BACKGROUND AND AIMS: Conventional biomarkers such as low-density lipoprotein (LDL) and high-density lipoprotein may fail to identify patients' risk for significant coronary artery disease (CAD). This study evaluates the...BACKGROUND AND AIMS: Conventional biomarkers such as low-density lipoprotein (LDL) and high-density lipoprotein may fail to identify patients' risk for significant coronary artery disease (CAD). This study evaluates the associations between multiple biomarkers and different CAD phenotypes, exploring a machine-learning biomarker-based patient clustering. METHODS AND RESULTS: We included 787 patients on primary prevention from the prospective ACTION registry (January 2024 to June 2025). All patients underwent coronary CTA and simultaneous biomarker testing, including LDL, high-density lipoprotein, triglyceride, apolipoprotein A-1, apolipoprotein B, lipoprotein(a) [Lp(a)], glycated hemoglobin (HbA1c), and high-sensitivity C-reactive protein. Of 382 patients (48.5%) with coronary artery calcium = 0, 42 (11%) had coronary plaque. These patients showed higher Lp(a) vs those without plaque (16.5 vs 11.5, P = .030), despite comparable SCORE2 risk (3.5% vs 3.0%, P = .284). Three biomarker-defined groups were identified after a machine learning unsupervised clustering: Cluster 1 had a favorable lipid profile with the lowest prevalence of CAD-Reporting and Data System (RADS) ≥ 3 (9.9%). Cluster 2 and 3, despite their significant intercluster differences in terms of Lp(a), LDL, and HbA1c levels, both showed a significantly higher prevalence of CAD-RADS ≥ 3 compared to cluster 1 (respectively 21.8% and 17.9%; vs cluster 1, P = .001). High-risk biomarker signatures were significantly associated to the prevalence of CAD-RADS ≥ 3, independently from the baseline SCORE2 (adjusted odds ratio 2.25; 95% confidence interval 1.32-3.82). CONCLUSIONS: Distinct biomarker signatures associate with distinct CAD prevalence and severity that conventional lipid markers fail to distinguish. Lp(a) appears relevant for early plaque detection in coronary artery calcium = 0 patients. A comprehensive biomarker evaluation may help identifying high-risk subgroups overlooked by a conventional assessment.
BACKGROUND: People living with HIV experience accelerated aging, increasing their risk of age-related diseases. Chronic inflammation may play an important role in premature vascular aging and myocardial fibrosis, leading...BACKGROUND: People living with HIV experience accelerated aging, increasing their risk of age-related diseases. Chronic inflammation may play an important role in premature vascular aging and myocardial fibrosis, leading to cardiac dysfunction. METHODS: We conducted a cross-sectional pilot study of matched veterans with and without HIV receiving care at the Providence VA Medical Center to explore the relationship between systemic inflammation, myocardial fibrosis, and subclinical cardiac disease in HIV. Participants were extensively phenotyped with questionnaires, physical exam, stress test, echocardiogram, cardiac MRI, coronary calcium score, and blood measurement of markers of inflammation and fibrosis. Multivariable linear regressions were used to investigate the associations. RESULTS: 21 veterans with HIV (mean age 54 years; 71% White, 29% Black) and 20 controls (mean age 56 years; 70% White, 30% Black) were included. We found higher growth differentiation factor (GDF)-15 blood levels, increased extracellular volume, and lower right heart function on MRI among patients with HIV, suggesting the presence of increased myocardial fibrosis and subclinical myocardial dysfunction in this population. CONCLUSION: Limited data from this pilot study suggest that HIV may be associated with increased cardiac fibrosis and decreased right ventricular function. This study highlights the need for larger longitudinal studies to better understand the trajectory of HIV-associated cardiac changes and help improve cardiac disease prevention in this population.
