[Determination of indications for coronary angiography in asymptomatic patients and patients with stable angina].

A high percentage of patients undergoing coronary angiography which revealed no coronary lesions persists among patients with stable CHD. This problem persists in spite of the application of existing recommendations for the management of patients with stable CHD. Data of Russian and foreign authors analyzed in this article, which dedicated to this subject.

[Predictive significance of integral indices in the diagnosis of ischemic heart disease. Dependence on the possibility to perform exercise stress test].

Integral indices are used for optimization of verification of coronary heart disease (CHD). When due to some reason it is not possible to carry out stress tests their pretest analogues gain special importance. The latter proposition has been confirmed in this study.

[Comparative evaluation of antiplatelet efectiveness drugs of original and reproduced enteric forms of acetylsalicylic acid (clinical study ICAR))].

The purpose of the study was a comparative study of antiplatelet activity of acetylsalicylic acid drugs, produced in gastro-resistant form trombopol 75 mg and aspirin cardio 100 mg in patients with high risk of cardiovascular events. Effect of trombopol 75 mg versus 100 mg aspirin cardio on platelet aggregation in 30 patients with high risk of cardiovascular events during 3 week treatment period was studied. Design method: blind, randomized, crossover method. Three weeks before the initial therapy, for those patients, who received antiplatelet platelet therapy at the time of inclusion in the study, this therapy was withdrew ("wash-out period"), after which patient was given one of the study drug (sequence of courses was s determined according to the scheme of randomization) with the recommendation of taking it daily in the morning at the same time. At each visit, before the next dose of the drug, blood samples for determination of ADP-induced platelet aggregation were taken, physical examination, measurement of blood pressure (BP) and heart rate were recorded, adverse events were recorded. Follow-up visit was performed 3 weeks later. 21 days after first study drug withdrawal, a second similar course of therapy with another drug was performed. Antiplatelet efficacy of aspirin was assessed by its effect on spontaneous and ADP- induced platelet aggregation. Aggregation activity was determined by turbidometric method by changing of translucent ability of the blood sample during the formation of aggregates after 2 minutes of exposure. As an inducer of aggregation ADP solutions of three concentrations (0.5, 1 and 2 mM) were used. No significant difference between compared drugs in influence on aggregation ability of platelets after 3 weeks of daily intake was found. No adverse events associated with taking of studied drugs were registered. It was concluded that, generic APD - trombopol 75 mg and aspirin cardio 100 mg were equivalent on antiplatelet efficacy and tolerability.

[Cardioprotective characteristics of the drug nicorandil in patients with coronary heart disease].

Nicorandil, opener of potassium channels, was studied in Russia and abroad. Its cardioprotective, anti-ischemic, pharmacokinetic and pharmacodynamic properties are reviewed as well as side effects and area of application in patients with stable coronary heart disease (CHD). The trial have found efficacy of nicorandil in prevention of anginal attacks. Also, the drug increases exercise tolerance. Administration of nicorandil is indicated before intervention on coronary arteries for reproduction of the effect of myocardial preconditioning. Nicorandil is recommended for treatment of patients with chronic stable coronary heart disease.

[Pharmacokinetics of domestic actoprotector drug Metaprot in healthy volunteers].

Pharmacokinetics of the actoprotector Metaprot, an original Russian drug, has been studied in a group of healthy adult volunteers. Metaprot in capsules was administrated orally as a single dose of 250 mg. The concentration of the active substance (ethylthiobenzimidazole) in the blood serum was determined by high-performance liquid chromatography (HPLC) with UV detection. The pharmacokinetic parameters were calculated by the model-independent method. The peak concentration of ethylthiobenzimidazole in plasma was Cmax = 0.91 +/- 1.05 microg/ml and the average time to peak concentration was t(max) = 1.06 +/- 0.16 h. A polymodal character of the distribution of pharmacokinetic parameters in the test group was revealed.

[First results of open randomized clinical study of Acridilol in combination therapy of patients with arterial hypertension and obesity or type 2 diabetes (Mellitus-Open Multicenter Clinical Study ACCORD)].

