Nebivolol In Patients Research Articles

Advantages of long-term combination pharmacotherapy with a beta-blocker and eplerenone in patients with ST-segment elevation acute coronary syndrome

Aim.To conduct a comparative analysis of the effect of long-term pharmacotherapy (12 months) using a β-blocker (nebivolol) and its combination with eplerenone in patients after ST-segment elevation acute coronary syndrome (STE-ACS) with heart failure with mildly reduced ejection fraction (EF) (HFmrEF) on the structural and functional cardiac parameters.Material and methods. We examined 130 patients with STE-ACS and HFmrEF after successful myocardial revascularization by percutaneous coronary intervention. The mean age of patients was 53,6 [46;57] years. Ten patients withdrew from the study due to personal reasons. Subsequently, patients were randomly divided into 2 treatment groups as follows: 60 patients received nebivolol; 60 patients received nebivolol and eplerenone. Patients were examined at two stages: 1st day of the disease before PCI and 12 months later. All patients underwent a clinical examination, echocardiography, followed by assessment of left ventricular (LV) EF, LV end-diastolic volume index (EDVI), LV endsystolic volume index (ESVI), LV myocardial index (LVMI), LV wall motion score index (WMSI), the ratio of peak early diastolic flow over peak late diastolic flow (E/A), the ratio of early diastolic transmitral flow velocity to the mitral annular velocity (E/e´).Results.Twelve-month pharmacotherapy with nebivolol in patients after STE-ACS showed an increase in LVEF by 7,2% (p<0,05), a decrease in WMSI by 13,0% (p<0,05), an increase in the E/A ratio by 11,1% (р<0,05), decrease in the E/e’ ratio by 7,2% (р<0,05). LV EDVI increased by 4,6% (p>0,05). Twelve-month combined pharmacotherapy with nebivolol and eplerenone showed an increase in LVEF by 16,0% (p<0,01), a decrease in LV ESVI by 17,9% (p<0,05), and a decrease in WMSI by 26,7% (p<0,01), LVMI — by 23,8% (р<0,01). At the same time, LV EDVI decreased by 0,7% (p>0,05). The E/A ratio increased significantly by 22,2% (<0,01), E/e’ decreased by 29,6% (р<0,01). Comparative analysis also found that combination therapy had a more pronounced positive effect on LVEF (p<0,05), ESVI (p<0,05), WMSI (p<0,05), LVMI (p<0,01), as well as diastolic function in the form of a significant increase in E/A (p<0,05) and E/e’ (p<0,01), which recovered to normal values.Conclusion.The advantages of long-term combination pharmacotherapy of nebivolol and eplerenone in HFmrEF patients after STE-ACS on both structural and functional cardiac parameters were established.

Real-world efficacy and safety of nebivolol in Korean patients with hypertension from the BENEFIT KOREA study.

The efficacy and safety of nebivolol in patients with hypertension is well established, but its effect in Asian patients with essential hypertension in the real world has not been studied. Adult South Korean patients with essential hypertension, with or without comorbidities, were enrolled to participate in this prospective, single-arm, open, observational study; 3011 patients received nebivolol either as monotherapy or add-on therapy. Changes in SBP, DBP and heart rate (HR) at 12 and 24 weeks were evaluated. Subgroup analysis for BP changes in newly diagnosed (de novo) patients and those receiving other antihypertensives at study entry were also conducted. Nebivolol significantly decreased mean SBP and DBP at 12 and 24 weeks compared with baseline (P < 0.0001). A significant reduction in HR was also observed at 12 and 24 weeks (P < 0.0001). The reductions of SBP and DBP were notably greater when nebivolol was used as monotherapy in de novo patients (P < 0.0001) and as add-on therapy to existing antihypertensives (angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors and calcium channel blockers; P < 0.0001). Majority of the reported adverse events were mild; the most common adverse events were dizziness (1.3%), headache (1.0%) and dyspnea (0.9%). Despite the limitations associated with observational studies, this real-world study in Asian patients with essential hypertension with and without comorbidities, demonstrated the efficacy and safety of once daily nebivolol, either as monotherapy or add-on therapy. NCT03847350.SDC Callout: Video Abstract, http://links.lww.com/HJH/B172.

