scholarly journals Systematic review of societal costs associated with stroke, bleeding and monitoring in atrial fibrillation

2019 ◽  
Vol 8 (14) ◽  
pp. 1147-1166
Author(s):  
Amber L Martin ◽  
Alessandra G Reeves ◽  
Samantha E Berger ◽  
Manuela Di Fusco ◽  
Gail D Wygant ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Hemorrhagic Stroke ◽  
Indirect Costs ◽  
International Normalized Ratio ◽  
Economic Consequences ◽  
Limited Data ◽  
Bleeding Events ◽  
Societal Costs ◽  
The Past ◽  
Societal Level

Aim: Economic consequences associated with the rise in nonvitamin K antagonist oral anticoagulant use on a societal level remain unclear. Materials & methods: Evidence from the past decade on the societal economic burden associated with stroke, bleeding and international normalized ratio monitoring in atrial fibrillation was collected and summarized through a systematic literature review. Results: There were 14 studies identified that reported indirect costs, which were highest among patients with hemorrhagic stroke and intracranial hemorrhage. The contribution of indirect costs to the total was marginal during acute treatment but substantially increased (30–50%) 2 years after stroke and bleeding events. Conclusion: Limited data were available on societal costs in atrial fibrillation and further research is warranted.

scholarly journals PREDICTORS OF MAJOR BLEEDING AMONG ATRIAL FIBRILLATION PATIENTS ON WARFARIN

2019 ◽  
pp. 547-550
Author(s):  
LAILA M MATALQAH ◽  
ALAA YEHYA ◽  
GHAITH M AL-TAANI
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Anticoagulation Therapy ◽  
International Normalized Ratio ◽  
Major Type ◽  
Bleeding Events ◽  
International Classification Of Disease ◽  
Asian Populations ◽  
Medical Reports ◽  
Major Bleeding Events

Objective: Bleeding is the most serious complication associated with anticoagulation therapy. The purpose of this study was to estimate the frequency of major bleeding related to warfarin and to identify its predictors in patients with atrial fibrillation (AF). Methods: Patients with AF treated with warfarin at Penang General Hospital in Malaysia were identified according to the international classification of disease, Ninth Revision, Clinical Modification (ICD-9). The medical reports of 1611 patients were reviewed, bleeding events were set as primary end point which were identified in 313 patients. Demographic and clinical data were retrieved and warfarin therapy-related parameters including dose, therapy duration, and prothrombin time-international normalized ratio (PT-INR) were recorded and analyzed using descriptive statistics. Results: Of the 313 patients, 28 patients with major bleeding events were identified. Gastrointestinal bleeding was the major type of bleeding, which accounts for 68% (n = 17) of the cases. The frequency of major bleeding events among all AF patients was 1.7%. High PT-INR value was found in 96.3% (n = 28) of the patients, thereby making it the primary predictor of bleeding events. Other predictors including, advanced age, other comorbidities such as hypertension and multiple anticoagulation therapy were also observed to be significant. Conclusion: Lower doses of warfarin are recommended to achieve target PT-INR range similar to that reported previously for Asian populations. A regular clinical review for bleeding predictors is essential for maximizing the time spent by the patient taking warfarin in the optimal therapeutic range and for making recommended therapy adjustment.

scholarly journals The societal costs of problem gambling in Sweden

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
T. Hofmarcher ◽  
U. Romild ◽  
J. Spångberg ◽  
U. Persson ◽  
A. Håkansson
Keyword(s):  
Public Health ◽  
Alcohol Consumption ◽  
Problem Gambling ◽  
Indirect Costs ◽  
Direct Costs ◽  
Economic Consequences ◽  
Public Health Issue ◽  
Societal Costs ◽  
Prevention And Treatment ◽  
Intangible Costs

