Safety Of Oral Anticoagulant Therapy Research Articles

Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation.

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15ml/min/1.73m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKAs) or direct anticoagulants (DOACs). Moreover, it remains unclear which is more effective and safer, because estimated creatinine clearance <25-30ml/min was an exclusion criterion in the randomized controlled trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint, as they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC versus OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in haemodialysis patients with AF and undergoing LAAC compared with patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient to consider individual risks and benefits of each treatment option is underlined.

P 020: Factors associated with effectiveness and safety of oral anticoagulant therapy in elderly population

P 020: Factors associated with effectiveness and safety of oral anticoagulant therapy in elderly population

Effectiveness and safety of oral anticoagulant therapy in a real-world cohort with atrial fibrillation: The SIESTA-A study protocol.

Oral anticoagulants (OACs) are first-line drugs for stroke prevention in patients with atrial fibrillation (AF). The introduction of new lines of therapy with direct oral anticoagulants (DOACs) has led to a decreased use of vitamin K antagonists (VKAs). Comparative analyses of DOACs in clinical trials are scarce and the comparator has mostly been warfarin. Their impact on health outcomes in observational studies has not always been consistent. The aim of this study is to evaluate the effectiveness and safety of DOACs and VKAs in patients with AF using Real-World Data (RWD). Population-based retrospective cohort study using RWD from actual practice. Period: January 2012-December 2020. Inclusion criteria: patients with AF who had not taken OACs in the previous 12 months. Exclusion criteria: <40 years, with severe mitral stenosis, or valvular heart disease or aortic and/or mitral valve procedures. Data source: The Andalusian Population Health Database, Spain. Outcome measures: a) Effectiveness: ischaemic stroke, transient ischaemic attack, systemic and pulmonary embolism, and death; b) Safety: gastrointestinal and intracranial haemorrhaging; Independent variables: age, sex, comorbidities, medication and health resource use, CHA2DS2-VASC, HAS-BLED, and analytical tests. Statistical analysis: crude incidence analysis, survival models, Kaplan-Meier, Cox regression analysis adjusted for possible confounding and paired analysis by propensity score matching.

Comparative analysis of oral anticoagulation therapy in Asian patients with atrial fibrillation and end-stage renal disease: a nationwide population-based cohort study

Abstract Background The efficacy and safety of direct oral anticoagulants (DOACs) in patients with end-stage renal disease (ESRD) on dialysis is unclear. Although the RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation), a prematurely stopped randomized controlled trial, has been recently reported, the risks of clinical outcomes comparing DOAC and warfarin in pateints with AF and ESRD is still inconclusive. Purpose To analyze comparative effectiveness and safety of oral anticoagulant therapy including warfarin, rivaroxaban, apixaban, and edoxaban in Asian patients with AF and ESRD Methods Using a Korean nationwide claims database, anticoagulated patients with AF and ESRD between 2014 and 2020 were included. The occurrence of ischemic stroke, major bleeding, all-cause death, and the net clinical outcome (NCO, the composite of all clinical outcomes) were evaluated. We firstly compared between pooled DOAC and warfarin, and also compared each DOAC (rivaroxaban, apixaban, and edoxaban) to warfarin. Inverse probability of treatment weighting using propensity scores were used to balance difference in baseline characteristics of each group. Results A total of 5503 patients were included (3484 with warfarin, 407 with rivaroxaban, 1273 with apixaban, and 339 with edoxaban). During a median 1.4-year (interquartile ranges 0.5-3.0 years) of follow-up, 345, 376, 2321, and 2617 of ischemic stroke, major bleeding, all-cause death, and the NCO were occurred (incidence rate, 3.44, 3.77, 22.11, and 27.35 per 100 person-years, respectively). to warfarin, DOAC was associated with significantly lower risks of major bleeding (hazard ratio, 95% confidence interval: 1.159, 0.929-1.440, p=0.187), all-cause death (0.667, 0.520-0.847, p&amp;lt;0.001), and NCO (0.816, 0.748-0.889, p&amp;lt;0.001), with a comparable risk of ischemic stroke (1.159, 0.299-1.440, p=0.001) (Figure A). For the comparison between each DOAC and warfarin (Figure B), apixaban showed a comparable risk of ischemic stroke with warfarin, however, rivaroxaban and edoxaban were associated with a higher risk of ischemic stroke than warfarin. Among 3 DOACs, only apixaban associated with a lower risk of major bleeding than warfarin (0.600, 0.434-0.812, p=0.001). All DOACs were associated with a lower risk of all-cause death than warfarin. Overall, apixaban and rivaroxaban showed a significantly lower risk of NCO than warfarin (0.799, 0.719-0.887, p&amp;lt;0.001 for apixaban vs. warfarin; 0.842, 0.732-0.963, p=0.013 for rivaroxaban vs. warfarin). The results were consistent in a competing risk analysis. Conclusion In this large-scale observational cohort study, DOAC might be associated with a lower NCO than warfarin in Asians patients with AF and ESRD on dialysis. In line with current guidelines, apixaban and rivaroxaban could be a reasonable choice to achieve better net clinical benefit than warfarin in patients with AF and ESRD who are needed anticoagulation therapy.

