According to the results of a study published early online in the New England Journal of Medicine, an extended course of thromboprophylaxis with apixaban is not superior to a shorter course of enoxaparin, in medically ill patients.   

The authors note that venous thromboembolism (VTE) is a common and potentially fatal complication in hospitalised surgical patients and medical patients who are acutely ill.  The benefits of providing such patients with pharmacological VTE prophylaxis during their hospital stay are well known; prophylaxis that extends beyond the hospital stay has also been shown to be of benefit in high-risk surgical patients.  Although studies have evaluated such extended prophylaxis in medical patients (e.g. rivaroxaban; enoxaparin), any benefits have been offset by an increased risk of major bleeding.

The current international, multicentre study (ADOPT) sought to evaluate the safety and efficacy of the oral factor Xa inhibitor apixaban in this setting.  Participants were acutely ill patients aged ≥40 years who had congestive heart failure, respiratory failure, or other medical disorders with at least one additional risk factor for VTE, and who were hospitalised with an expected stay of at least 3 days.  All had moderate to severely restricted mobility.  Participants were randomised to double-blind and double-dummy treatment with apixaban (2.5mg BD for 30 days; placebo injections) or enoxaparin (40mg once daily, for the duration of the hospital stay [minimum 6 days]; placebo tablets).    

The primary efficacy outcome was a composite of death related to VTE, fatal or non-fatal pulmonary embolism (PE), symptomatic deep-vein thrombosis (DVT), or asymptomatic proximal-leg DVT (detected with the use of systematic bilateral compression ultrasonography) during the 30-day treatment period.  The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated.

A total of 6528 subjects underwent randomisation, 4495 of whom could be evaluated for the primary efficacy outcome (2211 in the apixaban group and 2284 in the enoxaparin group).  The mean duration of exposure was 24.9 days for apixaban and 7.3 days for enoxaparin.  The main results reported were as follows:

• The primary outcome occurred in 2.71% of the apixaban group and 3.06% of the enoxaparin group (relative risk [RR] for apixaban: 0.87; 95% CI 0.62-1.23; p=0.44)

• A composite endpoint of total VTE (asymptomatic proximal DVT, proximal or distal symptomatic DVT, or PE) or death related to VTE occurred in 1.73% and 1.61%, respectively (RR 1.06; 95% CI 0.69 to 1.63).

• The rate of symptomatic DVT was lower among patients who received extended thromboprophylaxis with apixaban (0.15% versus 0.49% in those receiving enoxaparin) but this difference did not reach statistical significance.

• By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group and in 0.19% in the enoxaparin group (RR 2.58; 95% CI 1.02 to 7.24; P=0.04).  Major plus clinically relevant non-major bleeding occurred in 2.67% and 2.08%, respectively (RR 1.28; 95% CI 0.93-1.76; p=0.12)

The authors comment that their study was underpowered and therefore no clinically directive conclusion can be drawn.  In addition the results may not be applicable to typical populations of hospitalised medically ill patients, as screening for VTE with the use of compression ultrasonography is not routinely performed.  They suggest that the strategy of extended VTE prophylaxis with apixaban may still have promise, as an almost immediate increase in the risk of events was seen was enoxaparin was stopped, and they suggest that an even longer duration of extended prophylaxis may have resulted in positive findings, as the curves between apixaban and enoxaparin began to separate well after the final dose of enoxaparin was administered.

They conclude that their results do not provide evidence to justify a policy of extended prophylaxis in a broad population of medically ill patients after hospital discharge.  They do however go on to discuss the results of two other studies evaluating extended prophylaxis in medically ill patients – EXCLAIM and MAGELLAN.  They say that it is clear from the results of these that the risk of VTE increases beyond the time of hospital discharge, and that “more precise risk-stratification methods are needed to identify a narrower spectrum of medically ill patients who may benefit from extended prophylaxis.”