Daily Cardiology Research Analysis
Analyzed 179 papers and selected 3 impactful papers.
Summary
Analyzed 179 papers and selected 3 impactful articles.
Selected Articles
1. Zodasiran, an RNAi therapeutic targeting ANGPTL3, for treating patients with homozygous familial hypercholesterolaemia (GATEWAY): an open-label, randomised, phase 2 trial.
In 18 HoFH patients randomized to zodasiran 200 mg or 300 mg, LDL-C decreased by −35.7% and −39.9% at 6 months, with sustained pooled reductions (−40.7%) during a 12-month open-label extension. LDL-C lowering was larger in those on background PCSK9 inhibition (~−56% at 6 months). Safety was favorable with no drug-related severe adverse events or deaths.
Impact: First-in-class LDLR-independent RNAi lowering LDL-C in HoFH addresses a critical unmet need with robust effect size and quarterly dosing convenience.
Clinical Implications: If confirmed in phase 3, zodasiran could become a foundational therapy for HoFH, complementing or replacing LDLR-dependent agents and enabling deeper LDL-C reduction, especially in combination with PCSK9 inhibitors.
Key Findings
- LDL-C reductions at 6 months: −35.7% (200 mg) and −39.9% (300 mg).
- Sustained pooled LDL-C lowering of −40.7% during 12-month open-label extension.
- Greater LDL-C reduction with background PCSK9 inhibitor use (−55.8% at month 6; −51.9% at month 12).
- Favorable safety with no drug-related severe adverse events or deaths; common AEs included nasopharyngitis and dizziness.
Methodological Strengths
- Randomized, multicountry phase 2 design with dose comparison and trial registration.
- Consistent LDL-C lowering across randomized and extension phases with predefined endpoints.
Limitations
- Small sample size (n=18) and open-label design without a placebo comparator.
- Early study termination for business reasons and limited diversity of genetic backgrounds.
Future Directions: Conduct adequately powered, placebo-controlled phase 3 trials to confirm efficacy/safety, evaluate cardiovascular outcomes, and define positioning with PCSK9 inhibitors, lomitapide, and apheresis.
2. Updated Meta-Analysis of Catheter Ablation Versus Medical Therapy in Atrial Fibrillation With Heart Failure With Preserved Ejection Fraction.
Across 12 studies including 43,584 patients with AF and HFpEF, catheter ablation was associated with significantly lower composite cardiovascular events, all-cause mortality, and stroke versus medical therapy. The analysis was prospectively registered and used random-effects pooling, strengthening confidence in the findings.
Impact: This synthesis addresses a key evidence gap by focusing specifically on HFpEF, where rhythm control strategies have been uncertain, and demonstrates clinically meaningful benefits of ablation.
Clinical Implications: For symptomatic AF with HFpEF, early consideration of catheter ablation may reduce death, stroke, and heart failure events compared with medical therapy alone. Multidisciplinary evaluation should prioritize rhythm control candidacy.
Key Findings
- Included 12 studies with 43,584 patients with AF and HFpEF.
- Catheter ablation reduced the primary composite endpoint versus medical therapy (reported as HR 0.53, 95% CI 0.41–0.68).
- All-cause mortality and stroke were lower with ablation than with medical therapy.
- PROSPERO-registered; random-effects models were used.
Methodological Strengths
- Large aggregated sample size with prespecified registration (PROSPERO).
- Random-effects modeling across studies and comprehensive outcome assessment.
Limitations
- Heterogeneity across included studies and potential mix of observational and randomized evidence.
- Incomplete reporting of heterogeneity metrics and subgroup effects in the abstract.
Future Directions: Large, pragmatic RCTs in HFpEF focusing on rhythm-control-first strategies, standardized endpoints, and cost-effectiveness are needed to guide guideline updates.
3. A platelet transcriptomic signature of thromboinflammation predicts cardiovascular risk.
In 149 individuals profiled twice, a 42-gene thromboinflammation platelet signature (TIPS) correlated with monocyte–platelet aggregates, was reproducible, elevated in COVID-19 and myocardial infarction, and predicted future events after lower extremity revascularization (adjHR 1.55, P=0.006). TIPS was reduced by ticagrelor (P=0.002) but not aspirin.
Impact: Introduces a mechanistically anchored, modifiable platelet RNA biomarker that captures thromboinflammation and stratifies cardiovascular risk across cohorts.
Clinical Implications: TIPS may enable thromboinflammation-guided risk stratification and personalize antiplatelet strategies (e.g., preference for P2Y12 inhibition over aspirin in selected patients), pending prospective outcome trials.
Key Findings
- Developed a 42-gene platelet RNA signature (TIPS) correlated with monocyte–platelet aggregates and stable over time.
- TIPS elevated in COVID-19 (P=0.0002) and myocardial infarction (Padj=0.008).
- Predicted future cardiovascular events post lower extremity revascularization (adjHR 1.55, P=0.006).
- Ticagrelor reduced TIPS (P=0.002), whereas aspirin did not.
Methodological Strengths
- Prospective sampling at two time points with flow cytometry and RNA-seq.
- External correlations across cohorts and adjustment for demographics in outcome prediction.
Limitations
- Modest discovery sample size and need for prospective interventional validation of TIPS-guided care.
- Potential residual confounding and generalizability concerns beyond studied cohorts.
Future Directions: Prospective trials testing TIPS-guided antiplatelet strategies and integration into multi-omic risk scores for personalized cardiovascular prevention.