Key Points:

• The VICOTRIA trial previously demonstrated that vericiguat reduced the risk of  heart failure (HF) hospitalization or cardiovascular (CV) death in patients with recently decompensated HFrEF.
• The current VICTOR trial evaluated vericiguat vs placebo among those with stable, ambulatory HFrEF. 
• Although there was no significant difference in the primary endpoint of CV death or HF hospitalization, vericiguat significantly reduced CV death as well as overall worsening heart failure events in prespecified secondary analyses. 
• These findings suggests a positive impact of vericiguat on those with compensated, ambulatory HFrEF receiving contemporary guideline directed medical therapy (GDMT).  

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Key Points:

• VICTORIA and VICTOR and were randomized trials that evaluated vericiguat versus placebo in HFrEF patients with and without recent decompensation, respectively.
• This pre-specified pooled analysis of over 11,000 VICTOR and VICTORIA participants found that vericiguat reduced all-cause mortality, cardiovascular (CV) death, and heart failure (HF) hospitalizations.
• This benefit was most pronounced among those with a BNP ≤ 6000 pg/mL, a unique observation among HF drugs which warrants further research. 

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Key Points:

• The ABC-AF trial evaluated whether treatment recommendations based on biomarker-based risk scores could improve outcomes compared with standard guideline-based care in patients with atrial fibrillation (AF).
• Tailored management using the ABC-AF stroke and bleeding scores did not reduce the risk of stroke, death, or major bleeding.
• These results highlight the importance of validating precision medicine tools in prospective trials before routine clinical implementation.

Patients with atrial fibrillation (AF) are at elevated risk of stroke and often require oral anticoagulation (OAC). Although several validated biomarker-based risk scores (e.g., ABC-AF-stroke and ABC-AF-bleeding) have been developed to estimate individualized risk, their utility for guiding treatment decisions has not been rigorously tested in real-world clinical settings.

The ABC-AF trial, presented at ESC Congress 2025 and simultaneously published in Circulation, was a pragmatic, registry-based, randomized controlled trial designed to evaluate whether tailoring AF treatment based on individual ABC-AF risk scores could improve outcomes versus usual guideline-directed care.

Conducted across 39 Swedish sites, the open-label trial enrolled 3,933 patients with a median age of 73.9 years (34% women). Participants included those with both newly diagnosed and existing AF, with or without current OAC treatment. Patients were randomized 1:1 to receive either ABC-AF score-guided treatment or standard of care. In the intervention arm, plasma biomarkers were measured and risk scores calculated, and investigators received treatment recommendations based on individualized stroke and bleeding risk profiles. The primary outcome was a composite of stroke or death.

After a median follow-up of 2.6 years, the primary outcome occurred at a similar rate in both groups: 3.18 vs. 2.67 events per 100 patient-years (HR 1.19; 95% CI 0.96–1.48; p=0.12). There were no significant differences in the rates of stroke (HR 1.18; p=0.44), death (HR 1.21; p=0.13), or major bleeding (HR 1.08; p=0.50).

Although OAC use increased more in the active arm (97.8% vs. 92.6%), and there were shifts in the types of OACs used (increased apixaban and dabigatran, decreased rivaroxaban and warfarin), these changes did not translate into improved outcomes. Antiplatelet use decreased and statin use increased similarly in both groups.

Recruitment was stopped early due to a non-significant trend toward increased mortality in patients with CHA2DS2-VASc ≥3 in the intervention arm. Investigators noted that lower-than-expected event rates and underpowering may have limited the ability to detect a benefit.

“We found no benefit of individually tailored, multidimensional treatment recommendations based on ABC-AF-stroke and ABC-AF-bleeding scores compared with usual care,” said principal investigator Professor Jonas Oldgren (Uppsala University). “These findings emphasize the need for prospective testing of risk stratification tools in clinical settings before widespread implementation.”

Funded by the Swedish Research Council, the Swedish Heart-Lung Foundation, and Roche Diagnostics, ABC-AF underscores the importance of rigorous validation of personalized treatment strategies in AF.

Key Points:

• Uncontrolled and resistant hypertension remains a major challenge despite treatment with multiple antihypertensive agents.
• Baxdrostat, a selective aldosterone synthase inhibitor, significantly reduced systolic blood pressure (SBP) at 12 weeks compared to placebo in patients with treatment-resistant or uncontrolled hypertension.
• The effect of baxdrostat was sustained across all phases of the study, with no unanticipated safety concerns.

