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1.
Diltiazem versus metoprolol for the management of atrial fibrillation: A systematic review and meta-analysis.
Jafri, SH, Xu, J, Warsi, I, Cerecedo-Lopez, CD
The American journal of emergency medicine. 2021;:323-327
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Effect of plasma MicroRNA on antihypertensive response to beta blockers in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies.
Solayman, MH, Langaee, TY, Gong, Y, Shahin, MH, Turner, ST, Chapman, AB, Gums, JG, Boerwinkle, E, Beitelshees, AL, El-Hamamsy, M, et al
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2019;:93-98
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Abstract
β-blockers show variable efficacy as antihypertensives. Herein, we evaluated plasma miRNAs as biomarkers for defining antihypertensive response to β-blockers. Expression of 22 β-blocker pharmacodynamics-related miRNAs was assessed in baseline plasma samples from 30 responders and 30 non-responders to metoprolol from the PEAR-2 study (Discovery). Logistic regression was performed to identify miRNAs significantly associated with metoprolol response. Those miRNAs were profiled in baseline plasma samples from 25 responders and 25 non-responders to atenolol from the PEAR study (validation). In discovery, miR-101, miR-27a, miR-22, miR-19a, and let-7e were significantly associated with metoprolol response (P = 0.01, 0.017, 0.025, 0.025, and 0.04, respectively). In validation, miR-19a was significantly associated with atenolol response (P = 0.038). Meta-analysis between PEAR-2 and PEAR revealed significant association between miR-19a (P = 0.004), miR-101 (P = 0.006), and let-7e (P = 0.012) and β-blocker response. Hence, miR-19a, miR-101, and let-7e, which regulate β1-adrenergic receptor and other β-blocker pharmacodynamics-related genes, may be biomarkers for antihypertensive response to β-blockers.
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3.
Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension.
Juraschek, SP, Appel, LJ, Miller, ER
American journal of hypertension. 2017;(9):871-875
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Abstract
BACKGROUND There is little evidence guiding selection of nondiuretic, antihypertensive agents with a goal of lowering uric acid (SUA) and minimizing gout risk. METHODS In the African American Study of Kidney Disease and Hypertension (AASK) trial, African Americans with chronic kidney disease were randomly assigned to metoprolol (a beta-blocker), ramipril (an angiotensin-converting enzyme inhibitors [ACEi]), or amlodipine (a dihydropyridine calcium-channel blocker). SUA was measured at baseline and 12 months. Gout-related hospitalizations were based on ICD9 codes. Gout-related medication use (GRMs) was based on active prescriptions of allopurinol, colchicine, or probenecid during the baseline visit of the AASK cohort phase. We examined the effect of drug assignment on 12-month SUA (linear regression), gout-related hospitalization (Cox regression), and GRM (logistic regression). RESULTS Of the 630 participants, 40% were female with a mean age of 55 years (SD, 10), mean SUA of 8.2 mg/dl (2.0), and mean serum creatinine of 1.8 mg/dl (0.6). After 12 months, metoprolol increased SUA by 0.3 mg/dl, while ramipril or amlodipine had no effect on SUA. Compared to ramipril, metoprolol significantly increased 12-month SUA (0.40; 0.10, 0.70 mg/dl; P = 0.009), nonsignificantly increased risk of gout-related hospitalization (hazard ratio: 3.87; 0.82, 18.26; P = 0.09), and significantly increased the odds of GRM (odds ratio: 1.62; 1.03, 2.54; P = 0.04). While metoprolol was associated with a higher 12-month SUA compared with amlodipine (0.57; 0.18, 0.95; P = 0.004), there was no difference in gout-related hospitalizations or GRM. CONCLUSIONS Metoprolol increased SUA and GRM in African American adults. Health professionals treating patients with kidney disease at risk for gout should avoid metoprolol and possibly consider an ACEi. CLINICAL TRIALS REGISTRATION Trial Number NCT00582777.
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Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure.