Effect of Low-Dose Nebivolol in Patients with Acute Myocardial Infarction: A Multi-Center Observational Study.

The optimal dose of beta blockers after acute myocardial infarction (MI) remains uncertain. We evaluated the effectiveness of low-dose nebivolol, a beta1 blocker and a vasodilator, in patients with acute MI. A total of 625 patients with acute MI from 14 teaching hospitals in Korea were divided into 2 groups according to the dose of nebivolol (nebistol®, Elyson Pharmaceutical Co., Ltd., Seoul, Korea): low-dose group (1.25 mg daily, n=219) and usual- to high-dose group (≥2.5 mg daily, n=406). The primary endpoints were major adverse cardiac and cerebrovascular events (MACCE, composite of death from any cause, non-fatal MI, stroke, repeat revascularization, rehospitalization for unstable angina or heart failure) at 12 months. After adjustment using inverse probability of treatment weighting, the rates of MACCE were not different between the low-dose and the usual- to high-dose groups (2.8% and 3.1%, respectively; hazard ratio: 0.92, 95% confidence interval: 0.38 to 2.24, p=0.860). The low-dose nebivolol group showed higher rates of MI than the usual- to high-dose group (1.2% and 0%, p=0.008). The 2 groups had similar rates of death from any cause (1.1% and 0.3%, p=0.273), stroke (0.4% and 1.1%, p=0.384), repeat PCI (1.2% and 0.8%, p=0.428), rehospitalization for unstable angina (1.2% and 1.0%, p=0.743) and for heart failure (0.6% and 0.7%, p=0.832). In patients with acute MI, the rates of MACCE for low-dose and usual- to high-dose nebivolol were not significantly different at 12-month follow-up.

Influence of beta-blockers on mechanical dyssynchrony and cardiac remodeling in patients with ischemic chronic heart failure in the setting of revascularization

Introduction: Diastolic dysfunction (DD) and cardiac dyssynchrony (DS) are involved in the progression of chronic heart failure (CHF). A comparative analysis was conducted of the effect of a 6-month course of nebivolol and bisopr­olol on DD, DS and metalloproteinase-9 (MMP-9) level in patients with ischemic chronic heart failure with preserved ejection fraction (HFpEF) and with midrange ejection fraction (HFmrEF), as well as in patients with comorbid type 2 diabetes mellitus (T2DM) in the setting of coronary artery bypass grafting (CABG) after 6 months of therapy.&#x0D; Materials and methods: The study included 308 patients with CHF FC I-II, left ventricular ejection fraction (LVEF) &gt;40%, who had undergone CABG. The average dose of nebivolol in patients with DS 6 months later was 5.1±2.6 mg/day, and bisoprolol – 4.9±2.4 mg/day. Echocardiography (EchoCG) and evaluation of MMP-9 in blood plasma were performed. Mechanical myocardial asynchrony was determined by calculating the standard deviation of time to peak systolic myocardial velocity (TS-SD) and maximum segment delay (TS12) using a 6-basal and-midsegment model.&#x0D; Results and discussion: MMP-9 level in patients with CHF before CABG was 4.7 times higher (p&lt;0.001). MMP-9 correlated with LVEF (r=-0.60, p&lt;0.001), E/A (r=-0.49, p&lt;0.001), DT (r=0.43, p&lt;0.001), E` (r=-0.58, p&lt;0.001) and DS: TS12 (r=0.54, p&lt;0.001), TS-SD (r=0.49, p&lt;0.001). The six-month course of nebivolol improved the values of DS: TS12 – by 30% (p&lt;0.001), TS-SD – by 32% (p&lt;0.01) and reduced the MMP-9 level by 11% (p&lt;0.001). In patients with HFmrEF without DS nebivolol increased E/A by 19% (p&lt;0.01), E` – by 16% (P&lt;0.05), and decreased E/E’ by 9% (p&lt;0.05), DT – by 12% (p&lt;0.05). In patients with HFpEF and DM2, nebivolol reduced TS12 by 37% (p&lt;0.01), TS-SD – by 29% (p&lt;0.05) and MMP-9 – by 13% (p&lt;0.05).&#x0D; Conclusion: The positive effect of nebivolol on the DS, DD of the LV in patients with HFpEF, HFmrEF and with comorbid type 2 diabetes mellitus. The six-month course of nebivolol decreased the MMP-9 level in patients with ischemic CHF after CABG, including patients with T2DM.

