Key Points:

• Saphenous vein graft (SVG) failure is common after coronary artery bypass grafting (CABG), with an occlusion rates of 20% within the first year after surgery. 
• The role of LDL-cholesterol (LDL-C) lowering in preventing SVG failure is uncertain. 
• NEWTON-CABG Cardiolink 5 found that starting evolocumab with 21 days of CABG in addition to background statin therapy did not improve SVG patency at 2 years compared to placebo, despite substantial additional LDL-C lowering. 
• Further research is required to identify therapies that reduce the risk of SVG failure.

Continue reading →

Key Points:

• Dapagliflozin is a key component of GDMT for heart failure, but it is unknown whether inpatient initiation improves outcomes.
• The DAPA ACT HF-TIMI 68 was a randomized, double-blind trial which examined the efficacy and safety of in-hospital initiation of dapagliflozin in inpatients with HF.
• Dapagliflozin did not significantly reduce the risk of CV death or worsening HF at two months, but a pre-specified meta-analysis inclusive of three SGLT2is indicated a potential early benefit.

Continue reading →

Key Points:

• Optimization of GDMT is critical, particularly in the initial months after diagnosis of HFrEF.
• An AI-powered virtual assistant resulted in 100% of enrolled patients on maximally tolerated doses of all four pillars of GDMT by the end of the twelve week follow-up period, with 93% agreement with clinician recommendations by the end of the trial.

Continue reading →

Key Points:

• Chronic Chagas cardiomyopathy (CCC) patients are underrepresented in heart failure (HF) trials and have a worse prognosis than other etiologies
• The PARACHUTE-HF trial was the first randomized, phase IV study evaluating sacubitril-valsartan versus enalapril in patients with chronic Chagas cardiomyopathy (CCC) and heart failure with reduced ejection fraction (HFrEF) among over 900 patients across 100 sites in Latin America
• The study found ARNI was significantly favored over enalapril in a primary hierarchical composite outcome of time to cardiovascular death, first heart failure hospitalization, or relative change in NT-proBNP at 12 weeks (stratified win ratio 1.52; 95% CI 1.28-1.82; p < 0.001)
• The investigators concluded that this was the first randomized trial supporting specific pharmacologic therapy in a unique high-risk cohort (CCC patients), with need for future studies to better understand and treat such patients

Chronic Chagas cardiomyopathy (CCC), a severe form of heart failure (HF) resulting from Trypanosoma cruzi infection, affects millions, primarily in Latin America, but also increasingly in regions like North America and Europe due to migration. This condition carries a worse prognosis despite often affecting younger individuals with fewer comorbidities. Notably, patients with Chagas-related HF have been underrepresented in landmark HFrEF trials. PARACHUTE-HF is the first randomized study evaluating guideline-directed medical therapy (GDMT, specifically ARNI vs ACE inhibitor) in this population.

PARACHUTE-HF was an academic-led, open-label, randomized, blinded-endpoint adjudication trial conducted at over 80 sites across Brazil, Argentina, Mexico, and Colombia. A total of 922 patients with confirmed Chagas infection (by two positive serologies), LVEF ≤40%, NYHA II-IV symptoms, and elevated NT-proBNP (or recent HF hospitalization) were randomized 1:1 to sacubitril/valsartan (titrated to 200 mg BID) or enalapril (titrated to 10 mg BID). The primary outcome was a hierarchical composite – cardiovascular death, first HF hospitalization, and relative change in NT-proBNP at 12 weeks – analyzed via the win ratio approach.

Sacubitril/valsartan demonstrated a 52% higher likelihood of a superior outcome versus enalapril (win ratio 1.52; 95% CI, 1.28–1.82; p < 0.001). This benefit was primarily due to significantly greater NT-proBNP reduction: a logarithmic median drop of -30.6% vs -5.5%, translating to an adjusted geometric mean change ratio of 0.68 (95% CI, 0.62–0.75). Over a median follow-up of 25 months, rates of cardiovascular death (HR 0.95; 95% CI, 0.73–1.23) and first HF hospitalization (HR 0.92; 95% CI, 0.70–1.20) were comparable between groups. Discontinuation due to adverse events occurred in 6.1% for ARNI and 9.8% for enalapril; both appeared similarly well tolerated.

PARACHUTE-HF marks a milestone in Chagas-related HF research, demonstrating that sacubitril/valsartan results in superior biomarker improvements compared to enalapril in a previously neglected disease context. Although the trial wasn’t powered for mortality or hospitalization endpoints, the substantial NT-proBNP reduction, an established prognostic marker, suggests meaningful clinical potential. The trial also serves as a successful model for international collaboration addressing neglected cardiovascular diseases. This is best summarized by Principal Investigator Renato Lopes, MD, PhD: “Our study provides the first randomized trial evidence to support a pharmacological treatment specifically in this high-risk population. PARACHUTE-HF shows that much-needed studies to better characterize chronic Chagas cardiomyopathy and to define the benefit/risk of new therapies in this condition are possible.”

