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.
BACKGROUND: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a progressive disease with a significant burden of recurrent cardiovascular (CV) events. Acoramidis, an approved oral therapy for ATTR-CM, achieves early, near-complete (≥90%) TTR stabilization. In the phase 3 ATTRibute-CM (Efficacy and Safety of Acoramidis in Participants with Transthyretin Amyloid Cardiomyopathy) study, acoramidis significantly reduced the composite of all-cause mortality or first CV-related hospitalization (CVH), with an effect observed at month 3. Its efficacy on the burden of cumulative CV outcome events has not been reported. OBJECTIVES: This study was a post hoc exploratory recurrent-event analysis of the efficacy of acoramidis on the cumulative incidence of CV outcomes from ATTRibute-CM and its open-label extension. METHODS: Cumulative incidences of centrally adjudicated CV-related mortality (CVM) or recurrent CVH (first and, if applicable, subsequent CVH), recurrent CVH alone (month 30), and CVM (month 42) were measured in the modified intention-to-treat population (acoramidis, n = 409; placebo, n = 202). Mean cumulative events by treatment, and the difference between treatment groups were estimated by using a modified Andersen-Gill model. RESULTS: Acoramidis significantly reduced the cumulative risk of CVM or recurrent CVH through month 30 vs placebo (HR: 0.51; 95% CI: 0.43-0.62; P < 0.0001). A notable proportion of CV outcome events (19% of CVM or recurrent CVH events, 22% of CVH) occurred within the first 6 months. Numerically fewer cumulative events were observed with acoramidis compared with placebo at month 1, and the difference increased progressively, resulting at month 30 in 53 events avoided per 100 treated participants (95% CI: 29-79). At month 42, CVM was reduced with continuous acoramidis vs placebo-to-acoramidis (HR: 0.55; 95% CI: 0.39-0.79; P = 0.0011). The annualized frequency of recurrent CVH was significantly decreased through month 30 (relative risk ratio: 0.50; 95% CI: 0.35-0.69; P < 0.0001). CONCLUSIONS: Acoramidis significantly reduced the cumulative burden of CV outcomes in ATTR-CM over 30 months. Numerically fewer events were observed with acoramidis vs placebo by month 1, and the difference increased progressively over time, resulting in 53 events avoided per 100 treated patients at month 30. Almost one-fourth of the cumulative CV events occurred within the first 6 months. These exploratory findings suggest that cumulative event burden may occur early, highlighting the importance of timely evaluation, diagnosis and treatment in ATTR-CM.
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.
BACKGROUND: Red blood cells (RBCs) contribute to hemostasis and thrombosis by interacting with platelets via the FasL-FasR pathway to induce procoagulant activity and thrombin formation. Here, we identified a novel mechanism of platelet-RBC interaction via the CD36-TSP-1 (thrombospondin-1) signaling pathway that plays a prominent role in arterial thrombosis and abdominal aortic aneurysm (AAA) formation and progression. AAA is a life-threatening atherosclerotic-related disease, characterized by the progressive dilation of the abdominal aorta, due to chronic inflammation and extracellular matrix remodeling/degradation within the vessel wall. The objective of the present study was to elucidate a new mechanism of platelet-RBC interaction via the TSP1-CD36 axis and its significance for arterial thrombosis and the pathology of AAA. METHODS: TSP-1-deficient and CD36 cell-type-specific (RBCs and platelets) knock-out mice were analyzed in experimental mouse models of arterial thrombosis and AAA. Blood samples from patients with AAA from peripheral sites (laminar flow) and from inside the aneurysm segment (turbulent flow) were analyzed by flow cytometry and compared with age-matched controls. RESULTS: After platelet activation, platelet-released TSP-1 binds to CD36 at the RBC and platelet membrane to enhance procoagulant activity of both cells, leading to platelet aggregation and thrombosis. Patients with AAA exhibit enhanced procoagulant activity, elevated TSP-1 and CD36 plasma levels, as well as increased exposure of TSP-1 and CD36 at the RBC and platelet surface. In addition, biomechanically stress in the aneurysmal segment reinforces CD36 externalization on RBCs and platelets as well as the formation of platelet-RBC aggregates. In line, genetic deletion of either CD36 (RBC restricted) or TSP-1 protected mice against experimentally induced AAA formation. CONCLUSIONS: Our findings imply that CD36 on RBCs and platelets, as well as platelet-released TSP-1, contribute to procoagulant activity, playing a crucial role in arterial thrombosis and AAA progression.
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.
BACKGROUND: Traditional coronary angiography has inherent limitations in terms of lesion assessment and stenting. New guidance modalities to guide percutaneous coronary intervention (PCI) are now available. METHODS: We systematically searched PubMed, Embase, Cochrane, and Web of Science databases for the period from the time of construction to 25 April 2024. A network meta-analysis of randomized controlled trials (RCT) was performed to determine the optimal treatment strategy by comparing the short-term outcome and long-term prognosis of adverse cardiovascular outcomes in patients with coronary artery lesions after eight different PCI-guided modalities. The clinical outcomes included major adverse cardiovascular events (MACE), all-cause mortality, cardiac death, myocardial infarction, and target vessel revascularization (TVR). Risk ratios (RR) with 95% confidence intervals (CI) were calculated. RESULTS: Forty randomized controlled trials with a total of 38,107 patients were included. In the MACE subgroup up to 12 months, Intravascular Ultrasound-guided Percutaneous Coronary Intervention (IVUS-PCI) [RR = 1.60, 95%CI = (1.10, 2.30)], Optical Frequency Domain Imaging-guided Percutaneous Coronary Intervention (OFDI-PCI) [RR = 2.36, 95%CI = (1.05, 5.80)] and Quantitative Flow Ratio-guided Percutaneous Coronary Intervention (QFR-PCI) [RR = 1.45, 95%CI = (1.15, 1.83)] significantly reduced the incidence of MACE. In the MACE subgroup at 12 months, Fractional Flow Reserve-guided Percutaneous Coronary Intervention (FFR-PCI) [RR = 0.72, 95%CI = (0.49, 0.99)], IVUS-PCI [RR = 0.66, 95%CI = (0.43, 0.99)] and Optical Coherence Tomography-guided Percutaneous Coronary Intervention [RR = 0.59, 95%CI = (0.35, 0.92)] all significantly reduced the incidence of MACE in patients. FFR-PCI [RR = 0.42, 95%CI = (0.20, 0.75)] significantly reduced the incidence of cardiac death in patients compared to Angiography-guided Percutaneous Coronary Intervention (Angio-PCI). FFR-PCI [RR = 0.78, 95%CI = (0.62, 0.99)], OCT-PCI [RR = 0.59, 95%CI = (0.35, 0.97)], QFR-PCI [RR = 0.64, 95%CI = (0.45, 0.91)] were associated with a lower risk of myocardial infarction compared to Angio-PCI. The incidence of Target Vessel Revascularization (TVR) was significantly lower in patients who underwent IVUS-PCI [RR = 0.57, 95%CI = (0.36, 0.86)], OCT-PCI [RR = 0.47, 95%CI = (0.24, 0.95)] than in those who underwent Angio-PCI. However, there were no significant differences between the different guidance modalities and subgroup analyses in improving overall survival. CONCLUSION: IVUS and OCT were more effective in reducing MACE and TVR. This suggests that IVUS and OCT may be the best strategies in the interventional management of complex coronary lesions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42024567598.