation of MACE in the context of CAD trials. Methods A systematic review was conducted by searching Medline, Embase and Cochrane for double-blind pharmacological randomized-controlled trials among participants with CAD from 2012 to 2022 that reported MACE outcomes. Qualitative reviews were conducted based on the components of MACE, composite definitions, composite rationale, and the reporting of MACE. Results 30 trials, consisting of 77,692 patients were included, from which a total of 41 MACE analyses were extracted. The most commonly included components were cardiac death (56%), unplanned revascularisation (56%), followed by fatal or non-fatal MI (54%), non-fatal MI (44%) and stroke (39%), with cardiac death, non-fatal MI and non-fatal stroke being the most commonly used conglomerate (14%). A third of trials did not provide definitions of MACE, and all MACE composites in included trials were determined within the investigating committees without justification nor citation from guidelines. Notably, 27% of studies constructed MACE outcomes post hoc, with 7% observing a resultant change in statistical significance of the overall results. A fifth of studies deviated from the original MACE definition that was proposed within their protocol. There were inconsistencies in the definitions of the composite components, with 22 trials (73%) failing to specify whether the MI component in MACE was fatal or non-fatal. Similarly, 16 trials (53%) did not specify if stroke was fatal. In terms of the timing of MACE in patients presenting with multiple events, the majority of the trials (77%) did not specify how the event was assessed with, seven trials (23%) described the approach to recording the time to the first MACE event, while none of the trials considered the time to the event that conferred greatest clinical significance, nor provided a definition for it. Conclusion There is substantial heterogeneity in MACE definitions within CAD trials, where rationale behind its adjudication is often inadequately described, with suboptimal specification, inconsistent reporting, and publication bias within and across studies. Clinicians should be cautious when interpreting conclusions related to MACE, as the intervention is unlikely to affect all components of MACE, due to the susceptibility to "cherry-picking" of components to improve statistical outcomes. Harmonising the MACE definition would enhance transparency in clinical trial reporting, ensuring a robust measure of intervention efficacy and safety that can be easily compared across different trials.

Medication adherence and antithrombotic therapy outcomes: insights from a post-hoc analysis of the AFIRE trial

Abstract Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial established noninferiority in efficacy and superiority in safety endpoints of rivaroxaban monotherapy over rivaroxaban plus antiplatelet therapy (combination therapy) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, the impact of medication adherence to rivaroxaban on AFIRE study outcomes remains unclear. Purpose This post-hoc analysis aimed to explore the influence of medication adherence on AFIRE trial results. Methods Among 2,120 patients, participants were classified into adherent and non-adherent groups based on self-reported measures, which were further verified through on-site visits to the facilities. Adherent patients were defined as those who reported consistently taking their medication as prescribed. The primary efficacy endpoint comprised stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or all-cause death, including cerebral events. Analysis also examined differences in the primary efficacy endpoint between adherent and non-adherent patients. Results Of the 2,120 patients, 2,012 (94.9%) were adherent to rivaroxaban, while 108 (5.1%) were non-adherent. Among adherent patients, rivaroxaban monotherapy showed significantly better efficacy outcomes compared to combination therapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.54–0.98; p=0.04, Figure 1A). However, primary efficacy outcomes did not significantly differ among non-adherent patients (HR 0.64, 95% CI 0.23–1.81, p=0.40, Figure 1B). Adherent patients exhibited improved outcomes relative to non-adherent patients, though this difference was not statistically significant (HR 1.68; 95% CI 0.99–2.85; p=0.05, Figure 2A). In clinically high-risk patients with a history of angina pectoris, those who demonstrated adherence to medication (n=1281) exhibited significantly better efficacy outcomes compared to non-adherent patients (n=68) (HR 1.97; 95% CI 1.09–3.56; p=0.03, Figure 2B). Conclusions Rivaroxaban monotherapy versus combination therapy showed favorable efficacy outcomes in patients with good adherence, consistent with the overall AFIRE trial. However, these benefits were not observed in non-adherent patients. Adherence to rivaroxaban is crucial for achieving its maximum therapeutic effect as monotherapy.Figure1Figure2

