Daily Cardiology Research Analysis
Three impactful cardiology papers emerged today: multi-omics Mendelian randomization pinpointed distinct, non-overlapping drug targets for HFrEF vs HFpEF; the first randomized comparison of IVL, rotational atherectomy, and excimer laser showed IVL noninferior to RA for stent expansion in calcified lesions; and a meta-analysis of RCTs supports oral anticoagulation alone (vs adding antiplatelet) for AF with stable CAD, reducing major bleeding without increasing ischemic events.
Summary
Three impactful cardiology papers emerged today: multi-omics Mendelian randomization pinpointed distinct, non-overlapping drug targets for HFrEF vs HFpEF; the first randomized comparison of IVL, rotational atherectomy, and excimer laser showed IVL noninferior to RA for stent expansion in calcified lesions; and a meta-analysis of RCTs supports oral anticoagulation alone (vs adding antiplatelet) for AF with stable CAD, reducing major bleeding without increasing ischemic events.
Research Themes
- Multi-omics drug target discovery in heart failure subtypes
- Device strategy for calcified coronary lesions (IVL vs RA vs ELCA)
- Antithrombotic optimization in AF with stable CAD
Selected Articles
1. Large-scale multi-omics identifies drug targets for heart failure with reduced and preserved ejection fraction.
Using Mendelian randomization across >420,000 participants, the authors identified 70 HFrEF and 10 HFpEF causal targets, largely non-overlapping, highlighting the need for subtype-specific therapies. Druggable candidates include IL6R, ADM, and EDNRA for HFrEF and LPA for both subtypes; findings were replicated in >175,000 multi-ancestry participants.
Impact: This work delineates causal, druggable targets for HF subtypes at scale, offering a roadmap for precision therapeutics and re-prioritizing pipelines for HFrEF vs HFpEF.
Clinical Implications: While not immediately practice-changing, the prioritized targets (e.g., IL6R, ADM, EDNRA, LPA) inform trial design and companion biomarker strategies for subtype-specific HF therapies.
Key Findings
- Identified 70 causal targets for HFrEF and 10 for HFpEF; 58 were novel and targets were non-overlapping across subtypes.
- Validated roles of ubiquitin–proteasome system, SUMO pathway, inflammation, and mitochondrial metabolism in HFrEF.
- Druggable candidates include IL6R, ADM, EDNRA (HFrEF) and LPA (both HFrEF and HFpEF); 14 loci reclassified as HFrEF.
Methodological Strengths
- Large-scale Mendelian randomization integrating proteome and transcriptome with replication in >175,000 participants
- Systematic druggability profiling including efficacy, safety, and mechanism of action
Limitations
- Causal inference depends on MR assumptions and potential horizontal pleiotropy
- Translational impact requires interventional trials to confirm therapeutic efficacy
Future Directions: Prospective trials targeting prioritized pathways (e.g., IL6R, ADM/EDNRA signaling, LPA lowering) with subtype-specific enrollment and biomarker-guided stratification.
2. Anticoagulation and Antiplatelet Therapy for Atrial Fibrillation and Stable Coronary Disease: Meta-Analysis of Randomized Trials.
Pooling four RCTs (n=4,092), OAC monotherapy reduced major bleeding (HR 0.59) versus OAC+single antiplatelet without increasing ischemic events or mortality. Results support OAC alone for AF with stable CAD beyond the acute coronary period.
Impact: Resolves a common clinical dilemma by synthesizing randomized evidence favoring OAC monotherapy in AF with stable CAD, likely shaping guidelines and deprescribing practices.
Clinical Implications: In AF with stable CAD beyond the early post-ACS/PCI phase, prefer OAC monotherapy to minimize bleeding; reserve antiplatelet therapy for compelling coronary indications.
Key Findings
- No significant difference in ischemic composite outcomes between OAC monotherapy and OAC+SAPT (HR 0.90).
- Major bleeding significantly lower with OAC monotherapy (3.3% vs 5.7%; HR 0.59).
- Findings consistent across subgroups; exploratory signal suggests greater bleeding reduction in men.
Methodological Strengths
- Meta-analysis restricted to randomized trials with acquisition of unpublished data to refine estimates
- Prespecified subgroup analyses and harmonized outcome definitions
Limitations
- Only four RCTs; some were not powered for individual effectiveness endpoints
- Heterogeneity in OAC agents, SAPT use, and follow-up durations
Future Directions: Head-to-head trials or IPD meta-analyses stratifying by coronary complexity, time from PCI, and bleeding risk to refine patient-level recommendations.
3. Rotational Atherectomy, Lithotripsy, or Laser for Calcified Coronary Stenosis: The ROLLER COASTR-EPIC22 Trial.
In the first randomized 3-arm comparison of plaque-modification strategies for calcified lesions, IVL was noninferior to RA for OCT-assessed stent expansion, whereas ELCA did not meet noninferiority. Minimum stent area, procedural success, and complications were similar, with numerically fewer complications in IVL.
Impact: Directly informs device selection in calcified PCI, an area with procedural risk and uncertainty, by providing randomized evidence across three commonly used techniques.
Clinical Implications: For heavily calcified lesions, IVL can be considered an alternative to RA to achieve adequate stent expansion; ELCA may be reserved given failure to meet noninferiority.
Key Findings
- IVL met noninferiority vs RA for OCT-measured stent expansion; ELCA did not meet noninferiority.
- Minimum stent area, procedural success, and complication rates were similar across arms, with numerically fewer complications in IVL.
- Trial enrolled 171 patients with predominantly severe calcification (82.5%) across CCS and ACS presentations.
Methodological Strengths
- Randomized, three-arm, intention-to-treat noninferiority design with OCT core lab endpoint
- Balanced enrollment across CCS and ACS with high prevalence of severe calcification
Limitations
- Modest sample size limits power for clinical endpoints and subgroup analyses
- Noninferiority margin selection and device-specific operator experience may influence outcomes
Future Directions: Larger pragmatic trials powered for clinical outcomes and stratified by calcium severity, vessel size, and combination strategies (e.g., RA+IVL).