Weekly Cardiology Research Analysis
This week’s cardiology literature is dominated by actionable clinical trials and clarifying meta-analyses. A phase 3 randomized trial (ORION-16) shows inclisiran provides durable, well-tolerated LDL-C lowering in adolescents with heterozygous familial hypercholesterolaemia. An individual-patient-data meta-analysis across pivotal AF trials demonstrates that DOACs reduce rare but morbid systemic embolic events versus warfarin. A randomized sham-controlled intraoperative device trial (DrugSorb-ATR)
Summary
This week’s cardiology literature is dominated by actionable clinical trials and clarifying meta-analyses. A phase 3 randomized trial (ORION-16) shows inclisiran provides durable, well-tolerated LDL-C lowering in adolescents with heterozygous familial hypercholesterolaemia. An individual-patient-data meta-analysis across pivotal AF trials demonstrates that DOACs reduce rare but morbid systemic embolic events versus warfarin. A randomized sham-controlled intraoperative device trial (DrugSorb-ATR) shows safety and a CABG subgroup signal for reduced severe bleeding when surgery occurs within 48 hours of ticagrelor cessation.
Selected Articles
1. Efficacy and safety of inclisiran in adolescents with heterozygous familial hypercholesterolaemia (ORION-16): a two-part, randomised, multicentre clinical trial.
In a two-part, phase 3 randomized trial of 141 adolescents with HeFH on background lipid-lowering therapy, inclisiran 300 mg subcutaneously produced a between-group LDL-C reduction of −28.5% versus placebo at day 330 and sustained mean reductions (~−33.7%) at day 720. The drug was well tolerated; injection-site reactions were mild and there were no treatment-related serious adverse events.
Impact: First randomized multicenter evidence that PCSK9-targeting siRNA (inclisiran) safely achieves clinically meaningful, durable LDL-C lowering in adolescents with HeFH, filling a pediatric treatment gap with twice-yearly dosing.
Clinical Implications: Inclisiran can be considered as an adjunctive option for adolescents with HeFH who remain above LDL targets despite statin/ezetimibe, offering twice-yearly dosing that may improve adherence and long-term lipid control.
Key Findings
- LS mean LDL-C change at day 330: −27.1% (inclisiran) vs +1.4% (placebo); between-group difference −28.5% (95% CI −35.8 to −21.3; p<0.0001).
- Durability: mean LDL-C change at day 720 was −33.7% (SD 24.0).
- Safety: injection-site reactions (16% vs 6%) were mostly mild; no treatment-related serious adverse events or deaths.
2. Systemic Embolic Events in Atrial Fibrillation: An Individual Patient Data Meta-analysis of 71 683 Participants Randomized to NOAC Versus Warfarin.
An IPD meta-analysis of four pivotal AF trials (n=71,683) found systemic embolic events (SEE) occur at ~0.13% per patient‑year (versus 1.25% for ischemic stroke). DOACs significantly reduced SEE risk compared with warfarin, and SEE—though rare—carried mortality and morbidity comparable to ischemic stroke.
Impact: Clarifies DOAC benefit on a previously underrecognized but clinically important outcome (systemic embolism) using individual-patient data, strengthening indications for DOAC preference in AF.
Clinical Implications: Supports preferential use of DOACs over warfarin to reduce systemic embolic events in AF management and highlights the need for clinical pathways to recognize and manage SEE given its high morbidity.
Key Findings
- SEE incidence ~0.13% per patient‑year vs ischemic stroke 1.25% per patient‑year across 71,683 patients.
- DOACs significantly reduced SEE compared with warfarin across trials.
- SEE patients experienced mortality and morbidity comparable to ischemic stroke despite lower incidence.
3. Randomized, Sham-Controlled Trial of Intraoperative Ticagrelor Removal to Reduce Perioperative Bleeding.
In 140 randomized patients (132 treated) undergoing cardiac surgery within 48 hours of ticagrelor discontinuation, intraoperative DrugSorb-ATR was safe but did not meet the overall primary efficacy endpoint. In a prespecified isolated CABG subgroup, the device significantly reduced severe bleeding and large chest-tube drainage events (NNT to prevent a severe bleed = 6).
Impact: A rigorous sham-controlled RCT evaluating an intraoperative antiplatelet-removal device addresses a common perioperative risk; positive CABG subgroup findings suggest a path to safer urgent surgery when washout is infeasible.
Clinical Implications: Consider device‑enabled intraoperative ticagrelor adsorption for isolated CABG when adequate washout is not possible; larger, focused trials are needed before broad adoption.
Key Findings
- Primary safety endpoint met with similar 30‑day adverse events between device and sham groups.
- Primary efficacy endpoint neutral overall (WR 1.07; p=0.748); prespecified CABG supplementary endpoint favored DrugSorb-ATR (WR 1.59; p=0.041).
- CABG subgroup showed fewer large chest-tube drainage events (p=0.016) and fewer severe bleeding/CTD≥1L events (p=0.041); NNT to prevent a severe bleed = 6.