Stauffer, BL, Dow, CA, Diehl, KJ, Bammert, TD, Greiner, JJ, DeSouza, CA
Journal of the American Heart Association. 2017;(11)
Abstract
BACKGROUND Vascular endothelial fibrinolytic function is impaired in adults with prehypertension and hypertension and plays a mechanistic role in the development of atherothrombotic events. The influence of β-blockers on endothelial fibrinolysis is unknown. This study compared the effects of chronic nebivolol and metoprolol treatment on endothelial tissue-type plasminogen activator (t-PA) release in adults with elevated blood pressure (BP). METHODS AND RESULTS Forty-four middle-aged adults (36% women) with elevated BP completed a 3-month, double-blind, randomized, placebo-controlled trial comparing nebivolol (5 mg/d), metoprolol succinate (100 mg/d), and placebo. Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside before and after each intervention. In a subset, the dose-response curves to bradykinin and sodium nitroprusside were repeated with a coinfusion of the antioxidant vitamin C. At baseline, resting BP and endothelial t-PA release were comparable between the 3 groups. BP decreased to a similar extent (≈10 mm Hg) in the nebivolol- and metoprolol-treated groups. There was a substantial increase (≈30%; P<0.05) in the capacity of the endothelium to release t-PA following chronic treatment with nebivolol but not metoprolol or placebo. Mitigating oxidant stress with vitamin C coinfusion potentiated t-PA release (90%; P<0.05) at baseline in all groups. However, after the intervention, t-PA release was unchanged by vitamin C coinfusion in the nebivolol group only. CONCLUSIONS Nebivolol but not metoprolol improves endothelial t-PA release in adults with elevated BP. This may be an important vascular benefit of nebivolol. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01595516.
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Early Intravenous Beta-Blockers in Patients With ST-Segment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Intervention.
Roolvink, V, Ibáñez, B, Ottervanger, JP, Pizarro, G, van Royen, N, Mateos, A, Dambrink, JE, Escalera, N, Lipsic, E, Albarran, A, et al
Journal of the American College of Cardiology. 2016;(23):2705-2715
Abstract
BACKGROUND The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established. OBJECTIVES This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing the effect of early IV beta-blockers before PPCI in a general ST-segment elevation myocardial infarction (STEMI) population. METHODS STEMI patients presenting <12 h from symptom onset in Killip class I to II without atrioventricular block were randomized 1:1 to IV metoprolol (2 × 5-mg bolus) or matched placebo before PPCI. Primary endpoint was myocardial infarct size as assessed by cardiac magnetic resonance imaging (CMR) at 30 days. Secondary endpoints were enzymatic infarct size and incidence of ventricular arrhythmias. Safety endpoints included symptomatic bradycardia, symptomatic hypotension, and cardiogenic shock. RESULTS A total of 683 patients (mean age 62 ± 12 years; 75% male) were randomized to metoprolol (n = 336) or placebo (n = 346). CMR was performed in 342 patients (54.8%). Infarct size (percent of left ventricle [LV]) by CMR did not differ between the metoprolol (15.3 ± 11.0%) and placebo groups (14.9 ± 11.5%; p = 0.616). Peak and area under the creatine kinase curve did not differ between both groups. LV ejection fraction by CMR was 51.0 ± 10.9% in the metoprolol group and 51.6 ± 10.8% in the placebo group (p = 0.68). The incidence of malignant arrhythmias was 3.6% in the metoprolol group versus 6.9% in placebo (p = 0.050). The incidence of adverse events was not different between groups. CONCLUSIONS In a nonrestricted STEMI population, early intravenous metoprolol before PPCI was not associated with a reduction in infarct size. Metoprolol reduced the incidence of malignant arrhythmias in the acute phase and was not associated with an increase in adverse events. (Early-Beta blocker Administration before reperfusion primary PCI in patients with ST-elevation Myocardial Infarction [EARLY-BAMI]; EudraCT no: 2010-023394-19).
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Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol.
Neuman, RB, Hayek, SS, Poole, JC, Rahman, A, Menon, V, Kavtaradze, N, Polhemus, D, Veledar, E, Lefer, DJ, Quyyumi, AA
Journal of clinical hypertension (Greenwich, Conn.). 2016;(3):223-31
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Abstract
Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective β1 -antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12-week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-N(G) -monomethylarginine (L-NMMA) and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P<.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise-induced vasodilation with nebivolol compared with metoprolol in AAs with hypertension.