Preliminary outcomes of quantitative flow ratio-guided coronary bypass grafting in primary valve surgery: A propensity score weighted analysis

ObjectivesThe guidelines recommend fractional flow reserve-guided coronary artery bypass grafting (CABG) during primary valve surgery without evidence. Quantitative flow ratio (QFR) is a novel coronary angiography (CAG)-based fractional flow reserve measurement. We aimed to compare the early clinical outcomes between QFR-guided and CAG-guided CABG in these patients. MethodsThis observational study screened all 2081 patients admitted to our institution for elective primary mitral and/or aortic valve surgery from January 2017 to September 2020. Of them, all 188 patients with comorbid coronary artery lesions (visual estimated stenosis ≥50%) were included. Sixty-nine patients with QFR analysis received bypasses only for lesions with QFR ≤0.80 (QFR-guided group). The remaining 119 patients without QFR analysis received bypasses for all stenosis ≥50% (CAG-guided group). Propensity overlap weighting was used to neutralize the intergroup imbalance. The primary end point was major adverse cardiovascular events. ResultsAfter propensity score weighting, the baseline characteristics were comparable. Concomitant coronary artery bypass grafting was performed 58.1% versus 100% in the QFR-guided and CAG-guided groups, respectively. The mean number of grafts was significantly lower in QFR-guided group than in the CAG-guided group (0.9 ± 0.7 vs 1.6 ± 0.5 [P < .001]). The weighted 30-day incidence of major adverse cardiovascular events was numerically lower in the QFR-guided group than in the CAG-guided group, but not statistically significant (6.3% vs 11.8% [P = .429]). After a median follow-up of 31.6 months, the weighted risk of major adverse cardiovascular events and mortality were significantly lower in the QFR-guided group than in the CAG-guided group (major adverse cardiovascular events: hazard ratio, 0.45; 95% CI, 0.24-0.84; P = .012; mortality: hazard ratio, 0.38; 95% CI, 0.16-0.93; P = .029). ConclusionsCompared with CAG-guided coronary artery bypass grafting, QFR-guided CABG is associated with less grafting and better clinical outcome in primary valve surgery with comorbid coronary artery disease. To confirm this finding, the Quantitative Flow Ratio Guided Revascularization Strategy for Patients Undergoing Primary Valve Surgery With Comorbid Coronary Artery Disease trial (NCT03977129) is ongoing.

Cardiology Update 2024

Contemporary practice of cardiology is inspired by epistemological principles of Evidence Based Medicine. With rapidly evolving scientific data, it is imperative that clinicians are updated with the most recent evidence. We intend to review some of the most recent trials that may in the future impact our clinical practice. Here we discuss some practice changing trials in Coronary artery disease, heart failure and preventive cardiology.

Rationale and design of a comparison of angiography-derived fractional flow reserve-guided and intravascular ultrasound-guided intervention strategy for clinical outcomes in patients with coronary artery disease: a randomised controlled trial (FLAVOUR II)

IntroductionPercutaneous coronary intervention (PCI) guided by coronary angiography-derived fractional flow reserve (FFR) or intravascular ultrasound (IVUS) has shown improved clinical outcomes compared with angiography-only-guided PCI. In patients with intermediate stenoses,...

Abstract 17726: Nonischemic Cardiomyopathy in Patients With Coronary Artery Disease

