Hot Line 9: RIGHT, ONCO DVT and an SGLT2 inhibitor meta-analysis in patients with COVID-19
28 Aug 2023
With a final flourish, Hot Line 9 rounded off ESC Congress 2023’s cutting-edge trial presentations with insightful research across a broad range of cardiology.
The RIGHT trial was designed to test whether low-dose post-procedural anticoagulation (PPA) – frequently used after primary percutaneous coronary intervention for STEMI – is associated with improved outcomes. As discussed by Doctor Yan Yan (Beijing Anzhen Hospital - Beijing, China), each participating Chinese centre selected one of three PPA regimens (enoxaparin 40 mg/daily SC, unfractionated heparin 10 units/kg/hour IV adjusted to maintain activated clotting time between 150 and 220 seconds or bivalirudin 0.2 mg/kg/hour IV). In total, 2,989 low-to-intermediate risk patients were randomised to receive low-dose PPA or matching placebo for at least 48 hours. Superiority of PPA over placebo for the primary efficacy endpoint of all-cause death, non-fatal myocardial infarction, non-fatal stroke, definite stent thrombosis or any urgent revascularisation within 30 days was not observed (hazard ratio [HR] 1.00; 95% CI 0.63 to 1.57). However, a significant interaction for the type of anticoagulant versus placebo was seen in favour of enoxaparin (enoxaparin: HR 0.46; 95% CI 0.22 to 0.98; unfractionated heparin: HR 3.71; 95% CI 1.03 to 13.28; bivalirudin: HR 1.24; 95% CI 0.60 to 2.59, p for interaction=0.015), which warrants further study. There was no excess major bleeding globally or in any of the three anticoagulant groups.
The next presentation, by Doctor Yugo Yamashita (Kyoto University Graduate School of Medicine - Kyoto, Japan), described the ONCO DVT trial, which compared two different durations of edoxaban (12 months or 3 months) for isolated distal deep vein thrombosis (DVT) in 604 patients with active cancer. The primary endpoint of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death event at 12 months occurred in 1.0% of patients in the 12-month edoxaban group and in 7.2% of patients in the 3-month edoxaban group (odds ratio [OR] 0.13; 95% CI 0.03 to 0.44). Major bleeding occurred in 9.5% in the 12-month group and 7.2% in the 3-month group (OR 1.34; 95% CI 0.75 to 2.41). Prespecified subgroup analyses according to age, body weight and renal function did not affect the estimates on the primary endpoint. Dr. Yamashita comments, “This is the first and only randomised trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT. We expect that the results will change practice and clinical guidelines in the cardio-oncology field.”
Last, but not least, Professor Mikhail Kosiborod (Saint Luke's Mid America Heart Institute - Kansas City, USA) discussed a prospective meta-analysis that used aggregate data from three randomised controlled trials (DARE-19, RECOVERY and ACTIV-4A) to evaluate sodium–glucose co-transporter 2 (SGLT2) inhibitors in 6,096 patients hospitalised with COVID-19. The primary outcome of 28-day all-cause death occurred in 351 patients randomised to SGLT2 inhibitors and 382 patients randomised to usual care or placebo (OR 0.93; 95% CI 0.79 to 1.08; p=0.33), with consistency across trials. There was no evidence of benefit for other efficacy outcomes including 90-day all-cause mortality, progression to acute kidney injury or progression to invasive mechanical ventilation, extracorporeal membrane oxygenation or death. The incidence of reported serious adverse events was balanced between treatment groups. Although these findings do not support the use of SGLT2 inhibitors as standard care in this clinical setting, Prof. Kosiborod comments that their routine discontinuation during acute illness for patients that receive them for other indications such as heart failure, chronic kidney disease or type 2 diabetes does not appear to be warranted.