The combined primary endpoint of fatal or nonfatal PE, or DVT, occurred in 2.1% in the rivaroxaban group and 1.8% in the standard-therapy group, meeting the pre-specified criteria for non-inferiority (HR 1.12; 95% CI: 0.75-1.68). There were no significant differences in the primary safety outcome of bleeding (HR, 0.90; 95% CI: 0.76-1.07). However, major bleeding events favored rivaroxaban, with events in 1.1% vs. 2.2% of those on VKA (HR 0.49, CI 0.31-0.79, P=0.003). Efficacy and safety of fixed-dose rivaroxaban did not vary by age, sex, weight, glomerular filtration rate, or extent of initial PE.
Bottom line: In patients with symptomatic acute PE, rivaroxaban is noninferior to standard treatment with LMWH plus VKA and might have a safety benefit of less major bleeding. Rivaroxaban and other new oral anticoagulants are likely to be used more frequently as more data is accumulated, but at this time, the guidelines continue to recommend VKA and LMWH as first-line agents.
Citation: The EINSTEIN-PE Investigators, Büller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287-1297.
Coronary Stent Implantation Provides No Additional Benefit when Compared with Medical Therapy Alone in Patients with Stable Coronary Artery Disease
Clinical question: Does stent implantation lead to better outcomes when compared to medical therapy in patients with stable coronary artery disease (CAD)?
Background: It is unclear whether stent implantation improves outcomes any more than medical therapy in patients with stable CAD. This is a meta-analysis of trials comparing outcomes of coronary stent implantation with optimal medical therapy.
Study design: Meta-analysis of eight prospective randomized nonblinded trials comparing stent implantation plus medical therapy to medical therapy alone in patients with stable CAD. Outcomes of death, nonfatal myocardial infarction, unplanned revascularization, and persistent angina were compared between the two groups.
Setting: Varied.
Synopsis: Eight trials with 7,229 patients were included with an average follow-up of 4.3 years. In a pooled analysis, coronary stenting versus medical therapy was associated with similar risk of death (8.9% vs. 9.1% P=0.83); nonfatal myocardial infarction (8.9% vs. 8.1%, P=0.22); and persistent angina (29% vs. 33%, P=0.10). Coronary stenting was associated with decreased risk of unplanned revascularization, but the difference was not significant (21.4% vs. 30.7%, P=0.11).
Bottom line: In stable CAD, coronary stent implantation provides no additional benefit when compared to medical therapy.
Citation: Stergiopoulos K, Brown DL. Initial coronary stent implantation with medical therapy vs. medical therapy alone for stable coronary artery disease: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172:312-319.
Prolonged Versus Standard Duration Venous Thromboprophylaxis after Major Orthopedic Surgery
Clinical question: Should patients with hip or knee surgery receive venous thromboprophylaxis (VTE) prophylaxis for seven to 10 days post-operatively or for 21 days or more?
Background: Venous thromboembolism is the most frequent medical complication of knee and hip surgeries. Routine prophylaxis is recommended for minimum of seven to 10 days, but a longer duration might be more beneficial.
Study design: Systemic review and meta-analysis of eight randomized, controlled trials comparing different duration of VTE prophylaxis after hip fracture surgery and total hip or knee replacement.
Setting: Varied.
Synopsis: Eight trials with 2,917 patients met inclusion criteria. Pharmacological agents used for VTE prophylaxis in these trials were coumadin, enoxaparin, dalteparin, and fondaparinux. In patients with hip replacement, undergoing VTE prophylaxis for ≥21 days (compared with seven to 10 days) was associated with a decreased risk of pulmonary embolism (odds ratio [OR] 0.14, 95% CI 0.04-0.47), symptomatic DVTs (OR 0.36, 95% CI 0.16-0.81), asymptomatic DVTs (OR 0.48, 95% CI 0.31-0.75), and proximal DVTs (RR 0.29, CI 0.16-0.52). Prophylaxis for ≥21 days was also associated with an increased risk of minor bleeding (OR 7.55, 95% CI 1.51-37.64).