Introduction: Randomized trials in obstructive coronary artery disease (CAD) have largely shown no prognostic benefit from revascularization. While there are several potential reasons for the lack of benefit from coronary revascularization, an underexplored possibility is the presence of coexisting nonischemic myocardial pathology. Aim: We aimed to investigate the prevalence and prognostic significance of nonischemic cardiomyopathy (NICM) in CAD. Methods: We studied a large cohort of consecutive patients with obstructive CAD on coronary angiography who had cardiovascular magnetic resonance imaging (CMR) from 2004 to 2020 for clinical indications. CMRs were analyzed for this study for the presence and type of cardiomyopathy. Patients with normal left ventricular ejection fraction and no late gadolinium enhancement (LGE) were classified as having no cardiomyopathy. Ischemic cardiomyopathy (ICM) was defined by ischemic LGE or extensive hibernating myocardium in the absence of LGE. NICM was defined by nonischemic LGE, absence of LGE without hibernating myocardium, or morphological abnormalities of NICM such as left ventricular hypertrophy. The study endpoint was a composite of all-cause death or hospitalization for heart failure. Results: Among 3,027 patients (mean age 65 years, 24% women), 18% had no cardiomyopathy, 65% had only ICM, and 17% had NICM. Of those with NICM, 38% also had ICM (dual cardiomyopathy). At a median follow-up of 4.7 years, 1,112 patients experienced the study endpoint. On Kaplan-Meier analysis, patients with NICM had a higher cumulative incidence of the study endpoint compared with no cardiomyopathy and ICM (log-rank P&lt;0.001 for both comparisons). On multivariable regression analyses, NICM was associated with a greater risk for the study endpoint-hazard ratio (HR) 1.77; 95% confidence interval (CI) 1.43-2.19; P&lt;0.001 compared with no cardiomyopathy and HR 1.27; 95% CI 1.09-1.47; P=0.003 compared with ICM, after adjustment for potential confounders. Conclusions: NICM was identified in 1 in 6 patients with CAD and was associated with worse long-term outcomes compared with no cardiomyopathy and ICM. In patients with obstructive CAD, coexisting NICM may contribute to the lack of prognostic benefit from revascularization.

Nonischemic or Dual Cardiomyopathy in Patients With Coronary Artery Disease.

Randomized trials in obstructive coronary artery disease (CAD) have largely shown no prognostic benefit from coronary revascularization. Although there are several potential reasons for the lack of benefit, an underexplored possible reason is the presence of coincidental nonischemic cardiomyopathy (NICM). We investigated the prevalence and prognostic significance of NICM in patients with CAD (CAD-NICM). We conducted a registry study of consecutive patients with obstructive CAD on coronary angiography who underwent contrast-enhanced cardiovascular magnetic resonance imaging for the assessment of ventricular function and scar at 4 hospitals from 2004 to 2020. We identified the presence and cause of cardiomyopathy using cardiovascular magnetic resonance imaging and coronary angiography data, blinded to clinical outcomes. The primary outcome was a composite of all-cause death or heart failure hospitalization, and secondary outcomes were all-cause death, heart failure hospitalization, and cardiovascular death. Among 3023 patients (median age, 66 years; 76% men), 18.2% had no cardiomyopathy, 64.8% had ischemic cardiomyopathy (CAD+ICM), 9.3% had CAD+NICM, and 7.7% had dual cardiomyopathy (CAD+dualCM), defined as both ICM and NICM. Thus, 16.9% had CAD+NICM or dualCM. During a median follow-up of 4.8 years (interquartile range, 2.9, 7.6), 1116 patients experienced the primary outcome. In Cox multivariable analysis, CAD+NICM or dualCM was independently associated with a higher risk of the primary outcome compared with CAD+ICM (adjusted hazard ratio, 1.23 [95% CI, 1.06-1.43]; P=0.007) after adjustment for potential confounders. The risks of the secondary outcomes of all-cause death and heart failure hospitalization were also higher with CAD+NICM or dualCM (hazard ratio, 1.21 [95% CI, 1.02-1.43]; P=0.032; and hazard ratio, 1.37 [95% CI, 1.11-1.69]; P=0.003, respectively), whereas the risk of cardiovascular death did not differ from that of CAD+ICM (hazard ratio, 1.15 [95% CI, 0.89-1.48]; P=0.28). In patients with CAD referred for clinical cardiovascular magnetic resonance imaging, NICM or dualCM was identified in 1 of every 6 patients and was associated with worse long-term outcomes compared with ICM. In patients with obstructive CAD, coincidental NICM or dualCM may contribute to the lack of prognostic benefit from coronary revascularization.