BACKGROUND: In patients with mitral regurgitation (MR), atrial fibrillation (AF), or heart failure (HF), are common indications for mitral valve surgery (MVS). However, whether first-time admissions for AF and HF are ass...BACKGROUND: In patients with mitral regurgitation (MR), atrial fibrillation (AF), or heart failure (HF), are common indications for mitral valve surgery (MVS). However, whether first-time admissions for AF and HF are associated with similar prognostic impact remains unclear. AIM: To evaluate the risk of mortality after MVS among patients with recent hospitalization for AF or HF. METHODS: Using Danish nationwide registries (2000-2023), we identified patients undergoing first-time MVS for MR. Based on admissions within 6 months before surgery, patients were categorized as: (1) no new AF/HF (no first-time admission for AF or HF), (2) AF group (first-time admission for AF but not HF), or (3) HF group (first-time admission for HF, irrespective of admission for AF). We examined the 1-year rate of HF admission from discharge using multivariable Cox regression. From the date of MVS, we examined the rate of mortality. RESULTS: Compared with patients with no new AF/HF, the adjusted rate of admission for HF was significantly higher in the AF group (hazard ratio [HR] 1.55; 95% CI: 1.19-2.02) and the HF group (HR 1.67; 95% CI: 1.33-2.11). When examining mortality, we observed a higher 30-day risk among patients in the HF group, and no difference between groups beyond 30 days of follow-up. CONCLUSION: In patients undergoing MVS for MR, first-time admission for AF or HF within 6 months before MVS was associated with increased risk of admission for HF after MVS. Mortality appeared higher in the HF group during the initial 30 days postsurgery.
RATIONALE: People with HIV (PWH) are at increased risk of cardiovascular disease. Moderate lipid lowering with statins has been demonstrated to reduce cardiovascular risk among PWH. Accordingly, evaluation of more potent...RATIONALE: People with HIV (PWH) are at increased risk of cardiovascular disease. Moderate lipid lowering with statins has been demonstrated to reduce cardiovascular risk among PWH. Accordingly, evaluation of more potent lipid-lowering strategies for prevention is needed, especially for PWH at higher risk. Prior research suggests that proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors safely lower low-density lipoprotein cholesterol by 60% among people with HIV, but the impact of PCSK9 inhibitors on arterial inflammation, endothelial function, coronary plaque, or markers of immune dysfunction among PWH remains unknown. METHODS: The effect of PCSK9 inhibition on cardiovascular risk in treated HIV infection study is a randomized, placebo-controlled, and double-blinded clinical trial. Adults at least 40 years old with treated and virally suppressed HIV and at least one cardiovascular risk factor (primary prevention) or a prior cardiovascular event (secondary prevention) are randomized in a 2:1 ratio to alirocumab or a matching placebo injected subcutaneously. F-fluorodeoxyglucose positron emission tomography/computed tomography, coronary computed tomographic angiography, and flow-mediated dilation of the brachial artery are conducted at baseline and after 1 year of treatment. The primary study outcome is the change in arterial inflammation assessed using the target-to-background ratio of the most diseased arterial segment on positron emission tomography/computed tomography from baseline to 1 year, and key secondary endpoints will include the change in noncalcified coronary plaque on coronary computed tomographic angiography, change in endothelial function, and safety according to the intention-to-treat principle. ENROLLMENT: One hundred eighteen participants were randomized. The mean age was 59.5 years, and 6% were female. CONCLUSIONS: The effect of PCSK9 inhibition on cardiovascular risk in treated HIV infection study will provide evidence regarding the mechanisms by which potent lipid lowering with PCSK9 inhibitors may alter the pathogenesis of atherosclerosis among PWH. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT03207945.
BACKGROUND: The radial artery approach is the predominant access site for percutaneous coronary interventions (PCI) due to its safety profile. Most centers prefer the right-radial artery approach (RRA) due to historical...BACKGROUND: The radial artery approach is the predominant access site for percutaneous coronary interventions (PCI) due to its safety profile. Most centers prefer the right-radial artery approach (RRA) due to historical laboratory configurations. However, a reduction in operator radiation exposure (ORE) has been theorized for the left-radial artery approach (LRA) due to better shielding and more favorable subclavian artery anatomy. OBJECTIVES: To compare ORE between the LRA and RRA during cardiac catheterization. METHODS: We performed a meta-analysis of ORE comparing LRA and RRA. The ratio of means (ROM) was used to estimate the mean effect size. RESULTS: This analysis includes 10 studies with 5,168 procedures (LRA, n = 2,410 vs RRA, n = 2,758). Cumulative ORE favored the LRA with lower levels at the thorax (ROM = 0.68, 95% CI: 0.52, 0.88, P <.001), left wrist (ROM = 0.64, 95% CI: 0.45, 0.93, P = .02), and neck (ROM = 0.68, 95% CI: 0.53, 0.86, P <.001). Cumulative ORE did not favor either the LRA or RRA at the left eye (ROM = 0.83, 95% CI: 0.63, 1.11, P = .22). Heterogeneity was high for thorax, left eye, and left wrist but not for neck. Possible publication bias was not present for thorax, left eye, and neck while left wrist had possible publication bias (Egger test: P = .02). CONCLUSIONS: We recommend that the LRA should be the primary access site for operators in order to reduce ORE in laboratories with standard shielding configurations.
