Impact of genetic and clinical factors on dose requirements and quality of anticoagulation therapy in Polish patients receiving acenocoumarol: dosing calculation algorithm.

BACKGROUND: Despite the recent emergence of new oral anticoagulants, vitamin K antagonists remain the primary therapy in patients with atrial fibrillation and the only therapy licensed for use in patients with artificial heart valves. OBJECTIVE: The aim of this study was (a) to assess the impact of clinical and genetic factors on acenocoumarol (AC) dose requirements and the percentage of time in therapeutic range (%TTR) and (b) to develop pharmacogenetic-guided AC dose calculation algorithm. MATERIALS AND METHODS: We included 235 outpatients of the Institute of Cardiology (Warsaw), mean age 69.3, 46.9% women, receiving AC for artificial heart valves and/or atrial fibrillation. A multiple linear-regression analysis was performed using log-transformed effective AC dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other clinical factors as independent predictors. RESULTS: We identified factors that influenced the AC dose: CYP2C9 polymorphisms (P=0.004), VKORC1 polymorphisms (P<0.0001), age (P<0.0001), creatinine clearance lower than 40 ml/min (P=0.035), body mass (P=0.02), and dietary vitamin K intake (P=0.026). Clinical and genetic factors explained 49.0% of AC dose variability. We developed a dosing calculation algorithm that is, to the best of our knowledge, the first one to assess the effect of such clinical factors as creatinine clearance and dietary vitamin K intake on the AC dose. The clinical usefulness of the algorithm was assessed on separate validation group (n=50) with 70% accuracy. Dietary vitamin K intake higher than 200 mcg/day improved international normalized ratio control (%TTR 73.3±17 vs. 67.7±18, respectively, P=0.04). CONCLUSION: Inclusion of a variety of genetic and clinical factors in the dosing calculation algorithm allows for precise AC dose estimation in most patients and thus improves the efficacy and safety of the therapy.

[The frequency of risk factors of thromboembolic and hemorrhagic complications in patients treated with oral anticoagulants after heart valve replacement]. / Czynniki ryzyka powiklan zakrzepowo-zatorowych i krwotocznych u chorych leczonych doustnymi lekami przciwzakrzepowymi po zabiegu wszczepienia sztucznej zastawki serca.

UNLABELLED: Thromboembolic (TE) and hemorrhagic (H) complications are the most significant problems in patients treated with oral anticoagulants (OA) after implantation of artificial valvular prostheses of heart. This problem was discussed in worlds scientific literature, but was not comprehensive investigated in Polish population of patients. The aim of the study was to assess the frequency of TE and H complications and their influence on mortality and morbidity and to determine the risk factors related to clinical and hemodynamical patients status. MATERIAL AND METHODS: Between December 1997 and December 1998, 358 patients hospitalized in our Department were qualified for cardiac surgery. There were 177 women and 181 men with a mean age 56.9+/-10.3 (range 21-80 years), who underwent 144 mitral, 172 aortic, 42 both artificial heart valve replacement. All patients were followed prospectively. RESULTS: Follow up was 100% complete and averaged 36.7+/-12.1 months. The total follow-up was 1109.8 pty. Linearized incidents of death was 2.1%/pty (30 patients). TE events were in 30 patients (2.7%/pty). H events occurred in 46 patients (4.15%/pty). The TE and H complications were the most important causes of morbidity and mortality in observed population of patients after mechanical heart valve replacement. Frequency of complications was inside the broad spectrum of values presented in the literature. CONCLUSIONS: The independent risk factors of death were: lower EF (RR: 1.06; CI 95%: 1.02-1.08), advanced functional NYHA class in presurgery period (RR: 3.5; CI 95%: 1.1-8.2) and advanced functional NYHA class in postsurgery period (RR: 7.5; CI 95%: 3.6-15.5). The independent risk factor of TE as well H complications was an advanced functional NYHA class in perioperative period (respectively for TE and H complications RR: 4.2; CI 95%: 1.9-8.9 and RR: 3.2; CI 95%: 1.5-6.7). In the group with artificial heart valve in reference to the severe (class III) complications of postoperative period-independent risk factors were atherosclerosis risk factors (hypertension, hypercholesterolemia, diabetes and smoking) (RR: 2.4; CI 95%: 1.3-5.6).