The correlation between endothelial dysfunction and the treatment with nebivolol in patients with diabetes and angina pectoris undergoing coronary angioplasty

Aim: Evaluation the level of biomarker of endothelial dysfunction-nitric oxide (NO) and its evolution under treatment with nebivolol in patients with diabetes and stable angina pectoris (APS) undergoing coronary angioplasty (PCI).

The dynamics of the inflammatory status biomarker under the treatment with nebivolol in patients undergoing coronary angioplasty depending on the stent’s length

Aim: Evaluation of nebivolol effects on the level of inflammatory biomarker hs-CRP in patients exposed to percutaneous coronary interventions (PCI) depending on the length of the stent.

THE REGULATORY ADAPTIVE STATUS IN TESTING EFFICIENCY OF THERAPY WITH BISOPROSOL AND NEBIVOLOL IN PATIENTS WITH PAROXYSMAL SUPRA-VENTRICULAR TACHYCARDIA AND HYPERTENSION DISEASE

The purpose. To compare efficiency of application of Bisoprosol and Nebivolol in patients with paroxysmal supra-ventricular tachycardia against the background of hypertension disease considering their effect on regulatory adaptive status.Materials and method. The sampling consisted of 50 patients with paroxysmal supra-ventricular tachycardia against the background of hypertension disease stage I-II randomized to two groups for treatment with Bisoprosol (3,9±1,3 mg per day, n=25) or Nebivolol (3,8±1,2 mg per day, n=25). The combined therapy provided Lisinopril (7,5±2,5 and 7,4±2,4 mg per day)and in case of indications - Atorvastatin (15,4±3,8 mg per day, n=9 и 15,9±4,1 mg per day, n=9) and acetylsalicylic acid (91,5±14,7 mg per day, n=12 и 93,1±16,2 mg per day, n=14) correspondingly. Initially and after 6 months quantitative evaluation of regulatory adaptive status (by means of testing cardio-respiratory synchronism), echocardiography, triplex scanning of brachiocephalic arteries, six minutes walk testing, tredmilmetry, day monitoring of arterial pressure and electrocardiograms, subjective evaluation of life quality were implemented.Results. It is established that both schemes of combined therapy had comparable effect, controlled arterial hypertension, ameliorated functional and structural condition of heart. The application of Nebivolol positively effected regulatory adaptive status and in a greater degree increases tolerance to physical load and ameliorated life quality.Conclusion. The application of Nebivolol as compared with Bisoprosol in combined therapy is more preferable in patients with paroxysmal supra-ventricular tachycardia against the background of hypertension disease stage II-III due to positive effect of regulatory adaptive status.

Decreased risk of ventricular arrhythmias with treatment of nebivolol in patients with coronary slow flow

Coronary slow-flow (CSF) is an angiographic phenomenon characterised by delayed opacification of vessels in the absence of any evidence of obstructive epicardial coronary disease. QT interval dispersion (QTD) reflects regional variations in ventricular repolarisation and cardiac electrical instability and has been reported to be longer in patients with CSF. To examine QT duration and dispersion in patients with CSF and the effects of nebivolol on these parameters. The study population included 67 patients with angiographically proven normal coronary arteries and CSF, and 38 patients with angiographically proven normal coronary arteries without associated CSF. The patients were evaluated with 12-lead electrocardiography, and echocardiography before and three months after treatment with nebivolol. Compared to the control group QTcmax and QTcD were significantly longer in patients with CSF (p = 0.036, p = 0.019, respectively). QTcD significantly correlated with the presence of CSF (r = 0.496, p < 0.001). QTcmax (p = 0.027), QTcD (p = 0.002), blood pressure (p = 0.001), and heart rate (p < 0.001) values significantly decreased after treatment with nebivolol. Coronary slow flow is associated with increased QTD. Nebivolol reduced increased QTD in patients with CSF after three months.

