Antidote for new anticoagulants studied

February 14, 2013

A universal antidote for factor Xa inhibitors has entered phase 2 studies.

A “universal antidote” for factor Xa inhibitors has entered phase 2 studies in which the drug, currently called PRT4445 (Portola Pharmaceuticals), will be given to healthy volunteers who have been given a factor Xa inhibitor.

Oral anticoagulants with an antidote would have an important clinical advantage because currently there is no antidote available for these drugs. The lack of an antidote is especially problematic in episodes of uncontrolled bleeding or when emergency surgery is needed.

Antidotes for the current wave of approved and investigational oral anticoagulant alternatives to warfarin are an important research area. The lack of a reversal agent was one of the first concerns noted when the first of these new agents to be approved, dabigatran etexilate, became available.

According to the manufacturer, PRT4445 works with all factor Xa inhibitors. Study cohorts will take either apixaban or Portola’s investigational oral factor Xa inhibitor, betrixaban. That drug, which can be given once daily, is currently in trials for extended-duration prophylaxis for venous thromboembolism (VTE).

Source: Portola Initiates Phase 2 Study of PRT4445, Universal Antidote for Factor Xa Inhibitor Anticoagulants. [press release] South San Francisco, CA. http://www.marketwatch.com/story/portola-initiates-phase-2-study-of-prt4445-universal-antidote-for-factor-xa-inhibitor-anticoagulants-2012-12-10. Accessed December 29, 2012.

Stopping dabigatran is safe before ablation to treat atrial fibrillation

A recently published study indicates that stopping dabigatran 24 hours before radiofrequency catheter ablation for atrial fibrillation (AF) and resuming anticoagulation four hours after the procedure is just as safe and effective as treating patients with uninterrupted warfarin therapy.

In the study, 191 patients underwent ablation for AF (53% paroxysmal AF and 44% persistent AF) and received dabigatran for perioperative anticoagulation. These patients were asked to take only the morning 150-mg dose of dabigatran the day before the procedure and to skip the evening dose and the morning dose on the day of the ablation. Dabigatran was restarted four hours after vascular hemostasis was achieved after sheath removal. A control group of 572 patients was treated with uninterrupted warfarin and had an INR of 2.0 to 3.0 the day of ablation.

The prevalence of major and minor bleeding complications was 2.1% and 2.6%, respectively, in the dabigatran-treated patients, and 2.1% and 3.3%, respectively, among those who received warfarin. The difference between treatments was not statistically significant. Pericardial tamponade occurred in two patients (1.0%) who received dabigatran and seven patients (1.2%) treated with warfarin, a nonsignificant between-treatment difference. All patients with pericardial tamponade recovered.

Earlier studies investigating periprocedural anticoagulation with dabigatran reported less favorable outcomes than treatment with uninterrupted warfarin during ablation of AF, but these anticoagulation protocols withheld dabigatran for only 12 hours.

Source: Kim J, She F, Jongnarangsin K et al. Dabigatran vs warfarin for radiofrequency catheter ablation of atrial fibrillation. http://www.heartrhythmjournal.com/article/S1547-5271%2812%2901445-2/abstract. Accessed December 27, 2012.

Rivaroxaban may help prevent DVT recurrence 

New data from a pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE in the treatment of deep venous thrombosis (DVT) or pulmonary embolism suggests that rivaroxaban is similarly effective in preventing recurrence of VTE as enoxaparin followed by a vitamin-K antagonist and may be associated with less bleeding.

The EINSTEIN-DVT and EINSTEIN-PE trials had identical noninferiority designs comparing oral rivaroxaban (15 mg twice daily for three weeks, then 20 mg once daily thereafter for up to 12 months) with enoxaparin for five to 10 days followed by an oral vitamin-K antagonist. In total, 8,282 patients were enrolled in the two trials. The mean age was 57 in both treatment groups, and equal numbers of men and women participated.

Results of the pooled analysis showed a similar efficacy rate with the two treatments. The primary safety end point, major or non-major clinically relevant bleeding, was also similar in the two arms. But major bleeding alone appeared to be significantly reduced with rivaroxaban.

In addition, subgroup analysis showed reassuring results in specific high-risk populations. These populations included fragile elderly patients, cancer patients, and people with very large clots. Safety and efficacy were similar, with a trend toward lower bleeding rates with rivaroxaban.

Source: Hughes S. Rivaroxaban stands up to standard anticoagulation for VTE treatment. http://www.theheart.org/article/1486495.do. Accessed December 29, 2012. 

Anna D. Garrettis a clinical pharmacist and president of Dr. Anna Garrett, a health and wellness coaching company in Asheville, N.C.