BACKGROUND: Hypertension and obesity disproportionately affect veterans and contribute to cardiovascular disease. The sodium-restricted Dietary Approaches to Stop Hypertension eating pattern (DASH-SRD) reduces blood pres...BACKGROUND: Hypertension and obesity disproportionately affect veterans and contribute to cardiovascular disease. The sodium-restricted Dietary Approaches to Stop Hypertension eating pattern (DASH-SRD) reduces blood pressure (BP) and is guideline-recommended, but adherence is low in this population. We conducted a randomized trial of a remotely delivered dietary intervention to promote and sustain adoption of DASH-SRD in veterans with hypertension and obesity. METHODS: Veterans with hypertension and obesity received 2 weeks of home-delivered DASH-SRD meals after 2 weeks of ad-lib diet (Phase 1), then 5 telephone-delivered, dietitian-led motivational interviewing counseling sessions over 4 months, with or without a newly developed mobile application (Phase 2). DASH adherence (score 0-9 per 3-day food diary), clinic blood pressure (BP), and urinary sodium:potassium ratio was collected at baseline and at months 1 and 6 of Phase 2. Generalized estimating equations were used to evaluate changes in these parameters during the intervention. RESULTS: Sixty-one veterans (age 67 ± 8 years, 15% female, 16% non-White) with obesity (BMI 34.4 ± 5.2) and hypertension completed the trial. Dietary counseling session attendance was 96%. Between baseline and 6 months, DASH adherence score improved (1.8 ± 1.6-2.3 ± 1.4 points, P = .02), BP decreased (systolic 133 ± 17-128 ± 15 mmHg, P = .048; diastolic 73 ± 11-69 ± 12 mmHg, P = .03), and urinary sodium:potassium ratio declined (2.6 ± 1.1-1.5 ± 0.8, P < .001). There were no significant differences between the mobile application plus counseling and counseling-alone groups. CONCLUSION: In Veterans with hypertension and obesity, a brief interval of home-delivered meals followed by telephone dietitian counseling sustainably improved DASH-SRD adherence and reduced BP. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT03170375.
Thim T, Nissen H, Niemelä M
… +13 more, Eftekhari A, Jalanko M, Savontaus M, Jääskeläinen P, Hensey M, Jensen RV, Nørgaard BL, Frederiksen CA, Vase HØ, Pedersen L, Sørensen HT, Christiansen EH, Terkelsen CJ
INTRODUCTION: The COMPARE-TAVI trial framework was launched for direct comparison of transcatheter aortic valve implantation (TAVI) valves. The COMPARE-TAVI 1 trial, comparing Myval/Myval Octacor versus Sapien 3/Sapien 3...INTRODUCTION: The COMPARE-TAVI trial framework was launched for direct comparison of transcatheter aortic valve implantation (TAVI) valves. The COMPARE-TAVI 1 trial, comparing Myval/Myval Octacor versus Sapien 3/Sapien 3 Ultra transcatheter heart valves (THVs), was recently published. Here, we present the design and rationale for the COMPARE-TAVI 2 trial comparing the Evolut FX+ self-expandable THV with the Sapien 3 Ultra Resilia balloon-expandable THV. METHODS AND ANALYSIS: In the COMPARE-TAVI 2 trial (ClinicalTrials.gov NCT06470022), patients will be randomized 1:1 between the THVs. The trial will test whether the Evolut FX+ self-expandable THV is noninferior to the Sapien 3 Ultra Resilia balloon-expandable THV in terms of the combined 1-year primary composite endpoint of all-cause mortality, stroke, moderate/severe total aortic regurgitation, or moderate/severe hemodynamic THV deterioration, according to VARC-3 criteria. If noninferiority is proven, superiority analyses may apply. Based on a power of 80%, alpha level of 0.05, 1-sided test, noninferiority margin of 4.5%, and expected event rate of 12%, the necessary sample size has been estimated to be 1,364 patients. Prespecified secondary endpoints, including long-term follow-up for 10 years, will also be investigated. SUMMARY: The COMPARE-TAVI 2 will provide important information on the short- and long-term outcomes among patients treated with the Evolut FX+ self-expandable and the Sapien 3 Ultra Resilia balloon-expandable THVs.