Acute and 14-Day Hepatic Venous Pressure Gradient Response to Carvedilol and Nebivolol in Patients With Liver Cirrhosis

Alternative drug therapies are needed for the treatment of portal hypertension. The aim of this randomized study was to evaluate and compare the effects of carvedilol and nebivolol on the hepatic venous pressure gradient (HVPG) response in the patients with liver cirrhosis. In total, 20 cirrhotic patients were randomized into 2 groups and treated with carvedilol (n=10) or nebivolol (n=10). HVPG was measured at baseline, 60 minutes after the administration of carvedilol (25 mg) or nebivolol (5 mg), and after 14 days of carvedilol (25 mg) or nebivolol (5 mg) administered daily. RESULTS. Carvedilol significantly reduced HVPG from 22.2 mm Hg (SD, 4.4) to 15.2 mm Hg (SD, 3.7) after 60 minutes and to 16.4 mm Hg (SD, 2.9) after 14 days (P<0.01). Nebivolol reduced HVPG from 19.7 mm Hg (SD, 2.5) to 15.7 mm Hg (SD, 2.6) and 16.7 mm Hg (SD, 3.2), respectively (P<0.02). Carvedilol effectively decreased HVPG in a greater proportion of the patients after an acute probe (88% vs. 57%) and after 14 days of the treatment (88% vs. 28%, P<0.05) in comparison with nebivolol. Carvedilol and nebivolol reduce HVPG in cirrhotic patients; however, the effect of carvedilol on the HVPG reduction might be superior to that of nebivolol, especially after 14 days of treatment.

Placebo Effect and Efficacy of Nebivolol in Patients with Hypertension not Controlled with Lisinopril or Losartan: A Phase IV, Randomized, Placebo-Controlled Trial

Most patients with hypertension require more than one antihypertensive to achieve blood pressure (BP) control. The purpose of this trial was to assess the efficacy and tolerability of add-on nebivolol, a vasodilatory β-blocker, in patients with untreated or poorly controlled hypertension, receiving stable therapy with lisinopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin II receptor blocker). This was a phase IV double-blind, placebo-controlled trial conducted from August 2008 to March 2010 (ClinicalTrials.gov identifier: NCT00734630). Patients entered a 2-week, single-blind, placebo-only washout phase, followed by a 3- to 4-week open-label lead-in phase (lisinopril, 10-20 mg/day, or losartan, 50-100 mg/day), and a 12-week randomized, double-blind add-on treatment phase with placebo or nebivolol (5-40 mg/day). This study was conducted at 76 outpatient centers in the United States. Participants were men and women aged 18-85 years with a diagnosis of primary hypertension and seated trough systolic BP (SBP) at screening in the range of 170-200 mmHg if untreated, 155-180 mmHg if taking 1 antihypertensive medication, or 140-170 mmHg if taking 2 antihypertensive medications. The intervention was 12 weeks' treatment with nebivolol 5-40 mg/day added to a background therapy of lisinopril 10-20 mg/day or losartan 50-100 mg/day. Primary and secondary efficacy parameters were changes from baseline in seated trough cuff SBP and diastolic BP (DBP) at Week 12, respectively. Tolerability was assessed by monitoring treatment-emergent adverse events (TEAEs). A total of 491 patients were randomized to receive nebivolol (n=258) or placebo (n=233). Efficacy analyses were conducted for 256 nebivolol and 232 placebo patients (intent-to-treat population); completion rates were 88.8% and 85.8%, respectively. Mean baseline SBP/DBP values were 163.1/98.2 mmHg (nebivolol) and 162.4/96.8 mmHg (placebo). Nebivolol was associated with a non-significant mean±SD reduction in SBP (-10.1±16.9 mmHg) versus placebo (-7.3±15.9 mmHg, P=0.093) and significant mean DBP reduction (-7.8±10.1 mmHg vs -3.5±10.6 mmHg, P<0.001). Subgroup analysis suggested a significant effect on DBP for patients receiving background losartan treatment (-8.1±9.2 mmHg vs -3.1±9.4 mmHg, P<0.001), but not for those receiving lisinopril (-7.6±10.8 mmHg vs -3.8±11.6 mmHg, P=0.076). A total of 28% nebivolol-treated and 22% placebo-treated patients reported a TEAE, the most frequent being upper respiratory tract infection (4.3% and 2.1%, respectively), bradycardia (2.7% and 0%), headache (2.3% and 2.1%), and nasopharyngitis (2.3% and 0.9%). These data suggest that nebivolol, when added to lisinopril or losartan, results in an additional BP reduction; however, only the effect on DBP reached statistical significance. A subanalysis suggests that the effect on DBP may be stronger in losartan-treated than lisinopril-treated patients. A relatively strong placebo effect may limit data interpretation. Nebivolol was well tolerated, as there was no difference in TEAEs between nebivolol and placebo. This trial (NCT00734630) was funded by Forest Laboratories, Inc.