Key Points:

• Eighty percent of HF cases are diagnosed only during emergency hospital admissions, which negatively impacts survival rates and increases treatment costs
• The TRICORDER trial was a cluster randomized controlled study of 200 primary care practices across the UK, one using the AI-stethoscope and the other continuing with standard diagnostic practices
• Though an intention-to-treat analysis was negative, the per-protocol analysis showed increased detection of HF, AF, and VHD with use of the stethoscope 
• The trial found that, in a real-world analysis, utilization dropped to 60% over 12 months, but the pragmatic design of this trial might be useful for future AI implementation analyses

Continue reading →

Key Points:

• Hypertension (HTN) is a major driver of stroke and cardiovascular disease, especially in rural and resource-limited areas
• The IMPACT-BP trial was an open-label, randomized trial in rural South Africa (KwaZulu-Natal) comparing standard clinic-based care with two home-based, community health worker (CHW)-supported BP management strategies
• The home-based CHW model achieved a mean systolic BP reduction of -7.9 mmHg; the enhanced CHW model (with cellular-transmitting BP devices) achieved -9.1 mmHg vs standard-of-care (both p < 0.001) as well as improved HTN control (57.6% in standard care vs 76.9% (CHW) and 82.8% (enhanced CHW)) at 6 months, sustained through 12 months
• Furthermore, patient safety and retention were excellent, further supporting the benefit of CHWs in HTN and other chronic non-communicable diseases (NCDs). 

Continue reading →

Key Points:

• Many patients do not achieve BP goals in hypertension (HTN) due to adherence issues, so zilebesiran, a twice-yearly dosed RNA-i antihypertensive, may demonstrate benefit in these patients
• The KARDIA-3 trial was a phase 2, randomized, double-blind, placebo-controlled trial testing subcutaneous zilebesiran (300 or 600 mg) added to 2-4 background antihypertensives in adults with CVD or high CV risk
• The study was negative for its primary endpoint: at 3 months, office SBP was lower vs placebo by -5.0 mmHg with 300 mg and -3.3 mmHg with 600 mg (not significant after multiplicity adjustment).
• However, the trial was notable for signals of benefit, including larger ambulatory and nighttime BP reductions and a sizable effect in patients on diuretics with baseline SBP ≥140 mmHg (-9.2 mmHg at 3 months)

Continue reading →

Key Points:

• Olezarsen, an anti-sense oligonucleotide targeting APOC3 mRNA, is approved to lower triglycerides (TG) in adults with rare familial chylomicronemia, but its safety and efficacy in a broader populations is unknown. 
• In Essence-TIMI 73b, olezarsen significantly reduced TG by ~60% compared with placebo in patients with moderate or severe hypertriglyceridemia and elevated CV risk. 
• There was also improvement in other atherogenic lipid measurements with no major safety concerns apart from mild to moderate injection site reactions. 

Continue reading →

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).  

Continue reading →

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. 

Continue reading →

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.

Continue reading →

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.

Continue reading →

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

Continue reading →

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.

Continue reading →

Key Points:

• Standard cardiology practice recommends aspirin monotherapy indefinitely after DAPT for prevention of cardiovascular events after PCI, but some data has suggested clopidogrel therapy may be a superior alternative
• The SMART-CHOICE 3 trial is the first large multicenter trial to evaluate clopidogrel versus aspirin monotherapy among 5000 patients in 26 sites across South Korea
• The study found a significant improvement in major adverse cardiovascular and cerebrovascular outcomes among clopidogrel versus aspirin with no significant increase in bleeding
• This trial has ramifications for chronic coronary disease management in high risk ischemic patients after standard DAPT post-PCI

Continue reading →

Key Points:

• The FAME 3 trial tested whether percutaneous coronary intervention (PCI) could offer comparable long-term outcomes to coronary artery bypass grafting (CABG) in patients with multivessel coronary artery disease by limiting intervention to flow-limiting lesions as determined by fractional flow reserve (FFR)
• Among 1,500 patients, FFR-guided PCI as compared to CABG had similar death and stroke rates but PCI resulted in higher rates of myocardial infarction and repeat revascularization.
• These findings support shared decision-making in selecting revascularization strategies, highlighting the evolution of PCI outcomes in contemporary practice.

Continue reading →

Key Points:

• This study presents updated national data from the Race Associated Cardiac Event Registry (RACER) on cardiac arrest incidence and outcomes during long-distance running races in the United States between 2010 and 2023.
• Among over 29 million race finishers, cardiac arrest occurred at a rate of 0.60 per 100,000 finishers, with significantly higher rates in men (1.12 per 100,000) compared to women (0.19 per 100,000) and marathon participants (1.04 per 100,000) versus half-marathoners (0.47 per 100,000). The overall survival to hospital discharge improved to 66% during this period, a marked increase from earlier data.
• Although cardiac arrest during long-distance running races remains exceedingly rare, enhanced emergency preparedness—particularly rapid CPR and defibrillation—has significantly improved outcomes.

Continue reading →

Key Points:

• Prior trials have demonstrated limited benefit to intra-aortic balloon pump (IABP) use in acute myocardial infarction-related cardiogenic shock, but the role of IABP in heart failure-related cardiogenic shock (HF-CS) is not yet clear.
• The ALTSHOCK2 trial was designed to examine the utility of early IABP implantation in improving the primary endpoint of 60-day survival or bridge to heart replacement therapy (HRT) in HF-CS.
• There was no difference in the primary endpoint between early IABP and standard of care treatment.

Continue reading →