For patients with anemia and myocardial infarction (MI), the randomized, 3,504-patient MINT trial found that a liberal transfusion threshold (10 g/dL) may be preferable to a restrictive threshold (8 g/dL) in terms of dea...For patients with anemia and myocardial infarction (MI), the randomized, 3,504-patient MINT trial found that a liberal transfusion threshold (10 g/dL) may be preferable to a restrictive threshold (8 g/dL) in terms of death or MI. The relative effects of liberal versus restrictive transfusion in younger and older patients are unknown. The present prespecified MINT substudy found no significant interaction between age and transfusion strategy for death or MI, heart failure, revascularization procedures, cardiac death, pulmonary embolism or deep vein thrombosis, bacteremia or pneumonia, and death at 30 and 180 days. A liberal transfusion approach appears to be safe and may be the preferred transfusion strategy in anemic patients with MI, regardless of age. MINT Trial, ClinicalTrials.gov Number NCT02981407, https://www.minttrial.org/.
Herbert BM, Carson JL, Bertolet M
… +10 more, Alexander JH, Goodman SG, Fergusson DA, Ducrocq G, Lopes RD, Simon T, Steg PG, Hebert PC, Brooks MM, MINT Investigators
We conducted a series of analyses to estimate the per-protocol effect of restrictive versus liberal transfusion strategies on 30-day death and death or recurrent myocardial infarction (MI) among patients from the Myocard...We conducted a series of analyses to estimate the per-protocol effect of restrictive versus liberal transfusion strategies on 30-day death and death or recurrent myocardial infarction (MI) among patients from the Myocardial Ischemia and Transfusion (MINT) trial. Multiple analytic approaches were used to estimate the per-protocol effect, including analyses based on different definitions of adherence (site-reported, time-based, transfusion delay) and an instrumental variable analysis. Analyses based on adherence definitions found a restrictive strategy was associated with a substantially greater risk of 30-day death or recurrent MI, while the instrumental variable analysis estimated a moderate treatment effect similar to the original ITT result.
BACKGROUND: Post‑acute sequelae of SARS‑CoV‑2 infection (Long COVID) affect a substantial proportion of individuals, and among the many reported symptom clusters, autonomic dysfunction, particularly postural orthostatic...BACKGROUND: Post‑acute sequelae of SARS‑CoV‑2 infection (Long COVID) affect a substantial proportion of individuals, and among the many reported symptom clusters, autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS), represents an important subset. The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative developed by the National Institutes of Health included a platform trial (RECOVER-AUTONOMIC) designed to assess the safety, tolerability, and efficacy of 3 interventions-(1) coordinated nonpharmacologic care, (2) pharmacotherapy with intravenous immunoglobulin (IVIG), and (3) pharmacotherapy with ivabradine-in treating POTS in adults with Long COVID. METHODS: RECOVER-AUTONOMIC is a multicenter, randomized, double-blinded, placebo-controlled, platform trial employing a flexible, adaptive design. Participants are randomized to IVIG or ivabradine with matching placebo, and (in a factorial design) to either coordinated nonpharmacologic care or usual care. The primary endpoint is the change in orthostatic intolerance symptoms measured by the Orthostatic Hypotension Questionnaire/Orthostatic Intolerance Questionnaire from baseline to the end of intervention. Secondary endpoints include quality of life, functional performance, symptom burden, and safety. Exploratory endpoints include autonomic function testing, wearable sensor data, and longitudinal biomarker profiling. DISCUSSION: RECOVER-AUTONOMIC seeks to determine the benefits and risks of IVIG and of ivabradine, as well as of coordinated nonpharmacologic care, for the treatment of POTS in Long COVID. Results from this trial will offer the largest source of evidence to help guide the medical care of this population. TRIAL REGISTRATION: ClinicalTrials.gov-Platform: NCT06305780; Appendix A (intravenous immunoglobulin): NCT06305793; Appendix B (ivabradine): NCT06305806. Protocol available at https://trials.recovercovid.org/autonomic.