AIM: To study efficacy and safety of a preparation of carvedilol Acridilol (Akrikhin, Russia) in patients with mild and moderate arterial hypertension (AH) and obesity and/or compensated type 2 diabetes mellitus (DM). MATERIAL AND METHODS: Patients (n=592) suffering from mild to moderate AH in combination with DM and/or obesity participated in a randomized comparative open study with parallel groups. By means of randomization these patients were distributed into 2 groups: patients of group 1 (n=291) after washout period following withdrawal of previously taken b-blockers received acridilol for 24 weeks together with other antihypertensive therapy. In control group 2 (n=301) stable antihypertensive therapy was carried out during 24 weeks. Efficacy of hypotensive therapy was assessed during visits to physicians every 2 weeks throughout the whole study. At the beginning and in the end of the study we conducted assessment of biochemical parameters of carbohydrate and lipid metabolism, registered 12-lead ECG, and assessed status of anxiety and depression. RESULTS OF THE STUDY: At the background of the conducted treatment in patients of both groups significant lowering of hemodynamic parameters (systolic and diastolic BP and heart raid) was revealed, differences between groups by the 24-th week were statistically significant. By the end of the study target BP level was achieved in 96.8% of patients in carvedilol group and in 88% of patients of control group (p < 0.001). In both groups positive dynamics of parameters of anxiety-depression status of patients was noted while therapy with carvedilol (acridilol) led to statistically significant (p=0.01) improvement of status of depression compared with control treatment. Also necessity in hospitalization significantly decreased in patients of both groups: number of hospitalizations declined 5 times in acridilol group (p < 0.0001) and 3 times in control group (p < 0.0001). During the study 32 cases of adverse effects were registered: 17 at the background of therapy with acridilol and 15 at the background of control treatment (p=0.58), however most of them were of weak or moderate degree of severity. CONCLUSION: The results obtained demonstrate high efficacy and safety of the preparation of carvedilol acridilol in patients with combination pathology, high metabolic risk, and high risk of cardiovascular complications.

[Selection of therapy with nitrates in patients with stable effort angina: results of comparative study of common isosorbide dinitrate and long acting preparation of isosorbide-5-mononitrate].

AIM: To assess efficacy and tolerability of a novel drug form of isosorbide-5-mononitrate in patients with ischemic heart disease and stable effort angina as compared with common isosorbide dinitrate pills. MATERIAL AND METHODS: Patients with stable class II-III effort angina (n=30) were included into a randomized crossover study in which they received isosorbide dinitrate (nitrosorbide, 10-20 mg t.i.d.) and long acting isosorbide-5-mononitrate (ephox-long, 50-100 mg o.d.) for 3 weeks each. Efficacy of treatment was assessed by clinical data and treadmill exercise tests. Questionnaires were used for registration of frequency and intensity of attacks of headache. RESULTS: The use of both isosorbide dinitrate and 5-mononitrate was associated with significant improvements of exercise tolerance however effect of mononitrate lasted longer. Nitroglycerine requirement diminished during first week of use of both drugs and remained on this level by the end of 3-rd week of treatment with mononitrate but substantially rose by the end of treatment with dinitrate. Number of attacks of headache increased during first week of treatment with both drugs, became even higher by the end of use of dinitrate and decreased by the end of use of mononitrate. CONCLUSION: Long acting form of isosorbide-5-mononitrate ephox-long taken once daily provides sufficient antianginal effect throughout a day and is better tolerated than nitrosorbide preparation of isosorbide dinitrate with moderately prolonged activity.

[Assessment of the efficacy and tolerance of delayed-action nifedipine as the monotherapy or in combination with metoprolol in patients with arterial hypertension]. / Otsenka éffektivnosti i perenosimosti nifedipina prolongirovannogo deistviia v vide monoterapii i v kombinatsii s metoprololom u bol'nykh arterial'noi gipertoniei.

