Aspirin Plus Warfarin for Mechanical Valves
Aspirin Plus Warfarin for Mechanical Valves
abstract & commentary
Synopsis: Aspirin plus oral anticoagulants reduce thromboembolic events but not mortality in the first year after mechanical mitral valve replacement.
Source: Laffort P, et al. J Am Coll Cardiol 2000; 35:739-746.
Despite improved valve design, cardiac embolic events are still a problem with mechanical mitral valve replacement, especially in the early postoperative period. Thus, Laffort and colleagues from Pessac, France, randomized 229 patients who received St. Jude mitral valve replacements to aspirin (200 mg/day) plus oral anticoagulants (OAC) to an international normalized ratio (INR) of 2.5-3.5, or OAC alone beginning 48 hours after surgery. Transesophageal echocardiography (TEE) was performed at nine days and five months post-surgery, and all patients were followed for one year. The primary end point of the study was death, major thromboembolic event, or major hemorrhage at one year. Major thromboembolic events included stroke, acute myocardial infarction (MI) with normal coronary arteries, and valve thrombosis. Minor thromboembolic events were also assessed and included valve strands, nonobstructive valve thrombi, and transient ischemic attacks. Major hemorrhages were those requiring transfusion, cerebral hemorrhage, and those requiring surgical repair. At nine days, there was no difference in the incidence of valve strands, but minor thrombi were less frequent in the aspirin group (13% vs 5%; P = 0.03). Minor thrombi were small and located on the atrial side of the sewing ring. At five months, there was a high incidence of strands in both groups (61%), but thrombi were infrequent and less in the aspirin group (4% vs 8%; P = NS). The primary end point was higher in the aspirin group (29% vs 17%; P = NS) mainly because of more major hemorrhages (19% vs 8%; P = 0.02). Minor thromboembolic events were less in the aspirin group (8% vs 21%; P = 0.007), as were total thromboembolic events (9% vs 25%; P = 0.001).
| Table-One-Year Outcomes | |||
| Event | + Aspirin | - Aspirin | P |
| Death | 9% | 4% | NS |
| Major hemorrhage | 19% | 8% | 0.02 |
| Major TE | 1% | 4% | NS |
| Primary end point | 29% | 17% | NS |
| Minor TE | 8% | 21% | 0.007 |
| Total TE | 9% | 25% | 0.001 |
| Total events | 39% | 38% | NS |
| TE = thromboemboli | |||
Laffort et al conclude that aspirin plus oral anticoagulants reduce thromboembolic events but not mortality in the first year after mechanical mitral valve replacement because of an increase in hemorrhagic events.
Comment by Michael H. Crawford, MD
Although optimal anticoagulation has markedly reduced thromboembolic complications with mechanical prostheses in the mitral position, the continued occurrence of thromboembolic events (7% in this study) has prompted the search for adjuvant agents. A decade or more ago, dypyridamole plus warfarin was popular, but carefully done studies showed no overall benefit and its use declined. More recently, aspirin has been studied with mixed results. This study is unique for several reasons: it is the largest randomized trial of adjuvant aspirin; it focuses exclusively on the St. Jude valve, which is now the most commonly used; it uses the new recommended INR range of 2.5-3.5 for the newer prostheses; and TEE was included in the evaluation. Unfortunately, the overall results do not strongly endorse adjuvant aspirin use.
Aspirin significantly reduced thromboemboli, especially if TEE-documented thrombi are included, but a sharp increase in major hemorrhages (largely gastrointestinal) negated the overall benefit. In the aspirin group, there was only one thromboembolic event to a peripheral artery, whereas in the warfarin-alone group, there were 5:4 strokes and one prosthetic valve thrombosis. As expected, late events were related to the INR achieved. Three-quarters of the thromboemboli occurred in patients with INR less than 2.5 and three-fourths of the major hemorrhages occurred in patients with INR of more than 3.5. Thus, if INR could be controlled perfectly, complications could be reduced by 75%.
There were some limitations to this study. There was no placebo aspirin arm, but it is unlikely this influenced the results since there were no subjective end points. Also, it would have been interesting to see what 81 mg of aspirin would have done, but the American College of Chest Physicians’ recommendations are for 160 mg, which is closer to the 200 mg used. In addition, it would be nice to know from the reoperated patients what the strands seen on TEE were, since aspirin did not influence their incidence. With a 60% incidence at five months, clearly these strands cannot be implicated in embolic events.
Although there was no overall benefit of adjuvant aspirin, the reduction in embolic events is impressive and raises the question of whether there might be subgroups in which the risk benefit ratio was more favorable for adding aspirin. Laffort et al did not fully explore this issue, but noted that a prior history of thromboembolic events predisposed to future events. Perhaps in such patients, the benefit would outweigh the risk. Other studies have shown that patients with concomitant coronary artery disease (CAD) may benefit from adding aspirin. Finally, those with visible thrombi on TEE predischarge may be candidates for aspirin, but this requires TEE in all postoperative mechanical mitral valve replacements. Such an approach would need to be shown cost-effective to be widely adopted. At this time, most cardiologists confine adjuvant aspirin in mitral mechanical valve replacement patients with CAD and usually use 81 mg/day. Perhaps the indications should be broadened to include other high-risk patients, but this concept remains unproven.
In patients with mechanical mitral valve replacement, the addition of aspirin to warfarin should be considered with:
a. visible thrombi on echo.
b. a history of prior thromboemboli.
c. coronary artery disease.
d. All of the above
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