Everolimus-Eluting Stents or Bypass Surgery for Multivessel Disease in Diabetics: The BEST Extended Follow-Up Study

BackgroundDiabetes mellitus is associated with more complex coronary artery diseases. Coronary artery bypass grafting (CABG) is a preferred revascularization strategy over percutaneous coronary intervention (PCI) in diabetics with multivessel coronary artery disease (MVD). ObjectivesThis study sought to examine the different prognostic effects of revascularization strategies according to the diabetes status from the randomized BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trial. MethodsPatients (n = 880) with MVD were randomly assigned to undergo PCI with an everolimus-eluting stent vs CABG stratified by diabetics (n = 363) and nondiabetics (n = 517). The primary endpoint was the composite of death, myocardial infarction, or target vessel revascularization during a median follow-up of 11.8 years (IQR: 10.6-12.5 years). ResultsIn diabetics, the primary endpoint rate was significantly higher in the PCI group than in the CABG group (43% and 32%; HR: 1.53; 95% CI: 1.12-2.08; P = 0.008). However, in nondiabetics, no significant difference was found between the groups (PCI group, 29%; CABG group, 29%; HR: 0.97; 95% CI: 0.67-1.39; P = 0.86; Pinteraction= 0.009). Irrespective of the presence of diabetes, no significant between-group differences were found in the rate of a safety composite of death, myocardial infarction, or stroke and mortality rate. However, the rate of any repeat revascularization was significantly higher in the PCI group than in the CABG group. ConclusionsIn diabetics with MVD, CABG was associated with better clinical outcomes than PCI. However, the mortality rate was similar between PCI and CABG irrespective of diabetes status during an extended follow-up. (Ten-Year Outcomes of Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST Extended], NCT05125367; Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST], NCT00997828)

Risk prediction score for clinical outcome in atrial fibrillation and stable coronary artery disease

ObjectiveAntithrombotic therapy is essential for patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) because of the high risk of thrombosis, whereas a combination of antiplatelets and anticoagulants...

Short-Term Risk Stratification of Non–Flow-Limiting Coronary Stenosis by Angiographically Derived Radial Wall Strain

BackgroundDeferred revascularization of mildly stenotic coronary vessels based exclusively on physiological evaluation is associated with up to 5% residual incidence of future adverse events at 1 year. ObjectivesWe aimed to evaluate the incremental value of angiography-derived radial wall strain (RWS) in risk stratification of non–flow-limiting mild coronary narrowings. MethodsThis is a post hoc analysis of 824 non–flow-limiting vessels in 751 patients from the FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease) trial. Each individual vessel had ≥1 mildly stenotic lesion. The primary outcome was vessel-oriented composite endpoint (VOCE), defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction (nonprocedural), and ischemia-driven target vessel revascularization at 1-year follow-up. ResultsDuring 1-year follow-up, VOCE occurred in 46 of 824 vessels, with a cumulative incidence of 5.6%. Maximum RWS (RWSmax) was predictive of 1-year VOCE with an area under the curve of 0.68 (95% CI: 0.58-0.77; P < 0.001). The incidence of VOCE was 14.3% in vessels with RWSmax >12% vs 2.9% in those with RWSmax ≤12%. In the multivariable Cox regression model, RWSmax >12% was a strong independent predictor of 1-year VOCE in deferred non–flow-limiting vessels (adjusted HR: 4.44; 95% CI: 2.43-8.14; P < 0.001). The risk of deferred revascularization based on combined normal RWSmax and Murray–law-based quantitative flow ratio (μQFR) was significantly reduced compared with μQFR alone (adjusted HR: 0.52; 95% CI: 0.30-0.90; P = 0.019). ConclusionsAmong vessels with preserved coronary flow, angiography-derived RWS analysis has the potential to further discriminate vessels at risk of 1-year VOCE. (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease [FAVOR III China Study]; NCT03656848)

Antithrombotic monotherapy for stable coronary artery disease and atrial fibrillation patients with and without prior coronary artery revascularization: Insights from the AFIRE trial

