The possibilities of using beta-blocker bisoprolol in patients with stable angina with concomitant bronchial asthma.

Aim    To compare efficacy and safety of treatments with the calcium antagonist (CA) verapamil, the cardioselective ß-blocker (BB) bisoprolol, and a combination therapy with bisoprolol and amlodipine in patients with stable angina (SA) with concurrent mild and moderate, persistent bronchial asthma (BA). Material and methods    This open, prospective, randomized, comparative study included 120 patients with an IHD+BA comorbidity. Of these patients, 60 had mild persistent BA and 60 had moderate persistent BA. Each group was divided into 3 subgroup, each including 20 patients, based on the used regimen of antianginal therapy. Stepwise dose titration was performed every 2 weeks (subgroup 1 received the BB bisoprolol 2.5 mg - 5 mg - 10 mg; subgroup 2 received the CA verapamil 240 mg - 240 mg - 240 mg; subgroup 3 received bisoprolol 2.5 mg followed by the combination treatment with bisoprolol and amlodipine as a fixed combination 5+5 mg). All patients underwent a complete clinical and instrumental examination at baseline and at 2, 4, and 6 weeks of treatment. The antianginal effectivity and the effect on bronchial patency were evaluated. Results    In patients with SA and mild persistent BA, the study of external respiration function (ERF) at 2, 4, and 6 weeks of treatment did not detect any significant difference in the forced expiratory volume in 1 second (FEV1) between the treatment subgroups. In patients with SA and moderate persistent BA receiving the treatment, a significant decrease in FEV1 (р=0.022) was observed in subgroup 1 receiving bisoprolol 10 mg at 6 weeks of treatment. In subgroups 2 and 3 during the treatment, significant differences were absent. In patients with SA and mild or moderate persistent BA, the heart rate was significantly decreased in all three subgroups; however, in subgroup 2 receiving verapamil, the changes were considerably smaller than in other subgroups.Conclusion    The study results showed that the BB bisoprolol with dose titration every two weeks from 2.5 to 10 mg or the combination treatment with the BB bisoprolol and the CA amlodipine can be used as the antianginal therapy in patients with SA and mild persistent BA. The BB bisoprolol may be used in patients with SA and moderate persistent BA as the antianginal therapy, but only at doses not exceeding 5 mg to avoid the development of bronchial obstruction. The combination therapy with the BB bisoprolol 5 mg and the CA amlodipine 5 mg is indicated to enhance antianginal and vasoprotective effects.

[New opportunities to improve the treatment effectiveness of patients with stable angina].

Aim To study the antianginal and heart rate slowing effects in patients with stable angina (SA) who failed to achieve the heart rate (HR) goal and were switched from the beta-blocker (BB) metoprolol tartrate to a combination of metoprolol tartrate and ivabradine.Materials and methods The study included 54 patients with SA not higher than functional class (FC) III (35 (64.8 %) men and 19 (35.2 %) women) aged 59 [48; 77] years. Prior to the study start and at 4 and 8 weeks of follow-up, electrocardiography (ECG) and 24-h ECG monitoring (24h-ECGM) were performed for all patients. The follow-up period duration was 8 weeks. The antianginal and heart rate slowing effects of therapy were clinically evaluated by a decrease in frequency of anginal attacks and patients' requirement for nitrates, a decrease in HR, and the effect on 24h-ECGM indexes characterizing myocardial ischemia. At the first stage, all patients were prescribed metoprolol tartrate (Egilok®, Egis, Hungary) 25 mg twice a day. Patients with resting HR still higher than 70 bpm after 4 weeks of treatment were switched from metoprolol tartrate to a fixed ivabradine/metoprolol combination (Implicor®, Servier, France) 5 / 25 mg twice a day. Thus, based on achieving/ non-achieving the HR goal, two groups of patients were formed. Statistical analysis was performed with a STATISTICA 10,0 software package.Results After 4 weeks of therapy with metoprolol tartrate 25 mg twice a day, 18 (33.3%) patients of group 1 achieved the HR goal of 70 bpm, while  36 (66.7%) patients of group 2 did not achieve the goal. For further correction of HR, patients of group 2 were switched from metoprolol tartrate to ivabradine/metoprolol 5 / 25 mg twice a day. After 4 weeks of the ivabradine/metoprolol treatment, 31 (86.1 %) patients achieved the HR goal with median resting HR of 62 [56; 70] bpm. The number of angina attacks decreased from 6 [3; 8] to 2 [1; 3] per week (р<0.001). 24hECGM showed that the mean diurnal HR decreased from 81 [76; 96] to 66 [56; 76] bpm (р<0.001); mean night HR decreased from 69 [73; 80] to 52 [43; 60] bpm (р=0.012); and the ischemic ST segment depression was absent.Conclusion Only 33.3% of patients with stable angina achieved the HR goal on metoprolol tartrate 25 mg twice a day. Supplementing the beta-blocker metoprolol tartrate at the same dose with ivabradine allowed 86.1% of patients to achieve the HR goal and exerted a pronounced anti-anginal effect.

