Use of Anticoagulation in Elderly Patients with Atrial Fibrillation Who Are at Risk for Falls

Candice L Garwood, PharmD BCPS; Tia L Corbett, PharmD

Disclosures

The Annals of Pharmacotherapy. 2008;42(4):523-532. 

In This Article

Low-Dose Warfarin for Atrial Fibrillation

Low-dose warfarin therapy has been studied with the idea that if effective for stroke prevention, lower intensity doses of warfarin would provide a lower overall risk of bleeding. This is a strategy that may be considered by some in management of elderly AF patients who are at risk of falling. The BAATAF (Boston Area Anticoagulation Trial for Atrial Fibrillation) was an unblinded, randomized controlled trial that did support the use of low-intensity warfarin (prothrombin time ratio 1.2-1.5 times the control, corresponding INR 1.5-2.7) and found it to be more effective than placebo in stroke prevention (0.4% per year with low-dose warfarin vs 3.0% per year in the control group) (RRR 86%; 95% CI 0.4 to 0.49; p = 0.0022).[27] However, this is a broad target range that covers much of what we consider the therapeutic goal for AF, INR 2.0-3.0. Yet, more recent trials refute the conclusion that low-dose warfarin is optimal in AF. The SPAF III trial was a randomized, risk-stratified study of low-dose warfarin plus aspirin compared with adjusted-dose warfarin.[24] This trial found the rate of primary events in high-risk patients receiving low-dose warfarin plus aspirin combination therapy to be greater than primary event rates in the adjusted-dose warfarin group. Thus, the SPAF III findings support the idea that low-dose warfarin, even in combination with aspirin, is ineffective in high-risk patients with AF (1.9% with adjusted-dose warfarin vs 7.9% with low-dose warfarin plus aspirin) (RRR 74%; 95% CI 3.4 to 8.6; p < 0.0001).

Pengo et al.[22] performed a randomized, open-label trial of low-dose warfarin versus adjusted-dose warfarin and found that the rate of stroke was greater with low-dose warfarin compared with adjusted-dose warfarin in elderly patients with AF (3.7% per year with low-dose warfarin vs 0% per year with adjusted-dose warfarin, p = 0.025). The study was underpowered to identify a difference in the primary endpoint of combined stroke, systemic embolism, cerebral bleeding, and vascular death. The AFASAK 2 (Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation) study was a randomized, controlled trial with 4 arms comparing low-dose warfarin, low-dose warfarin plus aspirin, aspirin, and adjusted-dose warfarin.[21] AFASAK 2 did not show any difference in stroke prevention between the low-dose warfarin and adjusted-dose warfarin groups. The trial was halted early after release of the results from the SPAF III study and therefore was underpowered. However, AFASAK 2 did show a trend toward a lower stroke rate in elderly patients with AF taking adjusted-dose warfarin compared with the rate in patients on low-dose warfarin. A case-control analysis was performed to determine the relationship between the INR and the risk of ischemic stroke in patients with AF. When compared with an INR of 2.0, the analysis found an increase in the risk of stroke as INR values decreased. The stroke risk doubled with an INR below 1.7, tripled with an INR below 1.5, and increased by sevenfold with an INR below 1.3.[53] Although ACC/AHA/ESC guidelines do suggest that low-intensity warfarin treatment might be an option, recent trials advocate that low-dose warfarin is ineffective in stroke prevention in AF and still carries risk for bleeding.[21,24,27]

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