Abstract Background Problem gambling is a public health issue affecting both the gamblers, their families, their employers, and society as a whole. Recent law changes in Sweden oblige local and regional health authorities to invest more in prevention and treatment of problem gambling. The economic consequences of gambling, and thereby the potential economic consequences of policy changes in the area, are unknown, as the cost of problem gambling to society has remained largely unexplored in Sweden and similar settings. Methods A prevalence-based cost-of-illness study for Sweden for the year 2018 was conducted. A societal approach was chosen in order to include direct costs (such as health care and legal costs), indirect costs (such as lost productivity due to unemployment), and intangible costs (such as reduced quality of life due to emotional distress). Costs were estimated by combining epidemiological and unit cost data. Results The societal costs of problem gambling amounted to 1.42 billion euros in 2018, corresponding to 0.30% of the gross domestic product. Direct costs accounted only for 13% of the total costs. Indirect costs accounted for more than half (59%) of the total costs, while intangible costs accounted for 28%. The societal costs were more than twice as high as the tax revenue from gambling in 2018. Direct and indirect costs of problem gambling combined amounted to one third of the equivalent costs of smoking and one sixth of the costs of alcohol consumption in Sweden. Conclusions Problem gambling is increasingly recognized as a public health issue. The societal costs of it are not negligible, also in relation to major public health issues of an addictive nature such as smoking and alcohol consumption. Direct costs for prevention and treatment are very low. A stronger focus on prevention and treatment might help to reduce many of the very high indirect and intangible costs in the future.

scholarly journals Heparin dosing in uninterrupted anticoagulation with dabigatran vs. warfarin in atrial fibrillation ablation: RE-CIRCUIT study

EP Europace ◽  
2019 ◽  
Vol 21 (6) ◽  
pp. 879-885 ◽  
Author(s):  
Hugh Calkins ◽  
Stephan Willems ◽  
Atul Verma ◽  
Richard Schilling ◽  
Stefan H Hohnloser ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Unfractionated Heparin ◽  
Time Window ◽  
Dabigatran Etexilate ◽  
Study Drug ◽  
International Normalized Ratio ◽  
Similar Amount ◽  
Clotting Time ◽  
Bleeding Events ◽  
Activated Clotting Time

Abstract Aims To describe heparin dosing requirements in patients who underwent catheter ablation of atrial fibrillation with uninterrupted anticoagulation using dabigatran etexilate (dabigatran) or warfarin to attain therapeutic activated clotting time (ACT) in the RE-CIRCUIT® study. The RE-CIRCUIT study showed significantly fewer major bleeding events in the dabigatran vs. warfarin treatment group. Unfractionated heparin was administered during the procedure to maintain ACT >300 s. Methods and results Patients were randomly assigned to dabigatran 150 mg bid or international normalized ratio-adjusted warfarin. Ablation was performed with uninterrupted anticoagulation and continued for 8 weeks after the procedure. Heparin was administered after placement of femoral sheaths before or immediately after transseptal puncture. Ablation was performed in 635 patients (dabigatran, 317; warfarin, 318); data were available from 396 patients administered heparin (dabigatran, 191; warfarin, 205). Most frequent time window from last dose of study drug to septal puncture was 0 to <4 h in the dabigatran (41.3%) and 16 to <24 h in the warfarin arms (44.7%). Overall mean (standard deviation) heparin dose was similar between the dabigatran and warfarin groups [12 402 (10 721) vs. 11 910 (8359) IU, respectively]. Heparin dosing requirement to reach therapeutic ACT was lowest when time from last dose of dabigatran to septal puncture was 0 to <4 h. Conclusion Patients treated with dabigatran required a similar amount of unfractionated heparin as those treated with warfarin to achieve an ACT of >300 s during ablation. More heparin units were required when the time from the last dose of dabigatran to septal puncture increased.

scholarly journals Clinical significances of prothrombin time-international normalized ratio and activated partial thromboplastin time in patients with atrial fibrillation treated with direct oral anticoagulants

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Chao ◽  
Y.H Chan ◽  
S.A Chen
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Randomized Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Systemic Embolism ◽  
Bleeding Events ◽  
Factors Associated ◽  
Funding Sources

