Abstract
It is regrettable that my warning against intense warfarin regimens, such as are recommended in Britain and in North America,1Loeliger E.A. Therapeutic target values in oral anticoagulation: justification of Dutch policy and a warning against the so-called moderate-intensity regimens.Ann Hematol. 1992; 64: 60-65Crossref PubMed Scopus (31) Google Scholar was not taken into consideration in the update by Hirsh et al,2Hirsh J. Dalen J.E. Deykin D. Poller L. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range.Chest. 1992; 102: 312S-326SGoogle Scholar which appeared in the October 1992 supplement of Chest. My warning contains the recommendations made by the Federation of Dutch Thrombosis Centers, which together provide oral anticoagulation laboratory control for about 250,000 patients receiving active treatment. It is on good grounds that the Federation recommends 3.0 international normalized ratio (INR) as the target for primary and secondary prevention of venous thrombosis and thromboembolism, 3.5 INR in case of recurrence under the former regimen and for patients at risk for a cardiogenic embolism from any source (including tissue heart valve replacement) and those with atherothrombotic disease, and 4.0 INR for patients with mechanical heart valve prosthesis; the risk of hemorrhage at such levels remains acceptable. In sharp contrast to these recommendations, Hirsh et al propose to aim at levels between 2.5 and 3.5 INR in patients with artificial heart valves. In their argumentation, ironically, they refer to a recently completed randomized trial performed by the McMaster group, which shows that the degree of protection by oral anticoagulants when aiming at 3.0 to 4.5 INR was increased by the addition of aspirin in a dose of 100 mg/d without a significant increase in major bleeding or cerebral hemorrhage. In my view, Hirsh et al herewith support Dutch policy to aim at 3.5 to 4.8 INR without the addition of aspirin. Similar considerations hold for their argument for an optimal therapeutic range of 2.0 to 3.0 INR in patients with tissue heart valves; from the data presented by the McMaster group,3Turpie G.G. Gunstensen G. Hirsh J. Nelson H. Gent M. Randomized comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement.Lancet. 1988; 1: 1243-1245Google Scholar one is justified in concluding that 2.0 to 2.25 INR and 2.5 to 4.0 INR are equally ineffective in the protection of patients against systemic embolization.1Loeliger E.A. Therapeutic target values in oral anticoagulation: justification of Dutch policy and a warning against the so-called moderate-intensity regimens.Ann Hematol. 1992; 64: 60-65Crossref PubMed Scopus (31) Google Scholar Another major mistake made by Hirsh et al is the statement that in the two large-scale studies of the secondary prevention of myocardial infarction performed in The Netherlands and in Norway,4Sixty Plus Reinfarction Study Research Group A double-blind trial to assess long-term oral anticoagulant therapy in elderly patients after myocardial infarction.Lancet. 1980; 2: 989-994PubMed Google Scholar, 5Smith P. Arnesen H. Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction.N Engl J Med. 1990; 323: 147-152Crossref PubMed Scopus (530) Google Scholar both with intensive anticoagulation, there was no increase in bleeding complications. The bleeding complications observed in the Dutch study were even considered worthy of separate publication.6Sixty Plus Reinfarction Study Research Group Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction.Lancet. 1982; 1: 64-68PubMed Google Scholar Oral Anticoagulant Therapy RecommendationsCHESTVol. 105Issue 1PreviewDr. E. Loeliger is clearly upset with the ACCP recommendations for a less intense warfarin regimen. The ACCP members based their recommendations on the following considerations: Full-Text PDF
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