The first randomized trial to evaluate postprocedural anticoagulation (PPA) in patients undergoing a primary percutaneous coronary intervention (PCI) for an ST-segment elevation myocardial infarction (STEMI) did not associate significant benefit – or significant harm – with any of the three tested regimens relative to placebo.
There has been a signal from nonrandomized studies that PPA reduces the risk for ischemic events, but no controlled prospective trials have evaluated the risk-benefit relationship in STEMI patients, said Yan Yan, MD, a researcher in Beijing Anzhen Hospital.
The results of the randomized trial, called RIGHT, were presented at the annual congress of the European Society of Cardiology by Dr. Yan, on behalf of a team of coinvestigators led by Nie Shaoping, MD, PhD, a cardiologist affiliated with Capital Medical University, Beijing.
The bottom line is that Dr. Yan concluded.
Objective study
In her presentation, Dr. Yan explained that an objective study has been needed to validate the common use of empirically administered PPA. According to Dr. Yan, PPA is being offered to up to 40% of STEMI patients in Europe, with even higher rates in China.
In the investigator-initiated RIGHT trial, 2,856 STEMI patients undergoing PCI were randomized to PPA or placebo in a 1:1 ratio. In the PPA arm, patients received one of three low-dose anticoagulation regimens over 48 hours or until discharge if this was longer: 0.2 mg/kg per hour of bivalirudin administered intravenously; 40 mg of enoxaparin administered subcutaneously; or 10 U/kg per hour of unfractionated heparin (UFH) to maintain an activated coagulation time between 150 and 200 seconds.
Each of the 53 participating Chinese centers selected one of the anticoagulation regimens. Matching placebos were employed in the double-blind design. All received bivalirudin anticoagulation during PCI. Exclusion criteria included unstable disease, such as cardiogenic shock, prior coronary artery bypass grafting, or an indication for anticoagulation other than PPA.
For the composite primary endpoint of all-cause death, nonfatal MI, nonfatal stroke, stent thrombosis, or urgent revascularization at 30 days, there was no difference between PPA and placebo. The event rate in both arms was 2.5%.
There were also no significant differences between PPA and placebo for any of the secondary ischemic endpoints, which included the individual components of the primary endpoint and cardiovascular death.
For the primary safety endpoint of Bleeding Academic Research Consortium (BARC) grade 3-5 bleeding, the slight increase in events among those in the placebo group did not approach statistical significance (P = .551). On other definitions of bleeding, which were secondary endpoints, PPA and placebo also did not differ significantly.
Compared for safety, the three anticoagulation regimens performed similarly with no significant interaction for the primary endpoint (P = .679).
For efficacy, the differences did range sufficiently to produce a significant interaction (P = .01) with enoxaparin appearing to be more effective, UFH less effective, and bivalirudin falling in between. This led Dr. Yan to speculate that the three anticoagulants “may not be equivalent,” although she said larger trials are needed to explore potential differences.