Abstract Background Although the measurements of PT-INR or aPTT were not performed for patients with atrial fibrillation (AF) taking direct oral anticoagulants (DOACs) in randomized trials, these tests were commonly used and familiar to clinical physicians. We aimed to test whether there is an association between PT-INR or aPTT ratio and risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding among AF patients taking rivaroxaban or dabigatran, respectively. Methods This multi-center cohort study included 3,192 AF patients taking rivaroxaban and 958 patients taking dabigatran for stroke prevention whose data about PT-INR and aPTT were available. Results For patients treated with rivaroxaban, a higher INR level was not associated with a higher risk of major bleeding compared to an INR level &lt;1.1. The risk of IS/SE was lower for patients having an INR ≥1.5 compared to those with an INR &lt;1.1 (aHR: 0.57; [95% CI: 0.37–0.87]; P=0.0088) (Figure). On-label dosing of rivaroxaban and use of digoxin were independent factors associated with an INR ≥1.5 after taking rivaroxaban. For patients taking dabigatran, a higher aPTT ratio was not associated with a higher risk of major bleeding. The risk of IS/SE was lower for patients having an aPTT ratio of 1.1–1.2 and 1.3–1.4 than those with an aPTT ratio &lt;1.1. Conclusions In Asian AF patients, PT-INR or aPTT ratios were not associated with the occurrences of bleeding events for rivaroxaban or dabigatran. Patients taking rivaroxaban with an INR ≥1.5 were associated with a lower risk of IS/SE. Appropriate dosages of DOACs and the compliances of patients should be confirmed for patients taking rivaroxaban with an INR &lt;1.5. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Household Economic Consequences of Rheumatic Heart Disease in Uganda

2021 ◽  
Vol 8 ◽  
Author(s):  
Chinonso C. Opara ◽  
Yuxian Du ◽  
Yoshito Kawakatsu ◽  
Jenifer Atala ◽  
Andrea Z. Beaton ◽  
...  
Keyword(s):  
Heart Disease ◽  
Rheumatic Heart Disease ◽  
Indirect Costs ◽  
Coping Mechanisms ◽  
Economic Consequences ◽  
Health Coverage ◽  
Policy Reforms ◽  
Cross Sectional ◽  
The Past ◽  
Rheumatic Heart

Background: Rheumatic heart disease (RHD) has declined dramatically in wealthier countries in the past three decades, but it remains endemic in many lower-resourced regions and can have significant costs to households. The objective of this study was to quantify the economic burden of RHD among Ugandans affected by RHD.Methods: This was a cross-sectional cost-of-illness study that randomly sampled 87 participants and their households from the Uganda National RHD registry between December 2018 and February 2020. Using a standardized survey instrument, we asked participants and household members about outpatient and inpatient RHD costs and financial coping mechanisms incurred over the past 12 months. We used descriptive statistics to analyze levels and distributions of costs and the frequency of coping strategies. Multivariate Poisson regression models were used to assess relationships between socioeconomic characteristics and utilization of financial coping mechanisms.Results: Most participants were young or women, demonstrating a wide variation in socioeconomic status. Outpatient and inpatient costs were primarily driven by transportation, medications, and laboratory tests, with overall RHD direct and indirect costs of $78 per person-year. Between 20 and 35 percent of households experienced catastrophic healthcare expenditure, with participants in the Northern and Western Regions 5–10 times more likely to experience such hardship and utilize financial coping mechanisms than counterparts in the Central Region, a wealthier area. Increases in total RHD costs were positively correlated with increasing use of coping behaviors.Conclusion: Ugandan households affected by RHD, particularly in lower-income areas, incur out-of-pocket costs that are very high relative to income, exacerbating the poverty trap. Universal health coverage policy reforms in Uganda should include mechanisms to reduce or eliminate out-of-pocket expenditures for RHD and other chronic diseases.

