Extended-release Metoprolol Succinate Research Articles

Therapeutic Inefficacy and Proarrhythmic Nature of Metoprolol Succinate and Carvedilol Therapy in Patients With Idiopathic, Frequent, Monomorphic Premature Ventricular Contractions.

Antiarrhythmic drugs remain the first-line therapy for treatment of idiopathic ventricular arrhythmias. The aim of this study was to assess the therapeutic efficacy of extended-release metoprolol succinate (MetS) and carvedilol for idiopathic, frequent, monomorphic premature ventricular contractions (PVCs). Study population consisted of 114 consecutive patients: 71 received MetS and 43 received carvedilol. All patients underwent 24-hour Holter monitoring at baseline and during drug therapy. PVC-burden response to drug therapy was categorized as "good" (≥80% reduction), "poor" (either <80% reduction or ≤50% increase), and "proarrhythmic" responses (>50% increase) based on change in PVC burden compared with baseline. Most common presenting symptom was palpitations (65.8%), followed by coincidental discovery (29%). The mean MetS and carvedilol dosages were 65.57 ± 30.67 mg/d and 23.66 ± 4.26 mg/d, respectively. "Good," "poor," and "proarrhythmic" responses were observed in 11.3% and 16.3%, 63.4% and 67.4%, and 25.3% and 16.3% of patients treated with MetS and carvedilol, respectively. In patients with relatively high (≥16%) PVC burden, the sum of "poor"/"proarrhythmic" response was observed in 95.5% and 86.4% of patients treated with MetS and carvedilol, respectively. "Proarrhythmic" response was observed in 21.9% of the patients, particularly in the presence of relatively lower (≤10%) baseline PVC burden. Patients with "good" response during beta-blocker therapy had higher baseline daily average intrinsic total heart beats compared with patients with "poor"/"proarrhythmic" response combined (96,437 ± 26,488 vs. 86,635 ± 15,028, P = 0.047, respectively). Side effects and intolerance were observed in 5.6% and 18.6% of patients treated with MetS and carvedilol, respectively. MetS and carvedilol for idiopathic, frequent, monomorphic PVCs are frequently inefficient. Therapeutic efficacy decreases further in patients with relatively high (≥16%) PVC burden. Relatively higher baseline daily intrinsic total heart beats may be used to predict "good" response before beta-blocker therapy.

P351Therapeutic inefficacy and pro-arrhythmic nature of metoprolol succinate and carvedilol therapy in patients with idiopathic, frequent, monomorphic premature ventricular contractions

Abstract Funding Acknowledgements None Background Anti-arrhythmic drugs remain the first-line therapy for treatment of idiopathic ventricular arrhythmias in clinical practice. Purpose The aim of this study was to assess the therapeutic efficacy of extended-release metoprolol succinate (MetS) and carvedilol for idiopathic, frequent, monomorphic premature ventricular contractions (PVCs). Methods Study population consisted of 115 consecutive patients: 72 received MetS and 43 received carvedilol. All patients underwent 24-hour Holter monitoring at baseline and during drug therapy. PVC burden response to drug therapy was categorized as "Good" (≥80% reduction), "Poor" (either &amp;lt; 80% reduction or ≤ 50% increase) and "Pro-arrhythmic" response (&amp;gt; 50% increase) based on change in PVC burden compared to baseline. Results Presenting symptoms were palpitations in 69 (60%), shortness of breath/chest pain/syncope in 12 (10.5%), and coincidentally discovered in 34 (29.5%) patients. Mean MetS and carvedilol dosages were 65.57 ± 30.67 mg/day and 23.66 ± 4.26 mg/day, respectively. "Good", "Poor" and "Pro-arrhythmic" response was observed in 13.9% and 23.3%, 61.1% and 60.5%, and 25% and 16.2% of patients treated with MetS and carvedilol, respectively. In patients with relatively high (≥16%) PVC burden, "Poor" response was observed in 86.9% and 76% of patients treated with MetS and carvedilol, respectively. Side-effects and/or intolerance were observed in 5.5 % and 13.9 % of patients treated with MetS and carvedilol, respectively. Conclusions MetS and carvedilol for idiopathic, frequent, monomorphic PVCs is frequently inefficient. Therapeutic efficacy decreases further in patients with relatively high (≥16%) PVC burden. "Pro-arrhythmic" response was observed in approximately one quarter of the patients. All patients Metoprolol Succinate (n = 71) Carvedilol (n = 43) p value Good response,n (%) 7 (9.9) 7 (16.3) 0.38 Poor response,n (%) 46 (64.8) 29 (67.4) 0.38 Pro-arrhythmic response,n (%) 18 (25.4) 7 (16.3) 0.38 Patients with PVC burden≥%16 Metoprolol Succinate (n = 22) Carvedilol (n = 25) Good response,n (%) 1 (4.5) 3 (12) 0.56 Poor response,n (%) 20 (91) 20 (80) 0.56 Pro-arrhythmic response,n (%) 1 (4.5) 2 (8) 0.56 Therapeutic response to Metoprolol Succinate and Carvedilol

