[The study of hypotensive action of dinitrosyl-iron complex with glutathione containing drug oxacom in healthy volunteers].

On the basis of earlier executed studies of hypotensive effect of dinitrosyl iron complexes (DNIC) with glutathione, the drug has been created in industrial conditions named oxacom. Preliminary pharmacological studies of oxacom have not revealed negative qualities. The drug has been now tested in 14 healthy men in whom at single intravenous introduction it caused typical response - a decrease of diastolic as well as systolic arterial pressure on 24-27 mmHg through 3-4 min with subsequent very slow restoration in 8-10 hours. The heart rate after initial rise was quickly normalized. Echocardiography revealed unaltered cardiac output in spite of reduced cardiac filling by 28%. The multilateral analysis of clinical and biochemical data has revealed an absence of essential alterations which could lead to pathological consequences. The drug is recommended for carrying out of the second phase of clinical trial. The comparative study of the efficiency of hypotensive action of oxacom, S-nitrosoglutathione (GS-NO) and sodium nitrite (NO2) in rats has shown that the duration of effect was the greatest at oxacom action.

[Prolongation of enoxaparin therapy to one month promotes recanalization of the occlusively thrombosed deep veins].

AIM: To compare effects of prolongation of the treatment with therapeutic doses of enoxaparin to 1 month on recanalization of occlusively thrombosed deep veins (OTDV) of the limbs with results of standard therapy with unfractionated heparin (UFH). Both treatments were followed by warfarin administration. MATERIAL AND METHODS: Thirty patients were selected from 111 patients with a history of deep vein thrombosis (DVT) and/or pulmonary artery embolism according to the following criteria: the presence of occlusive thrombosis of one deep vein minimum; the absence of DVT for 12 months of follow-up. Patients of group 1 (n = 15) received standard therapy (UFH for at least 5 days) with switch to warfarin. Patients of group 2 (n = 15) received therapeutic doses of enoxaparin (1 mg/kg each 12 hours) for 30 days minimum with switch to warfarin. Follow-up was 12 months. Ultrasonic duplex angioscanning of the limbs was made at baseline, 1, 3, 6 and 12 months after treatment start. RESULTS: After follow-up month 1, 3 and 6 number of patients with occlusive DVT was significantly less in group 2. All the patients given enoxaparin achieved recanalization of OTDV within 3 months of treatment. OTDV recanalization was not achieved in 20% patients of group 1 even 12 months after treatment start. CONCLUSION: Prolongation of enoxaparin treatment to 1 month followed by warfarin treatment is superior to standard UFH treatment followed by warfarin in providing recanalization of OTDV within 3 months of treatment. Moreover, this treatment predicts persistence of recanalization within 12 months of anticoagulant therapy.

[Polymorphisms of genes CYP2C9 and VKORC1 in patients with venous thromboembolic complications in Moscow population: effects on stability of anticoagulant therapy and frequency of hemorrhage].