Abstract 215: Efficacy and Safety of Novel Oral Anticoagulants (NOACs) in Asian population with Non-Valvular Atrial Fibrillation (NVAF) - A Meta-Analysis

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Mayumi Fukuda ◽  
Daniel E Singer ◽  
Paul A Bain ◽  
Shoichiro Sato ◽  
Daiki Kobayashi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Hemorrhagic Stroke ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Asian Population ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Bleeding Events

Background and purpose: Asians have higher risk of intracranial hemorrhage (ICH) compared to non-Asians. Although recent clinical trials have shown non-vitamin K antagonist oral anticoagulants (NOACs) were favorable in preventing ICH as well as thrombotic events among patients with non-valvular atrial fibrillation (NVAF), it is unclear whether the efficacy and safety of NOACs are consistent among Asians. The purpose of this study is to assess the efficacy and safety of NOACs in Asians with NVAF. Methods: PubMed, Embase, Cochrane Central, Web of Science, the Western Pacific Index Medicus, Clinicaltrials.Gov and supplemented with conference abstracts were searched up to June 2014. Phase III randomized control trials that reported efficacy and safety of NOACs vs. warfarin in Asians and non-Asians with NVAF were identified. Each study was reviewed by two reviewers and differences were resolved by consensus. The end points analyzed were all stroke or systemic embolism, ischemic and hemorrhagic stroke, major or clinically relevant non major bleeding events (CRNM), and ICH. The hazard ratio (HR) with 95% confidence interval (CI) of each endpoint in NOACs compared to warfarin was extracted separately among Asians and non-Asians. Random-effects models were used to calculate pooled HR and 95% CI. Results: 5 eligible studies were identified. Total of 8928 Asians and 64023 non-Asians were included. All stroke or systemic embolism were significantly reduced with NOACs in Asians (HR: 0.72 [95% CI: 0.59-0.88], p=0.002) but not in non-Asians (HR: 0.82 [0.66-1.01], p=0.097). The risk of ischemic stroke was not decreased in Asians (HR: 0.88 [0.64-1.21], p=0.43) or non-Asians (HR: 0.98 [0.80-1.12], p=0.73), whereas the risk of hemorrhagic stroke was significantly decreased in both groups (HR: 0.28 [0.17-0.47], p<0.001 for Asians, HR: 0.37 [0.24-0.55], p<0.001, respectively). The risk of major bleeding or CRNM was significantly reduced in Asians (HR: 0.68 [0.56-0.83], p<0.001) but not in non-Asians (HR: 0.78 [0.60-1.0], p=0.21). The risk of ICH was significantly decreased in both groups (HR: 0.30 [0.21-0.42], p<0.001, HR: 0.41 [0.34-0.48], p<0.001, respectively). Conclusions: The efficacy and safety of NOACs in Asians with NVAF is consistent with the overall results.

Assessing Bleeding Risk in Atrial Fibrillation Patients: Comparing a Bleeding Risk Score Based Only on Modifiable Bleeding Risk Factors against the HAS-BLED Score. The AMADEUS Trial

2017 ◽  
Vol 117 (12) ◽  
pp. 2261-2266 ◽  
Author(s):  
María Esteve-Pastor ◽  
José Rivera-Caravaca ◽  
Alena Shantsila ◽  
Vanessa Roldán ◽  
Gregory Lip ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Risk Score ◽  
Bleeding Event ◽  
Bleeding Risk ◽  
Clinical Score ◽  
International Normalized Ratio ◽  
Bleeding Events ◽  
Modifiable Factors

