WASHINGTON – Treating acute venous thromboembolism with the fixed-dose oral factor Xa inhibitor apixaban significantly reduces subsequent all-cause hospitalizations, compared with conventional therapy with enoxaparin followed by warfarin, according to a secondary analysis of the landmark AMPLIFY trial.

The 21% reduction in the risk of hospitalization in the apixaban group during the 6 months following the initial VTE was driven mainly by fewer hospitalizations for recurrent VTE or major bleeding. There were also significantly fewer physician office visits by patients on apixaban than for those on enoxaparin/warfarin, Dr. Margot Johnson reported at the annual meeting of the American College of Cardiology.

An analysis of the cost savings associated with this reduction in hospitalizations seen in AMPLIFY is underway and will be reported later this year, added Dr. Johnson of King’s College Hospital in London.

AMPLIFY (Apixaban for the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis) was a randomized double-blind study of 5,365 patients with acute symptomatic VTE who were assigned to 6 months of treatment with apixaban (Eliquis) at 10 mg b.i.d. for 7 days followed by 5 mg b.i.d. or to enoxaparin followed by warfarin. In the previously reported primary outcomes (N. Engl. J. Med. 2013;369:799-808), apixaban showed noninferiority to the conventional regimen in terms of the rate of recurrent VTE or VTE-related death, and a highly significant superiority in terms of major bleeding, with a 69% risk reduction.

Dr. Johnson reported that during the 6-month study period, 5.72% of the apixaban group had one or more hospitalizations after the initial event, compared with 7.07% of the control group. This translated to a significant 21% relative risk reduction. For every 74 patients treated with apixaban instead of enoxaparin/warfarin, one hospitalization was avoided. Moreover, when a hospitalization occurred in apixaban-treated patients, the mean length of stay was shorter: 10.2 vs. 11.7 days in the enoxaparin-warfarin group.

The median time to a first hospitalization was 63 days in the apixaban group, compared with 34.5 days in controls.

The apixaban group’s advantage in terms of hospitalization risk was consistent across subgroups on the basis of age, body weight, sex, and renal function.

The number of emergency department visits during the 6-month follow-up period was similar in the two study arms. However, only 5.8% of the apixaban group visited a physician’s office, compared with 7.3% of controls. The reasons for these office visits were basically the same as for the hospitalizations: mostly recurrent VTEs and bleeding episodes. In the apixaban group, 35 patients had an office visit for recurrent VTE, compared with 61 controls. And 71 apixaban-treated patients made an office visit for bleeding episodes, compared with 130 controls.

Session cochair Dr. Emile R. Mohler commented on the finding that 37 patients in the apixaban group and 48 on enoxaparin/warfarin required hospitalization for recurrent VTE.

"It seems like we’re not doing a good enough job there. Either both of these anticoagulants don’t work well, or the patients aren’t taking the medication, or we’re not following up with them enough. I can’t remember the last time in my own clinical practice that somebody who took their medication came back within 6 months of having a VTE. It seems strange. I think there’s a lot of room for improvement," commented Dr. Mohler, professor of medicine and director of vascular medicine at the University of Pennsylvania, Philadelphia.

Dr. Johnson agreed about the room for improvement. But she added that, although the data she presented were based upon an intention-to-treat analysis, the results were the same – significantly fewer hospitalizations in the apixaban group – in a per-protocol analysis that excluded patients with less than 80% adherence to their study medication.

"One of the big things we saw in AMPLIFY is that whenever you stop an anticoagulant, you see the recurrence rate go up by about 10% per year. So it’s very important that these people continue their anticoagulation – and the more we can reduce their bleeding events, the more likely they are to comply with that therapy and be protected from having another VTE," she added.

Session cochair Dr. John P. Cooke commented that one underutilized aspect of treatment for acute VTE is compressive support, which he said has been given short shrift in the major practice guidelines.

"Often as physicians, we give patients a pill and we think that we’ve treated them. Compressive support is important in VTE," stressed Dr. Cooke, chair of the department of cardiovascular sciences at the Houston Methodist Research Institute and director of the Center for Cardiovascular Regeneration at the Houston Methodist DeBakey Heart and Vascular Center.

The AMPLIFY trial was sponsored by Bristol-Myers Squibb and Pfizer. Dr. Johnson reported having no financial conflicts.

bjancin@frontlinemedcom.com

Apixiban for VTE reduces subsequent hospitalizations