Monday, April 16, 2012

Topic Discussion: New anticoagulants and renal disease

2011 and 2012 has seen a series of publications regarding the novel agents for anticoagulation.  The three major ones that are up for discussion are: dabigatran, apixaban and rivaroxaban. While the former is a direct thrombin inhibitor, the later two are factor Xa direct inhibitors.  The ease of use is the dosing and no need for monitoring. What about in patients with decreased GFR? The image below (T S Potpara and G Y H Lip from Nature) summarizes the novel agents. Recently, several new oral anticoagulants have been tested in large trials involving thousands of patients with AF(RE-LY, ADOPT , ROCKET -AF). All of these new anticoagulants are partially eliminated by renal clearance. In CKD patients, therefore, the half-lives of these novel anticoagulants may be prolonged, resulting in enhanced antithrombotic efficacy. 

On the other hand, there might be a higher than normal bleeding risk in CKD patients with these compounds. While patients with GFR>30cc/min were included in all trials, the moderate to severe CKD with GFR<30 were not included in all three trials. It is interesting to note that of all the three new agents, only rivaroxaban is predominantly liver clearance making it perhaps the best agent of all three for CKD patients.  The ROCKET-AF trial excluded patients with an eGFR <30 mL/min, whereas the daily dose of rivaroxaban was reduced from 20 to 15 mg in patients with an eGFR of 30–49 mL/min based on available pharmacodynamic data and pharmacokinetic modelling.
So where do we stand? Unclear at this point.  While it is been suggested by the new ACCP 9th version of guidlines for thromboembolism to start using these agents, one has to watch for any post adverse events.  Especially, if there is acute kidney injury or if there is slow declining GFR, agents might have to be changed or dosages adjusted.  Time will tell. 

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