Use of Low-molecular-weight Heparins and New Anticoagulants in Elderly Patients with Renal Impairment

Elderly people with renal impairment are at high risk for venous thromboembolism (VTE) and acute coronary syndromes (ACS); however, they are also at increased risk for bleeding complications. Evidence-based data for the management of anticoagulation in elderly patients with severe renal impairment, in particular, are limited. These patients are frequently excluded from randomized clinical trials evaluating anticoagulants, confounding clinical decision making. Low-molecular-weight heparins (LMWHs), such as enoxaparin sodium and dalteparin sodium, provide a predictable anticoagulant effect across almost all patient populations; however, because they are primarily eliminated through the kidneys, elderly patients with moderate or severe renal impairment are potentially at risk for LMWH accumulation. Clinical evidence suggests that treatment with full-dose enoxaparin sodium could increase the risk for bleeding in elderly patients with severe renal impairment; however, this risk is ameliorated with approved dose adjustments. Dalteparin sodium has been evaluated in small studies within this population but no strategy for reduced dosing has been developed. There are limited clinical data on the use of fondaparinux sodium and, in particular, the new anticoagulants, such as dabigatran etexilate and rivaroxaban, in elderly patients with renal impairment. Evidence suggests that the clearance of fondaparinux sodium is mildly reduced in elderly patients, and more substantially reduced in patients with severe renal impairment; a dose reduction has recently been approved in Europe. Age and renal function appear to affect the exposure of dabigatran etexilate. A dose reduction is recommended in the elderly and in those with moderate renal function, but dabigatran etexilate is contraindicated in severe renal impairment. Rivaroxaban has been associated with increased exposure and pharmacodynamic effects in the elderly and those with renal impairment; at present there is no facility for dose reduction. Monitoring anticoagulant activity may help improve the safety profile of anticoagulants in elderly patients with renal impairment, particularly when approved dose reductions are unavailable. However, unlike the LMWHs, clinical surveillance of the new anticoagulants is challenging. In conclusion, extra care should be taken when anticoagulants are administered to elderly patients with renal impairment. Additional data are needed, particularly for the new anticoagulants, in order to guide the prevention and treatment of VTE and ACS, and to ensure the optimal safety profile in older patients with renal impairment.