Therapeutic quality control of oral anticoagulant therapy comparing the short‐acting acenocoumarol and the long‐acting phenprocoumon

Abstract

Summary. To investigate whether the different pharmacokinetics of acenocoumarol (t 1/2 ¼ 11 h) and phenprocoumon (t 1/2 ¼ 140 h) result in a different quality of anticoagulation, we studied patients from the Leiden anticoagulation clinic treated between 1998 and 1999 for more than 16 weeks. Two hundred and twenty-eight pairs were closely matched for indication for oral anticoagulant therapy (OAT), age, sex and date of start of treatment. Four hundred and fifty six patients with 7245 International Normalized Ratio (INR) checks yielded 230 patient-years. Quality of OAT calculated over the whole treatment period was higher with phenprocoumon as expressed by the number of INR checks in the therapeutic range (phenprocoumon: 42AE7%, acenocoumarol: 36AE5%, difference: 6AE1%, CI 95 of the difference: 3AE0-9AE3%) and by time in range (phenprocoumon: 46AE6%, acenocoumarol: 41AE6%, difference: 5AE0%, CI 95 of the difference: 1AE3-8AE6%). After the initial 6 weeks of OAT, the differences became more pronounced (difference: 6AE1%, CI 95 : 1AE8-10AE4%). The incidence of severe bleeding complications was similar (phenprocoumon: 0AE04/patient/year vs acenocoumarol: 0AE03/patient/ year) with a slight excess of minor bleeds with phenprocoumon (0AE19/patient/year vs 0AE06/patient/year). We conclude that phenprocoumon leads to a better quality of OAT than acenocoumarol. As there is no difference in major bleeding complications and only a small difference in minor bleeding complications, phenprocoumon is preferable to acenocoumarol for prolonged OAT.

Vitamin K1 supplementation to improve the stability of anticoagulation therapy with vitamin K antagonists: a dose-finding study

“…These three vitamin K antagonists have different half-lives and previous studies showed that the stability of anticoagulant therapy was better with the longer-acting phenprocoumon than with acenocoumarol. [15][16][17][18][19] A recent study showed better stability in patients treated with warfarin than in patients using phenprocoumon. 22 We performed a subgroup analysis in the group of patients treated with acenocoumarol.…”

“…11,12 Thirdly, the type of vitamin K antagonist that is used might influence the effect of vitamin K1 supplementation on the achieved stability, because longer acting vitamin K antagonists result in more stable control per se. [15][16][17][18][19] Finally, supplementation with vitamin K1 would only be useful in the clinic if the frequency of clinical endpoints, such as the number of hemorrhages or thrombotic events, is reduced.…”

Factors influencing vitamin K antagonists therapy / Factori care influențează terapia cu antagoniști ai vitaminei K

“…The majority of studies in literature are about warfarin, but there are also some studies on acenocoumarol and phenprocoumon (2,3).…”

“…An optimal therapeutic effect is obtained by achieving and maintaining constant INRs within therapeutic range (3).…”

Improvement in the regulation of the vitamin K antagonist acenocoumarol after a standard initial dose regimen: prospective validation of a prescription model

“…Cross-sectional studies in about 215,000 patients of these anticoagulation clinics, treated with acenocoumarol and phenprocoumon, showed that in the last few years the percentage of INR values within the therapeutic target range in the first 2 months after the start of the treatment was 62 (median), compared to 74% in the 3-6 months period after initiation and 78% after 6 months, respectively [2]. Another study [3] found that in the first 6 weeks after the start of acenocoumarol the INR values were only in 32.6% of patients and in only 32.4% of the time within the therapeutic target range [4].…”