Prevention of ischemic stroke in atrial fibrillation from the point of view of a neurologist. Standards and real clinical practice

The article outlines aspects of the current state of the problem of the priority choice of an oral anticoagulant for indefinite prevention of stroke and systemic thromboembolism in patients with atrial fibrillation. The advantages of direct oral angicoagulants over warfarin are presented, as well as a comparative analysis of the individual characteristics of the main direct oral angicoagulants from the point of view of personification of preventive therapy in accordance with modern treatment standards. The efficacy and safety of oral anticoagulant therapy has been reviewed in terms of the net clinical benefit. Particular attention is paid to the age-related aspects of choosing an anticoagulant for indefinite prophylaxis; an assessment of anticoagulants is presented in accordance with the FORTA concept, which regulates the use of drugs in elderly patients. In conclusion, recommendations are formulated for the choice of an anticoagulant in patients with atrial fibrillation in the most common clinical situations. As a general rule, the choice of a particular drug should be individualized based on risk factors, tolerability, net clinical benefit, patient preference, potential adverse interactions, and other clinical characteristics.

Relationship of health literacy and adherence to oral anticoagulation therapy in patients with atrial fibrillation: a cross-sectional study.

Oral anticoagulant therapy (OAT) has increased substantially due to the aging population and prevalence rise of atrial fibrillation (AF). Medication adherence is important to achieve effectiveness and safety of OAT. The study aim was to investigate the relationship between health literary (HL) and the adherence to OAT in patients with atrial fibrillation (AF). This is a cross-sectional study conducted in a public cardiology clinic in Brazil, 2019. Sociodemographic and clinical data were collected by the review of medical records and interviews with patients. The relation between health literacy (HL) and adherence to OAT was investigated by a multiple logistic regression model. Overall, 100 AF patients were included in this study, with average age of 68.8 ± 13.8 years and predominance of women (54 %). Inadequate HL was found in 79 % of the patients and non-adherence was identified in 66 % of the participants. Sex was the only variable with a statistically significant association with non-adherence to OAT. Men presented a 2.54-fold greater chance of non-adherence to OAT, when compared to the women (Odds ratio (OR) = 2.54; 95 % confidence interval (CI): 1.03-6.62; p = 0.047). No statistically significant relationship was found between inadequate HL and non-adherence to OAT (OR 1.48; 95 % CI, 0.47-4.61; p = 0.49). High rates of inadequate HL and non-adherence to OAT were identified in this study; however, this relationship did not prove to be statistically significant. Further studies are needed to investigate factors associated with non-adherence to OAT in large samples of vulnerable populations and strategies for its improvement in public health.

P2555Efficacy and safety of oral anticoagulant versus antiplatelet therapy for secondary prevention of cardiovascular disease in patients without atrial fibrillation

