Invasive procedures in the outpatient setting: managing the short-acting acenocoumarol and the long-acting phenprocoumon.

Treatment with vitamin K antagonists (VKAs) has to be interrupted when invasive procedures are planned. We compared various methods of interruption in patients on acenocoumarol or phenprocoumon in a prospective study. In patients on acenocoumarol (n = 141), 99 stopped three days before the intervention and 42 stopped two days before. All patients on phenprocoumon (n = 111) received vitamin K two days before the intervention, and 55 of these patients discontinued phenprocoumon, whereas 56 did not stop. In a subset of 30 patients we determined International Normalized Ratios (INRs) and coagulation factors II, VII, X and protein C. The mean INR after stopping acenocoumarol for three days was significantly lower than after two days (1.1 vs. 1.3, p = <0.0001), but its clinical relevance may be trivial. In patients using phenprocoumon, the mean INR on the day of the intervention was only slightly lower after stopping the VKAs (1.5 vs. 1.6, p = 0.0407), but a similar proportion of patients had an INR

VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation.

OBJECTIVE: Our objective was to assess the effects of VKORC1 and CYP2C9 genotypes on severe overanticoagulation and time to achieve stability and their contributions to dose requirement during the initial phase of acenocoumarol treatment. METHODS: A prospective follow-up study was conducted at 2 anticoagulation clinics in The Netherlands. We assessed the CYP2C9 genotype (CYP2C9*2 and CYP2C9*3 polymorphisms) and the VKORC1 C1173T genotype of the subjects and collected data on international normalized ratio, dose, comedication, and comorbidity. RESULTS: Of the 231 patients in the cohort, 150 (64.9%) had a VKORC1 C1173T polymorphism and 84 (36.4%) had a CYP2C9*2 or CYP2C9*3 allele. Only carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had an increased risk of severe overanticoagulation compared with subjects with no polymorphism or only 1 polymorphism (hazard ratio, 3.83 [95% confidence interval, 1.62-9.05]). The time to achieve stability was associated with the possession of the CYP2C9 genotype, not with the VKORC1 genotype (hazard ratio for CYP2C9*3 allele compared with CYP2C9 wild type, 0.59 [95% confidence interval, 0.40-0.87]). Patients with a VKORC1 polymorphism required significantly lower doses than VKORC1 CC wild-type patients. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (21.4% and 4.9%, respectively). CONCLUSION: Being a carrier of a combination of polymorphisms of VKORC1 and CYP2C9, rather than of one of these polymorphisms, is associated with severe overanticoagulation. The time to achieve stability is mainly associated with the CYP2C9 genotype.

Discrepancies between medication records of anticoagulation clinics and pharmacy records.

PURPOSE: To determine whether there were discrepancies between with coumarin anticoagulants interacting medications recorded in medical files of anticoagulation clinics (AC-records) and computerized records of community pharmacies (pharmacy records). METHODS: A descriptive study was conducted at two Dutch anticoagulation clinics (AC's). Records of with coumarin anticoagulants interacting drugs at the AC's were compared with the pharmacy records. A drug registered in the pharmacy records but not in the AC-records, was recorded as a discrepancy, while a drug registered in AC-records as well as in pharmacy records, was recorded as a match. RESULTS: Of the 117 identified interacting drugs registered in pharmacy records 32 (27%) were not registered in the AC-records. In four out of seven patients of whom the use of a pharmacokinetically interacting drug was not registered in the AC-records, several INR-values exceeded the upper therapeutic range. CONCLUSION: This study demonstrates that a substantial percentage of drugs of which an interaction with coumarin anticoagulants can be expected, is not registered in the medical files of anticoagulation clinics.

Acenocoumarol stabilization is delayed in CYP2C93 carriers.

OBJECTIVE: Our objective was to assess whether there is an association between the presence of allelic variants of the gene for cytochrome P450 (CYP) 2C9 and anticoagulation problems during the initial 3 to 6 months of acenocoumarol treatment. METHODS: A prospective follow-up study was performed at 2 anticoagulation clinics in the Netherlands. Included subjects started with a standard dose regimen as follows: 6 mg on the first day, 4 mg on the second day, and 2 mg on the third day. CYP2C9 genotypes were assessed, and data on international normalized ratio (INR), comedication, and comorbidity were collected. RESULTS: The CYP2C9 genotype of 231 subjects was assessed. Of these, 147 (63.6%) were wild-type subjects (CYP2C9*1/*1), 38 (16.5%) were carriers of CYP2C9*2, and 46 (19.9%) were carriers of CYP2C9*3. Compared with wild-type subjects, carriers of the CYP2C9*3 allele had (1) a lower chance to achieve stability in the first 6 months of therapy (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91; P <.05) and (2) an increased risk of severe overanticoagulation (INR >6.0) (hazard ratio, 3.80; 95% confidence interval, 1.54-9.39; P <.01). For both outcomes, there was no significant difference between carriers of the CYP2C9*2 allele and wild-type subjects. CONCLUSION: In carriers of the CYP2C9*3 allele more difficulties in terms of stabilization and overanticoagulation were found as compared with wild-type subjects or CYP2C9*2 carriers. CYP2C9 genotyping could be useful to identify potential candidates for more frequent INR controls to minimize problems with acenocoumarol anticoagulation status.

Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon.

Variability in the control of oral anticoagulant therapy has been associated with a heightened risk of complications. We compared control of anticoagulation between two commonly used coumarins, phenprocoumon and acenocoumarol, and among anticoagulation clinics. All qualifying patients were managed at six regional anticoagulation clinics in the Netherlands. This retrospective cohort study compiled data during a three-year period from a computerised dosing and management system. Anticoagulation control was expressed as the percent of time within the therapeutic range and stability expressed as the time-weighted variance in the international normalised ratio (INR). Data were available for 22,178 patients of whom 72% were treated with acenocoumarol. INRs of patients who received phenprocoumon were within the therapeutic range 50% of the time compared with 43% for acenocoumarol (OR 1.32, 95% CI 1.24-1.41). Moreover, patients on phenprocoumon required 15% fewer monitoring visits and had more stable INR values. These observations were consistent for all six clinics. There were also sizable differences between the clinics with respect to control and stability of anticoagulation that were stable from year-to-year and were unrelated to the drug used. With its longer half-life of three to five days, phenprocoumon produces more stable anticoagulation than acenocoumarol and should generally be the drug of choice when these are the available choices. The differences observed among clinics suggest that certain clinics employ policies and practices resulting in better control of anticoagulation.