AIM: To compare efficacy and safety of nifedipin-retard (cordaflex-retard, Egis, Hungary) used in monotherapy and in combination with metoprolol (egilok, Egis, Hungary) in patients with arterial hypertension (AH). MATERIAL AND METHODS: The study included 20 patients with AH stage I-II (12 males, 8 females, mean age 57.3 years, mean duration of the disease 8.6 years). Nifedipin-retard was given in a daily dose 40 mg/day (20 mg twice a day) in monotherapy and 20 mg/day in combination with metoprolol which was administered 50 mg twice a day (a daily dose 100 mg/day). The control examination consisted of a physical examination, measurement of arterial pressure (AP) by Korotkov, registration of heart rate, ECG, 24-h AP monitoring, echocardiography. RESULTS: By 24-h AP monitoring, a 4-week treatment with nifedipin-retard alone resulted in lowering of systolic arterial pressure. The combined treatment produced a more pronounced fall both in systolic and diastolic pressure. Diastolic left-ventricular function improved in combined therapy. Side effects observed in nifedipin-retard monotherapy got much more weaker when this drug combined with metoprolol. CONCLUSION: Combination of nifedipin-retard with metoprolol provides better clinical response and tolerance than monotherapy with nifedipin-retard.

[Effects of long-acting calcium antagonists--amlodipine and diltiazem in patients with stable angina of effort: comparative randomized controlled trial]. / Izuchenie deistviia dvukh antagonistov kal'tsiia prolongirovannogo deistviia--amlodipina i diltiazema u bol'nykh stabil'noi stenokardiei napriazheniia: dannye sravnitel'nogo randomizirovannogo issledovaniia.

AIM: To compare effectiveness of two long-acting calcium antagonists--amlodipin and diltiazem--in patients with ischemic heart disease (IHD) and stable angina of effort (SAE). MATERIAL AND METHODS: 31 IHD patients with SAE entered the double blind randomized trial. The patients received either amlodipin (5-10 mg once a day) or diltiazem (120-180 mg twice a day) for 4 weeks. Selection of the effective single dose and control over the drug effectiveness in regular intake was carried out using treadmill tests made at the height of the drug activity (peak effect) and before taking the next dose (end effect). RESULTS: 1 patient quitted the trial because of frequent anginal attacks while amlodipin administration. Both drugs showed positive effect in relation to exercise tolerance, peak effect of diltiazem was significantly higher than that of amlodipin, the end effect was the same. Amlodipin increased the heart rate at rest while diltiazem insignificantly decreased it. Amlodipin induced side effects more often, all of them were typical for dihydropiridin calcium antagonists. CONCLUSION: Amlodipin and diltiazem of prolonged action have pronounced antianginal effect, diltiazem being more effective and less toxic.

[Comparison of carvedilol and atenolol efficacy in patients with stable effort angina]. / Sravnenie éffektivnosti karvedilola i atenolola u bol'nykh so stabil'noi stenokardiei napriazheniia.

AIM: To compare effectiveness of carvedilol--beta-adrenoblocker with vasodilating action--with atenolol which is beta-adrenoblocker having no vasodilating activity in coronary heart disease (CHD) patients with stable effort angina. MATERIAL AND METHODS: The trial entered 28 CHD patients with a history of myocardial infarction (MI). All the patients had no contraindications to beta-adrenoblockers, had positive exercise tolerance test. After the control period of 7-10 days the patients received either carvedilol (14 patients) or atenolol (14 patients) in a mean daily dose 20.5 mg (6.25 to 50 mg) and 25.9 mg (12.5 to 100 mg), respectively, twice a day. The course of the treatment took 4 weeks. The effect was evaluated at treadmill exercise test. RESULTS: Both drugs diminished heart rate, carvedilol was less effective in this respect. Both drugs significantly prolonged time of exercise to the anginal attack and ST depression by 1.0 mm. Side effects arose in 6 and 4 patients, respectively. CONCLUSION: Carvedilol and atenolol are equally effective in the treatment of stable effort angina.

[Spirapril - a new long-acting ACE inhibitor: efficacy and safety in patients with arterial hypertension in combination with diabetes mellitus and impaired kidney function]. / Spirapril - novyi ingibitor angiotenzinprevrashchaiushchego fermenta dlitel'nogo deistviia: éffektivnost' i bezopasnost' u bol'nykh arterial'noi gipertoniei v sochetanii s sakharnym diabetom i narushennoi funktsiei pochek.