Antihypertensive drugs

Antihypertensive drugs

Health expenditure comparison of extended-release metoprolol succinate and immediate-release metoprolol tartarate

BackgroundMetoprolol, a selective beta-1 blocker, is available in two different salt forms in the market – metoprolol succinate (MS) and metoprolol tartarate (MT). Both the formulations are Food and Drug Administration approved for the treatment of hypertension. Several studies have shown similar efficacies between the two salts; however, they differ in their pharmacokinetic properties and are therefore priced differently. The primary objective of this study was to compare the overall health care expenditures of hypertensive patients on MT and MS to see if the price difference in the two preparations is offset by savings in overall expenditure.MethodsTwo cohorts of patients using MT and MS were selected from the 2008 Medical Expenditure Panel Survey. Propensity score matching technique was used to balance the cohorts on various parameters such as demographic information, insurance status, and comorbidity score. Patients using MT were matched to patients using MS on the logit of propensity score using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score. Multiple regression analysis was carried out to examine the association between health expenditure and type of metoprolol salt, adjusting for other covariates.ResultsA total of 742 patients were found to use metoprolol (MT-388, MS-354). After propensity score matching, a total of 582 patients were left in the sample for final analysis (291 patients in each cohort). The average annual health care expenditure was slightly higher in the MT cohort; however, after adjusting for covariates in a multivariate analysis, the difference was found to be statistically insignificant (P = 0.23).ConclusionBoth the products of metoprolol were found to have similar average annual total health care expenditure; however, MS once a day has higher out-of-pocket cost.

A Comparison of the Outcomes of Low Ejection Fraction Chronic Heart Failure Patients on Metoprolol Succinate With Those on Carvedilol

Introduction: A few studies have been conducted to compare metoprolol tartrate with carvedilol in chronic heart failure (CHF) patients. The most well known is the COMET trial which showed that carvedilol had a lower mortality rate and no change in the re-admission rates when compared to immediate-release metoprolol tartrate. The aim of this study was to assess the outcomes of low ejection fraction (EF) CHF patients on extended-release metoprolol succinate versus those on carvedilol. Hypothesis: There is no difference in the mortality or the re-admission rates in low EF CHF patients on metoprolol succinate versus those on carvedilol.

The experts debate: Perioperative beta-blockade for noncardiac surgery—proven safe or not?

Guidelines on perioperative management of patients undergoing noncardiac surgery recommend the use of prophylactic perioperative beta-blockers in high-risk patients who are not already taking them, and their continuance in patients on chronic beta-blockade prior to surgery. These recommendations were challenged recently by results of the Perioperative Ischemic Evaluation (POISE), a large randomized trial of extended-release metoprolol succinate started immediately before noncardiac surgery in patients at high risk for atherosclerotic disease. While metoprolol significantly reduced myocardial infarctions relative to placebo in POISE, it also was associated with significant excesses of both stroke and mortality. The merits and limitations of POISE and its applicability in light of other trials of perioperative beta-blockade are debated here by two experts in the field-Dr. Don Poldermans and Dr. P. J. Devereaux (co-principal investigator of POISE).