Chen W, Musa AZ, Odubela O
… +16 more, Onakomaiya D, Mishra S, Kanneh N, Colvin CL, Mariam Y, Idigbe I, Nwankwo C, Odejobi Y, Adewumi A, Oladele DA, Tayo B, Aifah AA, Hu J, Ogedegbe G, Iwelunmor J, Ezechi O
BACKGROUND: Improved access to antiretroviral therapy (ART) has increased survival among people living with HIV (PLWH) but also the burden of cardiovascular risk factors like hypertension. While the task-strengthening st...BACKGROUND: Improved access to antiretroviral therapy (ART) has increased survival among people living with HIV (PLWH) but also the burden of cardiovascular risk factors like hypertension. While the task-strengthening strategy for hypertension control (TASSH) is a viable integrated care model, evidence of its clinical impact in Africa is limited. This report presents baseline findings from a trial evaluating 2 implementation strategies for integrating TASSH into HIV care across primary health centers (PHCs) in Lagos, Nigeria. METHODS: A total of 3,504 PLWH on antiretroviral therapy in 30 PHCs were screened, and 830 were enrolled. Baseline data on patient sociodemographic, clinical, laboratory results, and lifestyle characteristics were gathered. RESULTS: Among the 3,504 screened, 1,046 (29.9%) had hypertension. Of the 830 enrolled, mean [SD] age was 49.4 [9.5] years, 63.5% were women, 69.5% had at least secondary school education, 92.3% were employed, and 84.6% earned less than 100,000 Naira (64.74 USD) monthly. The median BP was 150.0/95.3 mmHg, and 63.9% were overweight or obese. 25.8% continued previously prescribed antihypertensive medications, while 66.3% received new prescriptions. Additionally, 25.1% and 1.8% were alcohol users and current smokers, while 30.9% were physically inactive. CONCLUSIONS: The prevalence of hypertension among PLWH was higher than previously reported. Although most participants adopted healthy lifestyle behaviors, the majority were overweight or obese, and many were not on antihypertensive medications. These findings highlight the importance of integrating hypertension control into HIV care across PHCs in Nigeria. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04704336). Registered on January 11, 2021. https://clinicaltrials.gov/study/NCT04704336.
Morrow A, Young R, Abraham GR
… +24 more, Hoole S, Oliveira JMG, Greenwood JP, Arnold JR, Ferreira V, Rakhit R, Galasko G, Sinha A, Perera D, Al-Lamee R, Spyridopoulos I, Kotecha A, Clesham G, Ford TJ, Davenport A, Padmanabhan S, Kaski JC, Weir RA, Sattar N, Ambery P, Welsh P, McConnachie A, Berry C, PRIZE Study Group
Exercise treadmill testing measures functional capacity and inducible myocardial ischemia and has historically served as an endpoint in phase 2 trials. The Precision Medicine with Zibotentan in Microvascular Angina trial...Exercise treadmill testing measures functional capacity and inducible myocardial ischemia and has historically served as an endpoint in phase 2 trials. The Precision Medicine with Zibotentan in Microvascular Angina trial evaluated the selective endothelin-A receptor antagonist zibotentan as a potential disease-modifying therapy for microvascular angina. The trial had a randomized, double-blind, cross-over design and the primary outcome was exercise duration. Compared with placebo, zibotentan at a dose of 10-mg daily for 12-weeks did not improve exercise duration or angina symptoms. In this prespecified analysis, exercise duration was compared across four sequential study visits and the factors associated with within-trial changes were evaluated. Exercise test duration increased progressively in all participants during sequential trial phases, independent of treatment with either zibotentan or placebo. This improvement in exercise duration was associated with female sex (interaction p-value = .0213; effect estimate [95% confidence interval]) 34.95 [13.99, 55.78] seconds, P = .002). In conclusion, the exercise test has limitations as an objective endpoint of efficacy in randomized trials. PRIZE; https://clinicaltrials.gov/study/NCT04097314 Clinicaltrials.gov Registration: NCT04097314.
