RELY-Genetics, ARISTOTLE, RE-LY AF and Other Trials Focus on Clinical Responses to Oral Anticoagulants
RELY-Genetics, ARISTOTLE and the RE-LY AF Registry – all involving new oral anticoagulants – were presented on Aug. 29 as part of the last day of the ESC Congress 2012 in Munich. The updates follow on the heels of the WOEST trial -- the first randomized trial to evaluate treatment with clopidogrel alone compared with aspirin and clopidogrel among patients on oral anticoagulation therapy undergoing percutaneous coronary intervention (PCI) – the results of which were released on Aug. 28.
The WOEST trial found that the use of clopidogrel alone reduced the frequency of all bleeding events. Overall, of the 573 patients who were randomized, the primary outcome (total bleeding events at one year) occurred in 19.5 percent of the double therapy group versus 44.9 percent of the triple therapy group (p < 0.001). The primary outcome was the same among all tested subgroups. However, Anthony A. Bavry, MD, MPH, FACC, said in an ACC Clinical Trial Summary, "although the observed reduction in mortality is plausible, this trial was not powered to show a mortality difference; therefore, this outcome should be interpreted with caution."
In the RELY-Genetics trial, whole genome genotyping was conducted on 2,944 RE-LY Registry participants to see whether genetic variants could contribute to inter-individual variability in blood concentrations of the active metabolite of dabigatran etexilate, and influence the safety and efficacy of dabigatran. Results from the study showed that 32.8 percent of RE-LY trial participants carried the CES1 rs2244613 minor allele, which was associated lower dabigatran exposure and a lower risk of bleeding. The study authors noted that the interaction between treatment (warfarin versus all dabigatran) and carrier status was statistically significant (P=0.002) with carriers having less bleeding with dabigatran than warfarin (HR=0.59, 95 percent CI 0.46-0.76; P=5.2 x 10-5) in contrast to no difference in noncarriers (HR=0.96, 95 percent CI 0.81-1.14; P=0.65). There was no association with ischemic events.
The RE-LY AF Registry looked at 15,408 patients from 164 sites in 47 countries roughly one-year after being admitted to the emergency department (ED) with atrial fibrillation (AF) as either a primary or secondary diagnosis. Results from the study found that more than 10 percent of patients who are seen in an emergency department with AF die within one year, with rates of death twice as high in Latin America and Africa. Data also showed that globally more than 4 percent of AF patients experience a stroke within one year; however, there is considerable variability in the stroke rate from region to region significantly higher rates in China, South-East Asia and Africa. According to the study authors, the RE-LY AF Registry is the first to report on one-year outcomes for a large cohort of patients with AF from around the world, including low-income countries. Results show "very large unmet medical needs and large opportunities for improvement by applying currently generally available modalities for diagnosis, risk stratification and treatment of patients presenting with atrial fibrillation," they said.
The ARISTOTLE trial update focused on the efficacy of apixaban as compared with warfarin in relation to renal function in patients with AF. Results of the study, which looked at 7,587 patients with an eGFR of >50–80 mL/min and 3,017 patients with an eGFR of ≤50 mL/min, found that apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function as compared to warfarin. Study authors noted that patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban, when using creatinine-based estimates of GFR. "Our findings suggest that apixaban may be particularly suited to address the unmet need for a more effective and safe stroke prevention in patients with AF and renal dysfunction," they said.
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