AIM: To investigate frequency of carriage of genetic polymorphisms CYP2C9 and VKORC1 in patients with venous thromboembolic complications (VTEC) in Moscow population given warfarin treatment and effects of this carriage on stability of anticoagulation and frequency of hemorrhagic complications (HC) in warfarin treatment. MATERIAL AND METHODS: The study included 111 patients with the history of deep vein thrombosis and/ or pulmonary artery thromboembolism. All the patients received non-fractionated or low-molecular heparin for at least 5 days, then warfarin (target INR 2.0-3.0). Warfarin dose was selected empirically. Gene CYP2C9 and VKORC1 polymorphisms were studied. HC were endpoints. RESULTS: Genotype CYP2C9*1/*1 (a "wild" type) was detected in 94 (84.7%) patients. Of other genotypes - heterozygotes CYP2C9*1/*2 (4.5%) and CYP2C9*1/*3 (10.8%). Genotyping by VKORC1 detected genotype GG (a wild type) in 42.3%, genotype GA--in 48.6%, genotype AA--in 9.1% patients. A mean warfarin dose, supporting an adequaite INR, was asspciated with both genotype CYP2C9 and VKORC1. Warfarin doses were highest in carriers of wile genotypes CYP2C9 and VKORC1 (6,9 and 8,8 mg/day), the lowest--in patients with genotypes CYP2C9*1/*3 and VKORC1 (4,5 and 4,0 mg/day). The carriers of polymorphisms CYP2C9*1/*3 and VKORC1 showed less stable anticoagulation vs carriers of allele variants CYP2C9*1/*1, CYP2C9*1/*2 and genotypes GG, GA VKORC1. An HC rate depended, as a rule, on carriage of genotypes CYP2C9*1/*3 and AA VKORC1. The highest risk of HC was associated with genotype CYP2C9*1/*3. The results of multifactorial regression analysis also indicated that carriage of genotype CYP2C9*1/*3, a female gender and the range of INR in warfarin treatment > or = 2,66 are independent predictors of HC in VTEC patients on warfarin treatment. CONCLUSION: Carriage of gene CYP2C9 and VKORC1 polymorphisms affects suppoting dose of warfarin and rate of hemorrhage in patients with VTEC in Moscow population. Frequency of HC is the highest in carriers of genotypes CYP2C9*1/*3 and AA VKORC1, they need minimal supporting dose of warfarin. Carriage of genotype CYP2C9*1/*3 in line with a female gender and instability of INR is an independent predictor of HC in VTEC patients in Moscow population on warfarin treatment.

[Thrombin-activated inhibitor of fibrinolysis and efficacy and safety of long-term warfarin treatment in patients with venous thromboembolic complications].

AIM: To study effects of thrombin-activated fibrinolysis inhibitor (TAFI) on efficacy and safety of long-term anti-coagulant treatment in patients with venous thromboembolic complications (VTEC). MATERIAL AND METHODS: A total of 111 patients with a history of an episode of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE) entered the study. All the patients received unfractionated or low-molecular heparin for at least 5 days than switch on warfarin (target values of INR 2.0-3.0). Baseline blood levels of TAFI were measured. The patients were followed up for 18 months. Recurrent (DVT/TAFI and hemorrhagic complications (HC) were endpoints. Also, frequency of complete lysis of deep vein thrombi was assessed after 12 months of treatment. RESULTS: A TAFI level varied from 50 to 217% (median 106%, interquartile rage 90-133%). TAFI concentration positively correlated with fibrinogen and thromb size. The patients were divided into two groups depending on TAFI content: group 1 patients had low TAFI (under 25th percentile; < 90%); patients of group 2 had high TAFI (above 25th percentile; > 90%). Group 1 patients were characterized by less stable anticoagulation. This association did not depend on genetic characteristics which determine sensitivity to warfarin (CYP2C9 and VKORC1). Low TAFI was associated with reduced risk of DVT for 18 months and higher probability of complete lysis of the thrombi after 12 months of anticoagulant therapy compared to VTEC patients with high TAFI. No differences were found by TAFI level in patients with HC and without HC, but in HC patients low TAFI was associated with spontaneous hemorrhages and bleeding in therapeutic INR values. CONCLUSION: The results of this pilot study evidence that a TAFI level can be one of the factors influencing efficacy and safety of long-term anticoagulant therapy in patients with VTEC on warfarin treatment.

[Clopidogrel resistance in patients with acute coronary syndrome].