Amiodarone-induced neurotoxicity

A case of amiodarone-induced neurotoxicity is reported. A 76-year-old man arrived at the emergency department with complaints of increasing imbalance over the past 2.5 months after a recent discharge from the hospital. He reported that his balance had worsened over the past week and that he now must use a cane to walk. His medical history included coronary artery disease, peripheral vascular disease, hypertension, hyperlipidemia, and paroxysmal atrial fibrillation. Home medications included enteric-coated aspirin 325 mg orally daily, isosorbide dinitrate 20 mg orally twice daily, amiodarone hydrochloride 400 mg orally three times daily, hydralazine hydrochloride 10 mg orally four times daily, extended-release metoprolol succinate 142.5 mg (equivalent to metoprolol tartrate 150 mg) orally daily, simvastatin 80 mg orally daily, and warfarin sodium 2.5 mg orally daily. Physical examination of the patient revealed finger-to-nose dysmetria, unsteady gait with leftward prevalence, positive Romberg's sign, and inability to perform heel-to-toe walk. All radiographic imaging studies and laboratory test values ruled out acute pathologies, bleeding, masses, and ischemia. As there were no physiological findings for the patient's symptoms and after careful evaluation of the patient's drug regimen, the patient's amiodarone was discontinued. His ataxia began to slowly improve. All neurologic symptoms resolved completely five months after discontinuation of amiodarone. A 76-year-old man developed ataxia after taking amiodarone hydrochloride 400 mg orally three times daily for more than two months; the regimen was the intended loading dosage. The ataxia lessened over the first two weeks after the amiodarone was discontinued and resolved completely within five months after drug discontinuation.

Effects of Extended-Release Metoprolol Succinate in Patients Undergoing Non-Cardiac Surgery (POISE Trial): A Randomized Controlled Trial

Effects of Extended-Release Metoprolol Succinate in Patients Undergoing Non-Cardiac Surgery (POISE Trial): A Randomized Controlled Trial

Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial

Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial

Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial

Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial

Metoprolol prevented myocardial infarction but increased risk of stroke and death after non-cardiac surgery

Source Citation POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371:1839-47...

Metoprolol prevented myocardial infarction but increased risk for stroke and death after noncardiac surgery

Source Citation POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371:1839-47. 18479744

Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial

Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results. This randomised controlled trial, done in 190 hospitals in 23 countries, was designed to investigate the effects of perioperative beta blockers. We randomly assigned 8351 patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate (n=4174) or placebo (n=4177), by a computerised randomisation phone service. Study treatment was started 2-4 h before surgery and continued for 30 days. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00182039. All 8351 patients were included in analyses; 8331 (99.8%) patients completed the 30-day follow-up. Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint (244 [5.8%] patients in the metoprolol group vs 290 [6.9%] in the placebo group; hazard ratio 0.84, 95% CI 0.70-0.99; p=0.0399). Fewer patients in the metoprolol group than in the placebo group had a myocardial infarction (176 [4.2%] vs 239 [5.7%] patients; 0.73, 0.60-0.89; p=0.0017). However, there were more deaths in the metoprolol group than in the placebo group (129 [3.1%] vs 97 [2.3%] patients; 1.33, 1.03-1.74; p=0.0317). More patients in the metoprolol group than in the placebo group had a stroke (41 [1.0%] vs 19 [0.5%] patients; 2.17, 1.26-3.74; p=0.0053). Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm, and the importance and need for large randomised trials in the perioperative setting. Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol.

Sympathetic activation causes focal adhesion signaling alteration in early compensated volume overload attributable to isolated mitral regurgitation in the dog.

