Daily Cardiology Research Analysis

BACKGROUND: Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown. METHODS: Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion. The primary end point was major or clinically relevant nonmajor bleeding. RESULTS: A total of 1287 patients underwent randomization; the median age was 74 years, and 44% were women. At 3 months, the median reduction in free factor XI levels with abelacimab at a dose of 150 mg was 99% (interquartile range, 98 to 99) and with abelacimab at a dose of 90 mg was 97% (interquartile range, 51 to 99). The trial was stopped early on the recommendation of the independent data monitoring committee because of a greater-than-anticipated reduction in bleeding events with abelacimab. The incidence rate of major or clinically relevant nonmajor bleeding was 3.2 events per 100 person-years with 150-mg abelacimab and 2.6 events per 100 person-years with 90-mg abelacimab, as compared with 8.4 events per 100 person-years with rivaroxaban (hazard ratio for 150-mg abelacimab vs. rivaroxaban, 0.38 [95% confidence interval {CI}, 0.24 to 0.60]; hazard ratio for 90-mg abelacimab vs. rivaroxaban, 0.31 [95% CI, 0.19 to 0.51]; P<0.001 for both comparisons). The incidence and severity of adverse events appeared to be similar in the three groups. CONCLUSIONS: Among patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban. (Funded by Anthos Therapeutics; AZALEA-TIMI 71 ClinicalTrials.gov number, NCT04755283.).

BACKGROUND: Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient setting is unknown because previous studies lacked objective reference standards. METHODS: Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation. Derived cut points were tested in 3 additional validation cohorts (cohorts 4-6) in whom HFpEF was diagnosed by resting catheterization only (n=260), previous hospitalization for heart failure (n=447), or exercise echocardiography (n=517), respectively. RESULTS: Current recommended rule-out NT-proBNP threshold <125 pg/mL had 82% sensitivity (95% CI, 77%-88%) with a body mass index (BMI) <35 kg/m CONCLUSIONS: In patients with chronic unexplained dyspnea, current rule-in and rule-out NT-proBNP diagnostic thresholds lead to unacceptably high error rates, with important interactions by obesity and AF status. In our study, NT-proBNP provided little value in those with AF and dyspnea because the presence of AF is by itself a robust biomarker of HFpEF. Use of separate rule-in and rule-out diagnostic thresholds stratified by BMI reduces miscategorization and can guide more appropriate use of exercise testing for possible HFpEF.

IMPORTANCE: Nocturnal hypertension while asleep is associated with substantial increases in risk of cardiovascular disease (CVD) and death. Whether hypertension while supine is a risk factor associated with CVD independent of seated hypertension remains unknown. OBJECTIVE: To investigate the association between supine hypertension and CVD outcomes and by hypertension treatment status. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the Atherosclerosis Risk in Communities (ARIC) study, which was established in 1987 to examine cardiovascular risk factors among middle-aged adults from 4 communities in the US. Supine and seated blood pressure were measured in more than 13 000 middle-aged adults with longitudinal surveillance for CVD over 27 years. Participants with a history of coronary heart disease (CHD), heart failure, or stroke were excluded. Data were analyzed from May 2023 through December 2024. EXPOSURES: Supine hypertension (supine systolic blood pressure ≥130 or diastolic blood pressure ≥80 mm Hg) with and without seated hypertension (seated systolic blood pressure ≥130 or diastolic blood pressure ≥80 mm Hg). MAIN OUTCOMES AND MEASURES: Cox proportional hazard models with adjustment for CVD risk factors were performed to investigate the association of supine hypertension with and without seated hypertension with incident CHD, heart failure, stroke, fatal CHD, and all-cause mortality. RESULTS: Of 11 369 participants without known CVD (6332 female [55.7%] and 5037 male [44.3%]; 2858 Black [25.1%] and 8511 White [74.9%]; mean [SD] age 53.9 [5.7] years]), 16.4% (95% CI, 15.5%-17.2%) of those without seated hypertension had supine hypertension and 73.5% (95% CI, 72.2%-74.8%) of those with seated hypertension had supine hypertension. Supine hypertension was associated with incident CHD (hazard ratio [HR], 1.60; 95% CI, 1.45-1.76), heart failure (HR, 1.83; 95% CI, 1.68-2.01), stroke (HR, 1.86; 95% CI, 1.63-2.13), fatal CHD (HR, 2.18; 95% CI, 1.84-2.59), and all-cause mortality (HR, 1.43; 95% CI, 1.35-1.52) during a median (25th, 75th percentile) follow-up of 25.7 (15.4, 30.4) years, 26.9 (17.6, 30.5) years, 27.6 (18.5, 30.6 years), 28.3 (20.5, 30.7) years, and 28.3 (20.5 years, 30.7) years, respectively. There were no meaningful differences by seated hypertension status. Results were similar by hypertension medication use. Participants with supine hypertension alone had risk associations similar to those of participants with hypertension in both positions and significantly greater than those of participants with seated hypertension alone with the exception of fatal CHD; seated vs supine HRs were 0.72 (95% CI, 0.61-0.85) for CHD, 0.72 (95% CI, 0.60-0.85) for heart failure, 0.66 (95% CI, 0.51-0.86) for stroke, and 0.83 (95% CI, 0.74-0.92) for all-cause mortality. CONCLUSIONS AND RELEVANCE: Supine hypertension regardless of seated hypertension had a higher HR for CVD risk than seated hypertension alone. Future research should evaluate supine hypertension in the setting of nocturnal hypertension and as an independent target of blood pressure treatment.