AIM: to reveal the frequency of clopidogrel resistance in patients with acute coronary syndrome (ACS) and its impact on prognosis in these patients. SUBJECTS AND METHODS: Seventy-five clopidogrel-treated patients with ACS were followed up. Optical aggregometry was conducted using ADP 20 micromol. The resistance criteria were baseline platelet aggregation, platelet aggregation on day 7, % < 10%. Inflammatory markers (IL-6, IL-10, and C-reactive protein) were determined. Genetic polymorphisms (the IIIa subunit gene--Leu33Pro, the receptor P2Y(12) C18T and G36T gene, and the CYP3*A4(A-293G) gene) were studied. RESULTS: According to the accepted resistance criteria, 54 (72%) patients were sensitive to clopidogrel and 21 (28%) were resistant to the agent. The resistance was revealed in 7 (23%) of the patients with ECG ST-segment elevation and in 14 (31%) of those with ST-segment elevation. Before admission to the clinic, the unresponsive patients had significantly more frequently received the loading clopidogrel dose of 300 mg while that latter was 600 mg in the responsive patients. As compared with the responsive patients, the unresponsive ones showed a significantly lower baseline antibody level that was increased on day 7. The clopidogrel resistance determined by this criterion had no impact on prognosis. On dividing the patients by aggregation quartile values, poor manifestations insignificantly more frequently occurred in the third and fourth quartiles. No clear correlation was found between the occurrence of clopidogrel resistance and the activation of an inflammatory process. The monozygous variant of the receptor P2Y(12) CT18T gene was insignificantly more frequently encountered in the unresponsive patients. CONCLUSION: The laboratory phenomenon of clopidogrel resistance exists. Large multicenter studies of this issue are needed to identify simple and least expensive resistance methods and clear diagnostic criteria that enable the findings to be compared.

[Risk factors for venous thromboembolic complications and their association with D-dimer level].

AIM: to study the prevalence of various risk factors (RF) for venous thromboembolic events (VTEE) and their association with D-dimer levels. SUBJECTS AND METHODS: The clinical, demographic, anthropometric, anamnestic, and laboratory data were analyzed in 106 patients (73 men and 33 women) aged 18 to 78 years admitted to hospital with the first or recurrent episode of VTEE. RESULTS: RF and VTEE-associated diseases were identified in all patients. Over 90% of the patients had more 2 RFs. The most common RFs were the age above 40 years (85%) and overweight (82%), including obesity (42%). There was a preponderance of cardiovascular diseases in the pattern of VTEE-associated diseases. The direct causes (precipitating factors) of thrombosis were revealed in 57% of cases; the thrombotic episode was classified as idiopathic in 43%. Elevated D-dimer levels were found in 74% of the patients. Higher D-dimer content was seen in women, non-smokers, patients operated on for thrombosis, those who had 2 precipitating factors or more, and those who had a less than 30-day history of thrombosis. There was an inverse correlation between the elevated level of D-dimer and the duration of thrombosis by the moment of its identification (thrombus age). CONCLUSION: All patients who have experienced a venous thrombotic episode have various RFs for VTEE The content of D-dimer exceeds the normal value in most patients with VTEE. Among the RFs studied, thrombus age is the most important factor associated with elevated D-dimer levels in patients with VTEE

[Independent predictors of deep vein thrombosis (results of prospective 18 months study)].

We followed for 18 months 90 patients who had had deep vein thrombosis (DVE) and/or pulmonary embolism (PE) and received therapy with anticoagulants either for 3-12 months or for indefinitely long time. During follow-up rate of recurrent DVE was 16.7%, no recurrences of PE were registered. Predictors of recurrent PE were selected among 165 demographic, anthropometric, anamnestic, clinical, genetic, instrumental, and laboratory parameters, as well as risk factors of development of thromboembolic complications. According to results of multifactorial regression analysis we established the following independent predictors recurrent DVE during 18 months of follow-up: elevated level of DAdimer after 1 month of anticoagulant therapy (p=0.005; relative risk--relative risk [RR] 8.1, 95% confidence interval [CI] 1.9 to 34.8), homozygosity for C249T polymorphism in beta-fibrinogen gene (p=0.044; RR 8.4 95% CI 1.1 to 65.7), and percentage of all values of international normalized ratio within therapeutic interval 2.0-3.0 (p=0.009; RR 0.94, 95 CI 0.89 to 0.98).

