THE EFFECT OF STATIN ADDED TO ANTIHYPERTENSIVE THERAPY ON ARTERIAL STIFFNESS IN HYPERTENSIVE PATIENTS AT HIGH CARDIOVASCULAR RISK

Background. Little is known about the effect of statins addition to standard antihypertensive therapy on blood pressure level and vascular stiffness in high-risk hypertensive patients.The aim of the study was to assess the dynamics of vascular stiffness in hypertensive patients of high or very high cardiovascular risk under the influence of rosuvastatin addition to combined two-component amlodipine and lisinopril antihypertensive therapy.Materials and methods. We investigated 60 hypertensive patients who were randomized into two groups: the 1st group received a fixed amlodipine/lisinopril combination, the 2nd one followed the same regimen of therapy with addition of 20 mg rosuvastatin. Mean office and ambulatory blood pressure as well as central aortic blood pressure and pulse wave velocity were evaluated in both groups before and after 24-week follow-up period.Results. At end of follow-up period the office and average daily blood pressure significantly decreased in both groups, with more prominent office diastolic blood pressure decline in the 2nd one. The central aortic blood pressure equally decreased in both groups. The augmentation index significantly reduced in both groups, mostly in the 2nd one. The carotid-femoral pulse wave velocity declined in both groups to the same extent. The carotid-radial pulse wave velocity decreased statistically only in the second group.Conclusions. Addition of rosuvastatin to a fixed amlodipine/lisinopril combination in high/very high cardiovascular risk hypertensive patients was accompanied by more pronounced decline of diastolic blood pressure and augmentation index, as well as significantly reduction of pulse wave velocity

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Clinical features of post-COVID-19 period. Results of the international register “Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)”. Data from 6-month follow-up

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period

Drug Correction of Vascular Remodeling in Patients with Hypertension: Results of 52-Week Prospective Study ARTERIA-AG

Aim. To study the long-term dynamics of vascular remodeling in patients with hypertension and high and very high cardiovascular risk when statin is added to antihypertensive therapy with a fixed combination of calcium antagonist and angiotensin converting enzyme (ACE) inhibitor.Material and methods. Hypertensive patients (n=75) with high and very high cardiovascular risk (age 51.5 [44;58] years) were included in the study. Patients were randomized into two groups. The first group (n=36) received a fixed combination of amlodipine and lisinopril in starting dose of 5/10 mg/day. The second group (n=39) received the same antihypertensive therapy and additionally rosuvastatin (20 mg/day). The follow-up period was 52 weeks. The effect of therapy on the following parameters was evaluated: level of office and average daily blood pressure (BP), central BP in the aorta, augmentation index (AIx), pulse wave velocity (PWV), endothelium-dependent brachial artery vasodilation, carotid intima-media complex thickness, carotid arteries plaque height, and blood lipid profile indicators.Results. A significant decrease in office and average daily BP was found in both groups: from 171.5 (152;194)/104.5 (97;112) to 140.0 (129;154)/87.0 (83;95) mm Hg and from 142.1 (135;153)/86.7 (83;97) to 124.6 (119;133)/76.5 (73;80) mm Hg, respectively, in the 1st group; from 169.5 (160;190)/103.5 (95;109) to 135.0 (125;141)/83.0 (77;88) mm Hg and from 139.9 (136;152)/86.2 (80;92) to 125.1 (118;134)/74.0 (70;81) mm Hg, respectively, in the 2nd group (p<0.001 for all changes). The frequency of reaching the target office BP level was higher in the 2nd group (p=0.031). Significant decrease in total cholesterol by 33.1% and low-density lipoprotein cholesterol by 50.0% was observed in the group 2. Central BP in the aorta decreased in both groups; the degree of central BP reduction did not differ significantly. AIx decreased from 36.5 (24;41)% to 25.0 (15;36)% (p=0.04) in the 1st group and from 36.0 (30;41)% to 24.0 (20;32)% in the 2nd group (p<0.0001) with a more pronounced decrease in AIx after 24 weeks of therapy (-4.8% and -9.4%, respectively, p=0.036). This trend continued at the end of the observation (-6.4% and -10.8%, respectively, p=0.08). Carotid-femoral and carotid-radial PWV decreased only in the 2nd group from 9.5 (8.2;10.7) to 8.3 (7.6;8.9) m/s (p=0.003) and from 9,6 (8.5;10.6) to 8.4 (7.9;9.3) m/s (p=0.01), respectively. A significant decrease in the thickness of the intima-media from 1.08 (1.0;1.2) to 1.02 (0.9;1.1) cm (p<0.0001) and the height of the plaque from 2.2 (2,2;1.7) to 2.1 (2.1;1.7) mm (p=0.001) was found in the 2nd group.Conclusion. Addition of rosuvastatin to the fixed combination of amlodipine and lisinopril in treatment of hypertensive patients with high and very high cardiovascular risk was accompanied by a more frequent (compared with amlodipine and lisinopril only) achievement of the target office BP level and more pronounced reduction in the following indicators: augmentation index, carotid-femoral and carotid-radial PWV, intima-media thickness, plaque height, total cholesterol and low density lipoprotein cholesterol blood levels

