Idarucizumab for dabigatran reversal

August 3, 2015

Results from the REVERSE-AD prospective cohort study.

There are currently no reversal agents available for any of the newer oral anticoagulants. Interim data from the REVERSE-AD study suggests that idarucizumab is safe and effective for reversing the anticoagulant effects of dabigatran.

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REVERSE-AD is a prospective cohort study designed to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within four hours after the administration of idarucizumab. A key secondary end point was the restoration of hemostasis.

The interim analysis included 90 patients who received idarucizumab (51 patients in group A and 39 in group B). Among 68 patients with an elevated dilute thrombin time and 81 with an elevated ecarin clotting time at baseline, the median maximum percentage reversal was 100%. Idarucizumab normalized the test results in 88% to 98% of the patients, an effect that was evident within minutes. Concentrations of unbound dabigatran remained below 20 ng/ml at 24 hours in 79% of the patients.

Among 35 group A patients who could be assessed, hemostasis, as determined by local investigators, was restored at a median of 11.4 hours. Among 36 patients in group B who underwent a procedure, normal intraoperative hemostasis was reported in 33, and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient, respectively. One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated.

Sources: Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. NEJM 2015. Published online before print:http://www.nejm.org/doi/full/10.1056/NEJMoa1502000.

Newer oral contraceptives associated with higher VTE risk

A recently published study adds to the evidence showing increased venous thromboembolism (VTE) risk with newer vs. older combination oral contraceptives.

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U.K. researchers used two large databases with information pertaining to more than 10,000 females 15 to 49 years of age who experienced VTE compared to more than 40,000 controls who did not. They found that use of any combination oral contraceptive in the previous year was associated with significantly increased odds of VTE, relative to no past-year exposure.

However, newer oral contraceptives containing desogestrel, gestodene, drospirenone, or cyproterone were associated with a fourfold increase in VTE risk, while older contraceptives containing levonorgestrel, norethisterone, or norgestimate were associated with a 2.5-fold risk increase. (Cyproterone, gestodene, and norethisterone are not available in the United States.)

The number of extra VTE cases per year per 10,000 treated women was lowest for levonorgestrel and norgestimate, and highest for desogestrel and cyproterone.

Source: Vinogradova Y, Coupland C, Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: Nested case-control studies using the QResearch and CPRD databases. BMJ 2015;350:h2135.

 

Pharmacist monitoring improves dabigatran adherence

Newer oral anticoagulants offer a number of benefits to patients relative to convenience and an improved drug interaction profile. Since routine monitoring is not required, there is no reliable way to measure adherence, thus increasing the possibility of adverse outcomes in nonadherent patients.

In a study performed in the VA system, investigators sought to evaluate medication adherence with dabigatran. They collected dabigatran prescription information for 4,863 patients with nonvalvular atrial fibrillation at 67 VA sites. In addition, they interviewed 47 pharmacists at 41 sites to assess factors associated with improved adherence, such as meticulous patient selection, education, and follow-up.

Whereas 72% of patients were adherent (defined as ≥80% of prescribed days covered by prescription), 23% had a medication gap of more than 30 days. Factors associated with adherence were appropriate patient selection for dabigatran treatment and participation of a dedicated pharmacist. Adherence was also improved by the use of more intensive services, with clinician collaboration, for nonadherent patients.

Source: Shore S, Ho PM, Lambert-Kerzner A, et al. Site-level variation in and practices associated with dabigatran adherence. JAMA. 2015;313(14):1443–1450.