[Improving recanalization of deep veins and the "outcomes" of venous thromboembolic complications in prolonged therapy with enoxaparin].

OBJECTIVE: The study was aimed at comparing efficacy and safety of two diferent approaches to initial anticoagulant therapy: a standard approach (non-fractionated heparin [NFH]for not less than 5 days followed by changing over to warfarin) and an alternative one, i. e., prolongation of treatment with therapeutic doses of enoxaparinfor up to one month with switching to warfarin, also assessing the effect of initial anticoagulant therapy on the "outcomes" of venous thromboembolic complications (VTECs) during 12 months of treatment. MATERIAL AND METHODS: We followed up a total ofone hundred and eleven patients after endured episodes of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE). Group One patients (n=80) received the standard therapy (NFH for not less than 5 days followed by changing over to warfarin). For Group Two patients (n=31), NFH was replaced by therapeutic doses of enoxaparin (1 mg/kg each 12 hours) for at least 30 days, with the patients then transferred to warfarin according to the standard regimen. Ultrasonographic duplex scanning of limb vessels was performed at baseline, 1, 3, 6 and 12 months after initiation of therapy. The patients were followed up for 12months. The following end points were taken into account: DVT/PATE relapses, haemorrhagic complications. RESULTS: Improved patency ofdeep veins one month after initiation of treatment was observed in the both groups, however efficacy of enoxaparin turned out to be superior to that of the standard therapy in relation to a decreased number of occlusive thrombosis of veins - 9 versus 41 (p=0.005). Commencing from month two of treatment patients from the both groups began taking warfarin, however the number of occlusive thromboses of deep veins during 12 months of treatment was considerably lower as compared with that in the enoxaparin group, i. e. I versus 21 (p=0.013) after 3 months; with 1 vs 11 (p=0.009) after 6 months, and 0 vs 8 (p=0.013) after 12 months. The rate of DVT relapses and haemorrhagic complications during the first month of treatment was similar in the both groups. Startingfrom month two of therapy there were no DVT relapses in the enoxaparin group. Conclusions. Enoxaparin within the first month of treatment in patients having developed VTEC, with similar DVT complication rate, appeared to be superior to the standard therapy with NFH and warfarin in achieving recanalization of occlusively thrombosed veins, with its advantages in improving patency of deep veins preserving within 12 months. The use of enoxaparin was also associated with lower rate of DVT relapses during 12 months of treatment.

[Elevated D-dimer in patients with cardiovascular diseases free from thromboembolic complications: what is it associated with and what has to be done?].

PURPOSE: To study the factors associated with an elevated content of D-dimer in patients diagnosed as having cardiovascular diseases (CVD) with no apparent thromboembolic complications. MATERIAL AND METHODS: A retrospective analysis of 1,000 case histories of patients (624 men and 376 women) aged from 19 to 93 years and undergoing treatment at the Institute of Cardiology named after A.L. Myasnikov in 2009. The sole criterion for inclusion into the study was the fact of hospitalization for any CVD and an altered content of D-dimer. The D-dimer levels were determined by latex agglutination using reagent kits «ST ALIATES® D-DF¼ (Diagnostica Stago). The upper limit of the normal distribution of the D-dimer amounted to 0.5 µg/ml. RESULTS: Thromboembolic complications were encountered in 13% of patients. Search for increased D-dimer predictors was carried out amongst a total of 867 CVD patients with no manifest thromboembolic complications. The D-dimer levels ranged widely from 0.01 to 16.97 (median 0.32, interquartile range 0.20-0.63) mg/ml and exceeded the upper limit of the normal distribution in 32% of the patients. Based on the findings of the univariate analysis we selected 14 parameters with the level of significance P<0.05, associated with an elevated D-dimer content. These parameters included but were not limited to: female gender, age >68 years, a history of venous thromboembolic events, no cardiac angina, the presence of ciliary arrhythmia and functional class III-IV chronic cardiac insufficiency (CCI), decompensated CCI, the presence of a permanent artificial pacemaker, an acute inflammatory process, chronic obstructive pulmonary disease, active cancer, pulmonary hypertension, and dilatational cardiomyopathy. The subsequent multivariate analysis showed that female gender, age >68 years, an acute inflammatory process, pulmonary hypertension, and decompensated CCI were independent predictors of an elevated D-dimer level in patients with CVD without apparent thromboembolic complications. CONCLUSIONS: The D-dimer level exceeded the upper limit of the normal distribution in 32% of CVD patients without manifest thromboembolic complications. Independent predictors of elevated D-dimer in CVD patients with no visible thromboses are as follows: female gender, age >68 years, acute inflammation, pulmonary hypertension, and decompensation of CCI.