Background The HAS-BLED (hypertension, abnormal renal/liver function, previous stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly and drugs/alcohol consumption) score has been validated in several scenarios but the recent European guidelines does not recommend any clinical score to assess bleeding risk in atrial fibrillation (AF) patients and only focus on modifiable clinical factors. Purpose The aim of this study was to test the hypothesis that the HAS-BLED score would perform at least similarly to an approach only based on modifiable bleeding risk factors (i.e. a ‘modifiable bleeding risk factors score’) for predicting bleeding events. Methods We performed a comparison between the HAS-BLED score and the new ‘modifiable bleeding risk factors score’ in a post hoc analysis in 4,576 patients included in the AMADEUS trial. Results After 347 (interquartile range, 186–457) days of follow-up, 597 patients (13.0%) experienced any clinically relevant bleeding event and 113 (2.5%) had a major bleeding. Only the HAS-BLED score was significantly associated with the risk of any clinically relevant bleeding (Cox's analysis for HAS-BLED ≥ 3: hazard ratio 1.38; 95% confidence interval [CI], 1.10–1.72; p = 0.005). The ‘modifiable bleeding risk factors score’ ≥ 2 were non-significantly associated with any clinical relevant bleeding. The two scores had modest ability in predicting bleeding events. The HAS-BLED score performed best in predicting any clinically relevant bleeding (c-indexes for HAS-BLED, 0.545 [95% CI, 0.530–0.559] vs. the ‘modifiable bleeding risk factors score’, 0.530 [95% CI, 0.515–0.544]; c-index difference 0.015, z-score = 2.063, p = 0.04). The HAS-BLED score with one, two and three modifiable factors performed significantly better than the ‘modifiable bleeding risk factors scores’ with one, two and three modifiable risk factors. Conclusion When compared with an approach only based on modifiable bleeding risk factors proposed by European Society of Cardiology (ESC) AF guidelines, the HAS-BLED score performed significantly better in predicting any clinically relevant bleeding in this clinical trial cohort. While modifiable bleeding risk factors should be addressed in all AF patients, the use of a formal bleeding risk score (HAS-BLED) has better predictive value for bleeding risks, and would help decision-making in identifying ‘high risk’ patients for scheduling reviews and follow-up.

scholarly journals Anticoagulation Quality of Warfarin and the Role of Physician–Pharmacist Collaborative Clinics in the Treatment of Patients Receiving Warfarin: A Retrospective, Observational, Single-Center Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Sha Qiu ◽  
Na Wang ◽  
Chi Zhang ◽  
Zhi-Chun Gu ◽  
Yan Qian
Keyword(s):  
Atrial Fibrillation ◽  
Protective Factor ◽  
International Normalized Ratio ◽  
Bleeding Events ◽  
Average Interval ◽  
Single Center Study ◽  
Independent Risk Factors

Background: The management of patients receiving warfarin is complicated. This study evaluated the anticoagulation quality of warfarin, explored potential predictors associated with poor anticoagulation quality, and elucidated the role of clinical pharmacists in the management of warfarin treatment.Methods: We retrospectively collected data on patients who either initially received warfarin or returned to warfarin after withdrawal between January 1, 2015 and January 1, 2020. The primary outcome was time in therapeutic range (TTR), and a TTR of ≥60% was considered as good anticoagulation quality. The secondary outcomes included thromboembolic and bleeding events during the follow-up. We assessed the TTR of each participant and investigated the potential predictors of poor anticoagulation quality (TTR &lt; 60%) using logistic regression analysis. Additionally, we compared the warfarin anticoagulant quality and the incidence of clinical adverse events between atrial fibrillation patients in physician–pharmacist collaborative clinics (PPCCs) and general clinics.Results: Totally, 378 patients were included. The mean TTR of patients was 42.6 ± 29.8%, with only 32% of patients having achieved good anticoagulation quality. During a mean follow-up period of 192 ± 92 days, we found no significant differences in the incidences of thromboembolic events (5.0% vs. 5.1%, p = 0.967) and bleeding events (1.7% vs. 4.7%, p = 0.241) between patients with good and those with poor anticoagulation quality. The presence of PPCCs (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.25–0.90, p = 0.022) was an independent protective factor of poor anticoagulation quality, while the presence of more than four comorbidities (OR: 1.98, 95% CI: 1.22–3.24, p = 0.006) and an average interval of international normalized ratio monitoring of &gt;30 days (OR: 1.74, 95% CI: 1.10–2.76, p = 0.019) were independent risk factors of poor anticoagulation quality. Compared with atrial fibrillation patients in general clinics, patients in PPCCs were found to have a significantly increased mean TTR level (48.4% ± 25.7% vs. 38.0% ± 27.6%, p = 0.014).Conclusion: The anticoagulation quality of warfarin was relatively low at our institution. The presence of more than four comorbidities and an average interval of international normalized ratio monitoring of &gt;30 days independently contributed to poor anticoagulation quality. Meanwhile, the use of PPCC model improved the anticoagulation quality of warfarin.