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Ivabradine in Combination with Metoprolol Improves Symptoms and Quality of Life in Patients with Stable Angina Pectoris: A post hoc Analysis from the ADDITIONS Trial.
Werdan, K, Ebelt, H, Nuding, S, Höpfner, F, Stöckl, G, Müller-Werdan, U, ,
Cardiology. 2016;(2):83-90
Abstract
OBJECTIVES Elevated heart rate can increase myocardial oxygen demand and reduce myocardial perfusion, provoking myocardial ischemia and angina symptoms. We evaluated adding ivabradine to the therapy of patients on metoprolol. METHODS ADDITIONS (prActical Daily efficacy anD safety of Procoralan® In combinaTION with betablockerS) was a multicenter, 4-month, noninterventional, prospective, open-label trial that involved stable-angina patients. Along with metoprolol, patients received ivabradine (5 or 7.5 mg, b.i.d.). We investigated the effect of ivabradine on heart rate, angina attacks, nitrate consumption, quality of life (QoL) and tolerability as well as the influence of baseline heart rate. RESULTS Heart rate fell by 19.7 ± 11.2 bpm, with an 8-fold decrease in weekly angina attacks (1.7 ± 2.2 to 0.2 ± 0.7) and nitrate consumption (2.4 ± 3.4 to 0.3 ± 0.9). Patient numbers in Canadian Cardiovascular Society class I more than doubled (i.e. from 29 to 65%) and QoL improved (the EQ-5D index and visual analog scale scores rose from 0.68 ± 0.27 to 0.84 ± 0.20 and 58.1 ± 18.4 to 72.2 ± 15.5 mm, respectively). The effect of ivabradine was greater in patients with a baseline heart rate ≥70 bpm (mean reduction in heart rate -21.2 ± 10.4 bpm, with a relative reduction in angina attacks and short-acting nitrate consumption of 87.1 and 87.2%, respectively). CONCLUSIONS Ivabradine combined with metoprolol safely and effectively reduces heart rate, angina attacks and nitrate use, and improves QoL in stable-angina patients.
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Diltiazem vs. Metoprolol in the Management of Atrial Fibrillation or Flutter with Rapid Ventricular Rate in the Emergency Department.
Fromm, C, Suau, SJ, Cohen, V, Likourezos, A, Jellinek-Cohen, S, Rose, J, Marshall, J
The Journal of emergency medicine. 2015;(2):175-82
Abstract
BACKGROUND Diltiazem (calcium channel blocker) and metoprolol (beta-blocker) are both commonly used to treat atrial fibrillation/flutter (AFF) in the emergency department (ED). However, there is considerable regional variability in emergency physician practice patterns and debate among physicians as to which agent is more effective. To date, only one small prospective, randomized trial has compared the effectiveness of diltiazem and metoprolol for rate control of AFF in the ED and concluded no difference in effectiveness between the two agents. OBJECTIVE Our aim was to compare the effectiveness of diltiazem with metoprolol for rate control of AFF in the ED. METHODS A convenience sample of adult patients presenting with rapid atrial fibrillation or flutter was randomly assigned to receive either diltiazem or metoprolol. The study team monitored each subject's systolic and diastolic blood pressures and heart rates for 30 min. RESULTS In the first 5 min, 50.0% of the diltiazem group and 10.7% of the metoprolol group reached the target heart rate (HR) of <100 beats per minute (bpm) (p < 0.005). By 30 min, 95.8% of the diltiazem group and 46.4% of the metoprolol group reached the target HR < 100 bpm (p < 0.0001). Mean decrease in HR for the diltiazem group was more rapid and substantial than that of the metoprolol group. From a safety perspective, there was no difference between the groups with respect to hypotension (systolic blood pressure < 90 mm Hg) and bradycardia (HR < 60 bpm). CONCLUSIONS Diltiazem was more effective in achieving rate control in ED patients with AFF and did so with no increased incidence of adverse effects.
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Single dose ivabradine versus intravenous metoprolol for heart rate reduction before coronary computed tomography angiography (CCTA) in patients receiving long-term calcium channel-blocker therapy.