[Warfarin or enoxaparin: the choice for the patient with venous thrombosis in the first month of treatment].

AIM: To compare efficacy and safety of warfarin and enoxaparin used in the first month of treatment of patients with an episode of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE). MATERIAL AND METHODS: Sixty patients (34 males, 26 females, age 18-76 years) after the DVT/PATE episode were divided into two groups. Patients of group 1 received standard therapy (non-fractionated heparin -NFH followed by warfarin), patients of group 2 instead of NFH received enoxaparin (1 mg/kg each 12 hours for at least 30 days). Ultrasonic scanning of the limbs and determination of D-dimer were conducted before and after 1 month of treatment. End points were the following: recurrent DVT/PATE, death due to PATE, hemorrhagic complications. RESULTS: Improvement of deep vein patency after 1 month of anticoagulant treatment was observed in both the groups. Enoxaparin proved more effective in relation to reduction of the number of venous occlusions (9 and 50, respectively, after 1 month treatment (p < 0.001). Hemorrhagic complications were seen in both the groups with equal frequency (13.4%). These hemorrhagic episodes did not require discontinuation of the drugs. Baseline D-dimer was significantly higher in the enoxaparin group--1.51 (0.73-2.44) mcg/ml vs 0.93 (0.42-1.33) mcg/ml (p = 0.019). After treatment D-dimer level and number of patients with high D-dimer diminished in both groups. CONCLUSION: Enoxaparin proved more effective than warfarin in the first treatment month. In the same safety and prophylactic effect enoxaparin is more effective in recanalization of occusions in the deep veins.

[Action of a nitric oxide donor dinitrosyl complex of iron with glutathione on hemodynamics in rats and monkeys].

We studied action of a nitric oxide donor, dinitrosyl complex of iron (DNIC) with glutathione as a ligand on the hemodynamics of normotensive Wistar rats, spontaneously hypertensive rats (SHR), and monkeys. Intravenous DNIC introduction (2-120 mg/kg) rendered fast (1-2 min) hypotensive effect combined with increased heart rate by 10-25%. Second phase of the effect in Wistar rats was characterized by slowed recovery of arterial pressure and heart rate up to initial level. A gradual DNIC breakdown in blood occurred during this period associated with increased NO accumulation in organs with intensive oxidative metabolism (liver, heart, and kidney). Duration of hypotensive effect in all animals depended on dose, this dependence was most expressed in SHR.

[Is a three-month therapy with warfarin adequate for effective therapy of patients after an episode of venous thrombosis].