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Japan Cardiovascular Research Foundation under a contract with Bayer Yakuhin Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial demonstrated that rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban plus a single antiplatelet therapy regarding efficacy and superior for safety endpoints in patients with atrial fibrillation and stable coronary artery disease including patients not requiring revascularization [prior percutaneous coronary intervention (PCI) or bypass grafting (CABG)]. Purpose The aim of this post-hoc subgroup analysis was to investigate the efficacy and safety of rivaroxaban monotherapy compared to combination therapy in patients with and without prior revascularization. Methods Among 2,215 patients included in the modified intention-to-treat analysis in the AFIRE trial, 1445 patients (65.2%) had undergone previous PCI alone, and 252 (11.4%) had undergone previous CABG. The remaining 518 patients (23.4%) was categorized as a group without prior revascularization and then compared with a group with prior revascularization (PCI or CABG). The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis. Results In 1697 patients with prior revascularization, efficacy and safety endpoints of rivaroxaban monotherapy were superior to combination therapy (efficacy: HR 0.62, 95%CI 0.45-0.85, p=0.003; safety: HR 0.62, 95%CI 0.39-0.98, p=0.040), whereas there were no significant differences in efficacy and safety endpoints among 518 patients without prior revascularization (efficacy: HR 1.19, 95%CI 0.67-2.11, p=0.553; safety: HR 0.47, 95%CI 0.18-1.26, p=0.125). There was a borderline interaction of efficacy endpoint (P for interaction=0.055) by randomized treatment assignment (Figure 1 and Figure 2). Compared with combination therapy, the safety benefit of rivaroxaban monotherapy on any bleeding was significant in patients without prior revascularization (HR 0.59, 95%CI 0.38-0.93, p=0.022). Conclusions In patients with prior PCI or CABG, rivaroxaban monotherapy resulted in more favorable safety and efficacy outcomes than combination therapy. There was a borderline interaction for primary efficacy outcome between prior revascularization and anti-thrombotic therapy.

Rivaroxaban Monotherapy in AtrialFibrillation and Stable Coronary Artery Disease Across Body Mass IndexCategories.

The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial showed both noninferiority for efficacy and superiority for safety endpoints of rivaroxaban monotherapy compared with those of rivaroxaban plus antiplatelet therapy (combination therapy) in patients with atrial fibrillation and stable coronary artery disease. This study sought to evaluate outcomes of rivaroxaban monotherapy in those patients across body mass index (BMI) categories. Patients were categorized into 4 groups: underweight (BMI<18.5kg/m2), normal weight (BMI 18.5 to<25kg/m2), overweight (BMI 25 to<30kg/m2), and obesity (BMI≥30kg/m2). Efficacy (a composite of all-cause death, myocardial infarction, unstable angina requiring revascularization, stroke, or systemic embolism) and safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria) were compared between rivaroxaban monotherapy and combination therapy across BMI categories. This study analyzed 2,054 patients with a median age of 75.0 years and CHA2DS2-VASc score of 4. A significant interaction was not observed between BMI categories and effect of monotherapy for efficacy (P=0.83) and safety (P = 0.07), although monotherapy was superior to combination therapy for efficacy in normal weight (HR: 0.64; 95%CI: 0.44-0.95) and safety in overweight (HR: 0.25; 95%CI: 0.10-0.62), whereas a significant difference in the endpoints was not observed in the other BMI categories. Rivaroxaban monotherapy had a similar effect on prognosis across all BMI categories in patients with atrial fibrillation and stable coronary artery disease. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease [AFIRE]; UMIN000016612, NCT02642419).

The BEST trial is here - but is anyone listening?

The long-term outcome of the Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease trial has recently been published. This appraisal provides a critical evaluation of the main findings of the study.

Remote digital smart device follow-up in prospective clinical trials: early insights from ORBITA-2, ORBITA-COSMIC, and ORBITA-STAR.

