Hot Line 6: MULTISTARS AMI, CASTLE-HTx and FRAIL-AF
27 Aug 2023
Three important unaddressed clinical questions were explored in Hot Line 6 relating to the treatment of multivessel coronary artery disease (CAD), the treatment of atrial fibrillation (AF) in patients with advanced heart failure (HF) and the management of stroke risk in frail elderly patients with AF.
As presented by Doctor Barbara Stähli (University Hospital Zurich - Zurich, Switzerland), the MULTISTARS AMI trial investigated whether immediate complete revascularisation at the time of primary percutaneous coronary intervention (PCI) is as effective and safe as staged (within 19 to 45 days) multivessel PCI among 840 haemodynamically stable patients with acute STEMI and multivessel CAD. After 1 year, the primary endpoint – all-cause death, non-fatal myocardial infarction (MI), stroke, unplanned ischaemia-driven revascularisation or HF hospitalisation – occurred in 8.5% of patients in the immediate group and in 16.3% of patients in the staged group (risk ratio 0.52; 95% CI 0.38 to 0.72; p<0.001 for non-inferiority; p<0.001 for superiority). The median time from randomisation to staged procedures was 37 days. Non-fatal MI occurred in 2.0% of patients in the immediate group and in 5.3% of patients in the staged group (hazard ratio [HR] 0.36; 95% CI 0.16 to 0.80), while unplanned ischaemia-driven revascularisation was performed in 4.1% and 9.3%, respectively (HR 0.42; 95% CI 0.24 to 0.74). Rates of all-cause death, stroke and HF hospitalisation did not differ between groups. “The trial has implications for clinical practice,” notes Dr. Stähli, “as it demonstrated that immediate PCI of non-culprit lesions is as effective and safe as a staged procedure.” She adds that results were generally consistent across prespecified key subgroups, particularly among women and men, young and older patients, and patients with or without diabetes.
Next, Professor Christian Sohns (Heart and Diabetes Center NRW - Bad Oeynhausen, Germany) discussed the CASTLE-HTx trial, which compared AF ablation with medical therapy in patients with end-stage HF. This German trial enrolled 194 patients with symptomatic AF and end-stage HF who were eligible for heart transplantation. Patients had NYHA class ≥II, LVEF ≤35% and were fitted with a cardiac device for continuous monitoring. The study was stopped for efficacy 1 year after randomisation was completed. The primary endpoint of all-cause mortality, worsening HF requiring urgent heart transplantation or LV assist device implantation occurred in 8.2% of patients in the ablation group and 29.9% in the medical therapy group (HR 0.24; 95% CI 0.11 to 0.52; p<0.001). Prof. Sohns also cites “a reduction in AF burden and improved LVEF” and notes, “listing for transplantation should not be postponed given the long waiting times and high waitlist mortality.”
The FRAIL-AF trial investigated the efficacy and safety of switching frail elderly patients with AF from a vitamin K antagonist (VKA) to a non-vitamin K antagonist oral anticoagulant (NOAC). As explained by Doctor Linda Joosten (Julius Center for Health Sciences and Primary Care - Utrecht, The Netherlands), 1,330 patients aged ≥75 years, with a Groningen Frailty Indicator score ≥3, who were managed with VKAs at a participating Dutch thrombosis centre were randomised to continue on a VKA or to switch to a NOAC, with the choice of agent at the physician’s discretion. In patients with a mean age of 83 years, the HR for the primary outcome of major or clinically relevant non-major bleeding was 1.69 (95% CI 1.23 to 2.32) for switching to a NOAC relative to continuing a VKA. The HR for thromboembolic events was 1.26 (95% CI 0.60 to 2.61), indicating that the higher bleeding risk with NOACs was not offset by a lower risk of thromboembolic events.