AIM: To evaluate efficacy of 3 month therapy with warfarin in patients after an episode of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE), safety of the treatment. MATERIAL AND METHODS: 26 patients after DVT/PATE aged 18-74 were treated in the hospital with non-fractionated heparin for 10-14 days followed by warfarin. The dose was selected under the control of INR up to target values 2.0-3.0. Ultrasound angioscanning of the limbs was conducted at hospitalization, on discharge, 1 and 3 months after the discharge. D-dimer was measured at discharge, 1 and 3 months after the discharge. The patients were followed up for 3 months. The following end points were considered: recurrences of deep or surface vein thrombosis, PATE recurrence, death due to PATE, hemorrhagic complications. RESULTS: By ultrasound angioscanning significant positive results were not achieved. The level of D-dimer upon discharge was elevated in 18 (69.2%) patients (0.94, 0.41-1.69 mcg/ml). 3 month therapy with warfarin resulted in complete solution of all floting thrombs, achievement of recanalization of occlusive thrombosed deep vein in 20 (80%) patients, thrombosed vein number reduced from 4.0 to 3.0, p = 0.004. Deep vein thrombs disappeared only in 3 (11.5%) patients in 3 bmonths. Warfarin lowered D-dimer content to 0.23 mcg/ml (p < 0.001) in 1 month and to 0.12 mcg/ml (p < 0.001) in 3 moths after the discharge. 23 patients reached target 2.0-3.0 values and maintained them in therapeutic ranges. In DVT recurrence no PATE and PATE-related deaths were registered. Hemorrhagic complications arose in 5 patients, but they did not lead to warfarin discontinuation. CONCLUSION: Warfarin is effective for secondary prophylaxis of DVT/PAT, but this therapy failed to solve thrombs in the deep veins in many patients.

[Cytochrome P4502C9(CYP2C9) gene polymorphism and safety of therapy with warfarin].

Aim of the study was to investigate frequency and influence of alleles CYP2C9*2 and CYP2C9*3 on pharmacokinetics, pharmacodynamics and dosing regimen of warfarin and on development of hemorrhagic complications. We included 84 patients (mean age 62,8 +/- 10,5 years). Duration of follow-up varied between 1 month and 1 year. Carriage of allele variants was determined by polymerase chain reaction, measurement of plasma wafarin concentration was carried out with the help of high performance liquid chromatography. Wild type (CYP2C9*1/*1) was found in 68% of patients; overall frequency of 2C9*1/*1, *l/*3, *2/*2, *3/*3, *2/*3 genotypes was 32%. Average maintenance doses of warfarin for patients with allele variants CYP 2C9 *2 and 2C9 *3 were 3.6 and 3.1 mg/day, respectively, what was significantly lower than in wild type homozygotes (6.1 mg/day). Wild type homozygotes (1) had the highest warfarin clearance (3,51 ml/min). In carriers of 2C9 *2(2) and 2C9 *3(3) warfarin clearance was significantly lower (2.42 and 1.82 ml/min; p1 - 2 = 0,05; p1 - 3 = 0,0008). In carriers of allele variants CYP2C9*2, CYP2C9*3 values of international normalized ratio > 3,0 were met more often, especially in carriers of CYP2C9*3 (in 100% of cases) vs. 28% in wild type homozygotes (p=0,02). Carriers of CYP2C9*3 compared with wild type homozygotes had more hemorrhagic complications (67% and 16%, respectively, p=0,0008). Thus cytochrome P450 2C9 gene polymorphism influences frequency of development of hemorrhagic complications, metabolic clearance, and magnitude of warfarin maintenance dose.

[The influence of CYP2C9 genetic polymorphism on the pharmacokinetics and pharmacodynamics of warfarin in patients with constant atrial fibrillation].

CYP2C9 is the main enzyme participating in warfarin metabolism, of which genetic polymorphism is typical. The aim of the study was to investigate the influence of having allelic variants CYP2C9*2 and CYP2C9*3 on the pharmacokinetics, dosage regimen, and the rate of hemorrhage in patients with constant atrial fibrillation taking warfarin. Eighty-two patients with constant atrial fibrillation taking warfarin were included in the study. It was shown that in patients with CYP2C9*2 and CYP2C9*3 the clearance of warfarin and its dose were lower, while the episodes of excessive hypocoagulation and hemorrhage associated with warfarin were more frequent than in patients without these allelic variants. Basing on the results of the study, the authors propose an algorithm of choosing the initial warfarin dose depending on CYP2C9 genotype.

[Effect of acenocoumarol and aspirin on platelet function, markers of thrombinemia, and intracardiac thrombosis in patients with atrial fibrillation].