Despite widespread use of multiple medications, many patients with hypertension fail to achieve target blood pressure (BP) levels. In particular, patients with uncontrolled or treatment-resistant hypertension face persistently elevated BP despite being on two or more antihypertensive agents, including a diuretic. Aldosterone is a known contributor to treatment resistance, but efforts to safely and selectively inhibit aldosterone synthesis have historically been unsuccessful.

The BaxHTN trial, presented in a Hot Line session at the ESC Congress 2025 and simultaneously published in the New England Journal of Medicine, evaluated the efficacy and safety of baxdrostat, a first-in-class selective aldosterone synthase inhibitor. The randomized phase 3 trial enrolled 796 patients at 214 sites worldwide. Eligible participants had a seated SBP between 140 and 170 mmHg despite treatment with maximally tolerated antihypertensive regimens.

In the 12-week double-blind phase (Part 1), patients were randomized 1:1:1 to receive baxdrostat 1 mg, baxdrostat 2 mg, or placebo. The mean age was 62 years, and 39% were women; 73% had resistant hypertension. At week 12, placebo-adjusted reductions in seated SBP were −8.7 mmHg for the 1 mg dose and −9.8 mmHg for the 2 mg dose (both p<0.0001). Ambulatory 24-hour SBP also fell by 16.9 mmHg with the 2 mg dose, with night-time reductions of 11.7 mmHg. BP control (SBP <130 mmHg) was achieved in 40% of patients on baxdrostat 2 mg versus 18.7% on placebo.

Part 2 re-randomized patients to receive baxdrostat 2 mg or standard-of-care in an open-label extension. At the end of Part 2, mean SBP was 133 mmHg. In Part 3, patients previously receiving baxdrostat 2 mg were randomized to either continue treatment or switch to placebo for eight weeks. SBP rose in the placebo group (+1.4 mmHg) but continued to decline in the baxdrostat group (−3.7 mmHg; p=0.0016), confirming sustained BP-lowering efficacy.

Baxdrostat was generally well tolerated. Serious adverse events occurred in 1.9%, 3.4%, and 2.7% of the 1 mg, 2 mg, and placebo groups, respectively. Hyperkalemia led to treatment discontinuation in 0.8% and 1.5% of patients on baxdrostat 1 mg and 2 mg, respectively. There were no cases of adrenocortical insufficiency.

“These findings are an important advance in our understanding of hard-to-treat hypertension,” said principal investigator Professor Bryan Williams (University College London). “Baxdrostat achieved clinically meaningful BP reductions without unexpected safety concerns, offering new hope for patients with resistant or uncontrolled hypertension.”

Funded by AstraZeneca, the BaxHTN trial supports selective aldosterone synthase inhibition as a promising new strategy for patients whose blood pressure remains uncontrolled despite conventional therapy.

Key Points:

• Standard anticoagulation for provoked venous thromboembolism (VTE) is often discontinued after 3–6 months, but patients with enduring risk factors may remain at elevated risk for recurrence.
• The HI-PRO trial showed that extended use of low-intensity apixaban (2.5 mg twice daily) significantly reduced symptomatic VTE recurrence over 12 months compared to placebo.
• The intervention was well tolerated, with a low incidence of major bleeding.

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Key Points:

• Beta-blockers are widely used as first-line therapy for obstructive hypertrophic cardiomyopathy (HCM), despite limited evidence supporting their efficacy.
• In the MAPLE-HCM trial, aficamten monotherapy significantly improved exercise capacity, symptoms, and cardiac biomarkers compared with metoprolol in patients with symptomatic obstructive HCM.
• Benefits of aficamten were observed even in newly diagnosed or treatment-naïve patients, with no major safety concerns.

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Key Points:

• Evidence for NSTEMI management among older adults is limited, and further limited for frail older adults
• The SENIOR-RITA trial was a multicenter randomized trial of adults older than 75 with NSTEMI, finding that an invasive strategy is safe but not associated with reduced MACEs
• The SENIOR-RITA Frail Analysis was a prospective analysis of frail older adults to investigate the same question among this cohort
• This subgroup analysis similarly found that an invasive approach was safe but not associated with reduced MACEs compared to conservative management

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Key Points:

• LOSE-AF is the first randomized trial to rigorously assess the effect of structured weight loss on AF symptoms in older adults with persistent atrial fibrillation (AF).
• Although participants in the intervention group achieved sustained and safe weight loss, there was no significant difference in AF symptom burden or recurrence compared with usual care.
• The findings challenge existing recommendations for weight loss in older patients with persistent AF and suggest that weight loss alone is insufficient to improve rhythm outcomes in this population.

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