Recently, my patient presented to our emergency department with a massive acute pulmonary embolism. No clear risk factors were identified.
After about 2 weeks working with our anticoagulation nurses and being unable or unwilling to pay for a home INR monitor, she grew weary. She presented with her husband and asked whether there was anything other than warfarin that they could use that would be safe and effective.
We know alternatives are out there – but are we using them widely, and are they ready for prime time?
The search for new oral anticoagulants (NOACs), which presently includes the major classes of direct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors, continues in earnest. The DTI currently on the market is dabigatran. FXa inhibitors include rivaroxaban, apixaban, edoxaban, and betrixaban. NOACs offer the potential advantage of predictable effects and decreased monitoring.
Dr. Soheir S. Adam and her colleagues recently published a systematic review, comparing new oral anticoagulants (NOACs) with warfarin for atrial fibrillation and venous thromboembolism (Ann. Intern. Med. 2012;157:796-807).
The authors identified six randomized clinical trials involving more than 60,000 patients. Three evaluated NOACs for chronic atrial fibrillation (AF), and three evaluated them for venous thromboembolism (VTE). All studies compared these drugs to adjusted-dose warfarin. Data were combined for DTIs and FXa inhibitors.
For AF, NOACs were associated with decreased all-cause mortality (relative risk [RR], 0.88; 95% confidence interval: 0.82-0.96) and hemorrhagic stroke (RR, 0.48; 95% CI: 0.36-0.62), compared with warfarin.
For VTE, no differences between NOACs and warfarin were observed for all-cause mortality, VTE-related mortality, or recurrent deep vein thrombosis and pulmonary embolism. Rates of fatal bleeding were consistently lower with NOACs (RR, 0.60; 95% CI: 0.46-0.77] with no difference by drug class. The risk for gastrointestinal bleeding was increased with NOACs.
Although not statistically significant, the point estimate for the risk of myocardial infarction was higher with dabigatran (RR, 1.35; CI: 0.99-1.85) than with FXa inhibitors. More patients discontinued dabigatran (RR 1.62; CI: 1.23-2.15) than did FXa inhibitors.
The authors point out that the FDA has reported that dabigatran and warfarin were first and second, respectively, among anticoagulant drugs with reported adverse event reports. Dabigatran was associated with hemorrhages, renal failure, strokes, deaths, and cases of renal failure.
Overall, the findings suggest that bleeding risk may be increased with dabigatran among older patients or those with impaired renal function. Risk for MI also might be increased.
Rivaroxaban is approved by the FDA for the treatment of acute pulmonary embolism. Rivaroxaban should not be used in patients with a creatinine clearance of 30 mL/min or less, significant hepatic impairment, or during pregnancy. But if my patient is willing to pay the higher cost of this medication and assume the possible increased risk for GI bleeding, it may be reasonable to try.