Andexanet quickly reverses factor Xa inhibitor activity for DOACs

January 10, 2016

Andexanet alpha is designed to reverse the anticoagulant effects of factor Xa inhibitors.

Anna D. GarrettBleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet alpha is designed to reverse the anticoagulant effects of factor Xa inhibitors.

In a recent study, healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily. For each factor Xa inhibitor, a two-part randomized placebo-controlled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion. The primary outcome was the mean percent change in anti–factor Xa activity.

Less bleeding with rivaroxaban for venous thromboembolism

In apixaban-treated participants, anti–factor Xa activity was reduced by 94% among those who received an andexanet bolus, vs. 21% among those who received placebo. Thrombin generation was fully restored in 100% vs. 11% of the participants within 2 to 5 minutes. Among the rivaroxaban-treated participants, anti–factor Xa activity was reduced by 92% among those who received an andexanet bolus vs. 18% among those who received placebo. Thrombin generation was fully restored in 96% vs. 7% of the participants. These effects were sustained when andexanet was administered as a bolus plus an infusion. No serious adverse or thrombotic events were reported.

The manufacturer is pursuing an accelerated approval pathway with the FDA.

Siegal DM, Curnutte JT, Connolly SJ et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. NEJM 2015. Published online before print Nov 11,2015:DOI: 10.1056/NEJMoa1510991.

 

Manual thrombectomy may increase risk of stroke after PCI

Small trials have suggested that manual thrombectomy improves surrogate and clinical outcomes during primary percutaneous coronary intervention (PCI), but a larger trial has reported conflicting results.

To explore this further, researchers in a recent study randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy vs. PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days.

The primary outcome occurred in 6.9% of patients in the thrombectomy group versus 7.0% in the PCI-alone group. The rates of cardiovascular death and the primary outcome plus stent thrombosis or target-vessel revascularization were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group.

Jolly SS, Cairns JA, Yusuf S, et al. Randomized trial of primary PCI with or without routine manual thrombectomy. NEJM 2015; 372:1389-1398April 9, 2015DOI: 10.1056/NEJMoa1415098.

PPIs reduce risk of GI bleeding in MI patients

The use of proton-pump inhibitors (PPIs) is often recommended to prevent gastrointestinal bleeding (GIB) in patients with cardiac disease who take antithrombotics or nonsteroidal anti-inflammatory drugs (NSAIDs) and are considered at elevated risk for bleeding.

To address the question of whether to give them to all MI patients, investigators assessed risk for GIB in a nationwide cohort of 83,000 patients in Denmark who were hospitalized between 1997 and 2011 for a first MI and were administered single or dual antithrombotics and NSAIDs.

 

Overall, 3,229 GIB episodes occurred; 8.7% were fatal. Compared with patients who used antithrombotics and NSAIDs alone, those who used concurrent PPIs had a significantly lower risk for GIB (hazard ratio, 0.72). Concurrent use of PPIs with NSAIDs and dual antithrombotics was also associated with significant GIB risk reduction (HR, 0.41). Adjustment for specific types of NSAIDs and PPIs did not alter results.

See also: FDA approves new heart medication

Even though NSAIDs are not recommended in post-MI patients, they are still commonly used to treat pain. Despite these positive findings, NSAIDs should still be avoided whenever possible because of concerns about adverse cardiovascular effects.

Schjerning AMO, Lindhardsen  J, Gislason GH et al. Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: Nationwide study. BMJ 2015;351:h5096.