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Preventing venous thromboembolism in long-term care residents: Cautious advice based on limited data

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OPTIONS FOR THROMBOPROPHYLAXIS IN LONG-TERM CARE RESIDENTS

Options for thromboprophylaxis fall into two broad categories: anticoagulant drugs and mechanical devices.

Anticoagulant prophylactic drugs

The anticoagulant drugs used for prophylaxis (Table 1) are unfractionated heparin; the low-molecular-weight heparins enoxaparin (Lovenox), tinzaparin (Innohep), and dalteparin (Fragmin); and the factor Xa inhibitor fondaparinux (Arixtra).14

These agents have been assessed in randomized trials in surgical or acutely ill medical patients, although fondaparinux and tinzaparin are not approved for use in medical patients. Furthermore, none of them has been evaluated in residents of long-term care facilities.

The choice of anticoagulant for prophylaxis is determined largely by clinical factors.

Low-molecular-weight heparins are popular both in and out of the hospital because they have predictable pharmacokinetic properties, they come in convenient prefilled syringes, and they can be given once daily. However, some of them may bioaccumulate in patients with impaired renal function, as they are cleared primarily by the kidney.

Unfractionated heparin is likely to be safer in patients with severe renal insufficiency (creatinine clearance < 30 mL/min), as it is cleared via nonrenal mechanisms.

However, a recent single-arm trial of dalteparin 5,000 IU once daily in critically ill patients with severe renal insufficiency found no evidence of an excessive anticoagulant effect or of drug bioaccumulation.15 Dalteparin may thus be an alternative to unfractionated heparin in medical patients with impaired renal function.

Fondaparinux, a newer anticoagulant, is also given once daily. It is the anticoagulant of choice in patients who have had heparin-induced thrombocytopenia because it is not derived from heparin and likely does not cross-react with heparin-induced thrombocytopenia antibodies.16,17

Limited data on benefit of prophylactic anticoagulant drugs

As mentioned, the trials that confirmed the efficacy and safety of anticoagulant prophylaxis were in surgical patients and hospitalized medical patients, not elderly long-term care residents. The poor evidence for anticoagulant prophylaxis in these patients may be strengthened if extended-duration, out-of-hospital prophylaxis were shown to be effective in medical patients. Long-term care residents could more reasonably be compared with medical patients discharged home with a chronic or resolving illness than with those who are hospitalized.

There is some evidence, although with caveats, that extended anticoagulant prophylaxis, started after an acute illness has resolved, confers a benefit. A recent randomized trial compared extended-duration and short-duration prophylaxis (5 weeks vs 10 days) with enoxaparin 40 mg once daily in 4,726 medical patients with impaired mobility.18 The risk of any VTE event was 44% lower with extended-duration prophylaxis (2.8% vs 4.9%; P = .001) and the risk of symptomatic VTE was 73% lower (0.3% vs 1.1%; P = .004), and this benefit persisted 2 months after treatment was stopped (3.0% vs 5.2%; P = .0015). However, extended treatment conferred a fourfold higher risk of major bleeding (0.6% vs 0.15%; P = .019).

These findings should also be considered in terms of absolute benefit and harm. Treating 1,000 patients for 5 weeks instead of 10 days would prevent eight episodes of symptomatic VTE (absolute risk reduction = 0.8%, number needed to treat = 125) at the cost of four to five episodes of major bleeding (absolute risk increase = 0.45%, number needed to harm = 222). This is a modest net therapeutic benefit.

The therapeutic benefit would be greater if we consider all episodes of VTE, both symptomatic and asymptomatic. Treating 1,000 patients for 5 weeks would prevent 20 episodes of symptomatic or asymptomatic VTE (absolute risk reduction = 2.1%, number needed to treat = 48). However, the clinical importance of asymptomatic VTE is questionable.

Given these considerations, if extended-duration anticoagulant prophylaxis is considered, it should be for patients at highest risk to optimize both its net therapeutic benefits and its cost-effectiveness.

Mechanical prophylaxis

Mechanical thromboprophylactic devices—graduated or elastic compression stockings and intermittent pneumatic compression devices—are effective when used by themselves in surgical patients.13 However, in a randomized controlled trial in patients with ischemic stroke, the rate of VTE was 10.0% with graduated compression stockings in addition to “usual care VTE prophylaxis” vs 10.5% with usual care alone, and patients in the stocking group had a fourfold higher risk of developing skin breaks, ulcers, blisters, or necrosis (5% vs 1%; odds ratio 4.18; 95% CI 2.4–7.3).19 Furthermore, improperly fitted stockings, especially those that are thigh-length, can be uncomfortable to wear and difficult to apply.

Overall, the role of mechanical thromboprophylaxis in long-term care facilities is not clear. If it is considered, there should be a compelling reason to use it—for example, for patients at high risk in whom anticoagulants are contraindicated because of ongoing bleeding or a higher risk of bleeding (eg, recent gastrointestinal bleeding, hemorrhagic stroke, coagulopathy, or thrombocytopenia). Furthermore, if stockings are used, they should be properly fitted and routinely monitored for adverse effects, since elderly patients are likely to be most susceptible to skin breakdown.

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