BACKGROUND: Vasoactive medications constitute an integral component of the hemodynamic support strategy in patients with cardiogenic shock (CS). However, there is an emerging signal of harm associated with the commonly u...BACKGROUND: Vasoactive medications constitute an integral component of the hemodynamic support strategy in patients with cardiogenic shock (CS). However, there is an emerging signal of harm associated with the commonly used catecholamine, epinephrine (adrenaline), when used in the treatment of CS. The PAramedic randomized trial of Noradrenaline (norepinephrine) versus Adrenaline in the management of patients with cardiogenic shock (PANDA) was therefore designed to determine if the initial treatment with norepinephrine, compared with epinephrine, improves outcomes in patients with CS. METHODS AND DESIGN: The PANDA trial is a prehospital, open-label, single-blind, randomized controlled trial designed to assess the efficacy and safety of two commonly used catecholaminergic agents, norepinephrine and epinephrine, in the initial resuscitation of patients with suspected CS. Patients aged 18 years and older are eligible for recruitment by paramedics if there is clinical evidence of hypoperfusion, a measured systolic blood pressure of ≤90 mmHg despite adequate volume resuscitation with intravenous fluids, and the shock etiology is of a suspected cardiac cause (including cardiac arrest of an estimated duration of less than 30-minutes). Paramedics will randomize an anticipated 1,155 patients over an estimated 5-year period in a 1:1 ratio to receive an infusion of epinephrine or norepinephrine, which will be titrated to achieve a target systolic blood pressure of 100 mmHg. The primary efficacy outcome will be all-cause 28-day mortality. Recruitment commenced on February 28, 2024 and a total of 450 patients have been recruited thus far. IMPLICATIONS: The PANDA trial will determine if norepinephrine, compared to epinephrine, for the initial hemodynamic support in CS improves outcomes. The results will help inform future treatment recommendations for the management of patients with CS. TRIAL REGISTRATION: ACTRN12621000805875.
BACKGROUND: Hypertension represents a major contributor to the global cardiovascular (CV) disease burden, yet it remains inadequately controlled largely due to poor treatment adherence. Emerging digital health technologi...BACKGROUND: Hypertension represents a major contributor to the global cardiovascular (CV) disease burden, yet it remains inadequately controlled largely due to poor treatment adherence. Emerging digital health technologies hold promise for improving blood pressure (BP) management and CV outcomes, but the lack of evidence, unavailability in most countries, and out-of-pocket costs have hindered the widespread use of these technologies in clinical practice. OBJECTIVES: To assess in a randomized controlled trial whether a digital health intervention (DHI) based on the free Elfie solution compared to usual care will reduce systolic blood pressure (SBP) in adults with uncontrolled hypertension (SBP ≥ 140 mmHg). METHODS: This is a pragmatic, open-label, randomized parallel arm, international, multicenter clinical trial. Adult individuals with hypertension are randomly assigned to usual care or a DHI based on the Elfie solution. Elfie offers a comprehensive set of features designed to enhance self-monitoring, adherence and education, complemented with a gamification feature to boost engagement. The primary outcome is office SBP measured at 6 months. Secondary outcomes include medication adherence, diastolic BP, BP control achievement, hypertension knowledge, self-care, health-related quality of life and process outcomes assessing app usage and engagement. CONCLUSIONS: The ELFIE-HYPERTENSION trial is an international multicenter pragmatic randomized clinical trial, investigating the effects of an innovative, free and scalable DHI to improve BP control. If proven effective, this intervention can be easily and widely implemented in the management of hypertension in a variety of clinical settings globally. TRIAL REGISTRATION NUMBER: The trial is registered at the Clinicaltrials.gov (NCT06242483).
