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.

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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.

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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.

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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

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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). 

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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)

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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. 

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