Abstract Background Anticoagulation is the mainstay of prevention of arterial thromboembolism in patients with atrial fibrillation, but it could be effective also in secondary prevention of patients who are in sinus rhythm. Purpose We performed this meta-analysis to determine relative efficacy and safety of oral anticoagulant therapy (OAC) as compared with antiplatelet therapy (APT) in patients with prevalent cerebro-cardiovascular disease without atrial fibrillation. Methods Our systematic review of the literature published through January 31st, 2019 sought all phase III randomized controlled trials which compare OAC with APT in patients with sinus rhythm and report at least one of the following outcomes: ischemic stroke, death, myocardial infarction, and major bleeding, assessed at the longest available follow-up. We used random-effects models to estimate summary relative risk reduction (RRR) and 95% confidence intervals (95% CI). Results We identified a total of 9 randomized controlled trials including a total of 34,912 patients (ASA, n=17,726; adjusted-dose warfarin, n=4,460; rivaroxaban, n=12726), with a mean follow-up of 2.2 years. When compared with antiplatelet therapy, OAC was associated with reduced risk of ischemic stroke (RRR 38%, 95% CI: 1; 47; P=0.04; I2=72%) and myocardial infarction (RRR 13%, 95% CI: 0,23; P=0.05, I2=0%), but increased risk of major bleeding (RRR −52%, 95% CI: −129; −1; P=0.04; I2=76%). Compared to antiplatelet treatment, OAC did not significantly affect the risk of all-cause death (RRR 1%, 95% CI: −9; 10; P=0.86; I2=12%). Conclusions In sinus rhythm patients with prevalent cardiovascular disease, OAC reduces risk of ischemic stroke and myocardial infarction, but significantly increases risk of major bleeding. The choice of antithrombotic treatment does not appear to influence all-cause mortality.

Assessment of the bleeding risk of anticoagulant treatment in non-severe frail octogenarians with atrial fibrillation

BackgroundPhysicians estimate the frailty in elderly patients with atrial fibrillation (AF) to aid in the decision making with respect to oral anticoagulant (OAC) therapy. There are limited data on the safety of OAC therapy in non-severe frail elderly patients. We evaluated the risk factors of bleeding among non-severe frail octogenarians with AF taking OACs. MethodsAmong 430 consecutive AF patients aged 80 years and over with non-severe frailty, we enrolled 346 patients [167 men, 83.7 (81.0–85.0) years] who were newly initiated on OACs: dabigatran, rivaroxaban, apixaban, edoxaban, or warfarin. To measure the frailty, the clinical frailty scale (CFS) was used. Non-severe frailty was defined as a CFS score of <7. The clinical factors were compared between the patients with and without bleeding during the OAC therapy. ResultsOut of the 346 patients enrolled, 266 (76.9%) received direct OACs (DOACs) and 80 (23.1%) warfarin. Of the 266 patients receiving DOACs, there were 204 (76.7%) prescribed appropriately adjusted-dose DOACs based on the approved Japanese recommendations. Of the 80 warfarin-treated patients, 52 (65.0%) were prescribed appropriately adjusted-dose warfarin. During a follow-up of 32.7 (14.0–51.0) months, bleeding events were detected in 59 patients (17.1%). Among the clinical factors, a multivariate analysis found that having a low body mass index (BMI) (<18.5kg/m2) was associated with the development of bleeding [hazard ratio (HR): 3.26, 95% confidence interval (CI): 1.65–6.50, p<0.01)]. Moreover, having a low BMI remained an independent risk factor for bleeding in the patients treated with appropriately adjusted-dose OACs (HR: 2.17, 95% CI: 1.01–4.70, p=0.048). ConclusionsIn non-severe frail octogenarians with AF taking OACs, having a low BMI was the most significant factor associated with the development of bleeding.

Efficacy and safety of oral anticoagulant therapy in frail patients with atrial fibrillation.

Antithrombotic treatment of frail patients with AF presents various challenges. The fear of bleeding often leds to a large underuse of anticoagulant agents in these patients, although more recent data indicate that oral anticoagulation (especially with the newer, direct anticoagulants) is increasingly used. While there is a need for more real world data, available evidence suggests that non-vitamin K antagonist oral anticoagulants (NOACs) are an effective alternative to warfarin in frail patients with AF for preventing thromboembolic events, with a better safety profile. Logical considerations and evidence-base data related to the reduced bleeding risk (also including major bleeding and intracranial bleeding) of NOACs make these drugs the anticoagulant agents of choice in frail patients; however, in this setting an individualised approach should be taken, taking into consideration the risk of thromboembolic and bleeding events, other comorbidities and patient-related factors, rather than a generalised "one drug fits all" approach.