Lowering blood pressure with β-blockers in peripheral artery disease: the importance of comorbidity

Lowering blood pressure with β-blockers in peripheral artery disease: the importance of comorbidity

A COMPARATIVE STUDY OF EFFICACY AND TOLERABILITY OF ANTIANGINAL DRUGS OF DIFFERENT GROUPS — NITROVASODILATATOR (ISOSORBIDE-5-MONONITRATE SUSTAINED RELEASE) AND BETA-BLOCKER WITH VASODILATING ACTION (NEBIVOLOL) — IN PATIENTS WITH STABLE ANGINA

Aim. To compare the efficacy and safety of the slow-release isosorbide-5-mononitrate and of the nebivolol in patients with stable angina. Material and Methods. Patients (n=19) with ischemic heart disease (stable angina) were enrolled into randomized, double-blind, placebo-controlled, crossover study. They alternatively received nebivolol 5 mg QD or slow-release isosorbide-5-mononitrate 50 mg QD. The drug efficacy was assessed by changes in symptoms, angina attack number , sublingual nitroglycerin need, and treadmill test duration. Results. Patients treated with isosorbide-5-mononitrate shown significant increase in heart rate (HR) at rest in all time check-points in comparison with patients receiving placebo. HR significantly decreased 2 hours after nebivolol intake both single one and after 30 days of treatment (p&lt;0.001). Duration of treadmill exercise significantly increased (vs placebo) 2 hours after a single intake of both isosorbide-5-mononitrate (454.3±37.1 vs 310.6±13.3 s; p &lt;0.001) and nebivolol (428.6±33.3 vs 310.6±13.3 s; p&lt;0.01). In one month of treatment isosorbide- 5-mononitrate and nebivolol reduced a number of angina episodes vs placebo (5.6±2.1 and 4.3±1.4, respectively , vs 8.6±2.4 episodes per month; p&lt;0.05), the need for nitroglycerin (5.5±2.6 and 3.1±1.2, respectively , vs 6.7±2.2 sublingual tablets/month; p&gt;0.05). No significant differences of these indicators were found between studied drugs. Conclusion. Nebivolol 5 mg daily is not inferior to slow-release isosorbide-5-mononitrate 50 mg daily in antianginal efficacy , significantly reduces HR, and much less causes headache and other side effects.

A COMPARATIVE STUDY OF EFFICACY AND TOLERABILITY OF ANTIANGINAL DRUGS OF DIFFERENT GROUPS — NITROVASODILATATOR (ISOSORBIDE-5-MONONITRATE SUSTAINED RELEASE) AND BETA-BLOCKER WITH VASODILATING ACTION (NEBIVOLOL) — IN PATIENTS WITH STABLE ANGINA

Aim. To compare the efficacy and safety of the slow-release isosorbide-5-mononitrate and of the nebivolol in patients with stable angina. Material and Methods. Patients (n=19) with ischemic heart disease (stable angina) were enrolled into randomized, double-blind, placebo-controlled, crossover study. They alternatively received nebivolol 5 mg QD or slow-release isosorbide-5-mononitrate 50 mg QD. The drug efficacy was assessed by changes in symptoms, angina attack number , sublingual nitroglycerin need, and treadmill test duration. Results. Patients treated with isosorbide-5-mononitrate shown significant increase in heart rate (HR) at rest in all time check-points in comparison with patients receiving placebo. HR significantly decreased 2 hours after nebivolol intake both single one and after 30 days of treatment (p 0.05). No significant differences of these indicators were found between studied drugs. Conclusion. Nebivolol 5 mg daily is not inferior to slow-release isosorbide-5-mononitrate 50 mg daily in antianginal efficacy , significantly reduces HR, and much less causes headache and other side effects.