BACKGROUND: The completeness of revascularization in patients presenting with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) remains understudied. The SLIM trial previously demonstrated a s...BACKGROUND: The completeness of revascularization in patients presenting with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) remains understudied. The SLIM trial previously demonstrated a significant reduction in a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), repeat revascularization, and stroke with complete revascularization under a frequentist framework. This post hoc Bayesian re-analysis offers a probabilistic interpretation beyond conventional significance testing. METHODS: The primary composite endpoint was analyzed as in the original trial, while secondary endpoints of the composite were evaluated individually. Analyses under multiple priors assessed robustness. The minimal clinically important difference (MCID) was defined as 5% absolute risk difference (ARD) for the composite endpoint and 1% for individual endpoints. The primary model used a weakly informative prior on the log relative risk (RR) scale within a normal-normal Bayesian framework. RESULTS: Total 478 patients were randomized (complete: n = 240; culprit-only: n = 238). The posterior median RR for the composite endpoint was 0.41 (95% credible interval [CrI] 0.22-0.76), corresponding to an ARD of -7.9% (95% CrI -10.4% to -3.2%). The probability of any benefit was 99.8%, and the probability of meeting the MCID was 91.2%. For repeat revascularization, the ARD was -8.3% (95% CrI -10.0% to -4.5%), with a > 99.9% probability of clinically relevant benefit. For nonfatal MI, the ARD was -2.8% (95% CrI -4.2% to 0.9%), with a 94.8% probability of benefit. Results were consistent across all priors. CONCLUSION: Complete revascularization provides a high probability of clinically meaningful benefit in NSTEMI patients with MVD, primarily through reductions in nonfatal MI and repeat revascularization.
Drug eluting stents (DES) are the standard treatment for percutaneous coronary intervention (PCI) in real-world clinical practice. However, the implantation of DES is associated with significant limitations, such as the...Drug eluting stents (DES) are the standard treatment for percutaneous coronary intervention (PCI) in real-world clinical practice. However, the implantation of DES is associated with significant limitations, such as the development of neo-atherosclerosis and a persistent risk of stent failure during mid- and long-term follow-up. Currently, dual antiplatelet therapy (DAPT) after stent implantation is required for at least 1 month, with the majority of patients receiving DAPT treatment for 6 to 12 months, which carries an inherent increased risk of bleeding complications. Drug-coated balloons (DCB) are alternative to DES in some lesion settings, such as in-stent restenosis or small coronary artery disease (CAD), with promising initial results also in other clinical or lesion settings, such as acute coronary syndromes, de novo lesions and complex CAD. Although the safety of DCB has been shown in several studies, the optimal regimen and duration of antiplatelet therapy (APT) after DCB treatment remain unclear. In this study, we review the current evidence on protocol-mandated antiplatelet therapies across DCB studies and propose an antiplatelet algorithm for patients with CAD treated with DCB.
Baron DK, Weberndorfer V, Crijns HJGM
… +8 more, Hemels MEW, Tieleman RG, de Melis M, Schotten U, Linz D, Van Gelder IC, Rienstra M, RACE V Investigators
BACKGROUND: Atrial fibrillation (AF) may progress from paroxysmal AF (PAF) to more persistent forms, but the underlaying mechanisms are not well understood. The aim of this study was to assess the association between ath...BACKGROUND: Atrial fibrillation (AF) may progress from paroxysmal AF (PAF) to more persistent forms, but the underlaying mechanisms are not well understood. The aim of this study was to assess the association between atherosclerosis and AF progression in patients with PAF. METHODS: In this substudy of RACE V, 612 patients with PAF underwent extensive phenotyping at baseline and continuous rhythm monitoring. The association between atherosclerosis and AF progression was investigated. RESULTS: The median age was 64 (57-70) years, 257 (42%) were women, and the median CHADS-VA score was 2 (1-3). At baseline, 395 (65%) patients had atherosclerosis, defined by carotid/coronary imaging and/or history of vascular disease. Patients with atherosclerosis were older, had higher waist circumference, more hypertension, and lower eGFR than patients with no atherosclerosis. During a median of 3.4 (2.8-3.7) years follow-up, 108 (18%) patients had AF progression. The presence of atherosclerosis was associated with increased progression (21% vs. 12%; p = .004). In univariable analyses, atherosclerosis was a determinant of AF progression (OR: 2.04; 95% CI: 1.28-3.37; p = .004), and the association persisted following adjustment for established risk factors (OR: 2.23; 95% CI: 1.10-4.89; p = .034). CONCLUSIONS: In patients with paroxysmal AF, 65% of patients had atherosclerosis. Atherosclerosis was a determinant of AF progression after adjustment for established risk factors and comorbidities, suggesting that vascular disease may contribute directly to atrial remodelling and arrhythmia persistence.