Anticoagulation therapy in atrial fibrillation after intracranial hemorrhage

The effect of oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF) with a history of intracranial hemorrhage (ICH) is poorly defined. The purpose of this study was to evaluate the efficacy and safety of OAT in patients with AF with an ICH history. We retrospectively compared the composite end point, including thromboembolic and major bleeding events, between patients with AF with a history of ICH who were (OAT group, n = 254) and those who were not (no-OAT group, n = 174) taking OAT. During a mean follow-up of 39.5 ± 31.9 months, 5.5 and 3.1 major bleeding events/100 patient-years were observed in the OAT and no-OAT groups, respectively (P = .024). Recurrent ICH was observed only in patient with OAT. Thromboembolic events occurred in 2.4 and 8.3 events/100 patient-years in OAT and no-OAT groups, respectively (P < .001). There was no significant differences in composite end points between OAT and no-OAT groups (11.5 events/100 patient-years vs 7.9 events/100 patient-years; P = .154). Patients with OAT who achieved a time-in-therapeutic range of ≥60% of the international normalized ratio of 2.0-3.0 demonstrated a better cumulative survival free of the composite end point (P < .001) than did patients without OAT. Early (<2 weeks) OAT after an index ICH did not improve composite end points because of the increased incidence of major bleeding events. However, OAT at 2 weeks after an index ICH was associated with decreased clinical events including thromboembolic events and composite end point. In patients with AF who require anticoagulation and have a history of ICH, maintaining optimal OAT with time-in-therapeutic range ≥ 60% and the initiation of OAT at least 2 weeks after an index ICH were associated with improved clinical outcomes.

Effects of oral anticoagulant therapy in older medical in-patients with atrial fibrillation: a prospective cohort observational study.

Uncertainties about efficacy and safety of oral anticoagulant therapy (OAT) among older and frail medical patients with atrial fibrillation (AF) largely contribute to under-prescription of these drugs. In this prospective observational cohort study, we investigated mortality, and ischemic and hemorrhagic events, in hospital-discharged older patients with AF. Stroke and bleeding risk were evaluated using CHA2DS2-VASC and HAS-BLED scores. Comorbidity, frailty, cognitive and nutritional status and functional autonomy were evaluated using standardized scales. Independent associations between clinical variables, including OAT use, and all-cause mortality, fatal and non-fatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 452 patients included (mean age 81.6years, 54.9% women, roughly 30% cognitively impaired and/or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.6 and 2.8, respectively), 151 (33.4%) died during a mean follow-up period of 300.5days; ischemic and hemorrhagic stroke occurred in 4.0 and 0.4% of patients, respectively, and major bleedings in 6.2%. After multivariate analysis, OAT at discharge was associated with lower overall mortality and reduced occurrence of ischemic stroke, the first finding being confirmed in propensity score matched analysis. Among older vulnerable AF patients with high post discharge death rate, OAT was associated, among other multiple factors, with reduced mortality and lower occurrence of ischemic stroke.

Oral anticoagulant therapy in Italian patients 80 yr of age or older with atrial fibrillation: a pilot study of low vs. standard PT/INR targets

Oral anticoagulation therapy (OAT), which aims to prevent thromboembolism in patients with atrial fibrillation (AF), is underused in subjects who are over the age of 80 yr because of the associated bleeding risk. The aim of this study was to evaluate the efficacy and safety of OAT with low (2.0) vs. standard (2.5) PT/international normalised ratio (INR) targets in patients over the age of 80. Of 233 patients aged 80 yr or older with AF on OAT, 58 had unstable PT/INR values and achieved reduced targets. These patients were enrolled as a group (A) in a case-control study and were treated with a low (2.0) PT/INR target. They were compared with a second group (B) of 58 additional patients who were matched for age and CHADS scores and treated with a standard (2.5) PT/INR target. Group A OAT parameters were also compared before and after the PT/INR reduction. The time in the therapeutic range (TTR%), PT/INR values >5, haemorrhages and strokes were prospectively evaluated in the two groups after 2 yr of follow-up. Of the 116 enrolled patients, 55 group A and 57 group B patients were evaluated. The TTR was 72.59% in group A and 64.43% in group B (P < 0.01). The percent of PT/INR values >5 was 0.68% for group A and 1.42% for group B (P < 0.05). Haemorrhages and thromboses occurred only in group B patients. The before and after analysis in group A showed that a low INR target produced an increase in the TTR (53.05% vs. 72.59%; P < 0.0001) and a reduction in the PT/INR values > 5 (1.72% vs. 0.68%; P < 0.001). A low PT/INR target seems effective and safe in Italian patients with AF over the age of 80. Further trials are needed to confirm the hypothesis generated by this study.