AIM: To examine effectiveness and safety of quadropril. MATERIAL AND METHODS: Changes in blood pressure (BP), heart rate (HR), levels of glucose, potassium and creatinine, creatinine clearance were studied in 120 patients (48 males and 72 females, mean age 60.6 +/- 0.7 years) with mild to moderate arterial hypertension (AH) with average duration 13.8 +/- 0.7 years. The patients were divided into 3 groups: with AH (n = 40), AH + noninsulindependent diabetes mellitus (DM) (n = 43), AH and nephropathy (n = 37). 8-week treatment was performed with a standard dose of 6 mg/day (1 tablet of quadropril). Control examinations were made 2, 4 and 8 weeks after the treatment. RESULTS: After 8 weeks of treatment a decrease in systolic blood pressure in AH group was 24.0 +/- 3.0 mm Hg and in diastolic blood pressure 16.3 +/- 1.3 mm Hg (P < 0.001). In the group with DM this decrease was 22.4 +/- 2.8 mm Hg and 15.7 +/- 1.4 mm Hg (p < 0.001), respectively. In the group with nephropathy this decrease was 26.4 +/- 2.4 and 16.5 +/- 1.3 mm Hg (p < 0.001), respectively. Heart rate changed significantly only in diabetics: from 75.1 +/- 1.7 to 72.9 +/- 1.3 beats/min. Biochemical parameters in the hypertensive and diabetic patients did not change significantly. In the nephropathy group there was a significant decrease in creatinine and increase in creatinine clearance. Their level of glucose and potassium changed insignificantly. CONCLUSION: The treatment with quadropril results in a significant decrease in blood pressure, does not influence parameters of carbohydrate metabolism, improves nitrogen eliminating function of the kidneys.

[Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension]. / Sravnitel'noe izuchenie éffektivnosti spiraprila (kvadropril) i amlodipina. Rezul'taty randomizirovannogo issledovaniia u bol'nykh miagkoi i umerennoi arterial'noi gipertoniei.

AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.

[Symptomless myocardial ischemia: feasibility of diagnostic mistakes]. / Bessimptomnaia ishemiia miokarda: vozmozhnost' oshibochnoi diagnostiki.

AIM: To examine feasibility of ST segment depression on ECG in treadmill exercise test and 24-h ECG monitoring in subjects with coronarographically intact coronary arteries. MATERIALS AND METHODS: 9 males aged 41 to 52 years with chest pains unrelated to muscular load. They had neither stenosis of coronary arteries, nor arterial hypertension, valvular defects, disturbance of electrolyte metabolism. All of them have undergone treadmill exercise test and 24-h ECG monitoring. RESULTS: The exercise test provoked chest pain in none of the examinees. ST segment was depressed in one patient. 24-h monitoring registered depression of ST segment in one more patient. The rest 7 patients showed no changes in ST segment either in exercise test or 24-h ECG monitoring. CONCLUSION: It is confirmed that typical ischemic ECG changes (horizontal depression of ST segment) in healthy persons can occur and may be mistaken for silent myocardial ischemia.

[The calcium antagonists diltiazem and nifedipine: a comparison of their efficacy in single and long-term use in patients with stable stenocardia of effort]. / Antagonisty kal'tsiia diltiazem i nifedipin: sravnenie éffektivnosti pri odnokratnom i dlitel'nom primenenii u bol'nykh stabil'noi stenokardiei napriazheniia.

AIM: To compare efficacy of diltiazem and nifedipine in single dose and long-term treatment. MATERIALS AND METHODS: A randomised double-blind cross-over study enrolled 17 patients suffering from coronary heart disease (CHD) with stable angina of effort (SAE). For 1 month, each patient received diltiazem and nifedipine (60-90 mg 4 times a day and 20-30 mg 4 times a day, respectively). The effect was assessed by the pharmacodynamic test after the initial dose and in the end of each treatment course. RESULTS: In 14 eligible patients both drugs reduced the number of SAE attacks and nitroglycerin tablets, diltiazem efficiency being somewhat higher. Single doses of diltiazem and nifedipine produced the same action. In long-term treatment nifedipine effect became shorter, diltiazem effect did not change. Before the morning dose of nifedipine (11.5 hours after the previous dose) exercise tolerance of this drug worsened. This may be due to withdrawal syndrome. As to diltiazem, its exercise tolerance improved. CONCLUSION: In long-term treatment of CHD with SAE diltiasem is more effective and safe than nifedipine.