Patients with atrial fibrillation taking either indirect anticoagulant acenocumarol or most often prescribed antiaggregant aspirin were followed for 1 year. The results have shown that therapy with acenocumarol lowers content of D-dimer, prevents formation and promotes lysis of left auricular thrombi and lowers risk of development of ischemic stroke in patients with atrial fibrillation and high risk of thromboembolism. Therapy with aspirin in a dose providing maximal suppression of platelet function, does not lower D-dimer levels, does not promote lysis of left auricular thrombi and is inferior to acenocumarol in prevention of ischemic stroke.

[Pharmacogenetics of indirect anticoagulants: value of genotype for improvement of efficacy and safety of therapy].

The review is devoted to the contemporary state of the problem of pharmacogenetics of indirect anticoagulants. At present there are data about effects of allele variants of CYP2C9, VKORC1, APOE genes on efficacy and safety of therapy with indirect anticoagulants. Detection of these variants is a perspective way to individualization of therapy with indirect anticoagulants.

[Matrix metalloproteinases, C-reactive protein, and markers of thrombinemia in patients with stable angina and restenoses after percutaneous coronary interventions.]. / Matriksnye metalloproteinazy, C-reaktivnyi belok i markery trombinemii u bol'nykh so stabil'noi stenokardiei i restenozami posle chreskozhnykh koronarnykh vmeshatel'stv.

AIM: To elucidate relationships between blood levels of matric metalloproteinases (MMP), C-reactive protein (CRP), markers of thrombinemia, and development of restenosis after percutaneous coronary interventions (PCI) in patients with stable angina. MATERIAL: Patients (n=78, mean age 55.7+/-0.9 years) after successful PCI. METHODS: MMP-2, MMP-9, CRP, prothrombin fragments 1 and 2, thrombin-antithrombin complex and plasminogen activator inhibitor antigen were measured in blood plasma taken before PCI. Repeat coronary angiography was carried out in 31 patients 6-8 months after PCI. Exercise ECG was used for diagnosis of restenosis in other patients. More than 1 mm ST depression in same ECG leads as before PCI was used as criterion of restenosis. RESULTS: Overall sings of restenosis were found in 28 patients (35.9%). Patients with and without restenosis had similar contents of prothrombin fragments 1 and 2, thrombin-antithrombin complex, plasminogen activator inhibitor antigen and CRP, while patients with restenosis had significantly higher levels of MMP 2 and 9 (r<0.05). At multifactorial analysis level of MMP-9 was independently related to development of restenosis. CONCLUSION: Elevated level of MP-9 has predictive value in relation to development of restenosis.

[Long-Term Therapy With Indirect Anticoagulants in Patients With Nonvalvular Atrial Fibrillation (Prospective Follow-Up Study). Part II. Effectiveness and Safety]. / Dlitel'naia terapiia nepriamymi antikoaguliantami bol'nykh s mertsatel'noi aritmiei bez porazheniia klapanov serdtsa (prospektivnoe nabliudenie). Chast' II. Effektivnost' i bezopasnost' 3-letnei terapii.

AIM: To assess efficacy and safety of long-term international normalized ratio (INR) guided therapy with acenocoumarol in patients with nonvalvular atrial fibrillation. MATERIAL: Patients (n=100) with nonvalvular atrial fibrillation and at least 1 risk factor of thromboembolic complications. METHODS: Ischemic strokes, episodes of systemic thromboembolism and hemorrhagic complications were registered during 3 years of treatment with acenocoumarol (target INR 2.0-3.0). RESULTS: Annual rates of ischemic strokes, hemorrhagic complications and major bleeding were 0.7, 14.4 and 1.1%, respectively. No episodes of thromboembolism were registered in patients with history of thromboembolic complications. Basing on data collected predictors of bleeding complications in patients with atrial fibrillation during long term treatment with acenocoumarol were elucidated.