Bleeding Risk and Major Adverse Events in Patients With Previous Ulcer on Oral Anticoagulation Therapy

Bleeding is the major concern for patients receiving oral anticoagulation therapy (OAT), especially those with histories of gastrointestinal ulcer. The aim of this study was to evaluate the efficacy and safety of OAT in patients with nonvalvular atrial fibrillation with histories of ulcer. A composite end point, including major adverse cardiac events or major bleeding, was compared between patients with AF with previous ulcers who were (OAT+; n = 200) and were not (OAT- n = 230) receiving OAT. During the follow-up period of 3.3 ± 2.7 years, 28 (14%) and 66 (29%) OAT+ and OAT- patients, respectively, had major adverse cardiac events (p = 0.001). Major bleeding occurred in 46 OAT+ patients (23%) and 25 OAT- patients (11%) (p = 0.001). There was no significant difference in the composite end point between OAT+ and OAT- patients (29% vs 36%, p = 0.08). The incidence of major bleeding was significantly lower, decreasing from 30% to 14%, when OAT began after endoscopic confirmation of ulcer healing (p = 0.02). OAT+ patients who achieved time in the therapeutic range ≥60% for international normalized ratio (2.0 to 3.0) demonstrated better cumulative survival free from the composite end point than OAT- patients (p = 0.01). In conclusion, OAT in patients with nonvalvular AF with histories of gastrointestinal ulcer made no difference in the composite end point compared to absence of OAT. In OAT+ patients, maintaining an optimal international normalized ratio reduced the composite end point, and the confirmation of ulcer healing reduced the incidence of bleeding.

American Heart Association/American College of Cardiology Foundation guide to warfarin therapy.

### Mechanism of Action of Coumarin Anticoagulant Drugs Warfarin, a coumarin derivative, produces an anticoagulant effect by interfering with the cyclic interconversion of vitamin K and its 2,3 epoxide (vitamin K epoxide). Vitamin K is a cofactor for the carboxylation of glutamate residues to γ-carboxyglutamates (Gla) on the N-terminal regions of vitamin K–dependent proteins (Figure 1).1–6 These proteins, which include the coagulation factors II, VII, IX, and X, require γ-carboxylation by vitamin K for biological activity. By inhibiting the vitamin K conversion cycle, warfarin induces hepatic production of partially decarboxylated proteins with reduced coagulant activity.7,8 Figure 1. The vitamin K cycle and its link to carboxylation of glutamic acid residues on vitamin K–dependent coagulation proteins. Vitamin K1 obtained from food sources is reduced to vitamin KH2 by a warfarin-resistant vitamin K reductase. Vitamin KH2 is then oxidized to vitamin K epoxide (Vit KO) in a reaction that is coupled to carboxylation of glutamic acid residues on coagulation factors. This carboxylation step renders the coagulation factors II, VII, IX, and X and the anticoagulant factors protein C and protein S functionally active. Vit KO is then reduced to Vit K1 in a reaction catalyzed by vitamin KO reductase. By inhibiting vitamin KO reductase, warfarin blocks the formation of vitamin K1 and vitamin KH2, thereby removing the substrate (vitamin KH2) for the carboxylation of glutamic acids. Vitamin K1, either given therapeutically or derived from food sources, can overcome the effect of warfarin by bypassing the warfarin-sensitive vitamin KO reductase step in the formation of vitamin KH2. Carboxylation promotes binding of the vitamin K–dependent coagulation factors to phospholipid surfaces, thereby accelerating blood coagulation.9–11 γ-Carboxylation requires the reduced form of vitamin K (vitamin KH2). Coumarins block the formation of vitamin KH2 by inhibiting the …

Optimizing the efficacy and safety of oral anticoagulant therapy: high-quality dose management, anticoagulation clinics, and patient self-management.

Despite its widespread use, oral anticoagulation therapy suffers from a number of problems that lead to underuse and inadequate treatment. Problems include its narrow therapeutic index, the influence of many concomitant conditions or comorbidities, and the need for high-quality dose management. Poor management of oral anticoagulation is a prime factor influencing the occurrence of adverse events. As a result of these problems, special programs or anticoagulation management services (AMSs) have developed to manage oral anticoagulation. Such programs have demonstrated a significant improvement in outcomes compared with traditional or usual care (UC) by individual physicians. With the introduction of point-of-care prothrombin time monitors, the potential for patient self-testing and self-management has developed. Studies show the possibility of even further improvement in outcomes compared with UC, although the differences from those achieved with an AMS are less impressive.

