Hot Line 7: OPT-BIRISK, ARAMIS and DANPACE II
28 Aug 2023
Hot Line 7 was a fascinating mixed bag assessing different antiplatelet therapy regimens in high-risk patients, investigating a novel treatment for acute myocarditis and evaluating minimised atrial pacing in patients with sinus node dysfunction.
The optimal antiplatelet treatment regimen in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) who are at high risk for both ischaemic and bleeding events is a common scenario in real-world practice and an unresolved clinical question. As described by Professor Ya-Ling Han (General Hospital of Northern Theater Command - Shenyang, China), the Chinese OPT-BIRISK trial randomised 7,758 patients who completed 9- to 12-month dual antiplatelet therapy (DAPT) after drug-eluting stent implantation and who had both high bleeding and high ischaemic risk characteristics to receive clopidogrel 75 mg/day plus placebo or clopidogrel 75 mg/day plus aspirin 100 mg/day for 9 months.
The primary endpoint of Bleeding Academic Research Consortium types 2, 3, or 5 bleeding at 9 months after randomisation occurred in 2.5% of patients on clopidogrel monotherapy and in 3.3% of patients on clopidogrel plus aspirin (hazard ratio [HR] 0.75; 95% CI 0.57 to 0.97; p=0.03). The key secondary endpoint of major adverse cardiac and cerebral events (MACCE) occurred in 2.6% of patients on clopidogrel monotherapy and in 3.5% of patients on clopidogrel plus aspirin (HR 0.74; 95% CI 0.57 to 0.96; p<0.001 for non-inferiority; p=0.02 for superiority). The incidences of all-cause death, myocardial infarction, stroke, clinically driven revascularisation and stent thrombosis were not significantly different between the groups. Summing up, Prof. Han says that in this vulnerable trial population, “A strategy of extended P2Y12 inhibitor monotherapy with clopidogrel for an additional 9 months was superior to DAPT with aspirin and clopidogrel for reducing clinically relevant bleeding and ischaemic events during this period,” but notes that, “The increased rate of MACCE in the clopidogrel plus aspirin group was surprising and may be because haemorrhagic events, which are more common with ongoing DAPT, could be associated with an adrenergic state with increased platelet aggregation due to hypotension, remedial procedures to treat bleeding, and the cessation of anti-ischaemic medications.”
As presented by Doctor Mathieu Kerneis (Pitie Salpetriere APHP University Hospital - Paris, France), the ARAMIS trial is the first to evaluate inhibition of the interleukin-1β innate immune pathway, using anakinra, in patients with acute myocarditis, for which there are currently no specific treatments. The trial enrolled 120 symptomatic patients with increased cardiac troponin and acute myocarditis diagnosed using cardiac magnetic resonance imaging, who were randomised within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge on top of standard treatments. A short course of anakinra was not found to improve the primary endpoint of the number of days free of myocarditis complications (heart failure requiring hospitalisation, chest pain requiring medication, LVEF <50% and ventricular arrhythmias) within 28 days post-discharge: median of 30 days with anakinra versus 31 days with placebo (p=0.168). It was concluded that further trials are needed to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at high risk of complications and also to evaluate prolonged anti-inflammatory strategies in patients at low-to-moderate risk of complications.
To end the session, Doctor Mads Brix Kronborg (Aarhus University Hospital - Aarhus, Denmark) described the DANPACE II trial designed to investigate whether minimised atrial pacing reduces the incidence of atrial fibrillation (AF) in patients with sinus node dysfunction. A total of 539 patients with sinus node dysfunction and an indication for a first-time dual chamber (DDD) pacemaker were analysed following randomisation to either a base rate of 60 bpm and rate-adaptive DDD (DDDR-60 group) or to a base rate of 40 bpm and non-rate-adaptive DDD (DDD-40 group). After 2 years, the primary endpoint – episodes of AF lasting >6 minutes detected by the pacemaker – occurred in 46% of patients in each group (p=0.83). Similarly, there was no benefit observed in any of the secondary endpoints. Of note, significantly more patients in the DDD-40 group experienced syncope or presyncope compared with the DDDR-60 group (22% versus 13%; HR 1.71; 95% CI 1.13 to 2.59; p=0.01), further demonstrating that minimising pacing does not benefit patients with sinus node dysfunction.