Celik, O, Atasoy, MM, Ertürk, M, Yalçın, AA, Aksu, HU, Diker, M, Aktürk, IF, Atasoy, I
Acta radiologica (Stockholm, Sweden : 1987). 2014;(6):676-81
Abstract
BACKGROUND In patients with contraindication for beta-blockers who are also under long-term calcium channel-blocker therapy for any reason, ivabradine may be used as an alternative treatment to achieve the target heart rate. PURPOSE To assess whether single dose oral ivabradine in patients referred for coronary computed tomography angiography (CCTA) is safe and can significantly decrease heart rate compared to intravenous (i.v.) metoprolol in patients receiving long-term calcium channel-blocker therapy. MATERIAL AND METHODS One-hundred and twenty patients who were under calcium channel-blocker therapy referred for CCTA were randomized to premedication with single dose (15 mg) ivabradine (n = 63) or i.v. metoprolol (5-10 mg) (n = 62). Hearth rate (HR) was assessed at admission (HR1), prescan (HR2), and during CCTA scan (HR3) for all patients. Blood pressure (BP) was measured before medication (BP1) and immediately before CCTA scan (BP2). RESULTS Although the HR averages of two groups were not significantly different before medication (HRIv1 = 80 ± 7 bpm vs. HRβ1 = 81 ± 7 bpm; P = 0.42), significant HR reduction was observed in the ivabradine group (HRIv3 = 62 ± 7 bpm) when compared to the metoprolol group (HRβ3 = 66 ± 6 bpm; P = 0.001). Decreases in HR forivabradine (18 ± 6 bpm) was significantly higher than for metoprolol (15 ± 4 bpm; P = 0.003) without relevant side-effects. Ivabradine showed no significant effect on either systolic BP or diastolic BP (siBPIv1, 139 ± 10; siBPIv2, 138 ± 10; P = 0.260; diBPIv1, 81 ± 7; diBPIv2, 81 ± 6; P = 0.59). Nevertheless, metoprolol group demonstrated significant reduction in both SiBP and DiBP (siBPβ1, 136 ± 11; siBPβ2 130 ± 11; P < 0.001; diBPβ1, 81 ± 6; diBPβ2, 78 ± 6; P < 0.001). CONCLUSION Single dose ivabradine is safe and significantly more effective than i.v. metoprolol in decreasing HR in patients under calcium channel-blocker therapy.
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The effect of combined antihypertensive treatment (felodipine with either irbesartan or metoprolol) on erectile function: a randomized controlled trial.
Yang, L, Yu, J, Ma, R, Zhao, F, Lin, X, Liu, P, Hu, H, Bai, F
Cardiology. 2013;(4):235-41
Abstract
OBJECTIVES This study aimed to determine whether combining a calcium channel blocker with either an angiotensin II receptor blocker or a β-blocker would have similar effects on sexual function in men with hypertension. METHODS This prospective, randomized study (ClinicalTrials.gov: NCT01238705) included 218 male participants with untreated hypertension. Patients were randomized to treatment with felodipine combined with irbesartan or metoprolol for 48 weeks. Sexual function was evaluated at baseline and after 48 weeks of therapy. The levels of serum sex hormones and markers of oxidative stress were measured at the same time. RESULTS There was no significant difference in the prevalence of erectile dysfunction before and after treatment in either group (p > 0.05). There were also no differences in the levels of serum testosterone, sex hormone-binding globulin or 4-hydroxynonenal before and after treatment in either group (p > 0.05). In the felodipine-irbesartan group, sexual desire scores rose after treatment (p = 0.022) and the concentrations of serum 8-hydroxy-2'-deoxyguanosine and malondialdehyde declined (p < 0.001 and p = 0.002, respectively). The between-group differences for 8-hydroxy-2'-deoxyguanosine and malondialdehyde were not significant (p > 0.05, respectively). CONCLUSION The results suggest that felodipine-irbesartan may be more beneficial to the sexual desire of hypertensive male patients than felodipine-metoprolol. This effect was possibly relevant to irbesartan, which prevents oxidative stress to some extent.