We reported that left ventricular (LV) dilatation after 4 weeks of isolated mitral regurgitation (MR) in the dogs is marked by extracellular matrix loss and an increase in adrenergic drive. Given that extracellular matrix proteins and their receptor integrins influence beta-adrenergic receptor (beta-AR) responses in vitro, we tested whether beta1-AR activation modulates focal adhesion (FA) signaling and LV remodeling in these same dogs with isolated MR. Normal dogs were compared with dogs with MR of a 4-week duration and with MR dogs treated with beta(1)-AR blockade (beta(1)-RB) (extended-release metoprolol succinate, 100 mg QD) that was started 24 hours after MR induction. In MR LVs, a decrease in collagen accumulation compared with normal dogs was associated with a decrease in FA kinase tyrosine phosphorylation, along with FA kinase interaction with adapter and cytoskeletal proteins, p130(Cas) and paxillin, respectively, as determined by immunoprecipitation assays. There was increased phosphorylation of stress related molecules p38 mitogen-activated protein kinase (MAPK) and Hsp27 and survival signaling kinases extracellular signal-regulated kinase 1/2 and AKT, with no evidence of cardiomyocyte apoptosis. beta(1)-RB attenuated FA signaling loss and prevented p38 MAPK, Hsp27, and AKT phosphorylation induced by MR and significantly increased LV epicardial collagen content. However, beta(1)-RB did not improve LV endocardial collagen loss or LV dilatation induced by MR. Isolated myocytes from normal and MR dog hearts treated with beta(1)- or beta(2)-AR agonists demonstrated no difference in FA kinase, p38 MAPK, Hsp27, or AKT phosphorylation. These results showed that chronic stimulation of beta(1)-AR during early compensated MR impairs FA signaling that may affect myocyte/fibroblast-extracellular matrix scaffolding necessary for LV remodeling.

Treatment With Metoprolol Succinate, a Selective Beta Adrenergic Blocker, Lowers Blood Pressure Without Altering Insulin Sensitivity in Diabetic Patients

Insulin resistance is a risk factor for cardiovascular disease. Therapies to lower blood pressure should not decrease insulin sensitivity, especially among high-risk patients such as diabetics. This study examined the effect of the beta1-selective adrenergic receptor-blocking agent extended-release metoprolol succinate (ER metoprolol) on insulin sensitivity in type 2 diabetic patients with suboptimal blood pressure control. Diabetic patients with average blood pressure levels >130/85 mm Hg despite antihypertensive therapy had insulin sensitivity quantified by insulin clamp. ER metoprolol was then added to their ongoing therapy. Following 12 weeks of ER metoprolol plus other therapy, the insulin clamp study was repeated. There were no significant changes in measures of insulin sensitivity, plasma lipids, or hemoglobin A1c with use of ER metoprolol. When beta-blocker therapy is considered, it appears that this agent can be used to treat hypertension without adverse effects on insulin sensitivity in patients with type 2 diabetes, at least over the period of time treated.

Abstract 3295: De-induction of the Maladaptive Fetal Gene Program During Chronic Monotherapy with Metoprolol Succinate is Retained Following Withdrawal of Therapy in Dogs with Chronic Heart Failure

