November 15th, 2012
In Acute VTE, Novel Oral Anticoagulants and Conventional Therapy Show Similar Efficacy
Nicholas Downing, MD
Novel oral anticoagulants and vitamin K antagonists offer similar protection against venous thromboembolism recurrence, according to a BMJ meta-analysis. However, one of the newer agents, rivaroxaban, seems to offer better protection against bleeding.
The analysis included nine randomized controlled trials comparing apixaban, dabigatran, rivaroxaban, or ximelagatran (no longer on the market) with traditional vitamin K antagonists (e.g, warfarin) in nearly 17,000 patients with acute VTE. Follow-up ranged from 2 weeks to 12 months.
There were no significant differences between any of the novel anticoagulants and vitamin K antagonists with respect to recurrent VTE or all-cause mortality. The newer agents tended to lower the risk for major bleeding, but only the effect of rivaroxaban was statistically significant. An indirect comparison between rivaroxaban and dabigatran did not favor either drug for any outcome.
Asked to comment, David Green of Journal Watch Oncology and Hematology said: “The benefits of the new oral anticoagulants are that monitoring is not required and there are fewer interactions with other drugs; the downside is that there are no readily available reversing agents and experience is still accumulating about effectiveness and safety in various populations.”
2 Responses to “In Acute VTE, Novel Oral Anticoagulants and Conventional Therapy Show Similar Efficacy”
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With all due respect to the opinions of colleagues with similar backgrounds, I would like to weigh in. A drug, rivaroxaban, that offers reliable anticoagulant efficacy across a wide range of body weight and medical indications, permits life-style and pro-health dietary choices which include Vitamin K-rich vegetable options, and –although we do not have FDA sanctions for all of its clinical trial outcomes, –the option of permitting a dosing range that can support secondary prevention of coronary artery syndromes, VTE prophylaxis following major orthopedic surgery, prevention of stroke from atrial fibrillation and treatment of venous thrombosis/thromboembolism with a single daily dose of drug –is a remarkably appealing alternative to all that has gone before. I have no financial relationship with Janssen/ Johnson and Johnson pharmaceuticals — but intuit that this drug and others that resemble it will modify our therapeutic world in very beneficial ways. Contrary to what has been said on various internet posts, it is completely reversible with prothrombin complex concentrates, and I will challenge most of my colleagues to tell me when they last had to reverse anything related to an anticoagulant other than the accepted ridiculous and usually ineffective strategies for reversal of warfarin .
I think the jury is still out with regard to oral direct thrombin inhibitors. I have concerns about direct thrombin inhibition that requires twice daily dosing and may inhibit Protein C activation and secondarily inhibit the turnoff of Factors Va and VIIIa, but realize that conjecture and real biology may not be coherent. It is clear that the drug effect cannot be reversed without dialysis, but – as in any anticoagulant reversal — the drug T 1/2 is critical. If the drug was appropriately dosed, its T 1/2 is 12 hours. Use of either of these drugs, rivaroxaban or dabigatran, in patients with creatinine clearances of <30 s difficult — but this is not different from the use of all of the LMWHs and fondaparinux. We, like most medical centers, are developing assays — not normally needed for patients with normal renal function — to accommodate those patients who have unusual medical needs. It would be a wonderful to have large medical centers which accommodate patients with varied medical needs including renal dysfunction, collaborate in creating care plans for patients whose needs are not conventional., and we would be pleased to help in such and endeavor.
With all due respect to the opinions of colleagues with similar backgrounds, I would like to weigh in. A drug, rivaroxaban, that offers reliable anticoagulant efficacy across a wide range of body weight and medical indications, permits life-style and pro-health dietary choices which include Vitamin K-rich vegetable options, and –although we do not have FDA sanctions for all of its clinical trial outcomes, –the option of permitting a dosing range that can support secondary prevention of coronary artery syndromes, VTE prophylaxis following major orthopedic surgery, prevention of stroke from atrial fibrillation and treatment of venous thrombosis/thromboembolism with a single daily dose of drug –is a remarkably appealing alternative to all that has gone before. I have no financial relationship with Janssen/ Johnson and Johnson pharmaceuticals — but intuit that this drug and others that resemble it will modify our therapeutic world in very beneficial ways. Contrary to what has been said on various internet posts, it is completely reversible with prothrombin complex concentrates, and I will challenge most of my colleagues to tell me when they last had to reverse anything related to an anticoagulant other than the accepted ridiculous and usually ineffective strategies for reversal of warfarin .
I think the jury is still out with regard to oral direct thrombin inhibitors. I have concerns about direct thrombin inhibition that requires twice daily dosing and may inhibit Protein C activation and secondarily inhibit the turnoff of Factors Va and VIIIa, but realize that conjecture and real biology may not be coherent. It is clear that the drug effect cannot be reversed without dialysis, but – as in any anticoagulant reversal — the drug T 1/2 is critical. If the drug was appropriately dosed, its T 1/2 is 12 hours. Use of either of these drugs, rivaroxaban or dabigatran, in patients with creatinine clearances of <30 s difficult — but this is not different from the use of all of the LMWHs and fondaparinux. We, like most medical centers, are developing assays — not normally needed for patients with normal renal function — to accommodate those patients who have unusual medical needs. It would be a wonderful to have large medical centers which accommodate patients with varied medical needs including renal dysfunction, collaborate in creating care plans for patients whose needs are not conventional., and we would be pleased to help in such an endeavor.