Correspondence
Optimal Oral Anticoagulation for Patients with Mechanical Heart Valves
N Engl J Med 1995; 333:1504-1505November 30, 1995
- Article
To the Editor:
On the basis of a retrospective analysis of patients with mechanical heart valves who received high-intensity anticoagulation, Cannegieter et al. (July 6 issue)1 conclude that the target international normalized ratio (INR) in such patients should be 3.0 to 4.0. However, work demonstrating the benefit of adding aspirin to anticoagulant therapy in patients with mechanical heart valves was mentioned but not emphasized.
In a randomized, double-blind, placebo-controlled trial, Turpie et al. demonstrated that 100 mg of aspirin a day combined with anticoagulant therapy is highly effective in lowering mortality and morbidity from all causes in patients after heart-valve replacement.2 The findings of Turpie et al. have been corroborated by others.3 In terms of bleeding complications, adding aspirin to a high-intensity anticoagulation regimen (INR, 3.0 to 4.5) is hazardous, whereas the safety of adding aspirin to a moderate-intensity anticoagulation regimen (INR, 2.0 to 2.9) approximates the safety of a high-intensity regimen alone.4 The weight of current evidence thus favors the combination of 100 mg of aspirin and moderate-intensity anticoagulation (INR, 2.0 to 2.9) in patients with left-sided mechanical heart valves.
4 ReferencesClemens von Schacky, M.D.
University of Munich, D-80336 Munich, Germany1
Cannegieter SC ,Rosendaal FR ,Wintzen AR ,van der Meer FJM ,Vandenbroucke JP ,Briet E . Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995;333:11-17
Full Text | Web of Science | Medline2
Turpie AGG ,Gent M ,Laupacis A , et al. A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. N Engl J Med 1993;329:524-529
Full Text | Web of Science | Medline3
Hayashi J ,Nakazawa S ,Oguma F ,Miyamura H ,Eguchi S . Combined warfarin and antiplatelet therapy after St. Jude Medical valve replacement for mitral valve disease. J Am Coll Cardiol 1994;23:672-677
CrossRef | Web of Science | Medline4
Altman R ,Rouvier J ,Gurfinkel E , et al. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg 1991;101:427-431
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. von Schacky states that current evidence favors the combination of 100 mg of aspirin and moderate-intensity anticoagulation (INR, 2.0 to 2.9). We think this overstates the weight of the evidence. Altman et al.1 compared anticoagulant treatment at two levels of intensity (INR, 2.0 to 2.9 and 3.0 to 4.5) in combination with aspirin (330 mg) and dipyridamole (75 mg) twice daily. On the basis of a follow-up period of 52 patient-years in the lower-intensity group and 40 patient-years in the higher-intensity group, the authors concluded that the lower-intensity regimen is preferable. In the higher-intensity group, 10 patients had bleeding complications during the short follow-up period, which corresponds to an extremely high incidence of bleeding (25 cases per 100 patient-years). In comparison, among the 1608 patients treated with high-intensity anticoagulation in our study, the overall complication rates were 2.7 per 100 patient-years for bleeding and 0.7 per 100 patient-years for thromboembolism. In the optimal range of intensity (INR, 2.5 to 4.9), the combined rate was only 2 per 100 patient-years.
Von Schacky states that the combination of aspirin and high-intensity anticoagulation is hazardous. Yet he cites the study of Turpie et al.,2 who added aspirin to high-intensity anticoagulant treatment (INR, 3.0 to 4.5), as conclusive evidence of the superiority of the combined regimen. Even though Turpie et al. found that the combined treatment had a beneficial effect on morbidity and mortality from all causes, the incidence of bleeding was high in the combination group (8.5 per 100 patient-years).
In the study by Hayashi et al.,3 warfarin alone was compared with warfarin plus antiplatelet therapy, which consisted of dipyridamole or ticlopidine. In only 29 selected patients, a minimal dose of aspirin (10 to 40 mg) was added. Moderate-intensity anticoagulation was used. The incidence of thromboembolism was lower in the antiplatelet group, but no clear data on bleeding were provided.
No study has thus far compared high-intensity anticoagulation alone with moderate-intensity anticoagulation in combination with aspirin, and the current evidence does not support the superiority of the latter approach. Until reliable data are available, it is premature to state that combination therapy is preferable.
3 ReferencesS.C. Cannegieter, M.D.
F.R. Rosendaal, M.D.
University Hospital Leiden, 2300 RC Leiden, the Netherlands1
Altman R ,Rouvier J ,Gurfinkel E , et al. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg 1991;101:427-431
Web of Science | Medline2
Turpie AGG ,Gent M ,Laupacis A , et al. A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. N Engl J Med 1993;329:524-529
Full Text | Web of Science | Medline3
Hayashi J ,Nakazawa S ,Oguma F ,Miyamura H ,Eguchi S . Combined warfarin and antiplatelet therapy after St. Jude Medical valve replacement for mitral valve disease. J Am Coll Cardiol 1994;23:672-677
CrossRef | Web of Science | Medline
