Anticoagulation; New Pharmacologic Methods to Prevent Venous Thromboembolism in Older Adults: A Meta-Analysis

Abstract

To conduct a meta-analysis of randomized controlled trials that used newly approved drugs to prevent venous thromboembolism (VTE) in older adults. PubMed, EMBASE, and International Pharmaceutical Abstracts (through July 2012). Full-text clinical trial reports were included if they (1) had a randomized controlled design, (2) used a pharmacologic method approved or anticipated to be approved in the US, (3) enrolled at least 300 subjects, (4) enrolled subjects with a mean age of 65 years or older or performed a subgroup analysis in adults in that population, and (5) scored at least 7 of 8 on quality criteria for clinical trials. Twenty unique studies met the inclusion criteria. The most common indications for pharmacologic VTE prophylaxis in the identified studies were orthopedic procedures involving the lower extremities and general surgery. Only 2 studies enrolled acutely ill patients admitted to hospital medical services. Fondaparinux (5 studies) was more effective than enoxaparin in preventing VTE (OR 0.5, 95% CI 0.37-0.67; p < 0.00001) but had more bleeding (OR 1.48, 95% CI 1.05-2.08; p = 0.03). Dabigatran 150 mg once daily (3 studies) was less effective than enoxaparin in preventing VTE (OR 1.30, 95% CI 1.09-1.56; p = 0.004) with a similar bleeding risk (OR 0.74, 95% CI 0.46-1.22; p = 0.24). Dabigatran 220 mg once daily (4 studies) was as effective as enoxaparin in preventing VTE (OR 1.02, 95% CI 0.83-1.26; p = 0.84) and had similar bleeding (OR 1.08, 95% CI 0.66-1.76; p = 0.76). Rivaroxaban (4 studies) was more effective than enoxaparin in preventing VTE (OR 0.38, 95% CI 0.23-0.61; p < 0.0001) with a trend toward a higher rate of bleeding (OR 1.8, 95% CI 0.90-3.60; p = 0.09). Apixaban (5 studies) was more effective than enoxaparin in preventing VTE (OR 0.64, 95% CI 0.43-0.96; p = 0.0002) and had a similar rate of bleeding (OR 0.71, 95% CI 0.42-1.21; p = 0.21). When compared to enoxaparin, newer drugs exhibit slightly different safety and efficacy profiles when used for VTE prevention in older adults undergoing major orthopedic surgery. There are insufficient data for other indications. The benefits and risks of new pharmacologic methods of VTE prevention are unclear in the oldest old (age ≥ 85 years) and in those admitted to a hospital for an acute medical illness or to a skilled nursing facility.