Daily Cardiology Research Analysis
Three impactful cardiology studies stood out: a post hoc recurrent-event analysis from a phase 3 trial showed acoramidis markedly reduces cumulative cardiovascular outcomes in transthyretin amyloid cardiomyopathy; a mechanistic Circulation Research study identified a thrombospondin‑1/CD36 axis driving platelet–RBC procoagulant activity relevant to arterial thrombosis and abdominal aortic aneurysm; and a network meta-analysis of 40 RCTs found IVUS and OCT guidance reduce adverse events after PCI.
Summary
Three impactful cardiology studies stood out: a post hoc recurrent-event analysis from a phase 3 trial showed acoramidis markedly reduces cumulative cardiovascular outcomes in transthyretin amyloid cardiomyopathy; a mechanistic Circulation Research study identified a thrombospondin‑1/CD36 axis driving platelet–RBC procoagulant activity relevant to arterial thrombosis and abdominal aortic aneurysm; and a network meta-analysis of 40 RCTs found IVUS and OCT guidance reduce adverse events after PCI.
Research Themes
- Disease-modifying therapy in cardiac amyloidosis
- Mechanistic links between thrombosis and vascular remodeling (TSP-1/CD36)
- Imaging-guided PCI (IVUS/OCT) improves outcomes
Selected Articles
1. Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis From ATTRibute-CM.
In a post hoc recurrent-event analysis of the phase 3 ATTRibute-CM trial (mITT n=611), acoramidis halved the cumulative risk of CV mortality or recurrent CV hospitalizations by 30 months and reduced CV mortality through 42 months with continuous therapy. Benefits appeared as early as one month and grew progressively, avoiding 53 events per 100 treated by 30 months.
Impact: This analysis demonstrates robust reductions in cumulative event burden with a TTR stabilizer, underscoring the value of early, sustained treatment in ATTR-CM.
Clinical Implications: Prompt evaluation for ATTR-CM and early initiation of acoramidis could reduce recurrent hospitalizations and mortality burden; clinicians should consider cumulative events in decision-making and prioritize continuous therapy.
Key Findings
- Acoramidis reduced cumulative CV mortality or recurrent CV hospitalization through 30 months (HR 0.51, 95% CI 0.43–0.62).
- By month 30, 53 events were avoided per 100 treated participants versus placebo (95% CI 29–79).
- Continuous acoramidis lowered CV mortality through 42 months compared with placebo-to-acoramidis (HR 0.55, 95% CI 0.39–0.79).
- Nearly one-fifth of cumulative events occurred within 6 months, indicating early event burden.
Methodological Strengths
- Recurrent-event modeling (modified Andersen–Gill) capturing total event burden beyond first events.
- Centrally adjudicated CV outcomes and use of modified intention-to-treat population with OLE data.
Limitations
- Post hoc exploratory analysis; randomization does not apply to recurrent-event framework and OLE period.
- Generalizability to broader ATTR-CM populations and competing therapies requires caution.
Future Directions: Prospective trials powered for recurrent-event endpoints and head-to-head comparisons with other disease-modifying therapies; implementation studies optimizing early diagnosis and workflow.
2. Interplay Between Thrombospondin-1 and CD36 Modulates Platelet-RBC Interaction in Thrombosis and Abdominal Aneurysm Formation.
Using cell-type–specific knockouts and human AAA samples, the study identifies a TSP‑1→CD36 pathway whereby activated platelets release TSP‑1 that binds CD36 on platelets and RBCs, amplifying procoagulant activity and thrombosis. Disruption of CD36 (on RBCs) or TSP‑1 protected mice from experimental AAA, and AAA patients showed elevated TSP‑1/CD36 and platelet–RBC aggregates.
Impact: Reveals a previously unrecognized RBC–platelet mechanism driving thrombosis and aneurysm biology, nominating CD36/TSP‑1 as translational targets.
Clinical Implications: CD36 or TSP‑1 inhibition may attenuate procoagulant activity and aneurysm progression; biomarkers (TSP‑1/CD36 surface exposure) could refine risk stratification in AAA.
Key Findings
- Platelet-released TSP‑1 binds CD36 on RBCs and platelets to enhance procoagulant activity and thrombosis.
- AAA patients showed elevated plasma TSP‑1 and CD36 and increased cell-surface exposure with augmented platelet–RBC aggregates.
- Cell-specific deletion of CD36 (RBCs) or TSP‑1 protected mice from experimental AAA.
- Biomechanical stress within aneurysms reinforced CD36 externalization and procoagulant interactions.
Methodological Strengths
- Cell-type–specific genetic models (RBC- and platelet-restricted CD36 KO) and TSP‑1 KO validating causality.
- Translational linkage using human AAA samples from distinct flow environments and flow cytometry phenotyping.
Limitations
- Preclinical and ex vivo human sample data without interventional clinical trials.
- Quantitative human sample sizes and prospective prognostic validation are not detailed in the abstract.
Future Directions: Develop pharmacologic inhibitors/antagonists of TSP‑1/CD36 and test in translational models and early-phase trials; assess TSP‑1/CD36 as biomarkers for AAA progression and thrombotic risk.
3. Impact of percutaneous coronary intervention with different guidance modalities in patients with coronary artery lesions: a network meta-analysis and systematic review.
Across 40 RCTs (n=38,107), intravascular imaging (IVUS/OCT) and physiologic guidance (FFR/QFR) reduced adverse outcomes versus angiography alone. IVUS and OCT consistently lowered MACE and target vessel revascularization, while FFR reduced cardiac death and MI; overall survival did not significantly differ.
Impact: Provides synthesis of high-level evidence favoring IVUS/OCT guidance for reducing MACE/TVR and supports broader use of FFR to lower hard events, informing PCI practice and guideline updates.
Clinical Implications: Adopt IVUS/OCT guidance, particularly in complex lesions, to reduce MACE and repeat revascularization; use FFR to guide lesion selection and lower MI/cardiac death risk; consider resource allocation to increase intravascular imaging availability.
Key Findings
- IVUS- and OCT-guided PCI reduced MACE and TVR versus angiography-guided PCI.
- FFR-guided PCI reduced cardiac death (RR 0.42) and MI versus angiography; OCT and QFR also reduced MI.
- No significant differences in overall survival across guidance modalities within available follow-up windows.
Methodological Strengths
- Network meta-analysis of 40 randomized trials with >38,000 participants and PROSPERO registration.
- Comparative evaluation across eight PCI guidance strategies with multiple clinical endpoints.
Limitations
- Heterogeneity in trial designs, lesion complexity, operator expertise, and device generations.
- Limited head-to-head comparisons and potential publication bias may influence estimates.
Future Directions: Head-to-head pragmatic trials of IVUS vs OCT in specific complex subsets; cost-effectiveness and implementation studies to expand imaging access; long-term mortality-focused follow-up.