Smart devices are a fundamental media for acquisition, processing, storage, and transfer of digital health data. The global penetration and high frequency usage of smart devices such as smartphones and fitness monitors provide us an opportunity for incorporation into clinical trials to generate more clinically meaningful data. Reporting of angina can significantly vary between patients and also within patients at different timepoints. Furthermore, the nature of angina can lead to variation in ways patients adapt their activities of daily living and hence reporting of symptoms and quality of life. Current clinical trials investigating the effects of intervention on angina do not accurately incorporate these patient centred outcomes and considerations. Hence, methods to contemporaneously assess daily angina burden in a convenient, patient focused, and cost-effective manner are priorities for contemporary clinical trials to address. In this article, we provide our insights into the use of remote digital smart devices in clinical trials of stable coronary artery disease conducted by our research group. We discuss how our experiences from previous trials necessitated its incorporation and will provide us with important data that will inform clinical practice. We discuss the benefits and current challenges and limitations of smart device incorporation while providing our procedural workflow for how we incorporated smart devices into our clinical trials for others to consider. We hope that this approach will allow us to understand the perceptions and implications of angina on patient lives with greater granularity than previously explored.

Effect of rivaroxaban monotherapy vs. combination with anti-platelet therapy in patients with atrial fibrillation and stable coronary artery disease across different body mass index categories

Abstract Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial showed both noninferiority for efficacy and superiority for safety endpoints of rivaroxaban monotherapy compared to rivaroxaban plus antiplatelet therapy (combination therapy) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, no accumulating evidence regarding efficacy and safety of these fixed-dose direct oral anticoagulant therapy was available in underweight and obese patients. Purpose The aim of this post-hoc analysis of the AFIRE trial was to evaluate outcomes of rivaroxaban monotherapy (vs. combination therapy) in patients with AF and stable CAD across body mass index (BMI) categories. Methods Patients were categorized into groups 1 (underweight: BMI of &amp;lt;18.5 kg/m2), 2 (normal: BMI of 18.5 to &amp;lt;25 kg/m2), 3 (overweight: BMI of 25 to &amp;lt;30 kg/m2), and 4 (obesity: BMI of ≥30 kg/m2). Efficacy (a composite of all-cause death, myocardial infarction, unstable angina requiring revascularization, stroke, or systemic embolism) and safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria) were compared between rivaroxaban monotherapy and combination therapy across BMI categories. Results We analyzed 2,054 patients with a median age of 75.0 (interquartile range [IQR], 69 to 80)) years old and CHA2DS2-VASc of 4 (IQR, 3 to 5). Group 1 through 4 included 72 (3.5%), 1,158 (56.4%), 680 (33.1%), 144 (7.0%) patients and 62.3%, 52.3%, 36.2%, and 30.3% were received reduced dose of rivaroxaban, respectively. Although the sample sizes for group 1 and 4 were limited, monotherapy was superior to combination therapy for efficacy in group 2 (hazard ratio [HR], 0.64; 95% CI, 0.44 to 0.95) and safety in group 3 (HR, 0.25; 95% CI, 0.10 to 0.62), whereas a significant difference in the endpoints was not observed in the other BMI categories. Impact of monotherapy on endpoints did not have a significant interaction in BMI. Conclusions Rivaroxaban monotherapy had similar effect on prognosis across all BMI categories in patients with AF and stable CAD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Japan Cardiovascular Research Foundation based on a contract with Bayer Yakuhin, Ltd

One-Year Follow-Up of Vascular Intervention Trials Disrupted by the COVID-19 Pandemic: A Use-Case landscape

IntroductionThe COVID-19 pandemic had an unprecedented impact on cardiovascular clinical research. The decision-making and state of study operations in cardiovascular trials 1-year after interruption has not been previously described. MethodsIn the spring of 2020, we created a pandemic impact task force to develop a landscape of use case scenarios from 17 device trials of peripheral artery disease (PAD) and coronary artery disease (CAD) interventions. In conjunction with publicly available (clinictrials.gov) study inclusion criteria, primary endpoints and study design, information was shared for this use-case landscape by trial leadership and data owners. ResultsA total of 17 actively enrolling trials (9 CAD and 8 PAD) volunteered to populate the use case landscape. All 17 were multicenter studies (12 in North America and 5 international). Fifteen studies were industry-sponsored, of which 13 were FDA approved IDEs, one was PCORI-sponsored and two were sponsored by the NIH. Enrollment targets ranged from 150 to 9000 pts. At the time of interruption, 5 trials were <20 % enrolled, 9 trials were 50–80 % enrolled and 3 trials were >80 % enrolled. At 1 year, the majority of studies were continuing to enroll in the context of more sporadic but ongoing pandemic activity. ConclusionsAt 1 year from the first surge interruptions, most trials had resumed enrollment. Trials most heavily interrupted were trials early in enrollment and those trials not able to pivot to virtual patient and site visits. Further work is needed to determine the overall impact on vascular intervention trials disrupted during the COVID-19 pandemic.