SMOKING STATUS AND EFFECTIVENESS OF ANTIHYPERTENSIVE VASODILATING

Aim. To compare antihypertensive effectiveness of carvedilol, nebivolol, and amlodipine in smokers and non-smokers with arterial hypertension (AH).Material and methods. The study included 130 patients with Stage 1–2 AH, aged 30–55 years, who were randomised into three treatment groups: carvedilol (n=56), nebivolol (n=44), and amlodipine (n=30). Each group was also divided into two subgroups of smokers and nonsmokers (never-smokers or ex-smokers who stopped smoking at least one year ago). At baseline and after 8 weeks of the treatment, the dynamics of office blood pressure (BP) levels, parameters of 24-hour BP monitoring, and lung function were compared across the subgroups.Results. After 8 weeks of the treatment, office BP levels reduced significantly and comparably in all subgroups. According to the results of 24-hour BP monitoring, smokers from the carvedilol group did not demonstrate any marked BP dynamics, in contrast to their non-smoking peers. Smokers treated with nebivolol demonstrated no reduction in mean 24-hour levels of systolic BP (SBP), with some reduction in mean 24-hour and mean daytime levels of diastolic BP (DBP), as well as a decrease in SBP and DBP variability. Amlodipine effectively reduced mean 24-hour BP levels in both smokers (by 10,0/8,0 mm Hg) and non-smokers (by 11,3/6,5 mm Hg), with similar dynamics of mean daytime SBP and DBP and mean nighttime SBP. Lung function parameters in smokers receiving amlodipine did not change, while the β-adrenoblocker treatment negatively affected these parameters in smokers. In the carvedilol group, smokers demonstrated a significant reduction in FEV1; in the nebivolol group, FEV1, FLC, and their ratio significantly decreased in smokers.Conclusion. In young and middle-aged smokers with AH, antihypertensive effects, as assessed with the 24-hour BP monitoring, were weaker for carvedilol (SBP and DBP) and nebivolol (DBP). Amlodipine was highly effective in both smokers and non-smokers. Therefore, amlodipine could be recommended as one of the first-choice medications for smoking patients with AH

EFFICACY AND SAFETY OF VASOACTIVE BETA-BLOCKERS IN ACUTE PHARMACOLOGICAL TEST IN HYPERTENSIVE PATIENTS OF DIFFERENT AGES

Aim. To evaluate a short-term efficacy and safety of nebivolol and carvedilol in hypertensive patients of different ages in acute pharmacological test (APT).Material and methods. 119 patients with arterial hypertension (HT) 2-3 degrees aged 33-89 y.o. were involved into the study. Patients were split into 2 groups according to age: young and middle-aged patients (30-59 y.o.); elderly and senile patients (≥60 y.o.). All patients were randomized for carvedilol (12.5 mg once daily) or nebivolol (5 mg once daily) therapy after wash-out period (3-10 days). Ambulatory blood pressure monitoring (ABPM) was performed one day before and one day after first drug taking and ABPM indices were compared.Results. APT with carvedilol and nebivolol in patients of young and middle age showed significant antihypertensive effect on systolic (-6.9 and -6.0 mm Hg, resp.), diastolic (- 4.6 and -4.7 mm Hg, resp.) and pulse (-1.7 and -1.4 mm Hg, resp.) blood pressure (BP). In patients of elderly and senile age the first daily dose of nebivolol did not have influence on systolic and pulse BP (-2.73 and +0.50 mm Hg, resp., p&gt;0.05), unlike carvedilol (-5.27 and -1.43 mm Hg, resp. p&lt;0.05). Carvedilol and nebivolol increased of hypotension time index for diastolic BP in younger (7,6 and 7,7%, resp.) and elder (11 and 8,2% resp.) patients.Conclusion. Carvedilol in initial dose reduces systolic and pulse BP more significantly than nebivolol does in hypertensive elderly and senile patients. Increase of hypotension time index for diastolic BP revealed for both drugs can limit their use in patients with initially low diastolic BP.</p

EFFICACY AND SAFETY OF VASOACTIVE BETA-BLOCKERS IN ACUTE PHARMACOLOGICAL TEST IN HYPERTENSIVE PATIENTS OF DIFFERENT AGES

Aim. To evaluate a short-term efficacy and safety of nebivolol and carvedilol in hypertensive patients of different ages in acute pharmacological test (APT).Material and methods. 119 patients with arterial hypertension (HT) 2-3 degrees aged 33-89 y.o. were involved into the study. Patients were split into 2 groups according to age: young and middle-aged patients (30-59 y.o.); elderly and senile patients (≥60 y.o.). All patients were randomized for carvedilol (12.5 mg once daily) or nebivolol (5 mg once daily) therapy after wash-out period (3-10 days). Ambulatory blood pressure monitoring (ABPM) was performed one day before and one day after first drug taking and ABPM indices were compared.Results. APT with carvedilol and nebivolol in patients of young and middle age showed significant antihypertensive effect on systolic (-6.9 and -6.0 mm Hg, resp.), diastolic (- 4.6 and -4.7 mm Hg, resp.) and pulse (-1.7 and -1.4 mm Hg, resp.) blood pressure (BP). In patients of elderly and senile age the first daily dose of nebivolol did not have influence on systolic and pulse BP (-2.73 and +0.50 mm Hg, resp., p&gt;0.05), unlike carvedilol (-5.27 and -1.43 mm Hg, resp. p&lt;0.05). Carvedilol and nebivolol increased of hypotension time index for diastolic BP in younger (7,6 and 7,7%, resp.) and elder (11 and 8,2% resp.) patients.Conclusion. Carvedilol in initial dose reduces systolic and pulse BP more significantly than nebivolol does in hypertensive elderly and senile patients. Increase of hypotension time index for diastolic BP revealed for both drugs can limit their use in patients with initially low diastolic BP