[Skeletal myopathy associated with concomitant use of statin and cyclosporin in a heart transplant patient - case report]. / Miopatia zwiazana ze stosowaniem statyny wraz z cyklosporyna po transplantacji serca.

62-year-old woman after heart transplantation due to congestive heart failure of ischemic origin with history of hyperlipidemia was treated with cyclosporin and statin. Concomitant use of these agents caused clinical and biochemical symptoms of skeletal myopathy. After statin withdrawal the symptoms of myopathy disappeared.

Patient education and quality of home-based rehabilitation in patients older than 60 years after acute myocardial infarction.

PURPOSE: Because only one-third of eligible patients participate in formal cardiac rehabilitation, home-based programs constitute a suitable alternative. We examined effectiveness of a minimal educational intervention on patient fitness and activity levels through the use of simple motivational tools including verbal encouragement and the provision of a booklet containing exercise guidelines and exercise diary. METHODS: We enrolled 186 patients (age, 60 ­ 78 years; mean age, 69 years; 140 men) who were admitted to the outpatient clinic of Warsaw Institute of Cardiology in 2007-2009 after acute myocardial infarction. Of these, 61.3% had coronary angioplasty with stenting and 30.7% had coronary artery bypass. Patients were randomly assigned into an intervention group receiving minimal educational intervention or control. At baseline and 3 months, assessment was made of cardiopulmonary fitness and autonomic tone with exercise testing. Leisure-time physical activity and atherosclerosis risk factors were assessed at baseline and after 3 and 12 months. RESULTS: At baseline, exercise test results and leisure-time activity levels were not significantly different between groups. After 3 months, we noted statistically significant differences in exercise test responses between the intervention group versus control: peak workload 57.3 ± 2.3 versus 47.2 ± 2.2 kJ (P < .04) and heart rate recovery 26.5 3.3 versus 23.7 4.2 bpm (P < .001). Leisure-time activity was greater in the intervention group than in control, 3.9 versus 2.3 h/wk (P < .001). Improvement in atherosclerosis risk factors during the course of the study was similar between groups. CONCLUSION: Minimal educational intervention is an effective and safe form of promoting physical activity in older patients after myocardial infarction.

[Thromboembolic and haemorrhagic complications in patients treated with anticoagulants after artificial heart valve replacement. Risk factors dependent on quality of anticoagulant treatment]. / Powiklania zakrzepowo-zatorowe i krwotoczne u pacjentów po wszczepieniu sztucznej zastawki serca leczonych doustnymi lekami przeciwzakrzepowymi. Czynniki ryzyka zalezne od jakosci leczenia przeciwzakrzepowego.

UNLABELLED: Thromboembolic (TE) and hemorrhagic (H) complications are the most significant causes of morbidity and mortality in patients treated with oral anticoagulants (OA) after implantation of artificial valvular prostheses. The risk of complications is dependent on recommended target INR ranges and quality of anticoagulation treatment. We studied 358 patients with a mean age 56.9 +/- 10.3 (who underwent 144 mitral, 172 aortic, 42 both artificial heart valve replacement). The follow up was averaged 36.7 +/- 12.1 month. Linearized incidents of TE events was 2.7%/pty, H events--4.15%/pty. The quality of anticoagulant treatment based on following parameters: averaged INR +/- SD, percentage measurements of INR within the target range 2.5-3.5, within the broad range 2-4 and under 2 and over 5. Average frequency of tests, SD/averaged INR X 100%--was similar in patients with TE and H complications and event free patients. Significant differences were found when a shorter period of time-3 months preceding the TE or H incident was analized compared with the average results of measurements of event free patients. The patients with TE and H complications have statistically significant higher fluctuation ratio than event free patients (respectively: 1.09 -/+ 0.71 and 1.71 -/+ 1.06 vs 0.5 -/+ 0.32, p = 0.04 and 0.02 ) CONCLUSIONS: 1. The risk of TE and H complications was dependent on high fluctuation of INR values in the period of 3 months before the event. 2. The worse control of measurements of INR in the period of 3 months before the event in comparison with yearly values within the recommended target ranges show, that TE and H complications are directly dependent on period of poor INR control.