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Longer Warfarin Therapy after AVR May Be Beneficial
Although current guidelines recommend 3 months of warfarin treatment after bioprosthetic aortic valve replacement (AVR) surgery, this recommendation is limited to the results of a single retrospective study. Now a study of >4000 patients identified through a large registry found that prolonged therapy with the anticoagulation medication may lower the rate of cardiovascular death [JAMA. 2012;308(20):2118-2125].
Shorter life expectancy and lack of need to use anticoagulation therapy in the long run are the reasons biologic prostheses are preferred to mechanical AVR replacement in elderly patients >65 years of age. Particularly in this patient population, the tradeoff between thromboembolic complications due to valve implant and bleeding events as adverse effects from anticoagulation therapy must be balanced. However, appropriate length of therapy following surgery has not been established because the risk of adverse events when treatment is discontinued is unknown.
Using the Danish National Patient Registry, the researchers identified 4075 patients who had bioprosthetic AVR surgery between January 1, 1997, and December 31, 2009. The study’s aim was to determine whether discontinuation of warfarin treatment was associated with increased risk of thromboembolic complications, bleeding incidents, and cardiovascular deaths during a period of 13 years. Average age of the patients was 75 years and 41% were women. Patients were excluded if they were receiving warfarin treatment before surgery or had a diagnosis of atrial fibrillation within 30 days after surgery. The median follow-up was 6.57 person-years.
The researchers determined the incident rate ratios (IRRs) of strokes, thromboembolic events, cardiovascular deaths, and bleeding incidents by discontinuing warfarin as opposed to continued treatment at 30 to 89 days, 90 to 179 days, 180 to 364 days, 365 to 729 days, and at least 730 days after surgery. Overall, 361 patients (8.9%) experienced a stroke, 615 (15.1%) had a thromboembolic event, and 364 (8.9%) had a bleeding incident after the date of surgery. During the observation period, 1156 patients died, with 879 (76.0%) of these deaths attributed to cardiovascular disease. Within 30 days after surgery, 109 patients (2.7%) experienced a stroke, 201 patients (5.0%) experienced thromboembolic events, and 75 patients (1.8%) had a bleeding episode. The 30-day mortality was 6.0% and 1-year mortality was 10.9%.
The adjusted IRR for patients not treated with warfarin compared with those treated with warfarin were 2.46 for stroke (95% confidence interval [CI], 1.09-5.55); 2.93 for thromboembolic events (95% CI, 1.54-5.55); 2.32 for bleeding incidents (95% CI, 1.28-4.22); and 7.61 for cardiovascular deaths (95% CI, 4.37-13.26) within 30 to 89 days after surgery; and 3.51 (95% CI, 1.54-8.03) for cardiovascular deaths within 90 to 179 days after surgery. The researchers calculated that for every 23 patients not being treated with warfarin between 3 and 6 months, there was 1 additional cardiovascular death; and for every 74 patients being treated with warfarin, 1 patient experienced a bleeding complication requiring hospital admission.
Study limitations noted by the investigators included lack of access to information regarding the international normalized ratio. Similarly, the researchers were unable to monitor adherence to treatment. Furthermore, the main limitation of the databases is the lack of comprehensive clinical information related to important risk factors, which could potentially influence outcome. Finally, reliance on administrative databases induced a risk of time-varying measurement errors of exposure as well as biases from survival effects.
The researchers concluded that discontinuing warfarin therapy within 3 months after surgery is associated with a significant increase in the risk of stroke, thromboembolic complications, and cardiovascular death. The study also demonstrated that stopping warfarin treatment within 6 months after surgery was associated with a significant increase in the risk of cardiovascular death.
“Our study challenges current guidelines on the duration of anti-thrombotic treatment after AVR surgery with biological valves by presenting results suggesting that these patients will gain from an additional 3 months of warfarin treatment in terms of reduced cardiovascular death without risking a significant increase in bleeding events,” commented the researchers.