Postoperative Atrial Fibrillation in Adults with Obstructive Sleep Apnea Undergoing Coronary Artery Bypass Grafting in the RICCADSA Cohort.

Postoperative atrial fibrillation (POAF) occurs in 20–50% of patients with coronary artery disease (CAD) after coronary artery bypass grafting (CABG). Obstructive sleep apnea (OSA) is also common in adults with CAD, and may contribute to POAF as well to the reoccurrence of AF in patients at long-term. In the current secondary analysis of the Randomized Intervention with Continuous Positive Airway Pressure (CPAP) in Coronary Artery Disease and Obstructive Sleep Apnea (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT 00519597), we included 147 patients with CABG, who underwent a home sleep apnea testing, in average 73 ± 30 days after the surgical intervention. POAF was defined as a new-onset AF occurring within the 30 days following the CABG. POAF was observed among 48 (32.7%) patients, occurring within the first week among 45 of those cases. The distribution of the apnea-hypopnea-index (AHI) categories < 5.0 events/h (no-OSA); 5.0–14.9 events/h (mild OSA); 15.0–29.9 events/h (moderate OSA); and ≥30 events/h (severe OSA), was 4.2%, 14.6%, 35.4%, and 45.8%, in the POAF group, and 16.2%, 17.2%, 39.4%, and 27.3%, respectively, in the no-POAF group. In a multivariate logistic regression model, there was a significant risk increase for POAF across the AHI categories, with the highest odds ratio (OR) for severe OSA (OR 6.82, 95% confidence interval 1.31–35.50; p = 0.023) vs. no-OSA, independent of age, sex, and body-mass-index. In the entire cohort, 90% were on β-blockers according to the clinical routines, they all had sinus rhythm on the electrocardiogram at baseline before the study start, and 28 out of 40 patients with moderate to severe OSA (70%) were allocated to CPAP. During a median follow-up period of 67 months, two patients (none with POAF) were hospitalized due to AF. To conclude, severe OSA was significantly associated with POAF in patients with CAD undergoing CABG. However, none of those individuals had an AF-reoccurrence at long term, and whether CPAP should be considered as an add-on treatment to β-blockers in secondary prevention models for OSA patients presenting POAF after CABG requires further studies in larger cohorts.

The impact of kidney function in patients on antithrombotic therapy: a post hoc subgroup analysis focusing on recurrent bleeding events from the AFIRE trial

BackgroundThe success of antithrombotic therapies is assessed based on thrombotic and bleeding events. Simultaneously assessing both kinds of events might be challenging, and recurrent bleeding events are often ignored. We tried to confirm the effects of kidney function on outcome events in patients undergoing antithrombotic therapy.MethodsAs a post hoc subgroup analysis of the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial, a randomized clinical trial with a median follow-up of 36 months, patients were divided into high and low estimated glomerular filtration rate (eGFR) groups with a cutoff value of 50 mL/min. The cumulative incidence of bleeding and crude incidence of recurrent bleeding per 100 patient-years were calculated. We used the Cox regression model with multiple failure time data for recurrent bleeding events.ResultsAmong 2092 patients, 1386 (66.3%) showed high eGFR. The cumulative bleeding events per 100 patients at 1 year were 5.4 and 6.2 in the high and low eGFR groups, respectively. The difference continued to increase over time. The hazard ratio for time to the first bleeding event in the high eGFR group was 0.875 (95% confidence interval 0.701–1.090, p = .234) and that for the first composite event was 0.723 (95% confidence interval 0.603–0.867, p < .000). The recurrent bleeding events per 100 person-years were 11.3 and 15.3 in the high and low eGFR groups, respectively, with a rate ratio of 0.738 (95% confidence interval 0.615–0.886, p = .001). During the observation period, the risk of bleeding changed with time. It peaked soon after the study enrollment in both groups. It decreased continuously in the high eGFR group but remained high in the low eGFR group.ConclusionsWe reaffirmed that kidney function affects bleeding events in patients on antithrombotic therapy, considering recurrent events. Patients should have detailed discussions with physicians regarding the possible bleeding events when continuing antithrombotic therapy, especially in patients with decreased kidney function.Trial registrationUMIN Clinical Trials Registry, UMIN000016612. ClinicalTrials.gov, NCT02642419. Registered on 21 October 2015.