The course of chronic obstructive lung disease with co-existing chronic heart failure in patients treated with nebivolol

Summary. The present study was aimed at investigation of clinical course of co-existing chronic heart failure (CHF) and COPD and influence of a selective β1-blocker (BB) nebivolol on clinical course of COPD and respiratory function in patients with ischemic CHF. Results showed that a combined therapy of CHF including nebivolol significantly increased effectiveness of CHF treatment irrespective of presence of COPD and did not worsen bronchial obsrtuction. Administration of Nebivolol in patients with coexisting CHF and COPD under the standard therapy did not reduce airflow parameters.

Influence of Diabetes Mellitus and Hyperglycemia on Prognosis in Patients ≥70 Years Old With Heart Failure and Effects of Nebivolol (Data from the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure [SENIORS

The beneficial effects of beta blockers in younger patients with heart failure (HF) due to systolic dysfunction are well established. However, data from patients > or =70 years old with diabetes mellitus and HF are lacking. The Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS] tested the efficacy of the vasodilator beta blocker nebivolol in patients > or =70 years old with HF and impaired or preserved left ventricular ejection fraction. In the present analysis, we evaluated the association between diabetes mellitus and baseline glucose levels on the primary outcome (all-cause mortality and cardiovascular hospitalization) and secondary end points, including all-cause mortality, cardiovascular hospitalizations, and cardiovascular mortality. Of 2,128 patients, 555 (26.1%) had diabetes mellitus. Of the 555 patients with diabetes mellitus, 223 (40.2%) experienced the primary end point compared to 484 (30.8%) of the 1,573 nondiabetic patients (p <0.001). For the nondiabetic patients, the rate of the primary outcome for placebo compared to nebivolol was 33.7% for the placebo group and 27.8% for the nebivolol group (hazard ratio 0.78, 95% confidence interval 0.65 to 0.93; p = 0.006). In the diabetic subset, the rate was 40.3% for the placebo group and 40.1% for the nebivolol group (hazard ratio 1.04, 95% confidence interval 0.80 to 1.35, p = 0.773). The subgroup interaction p value was 0.073. The baseline glucose levels in the nondiabetic patients did not significantly affect the outcomes. The effect of diabetes mellitus on outcome was independent of the left ventricular ejection fraction and was most pronounced in those with HF due to a nonischemic etiology. In conclusion, in patients > or =70 years old with HF, diabetes mellitus was associated with a worse prognosis. Nebivolol was less effective in the patients with diabetes and HF than in those with HF but without diabetes who were > or =70 years old.

Nebivolol Efficacy and Safety in Patients with Stage I‐II Hypertension

Nebivolol is a novel, beta(1)-adrenergic receptor blocker with vasodilatory properties mediated through activation of the L-arginine/nitric oxide pathway. This multicenter, double-blind, parallel-group, placebo-controlled study investigated the antihypertensive efficacy and safety of nebivolol in patients with stage I through stage II hypertension (sitting diastolic blood pressure [SiDBP] > or = 95 mm Hg and < or = 109 mm Hg). A total of 811 patients were randomized to placebo or nebivolol 5 mg, 10 mg, or 20 mg once daily for 12 weeks. The primary efficacy endpoint was the reduction in mean trough SiDBP from baseline. At study end, the least squares mean reductions in trough SiDBP from baseline with nebivolol 5 mg, 10 mg, and 20 mg were - 7.8 mm Hg, - 8.5 mm Hg, and - 9.1 mm Hg, respectively, compared with - 4.6 mm Hg for placebo (P = .002 for nebivolol 5 mg, P<.001 for nebivolol 10 mg and 20 mg, vs placebo). Nebivolol treatment also produced reductions in trough sitting systolic blood pressure; however, only the 20 mg dose was statistically significant compared with placebo (-6.7 mm Hg vs - 0.4 mm Hg; P<.001). Response rates (defined as an average trough SiDBP < 90 mm Hg or a decrease by > or = 10 mm Hg from baseline at the end of the study) ranged from 66.0% to 68.9% with nebivolol 5-20 mg, compared with 49.3% with placebo (P< or =.009). Nebivolol 5 mg and 10 mg doses were well tolerated, with an overall adverse event incidence comparable to placebo. Once-daily nebivolol is an effective antihypertensive agent in patients with stage I-II hypertension.