Background: Chronic therapy with extended release metoprolol succinate (MET), a selective β1 adrenergic receptor blocker, improves left ventricular (LV) function and attenuates global LV remodeling in dogs with chronic heart failure (HF). We previously showed that chronic therapy with β-blockade results in de-induction of the fetal gene program (FGP) in LV myocardium of dogs with HF. In this study, we tested the hypothesis that in dogs with HF withdrawal of chronic MET does not lead to re-induction of FGP. Methods: Studies were performed in 17 intracoronary microembolization-induced HF dogs randomized to 3 months oral therapy with MET (100 mg, once daily, n=11) or no therapy at all (Controls, n=6). In dogs randomized to MET, 6 were sacrificed after 3 months of therapy and in the remaining 5, MET was withdrawn after 3 months of therapy and dogs were observed for 6 weeks after withdrawal of MET (MET-W) and then sacrificed. LV tissue was also obtained from 6 normal (NL) dogs for comparison. mRNA expression of the FGP genes namely, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), sarcoplasmic reticulum calcium ATPase (CAA), cardiac β-1 adren-ergic receptor (AR) and α-myosin heavy chain isoform (α-MHC) was measured using reverse transcriptase polymerase chain reaction (RT-PCR) and bands were quantified in densitometric units (du). Results: In Controls, mRNA expression of ANP and BNP increased and expression of CAA, β 1-AR and α-MHC decreased. Treatment with MET decreased expression of ANP and BNP and increased expression of CAA, β 1-AR and α-MHC. Except for α-MHC, the improvement in FGP seen during MET treatment was preserved in MET-W dogs. Conclusions: Withdrawal of MET is associated with sustained de-induction of the FGP in LV myocardium of dogs with HF. This observation supports the concept that chronic β-blockade therapy in HF confers lasting reversal of LV remodeling and molecular recovery of the failing myocardium.

Metoprolol Reverses Left Ventricular Remodeling in Patients With Asymptomatic Systolic Dysfunction

There are no randomized, controlled trial data to support the benefit of beta-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether beta-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction. Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months. Echocardiographic assessments of left ventricular end-systolic volume, end-diastolic volume, mass, and ejection fraction were performed at baseline and at 6 and 12 months. The 149 patients randomized to the 3 treatment groups (200 mg, n=48; 50 mg, n=48; and placebo, n=53) were similar with regard to all baseline characteristics including age (mean, 66 years), gender (74% male), plasma brain natriuretic peptide (79 pg/mL), left ventricular end-diastolic volume index (110 mL/m2), and left ventricular ejection fraction (27%). At 12 months in the 200-mg group, there was a 14+/-3 mL/m2 decrease (least square mean+/-SE) in end-systolic volume index and a 6+/-1% increase in left ventricular ejection fraction (P<0.05 versus baseline and placebo for both). The decrease in end-diastolic volume index (14+/-3) was different from that seen at baseline (P<0.05) but not with placebo. In the 50-mg group, end-systolic and end-diastolic volume indexes decreased relative to baseline but were not different from what was seen with placebo, whereas ejection fraction increased by 4+/-1% (P<0.05 versus baseline and placebo). Beta-blocker therapy can ameliorate left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Therapy With Cardiac Contractility Modulation Electrical Signals Improves Left Ventricular Function and Remodeling in Dogs With Chronic Heart Failure

This study examined the effects of long-term delivery of cardiac contractility modulation (CCM) electric signals on left ventricular (LV) function and global, cellular, and molecular remodeling in dogs with chronic heart failure (HF). Acute studies in dogs with experimentally induced HF showed that CCM signals applied to the failing myocardium during the absolute refractory period improved LV function without increasing myocardial oxygen consumption. In one study, dogs with intracoronary microembolization-induced HF were randomized to 3 months of active CCM monotherapy or to a sham-operated control group. In another study, 19 HF dogs were randomized to 3 months chronic monotherapy with extended release metoprolol succinate (MET-ER), MET-ER with CCM, or no therapy at all (control group). In CCM-only treated dogs, LV ejection fraction (EF) increased (27 +/- 1% vs. 33 +/- 1%, p < 0.0001) compared with a decrease in sham-operated control animals (27 +/- 1% vs. 23 +/- 1%, p < 0.001). The increase in EF seen with CCM-treated dogs was accompanied by reduced LV volumes, improved myocardial structure, reversal of the maladaptive fetal gene program, and an improvement in sarcoplasmic reticulum calcium cycling proteins. Dogs treated with a combination of MET-ER and CCM showed a greater increase in LV EF and a greater reversal of LV global, structural, and biochemical remodeling compared with dogs treated with MET-ER alone. In dogs with HF, long-term CCM therapy improves LV systolic function. The improvements are additive to those seen with beta-blockers. These findings are further strengthened by the concomitant benefits of CCM therapy on LV global, cellular, and biochemical remodeling.