Yoga-Based Cardiac Rehabilitation: Current Perspectives from Randomized Controlled Trials in Coronary Artery Disease

Coronary artery disease carries a high morbidity and mortality worldwide, and exercise-based cardiac rehabilitation programmes play a large role in secondary prevention. Exercise-based rehabilitation programmes are expensive, and in certain subgroups uptake is poor. Yoga has been suggested to show improvements in cardiovascular health which would support its use in cardiac rehabilitation programmes. We carried out a review of current randomized controlled trials to determine if yoga-based cardiac rehabilitation leads to reduced cardiac risk factors, and improved physiological and psychological outcomes in patients with coronary artery disease compared to standard care. Six randomized controlled studies were identified after a medical database search, and meta-analysis was carried out for the different outcomes. Overall, the addition of yoga to standard care resulted in improved subjective feeling of cardiac health and quality of life. There was also a trend towards improvement in left ventricular systolic function. Improvement in cardiac risk factors, MACE and psychological health in this cohort has still to be proven, but was not inferior to standard or enhanced care, and the benefits became more pronounced at longer follow-up. Future studies with longer follow-up and larger patient numbers would aid in accurately assessing the long-term benefit of yoga-based rehabilitation.

Antithrombotic Therapy for Atrial Fibrillation and Coronary Artery Disease in Patients With Prior Atherothrombotic Disease: A Post Hoc Analysis of the AFIRE Trial.

BackgroundAmong patients with atrial fibrillation and stable coronary artery disease, those with histories of atherothrombotic disease are at high‐risk for future ischemic events. This study investigated the efficacy and safety of rivaroxaban monotherapy in patients with atrial fibrillation, coronary artery disease, and histories of atherothrombotic disease.Methods and ResultsThis was a post hoc subanalysis of the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial. Patients with non‐valvular atrial fibrillation and coronary artery disease were recruited and randomized to receive the rivaroxaban monotherapy or combination therapy with rivaroxaban plus antiplatelet drug. For the purpose of this sub‐study, participants were divided into 2 subgroups, including the atherothrombosis group (those with histories of myocardial infarction, stroke, and/or peripheral artery disease; n=1052, 47.5%) and non‐atherothrombosis group (n=1163, 52.5%). The efficacy end point included cardiovascular events or all‐cause death, while the safety end point was major bleeding. Net adverse events consisted of all‐cause death, myocardial infarction, stroke, or major bleeding. In the atherothrombosis group, rivaroxaban monotherapy was significantly associated with a lower risk of net adverse events when compared with combination therapy (hazard ratio [HR], 0.50; 95% CI, 0.34–0.74; P<0.001), with a decrease in both efficacy (HR, 0.68; 95% CI, 0.47–0.99; P=0.044) and safety (HR, 0.37; 95% CI, 0.19–0.71; P=0.003) end points. By contrast, there were no differences between treatment outcomes for the non‐atherothrombosis group.ConclusionsRivaroxaban monotherapy significantly reduced net adverse events as compared with combination therapy for patients with atrial fibrillation, coronary artery disease, and prior atherothrombotic disease.RegistrationURL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000016612. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419.