Efficacy and tolerability of nebivolol monotherapy by baseline systolic blood pressure: A retrospective analysis of pooled data from two multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging studies in patients with mild to moderate essential hypertension

Background: In clinical studies, nebivolol at doses of 2.5 to 40 mg once daily was associated with significant decreases in systolic blood pressure (SBP) and diastolic BP (DBP) in patients with hypertension and was well tolerated. Objectives: This post hoc analysis of pooled data from 2 previously published registration studies was conducted to further evaluate the antihypertensive efficacy and tolerability of nebivolol in patients with mild to moderate (stage 1–2) hypertension. Methods: The 2 trials were similarly designed multicenter, 12-week, randomized, double-blind, placebocontrolled, parallel-group, dose-ranging studies in patients 18 years of age and older with stage 1 or 2 hypertension (SBP 140–159 mm Hg and/or DBP 90–99 mm Hg [stage 1] or SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg [stage 2]). The primary efficacy end point of the 2 studies was the change from baseline in mean trough SiDBP at week 12. A secondary end point was the change from baseline to week 12 in mean trough sitting SBP (SiSBP). The present analysis included only patients who received nebivolol 5, 10, or 20 mg (the doses were common to both studies) or placebo, including analyses stratified by baseline SBP, although DBP represented a criterion for entry into the studies. Baseline SBP stratification levels were 140 to 149 mm Hg, 150 to 159 mm Hg, 160 to 169 mm Hg, and 170 to 179 mm Hg. For the tolerability analysis, the prevalences of treatment-emergent adverse events (AEs) were compared between the 3 nebivolol dose groups and the placebo group. Results: Of the 1716 randomized patients who received study medication in the 2 trials, data from 1385 patients were included in this pooled analysis (759 men, 626 women; median age, ~54 years; 13.6% black). Mean (SD) baseline SiSBP and SiDBP values were 151.9 to 152.7 and 99.2 to 99.5 mm Hg, respectively. Reductions from baseline in trough SiSBP were −10.8 (13.5), −10.7 (14.7), and −12.4 (15.5) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with −4.5 (13.4) mm Hg with placebo (all, P < 0.001). Reductions from baseline in trough SiDBP (the primary end point) were −9.8 (7.9), −10.5 (8.2), and −11.1 (8.6) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with −5.1 (8.1) mm Hg with placebo (all, P < 0.001). In a subgroup of 1227 patients stratified by baseline SBP, the reductions in SBP and DBP were significantly greater ( P < 0.03 and P < 0.001, respectively) with nebivolol at each dose compared with placebo in those with baseline SBP of 140 to 149 mm Hg and 150 to 159 mm Hg (the lowest 2 baseline strata); in the highest 2 baseline strata (SBP 160–169 and 170–179 mm Hg), the reductions in SBP with nebivolol 5 mg and nebivolol 20 mg in the 160 to 169-mm Hg baseline SBP stratum and in DBP with nebivolol 20 mg in the 170 to 179-mm Hg baseline stratum were significantly greater ( P < 0.03) compared with placebo. The most common AE in the nebivolol 5−, 10−, and 20-mg groups and the placebo group was headache (36/409 [8.8%], 25/410 [6.1%], 27/410 [6.6%], and 10/156 [6.4], respectively), fol-lowed by fatigue (9/409 [2.2%], 10/410 [2.4%], 25/410 [6.1%], and 3/156 [1.9%]) and dizziness (6/409 [1.5%], 9/410 [2.2%], 15/410 [3.7%], and 4/156 [2.6%]). Conclusion: The present analysis of pooled data from 2 previously published registration studies found that nebivolol was associated with significant reductions in BP compared with placebo in these patients with stage 1 or 2 hypertension, with a tolerability similar to that of placebo.

