Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement

Abstract

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Anticoagulation and antiplatelet therapy in patients with prosthetic heart valves

“…Substantial evidence suggests that aspirin is an effective antithrombotic at 75–150 mg per day, with further increases amplifying the bleeding risk without protective benefit 40 . This may explain the discordance between these studies and others with more positive overall findings, which tended to use maximal doses of 100 mg per day 35,36 …”

“…Such studies have consistently found the addition of antiplatelets successfully reduced the incidence of thromboembolic events. [32][33][34][35][36][37] However, this is often at the price of increased bleeding risk, leading to ambiguity over whether there is truly a net benefit. [32][33][34]38 Where the risk of hemorrhage is increased by concomitant antiplatelet use, the increase is often predominantly due to minor bleeding events that pose no serious or long-term complications.…”

“…Furthermore, two studies which reported particularly low bleeding rates in anticoagulated groups, both with and without aspirin, used relatively low INR targets (1.8-2.5). 35,36 Thus, the available evidence encourages the use of VKA-antiplatelet combination therapy to maximize protection against thrombosis whilst using a conservative INR target to mitigate bleeding risk. In some cases, the trials were non-randomized, with clinicians permitted to determine the allocation of patients to dual therapy or anticoagulant monotherapy.…”

“…Studies have most commonly assessed the addition of aspirin or dipyridamole to standard VKA monotherapy (Table 2). Such studies have consistently found the addition of antiplatelets successfully reduced the incidence of thromboembolic events 32‐37 . However, this is often at the price of increased bleeding risk, leading to ambiguity over whether there is truly a net benefit 32‐34,38 …”

“…As such, many studies that have recorded increased hemorrhage concluded that this risk was outweighed by the benefit of reduced thrombosis rates. 32,33 Moreover, most studies have found that the addition of aspirin or dipyridamole caused a similar, [34][35][36] or occasionally lower, 32,39 overall mortality when compared to anticoagulation alone, further suggesting that their protective benefits offset any added risk.…”