SummaryOral anticoagulant therapy has been shown to be effective for scveral indications. The optimal intcnsity of anticoagulation for each indication, howcver, is largely unknown. To determinc this optimal intensity, randomiscd clinical trials are conducted in which two target levcls of anticoagulation are compared. This approach is incfficicnt, since the choice of the target levels will bc arbitrary. Moreover, the achieved intcnsity is not taken into account.Wc propose a mcthod to determine the optimal achieved intensity of anticoagulation. This method can bc applied wilhin a clinical trial äs an "efficacy-analysis", but also on data gathered in day-to-day paticnt carc.In this method, INR-specific incidence ratcs of events, either thromboembolic or hemorrhagic, are calculated. The numerator of the incidence rate is based on data on the INR at the time of the cvent. The denominator consists of the pcrson-time at each INR value, summed over all patients, and is calculated from all INR measurements of all patients during the follow-up interval. This INR-specific person-time is calculated with the assumption of a linear incrcase or decreasc between two consecutive INR determinations. Since the incidence rates may bc substratificd on covariates, efficient assessmcnt of the effects of other factors (e. g. agc, scx, comedication) by multivariale regression analysis bccomes possiblc.This method allows the determination of the optimal pharmacological effects of anticoagulation, which can form a rational starting point for choosing the target levels in subscquent clinical trials.

The intensity of anticoagulant therapy for patients with prosthetic heart valves is optimal when the INR is between 2.5 and 4.9. To achieve this level of anticoagulation, a target INR of 3.0 to 4.0 is recommended.

See also H. T. Sørensen. Cancer and subsequent risk of venous thromboembolism. This issue, pp 527-8. Summary. Background: The incidence of venous thrombosis (VT) for cancer patients is increased compared with patients without cancer, but estimations of the incidence for different types of cancer have rarely been made because of the low incidence of various types of cancer. Large registries offer an opportunity to study the risk of VT in large cohorts of cancer patients, which is essential in decisions on prophylactic anti-coagulant treatment. Methods: This cohort study estimates the incidence of VT in cancer patients by using record linkage of a Cancer Registry and an Anticoagulation Clinic database in the Netherlands. Cumulative incidences in patients with different types of malignancies were estimated. We calculated relative risks (RRs) in relation to the presence of distant metastases and treatment. Results: Tumors of the bone, ovary, brain, and pancreas are associated with the highest incidence of VT (37.7, 32.6, 32.1, and 22.7/1000/0.5 year). Patients with distant metastases had a 1.9-fold increased risk [RR adj : 1.9; 95% confidence interval (CI): 1.6-2.3]. Chemotherapy leads to a 2.2-fold increased risk (RR adj : 2.2; 95% CI: 1.8-2.7) and hormonal therapy leads to a 1.6-fold increased risk (RR adj : 1.6; 95% CI: 1.3-2.1) compared with patients not using these treatment modalities. Patients with radiotherapy or surgery did not have an increased risk. Conclusions: We compared the overall incidences of VT in the first half year in our study to the risk of major bleeding as described in the literature. For patients with distant metastases, for several types of cancer, prophylactic anti-thrombotic treatment could be beneficial.

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Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.).