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>0.05), unlike carvedilol (-5.27 and -1.43 mm Hg, resp. p<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.

Efficacy of Nebivolol on Flow-Mediated Dilation in Patients With Slow Coronary Flow

Slow coronary flow (SCF) is the phenomenon of slow progression of angiographic contrast in the coronary arteries in the absence of stenosis in the epicardial vessels in some patients presenting with chest pain. There are no definite treatment modalities for patients with SCF. Our aim was to investigate the efficacy of nebivolol in patients with slow coronary flow by monitoring its effects on endothelial function and different markers of inflammation. Forty-two patients (16 females, 26 males; mean age, 55 +/- 10) with slow coronary flow (SCF) were included in the study. After baseline assessment, the patients were administered nebivolol 5 mg once daily. After 12 weeks of nebivolol therapy, the biochemical and ultrasonographic examinations were repeated. Chest pain relief was detected in 38 patients after treatment (90%). Systolic and diastolic blood pressure and high sensitive CRP were significantly decreased after nebivolol therapy. Among brachial artery dilation variables that reflect endothelial function, basal resistive index (RI), post-flow mediated dilation RI, and post-nitrate mediated dilation RI were significantly decreased after therapy. Nebivolol is effective at improving endothelial function in patients with SCF. It controls chest pain, decreases CRP, and has favorable effects on brachial artery dilation variables in patients with coronary slow flow.

The influence of CYP2D6 phenotype on the clinical response of nebivolol in patients with essential hypertension

* The variability in drug metabolism has been recognized as an important factor in the occurrence of adverse effects or lack of therapeutic efficacy. * The metabolism of the third-generation beta(1)-receptor antagonist nebivolol has been shown to be highly dependent on cytochrome P450 2D6 enzymatic activity in preclinical studies. * This paper assesses the role of a cytochrome P450 2D6 gene defect on the antihypertensive response to nebivolol in a clinical setting. * Despite significant differences in drug disposition, the chronic administration of nebivolol produced similar efficacy and tolerability in hypertensive patients either characterized as poor or extensive metabolizers of the drug. * The study offers insight into the relative contribution of nebivolol enantiomers in systemic blood pressure control. Nebivolol is a beta(1)-adrenergic receptor antagonist with vasodilating properties used in the treatment of hypertension. It is administered as a racemic mixture (D- and L-nebivolol) and is highly metabolized by the cytochrome P-450 2D6 (CYP2D6). The purpose of this study was to determine the role of CYP2D6 phenotypes on the efficacy and tolerability of nebivolol during chronic administration to patients with essential hypertension. Two hundred and eighteen patients were genotyped and phenotyped for CYP2D6 activity, allowing to find and match 14 poor metabolizers (PMs) with 23 extensive metabolizers (EMs). Patients took rac-nebivolol 5 mg daily for 12 weeks. Blood pressure (BP), heart rate, adverse events, plasma levels of the two enantiomers D- and L-nebivolol and their corresponding hydroxymetabolites were assessed. The metabolic disposition of nebivolol was enantioselective and highly influenced by CYP2D6 phenotypes. Mean steady-state plasma concentrations of D- and L-nebivolol were 10- and 15-fold greater in PMs than in EMs, respectively (P < 0.0001). Despite these differences in the pharmacokinetics of nebivolol, EMs and PMs displayed similar BP responses. Mean reductions in sitting systolic and diastolic BPs were -11/-10 +/- 9/4 mmHg in EMs and -11/-9 +/- 10/5 mmHg in PMs. Side-effects were mild to moderate and not different between groups. Polymorphisms in the gene encoding CYP2D6 significantly influenced the metabolism of nebivolol, but not its antihypertensive efficacy and tolerability. The similar clinical response between EMs and PMs could be explained by the contribution of active hydroxylated metabolites of nebivolol to its antihypertensive actions in EMs.