scholarly journals Plasma Warfarin Level and International Normalized Ratio do not Correlate with Bleeding Events in Indonesian Patients of Minangkabau Ethnicity with Atrial Fibrillation

2020 ◽  
Vol 8 (B) ◽  
pp. 192-197
Author(s):  
Rahmatini Rahmatini ◽  
Gestina Aliska ◽  
Elly Usman ◽  
Mefri Yanni ◽  
Cimi Ilmiawati
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Concentration ◽  
Medical Records ◽  
High Performance ◽  
International Normalized Ratio ◽  
Tertiary Hospital ◽  
Therapeutic Window ◽  
Bleeding Events ◽  
Risk Of Bleeding ◽  
Number Of Patients

BACKGROUND: Warfarin is the mainstay of anticoagulant therapy to prevent thromboembolism in atrial fibrillation (AF). It has a narrow therapeutic window, rendering monitoring prothrombin time necessary using the international normalized ratio (INR). However, INR value is not always correlated with the clinical risk of bleeding. AIM: We aimed to monitor plasma warfarin concentration and to analyze its correlation with bleeding events in Indonesian patients of Minangkabau ethnicity with AF. METHODS: We consecutively recruited outpatients with AF from January to November 2017 at a tertiary hospital in West Sumatera, Indonesia. At the time of the study, patients had received at least 5 weeks of warfarin. Their characteristics were obtained from medical records, and INR data were collected. Warfarin plasma concentration was analyzed using high-performance liquid chromatography. RESULTS: There were a total of 45 patients (25 males and 20 females; mean age 54.6 years). The number of patients with INR value lower than, within, and higher than target value (2.0–3.0) was 25, 12, and 8, respectively. Half of the patients (n = 23; 51.1%) had subtherapeutic plasma warfarin levels and nearly half (n = 20; 44.4%) of the patients had therapeutic plasma warfarin levels. INR value was not significantly correlated with plasma warfarin level (r = 0.273; p = 0.07). Bleeding events occurred in 14 patients. INR value was not significantly different (p = 0.12), while the plasma warfarin level was marginally significantly different (p = 0.05) between those with bleeding and no bleeding events. CONCLUSION: Neither warfarin plasma concentration nor INR was correlated with bleeding events in Indonesian patients of Minangkabau ethnicity with AF.

Effect of Fixed Minidose Warfarin, Conventional Dose Warfarin and Aspirin on INR and Prothrombin Fragment 1 + 2 in Patients with Atrial Fibrillation

1997 ◽  
Vol 77 (05) ◽  
pp. 0845-0848 ◽  
Author(s):  
B G Koefoed ◽  
C Feddersen ◽  
A L Gulløv ◽  
P Petersen
Keyword(s):  
Atrial Fibrillation ◽  
International Normalized Ratio ◽  
Coagulation System ◽  
Nonvalvular Atrial Fibrillation ◽  
Treatment Groups ◽  
Prothrombin Fragment ◽  
Conventional Dose ◽  
Dose Warfarin ◽  
Significant Difference ◽  
Changes Over Time

SummaryThe efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well- documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to investigate the effect on the coagulation system of the treatments, the International Normalized Ratio of the prothrombin time (INR) and prothrombin fragment 1 + 2 (F1 +2) were monitored at baseline and after three months of treatment in 100 patients consecutively included in the trial. At baseline no differences in INR and F1+2 between the four treatment groups were present. After three months of therapy the level of INR increased significantly from baseline in patients receiving warfarin in any dose and the level of F1+2 decreased significantly by combined minidose warfarin-aspirin and by dose adjusted warfarin. When comparing the changes over time in FI +2 (three-month value minus baseline value) during therapy with fixed minidose warfarin, combined minidose warfarin-aspirin and aspirin alone no significant difference between the groups was found. In conclusion, INR was changed by all three warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1+2.

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