High-Frequency ECG for Detection of Myocardial Ischemia Associated with Right Coronary Artery Stenosis in IHD Patients.

The aim of the investigation was to study the parameters of high-frequency ECG in leads V1, V3R, V4R, V5R, V6R as additional diagnostic criteria for detecting the areas of myocardial ischemia associated with stenosis of the right coronary artery (RCA) in IHD patients. MATERIALS AND METHODS: The study involved 47 patients who underwent selective coronary angiography (SCA) for detection of IHD. The patients were divided into two groups based on the SCA results: group 1 included 28 patients with hemodynamically significant RCA stenosis; group 2 consisted of 19 patients with hemodynamically non-significant RCA stenosis. Prior to SCA, all patients underwent resting high-frequency ECG recording in 12 conventional leads and in leads V3R-V6R for 5 min. The study also involved 15 volunteers with no history of cardiovascular disease or IHD symptoms (control group) who underwent ECG in the same leads. The resulting data were processed and analyzed using the ArMaSoft-12-Cardio software (©ArMaSoft, 1995-2019, Russia), which made it possible to determine the presence or absence of reduced amplitude zones (RAZ) of the QRS complex in all morphological variants, the root-mean-square (RMS) deviation, and excess kurtosis. RESULTS: Statistically significant differences in the RAZ parameter of the QRS complex were revealed in high-frequency ECG of patients with hemodynamically significant and non-significant RCA stenosis. The RAZ sum in leads V1, V3R, V4R, V5R, V6R was 7.86±0.77 and 3.58±0.53, respectively, while in patients with no IHD signs, it equaled 1.87±0.43 (p=0.00001).The RMS value in patients with no IHD signs was 3.89±0.42, in patients with hemodynamically non-significant and significant RCA stenosis it equaled 3.51±0.34 and 2.73±0.24, respectively (p=0.008).The kurtosis value was statistically significantly higher in patients with hemodynamically significant stenosis (1.07±0.12), in contrast to those with hemodynamically non-significant stenosis and without IHD (0.78±0.05 and 0.64±0.03, respectively).An average correlation between the value of coronary stenosis and the sum of RAZ scores was found (r=0.66).However, RMS and kurtosis parameters correlate with the degree of RCA stenosis at a lower level.According to ROC analysis, the RAZ parameter showed better diagnostic results compared to RMS and kurtosis. Given the nonparametric nature of the available data, the prognostic capabilities of the studied parameters can be considered satisfactory as shown by the results of binary logistic regression. CONCLUSION: The RAZ parameter of high-frequency ECG in leads V1, V3R, V4R, V5R, V6R may serve as an additional diagnostic criterion for identifying the areas of myocardial ischemia associated with RCA stenosis in IHD patients.