Genetic control of anticoagulation

In the past two decades, several measures have substantially improved the safety of oral anticoagulant therapy with coumarin derivatives in patients with venous and arterial thromboembolic disorders. Among these measures are the use of more sensitive prothrombin-time reagents and the introduction by WHO of the international normalised ratio (INR); 1 the adoption of less intensive levels of anticoagulation (reflected by lower INR values), which had the same antithrombotic efficacy yet produced less haemorrhagic complications than did more intensive anticoagulation; 1 the organisation of specialist anticoagulant clinics; and the use of computerised systems for adjustment of drug doses. 2 Poller L Shiach CR MacKallum PK et al. Multicentre randomised study of computerised anticoagulant dosage. Lancet. 1998; 352: 150509 Summary Full Text Full Text PDF Scopus (214) Google Scholar On the whole, these measures have increased physicians' and patients' confidence, which has led to a world wide increase in the use of oral anticoagulant therapy. 1 Hirsh J Dalen JE Deykin D Poller L Bussey H Oral anticoagulants: mechanism of action, clinical effectiveness and optimal therapeutic range. Chest. 1995; 108: 23146 Google Scholar Yet, bleeding is still a dreaded complication with, and sometimes a deterrent to, the use of this therapy, particularly among the many elderly patients who need anticoagulants for the treatment of atrial fibrillation. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complicationsWe have shown that there is a strong association between CYP2C9 variant alleles and low warfarin dose requirement. CYP2C9 genotyping may identify a subgroup of patients who have difficulty at induction of warfarin therapy and are potentially at a higher risk of bleeding complications. Full-Text PDF

Improved therapeutic safety of oral anticoagulant therapy in Germany: the Saarland model.

In contrast to other European countries, in Germany more than 90% of oral anticoagulated patients are controlled by general practitioners. The International Normalized Ratio (INR) system in laboratory control is not in widespread use, often leading to misinterpretations of prothrombin time (PT) measurements. To improve the management of anticoagulated patients, a model was developed, consisting of different questionnaires and on the base of the INR system. Since 1993, 60 patients in our Department's outpatient anticoagulant clinic and since 1996 16 patients in the office of a general practitioner were followed for 146.32 patient years. There were no thromboembolic events and no major bleedings during follow-up. A total of 126 minor bleedings occurred in 30 patients. There were no significant differences in INR values and stable phases between the two centers; however, significantly shorter stable phases in patients with bleeding episodes were noted. Thus, this model seems to be useful also in general practitioners' hands.

Bleeding complications in oral anticoagulant therapy. An analysis of risk factors.

Insufficient data are available about the safety of oral anticoagulant therapy. The specialized organization of thrombosis services in the Netherlands can provide important information on the bleeding risk and various risk factors for bleeding in patients receiving oral anticoagulant therapy. In a follow-up study over a 12-month period beginning in January 1988 on all patients treated by the Leiden Thrombosis Service, the frequency of bleeding complications was assessed. A Poisson regression model was used to assess the relative contribution to the bleeding risk of age, sex, target zone (intensity of anticoagulant effect aimed at), achieved intensity of anticoagulant therapy (International Normalized Ratio), and the type of coumarin derivative used. Six thousand eight hundred fourteen patients experienced 1003 bleeding complications (16.5 per 100 treatment-years), 162 of which were major bleeds (2.7 per 100 treatment-years). Bleeding increased significantly with age (32% increase for all bleeding, 46% for major bleeding for every 10-year increase in age in comparison with age < 40 years). Women had more minor bleeding complications than men, whereas both sexes experienced major bleeding in an equal frequency. There was no influence of target zone, while every one-point increase in International Normalized Ratio gave 42% more major bleeding (54% more regarding all bleeding). Use of acenocoumarol resulted in fewer bleeds (26% less regarding all bleeding and 46% less regarding major bleeding) than use of phenprocoumon. The risk of anticoagulant therapy in a routine, real-life situation is similar as in the setting of several well-organized clinical trials. The risk of bleeding complications rises significantly with age and with the achieved intensity of anticoagulation, and is dependent on the type of coumarin derivative that is used.