INTRODUCTION: Catheter-based interventions (CBI) have yielded promising data in selected patients with acute pulmonary embolism (PE). Despite growing clinical use, high-quality comparative evidence on the efficacy and sa...INTRODUCTION: Catheter-based interventions (CBI) have yielded promising data in selected patients with acute pulmonary embolism (PE). Despite growing clinical use, high-quality comparative evidence on the efficacy and safety of CBI, especially in relation to standard anticoagulation or systemic thrombolysis, is limited. As new randomized controlled trials (RCTs) rapidly accumulate, this living evidence synthesis will aim to systematically and continuously evaluate the comparative efficacy and safety of reperfusion strategies vs standard of care in patients with high- and intermediate-risk acute PE. METHODS: This living systematic review and meta-analysis will include RCTs comparing reperfusion strategies to standard of care in adult patients with high- or intermediate-risk PE. The primary analysis will pertain to trials that are powered and designed to assess hard clinical outcomes, such as death and hemodynamic deterioration. A secondary analysis will include additional studies reporting clinical outcomes, including those primarily evaluating hemodynamic or surrogate outcomes. Analyses will be stratified by PE severity (high- and intermediate-risk) and also conducted using a frequentist network meta-analysis framework. The review is ongoing, with new eligible trials added prospectively. RESULTS: As of the initial search on 28 May 2025, 23 RCTs are included. Thirteen additional ongoing trials were identified for future inclusion, including trials with clinical outcomes such as PEITHO-3, HI-PEITHO, PEERLESS II, PE-TRACT, and PRAGUE-26 for intermediate-risk PE, and CATCH-PE II, PERSEVERE, and TORPEDONL for high-risk PE. CONCLUSION: This living meta-analysis will offer continuously updated, comparative evidence on reperfusion strategies for acute PE, with a focus on informing the role of catheter-based interventions in clinical decision-making. REGISTRATION:PROSPERO: CRD420251207053. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251207053.
INTRODUCTION: Both percutaneous left atrial appendage occlusion (LAAO) and nonvitamin K antagonist oral anticoagulants (NOACs) are noninferior to warfarin for stroke prevention in high-risk patients with atrial fibrillat...INTRODUCTION: Both percutaneous left atrial appendage occlusion (LAAO) and nonvitamin K antagonist oral anticoagulants (NOACs) are noninferior to warfarin for stroke prevention in high-risk patients with atrial fibrillation (AF). However, there is limited data comparing LAAO with NOACs. The CATALYST trial compares a dual-seal LAAO device (Amplatzer™ Amulet™) to NOACs in AF patients indicated for thromboprophylaxis. METHOD: CATALYST is a prospective, multicenter, randomized controlled, open-label trial with an adaptive statistical design. Up to 2,650 AF patients with CHADS-VASc score ≥2 (men) or ≥3 (women) will be randomly assigned to LAAO or NOAC at 123 global sites. Patients randomized to NOACs take the appropriate labeled dose with compliance monitored at each visit, while LAAO patients receive dual antiplatelet therapy followed by aspirin monotherapy for ≥12 months postimplant. Patients are followed through 5 years, with postimplant cardiac imaging at 3- and 12-months. There are three co-primary endpoints: (1) ischemic stroke, systemic embolism, or cardiovascular death through 2 years, tested for noninferiority; (2) major or clinically relevant nonmajor bleeding through 2 years, tested for superiority; and (3) ischemic stroke or systemic embolism through 3 years, tested for noninferiority. The following secondary endpoints will be tested if the primary endpoints are met: (1) all-bleeding, tested for noninferiority; (2) followed by testing for superiority; (3) disabling or fatal strokes, tested for superiority; all through 2 years. CONCLUSIONS: CATALYST is evaluating the safety and effectiveness of a dual seal LAAO device compared to NOACs in patients with AF at increased risk of stroke. CLINICAL TRIAL REGISTRATION: URL https://clinicaltrials.gov; Unique Identifier NCT04226547.