A “beta” way to treat hypertension

As we have learned more about the pathophysiology of hypertension, a host of new drug classes have been developed to target these various mechanisms. Many of these agents have much less in the way of side effects than earlier drugs; angiotensin converting enzyme (ACE) inhibitors and angiotensin 2 receptor antagonists, to cite two examples, are now widely used in children.These drugs have displaced other categories of agents which, although effective, often had unacceptable side effects in children. Beta blockers such as propranolol, for example, have been less frequently employed because of troublesome features such as a sedating effect. Recently, however, new classes of beta blockers, with a more cardioselective profile and greater tolerability, have been used widely in adults. There has been a paucity of data upon which to base pediatric use of these agents. As we have learned more about the pathophysiology of hypertension, a host of new drug classes have been developed to target these various mechanisms. Many of these agents have much less in the way of side effects than earlier drugs; angiotensin converting enzyme (ACE) inhibitors and angiotensin 2 receptor antagonists, to cite two examples, are now widely used in children. These drugs have displaced other categories of agents which, although effective, often had unacceptable side effects in children. Beta blockers such as propranolol, for example, have been less frequently employed because of troublesome features such as a sedating effect. Recently, however, new classes of beta blockers, with a more cardioselective profile and greater tolerability, have been used widely in adults. There has been a paucity of data upon which to base pediatric use of these agents. Efficacy and Safety of Extended Release Metoprolol Succinate in Hypertensive Children 6 to 16 Years of Age: A Clinical Trial ExperienceThe Journal of PediatricsVol. 150Issue 2PreviewTo evaluate the efficacy, tolerability, and blood pressure (BP) lowering effect of extended release metoprolol succinate (ER metoprolol) in children 6 to 16 years of age with established hypertension. Full-Text PDF Is There a Role for β-Adrenergic Blockers in Treating Hypertension in Children?The Journal of PediatricsVol. 150Issue 2PreviewOver the past decade, it has been recognized that hypertension exists in children and adolescents, that pediatricians should screen for and evaluate it, and that the ideal goal is to prevent the long-term cardiovascular consequences of elevated blood pressure. Two parallel developments have influenced the choice of antihypertensive agent for children with persistent elevated blood pressure. The first development is the concept that drug testing is needed to ensure the efficacy and safety of any drug in children. Full-Text PDF

Efficacy and Safety of Extended Release Metoprolol Succinate in Hypertensive Children 6 to 16 Years of Age: A Clinical Trial Experience

To evaluate the efficacy, tolerability, and blood pressure (BP) lowering effect of extended release metoprolol succinate (ER metoprolol) in children 6 to 16 years of age with established hypertension. Patients were randomized to one of four treatment arms: placebo or ER metoprolol (0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg). Data were analyzed on 140 intent-to-treat patients. Mean age (+/-SD) was 12.5 +/- 2.8 years and mean baseline BP was 132/78 +/- 9/9 mmHg. Following 4 weeks of treatment, mean changes in sitting BP were: placebo = -1.9/-2.1 mmHg; ER metoprolol 0.2 mg/kg = -5.2/-3.1 mmHg; 1.0 mg/kg = -7.7/-4.9 mmHg; 2.0 mg/kg = -6.3/-7.5 mmHg. Compared with placebo, ER metoprolol significantly reduced systolic blood pressure (SBP) at the 1.0 and 2.0 mg/kg dose (P = .027 and P = .049, respectively), reduced diastolic blood pressure (DBP) at the 2.0 mg/kg dose (P = .017), and showed a statistically significant dose response relationship for the placebo-corrected change in DBP from baseline. There were no serious adverse events or adverse events requiring study drug discontinuation among patients receiving active therapy. These data indicate that ER metoprolol is an effective and well-tolerated treatment for hypertension in children.