Prospective Clinical Trial Comparing IV Esmolol to IV Metoprolol in CT Coronary Angiography: Effect on Hemodynamic, Technical Parameters and Cost.

BACKGROUND: Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost. MATERIALS AND METHODS: Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality. RESULTS: Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status. CONCLUSION: Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.

Cost-effectiveness of nitrendipine and hydrochlorothiazide or metoprolol to treat hypertension in rural community health centers in China.

OBJECTIVES: The objective of this article is to compare blood pressure (BP)-lowing effects of nitrendipine and hydrochlorothiazide and nitrendipine and metoprolol, and estimate the economic effect of these therapies on hypertension. METHODS: Outpatients (N = 793) 18-70 years of age with stage 2 or severe hypertension (SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg) were recruited from four randomly selected rural community health centers in Beijing and Jilin. After drug wash out, they were randomly divided into nitrendipine and hydrochlorothiazide group or nitrendipine and metoprolol group. The costs of drug treatment for hypertension were calculated and general estimation, whereas effectiveness was measured as a reduction in SBP and DBP at the end of a 24-week study period. RESULTS: Overall, 623 patients were eligible for the study and after a 24-week follow-up, SBP and DBP were 131.2/82.2 mmHg for the nitrendipine and hydrochlorothiazide group and 131.4/82.9 mmHg for the nitrendipine and metoprolol group and these were not significantly different (P = 0.7974 SBP and P = 0.1166 DBP). Comparing with nitrendipine and metoprolol, the cost of nitrendipine and hydrochlorothiazide was less, and its effectiveness was similar. The cost/effect ratio (US$/mmHg) was 1.4 for SBP and 2.8 for DBP for the nitrendipine and hydrochlorothiazide group, and 1.9 and 3.8 for the nitrendipine and metoprolol group's SBP and DBP values, respectively. The incremental cost per patient for achieving target BP was 5.1. Adverse events were mild or moderate and there were no differences between treatment groups. CONCLUSION: Treating hypertension with nitrendipine and hydrochlorothiazide was cost-effective than nitrendipine and metoprolol, and these data will allow more reasonable and efficient allocation of limited resources in low-income countries.

Cost-effectiveness analysis of nebivolol and metoprolol in essential hypertension: a pharmacoeconomic comparison of antihypertensive efficacy of beta blockers.

OBJECTIVE: To estimate and compare the cost-effectiveness and safety of nebivolol with sustained-release metoprolol in reducing blood pressure by 1 mm of Hg per day in hypertensive patients. MATERIALS AND METHODS: This was a prospective, randomized, open label, observational analysis of cost-effectiveness, in a questionnaire-based fashion to compare the cost of nebivolol (2.5 mg, 5 mg, 10 mg) and sustained released metoprolol succinate (25 mg, 50 mg, 100 mg) in hypertensive patients using either of the two drugs. A total of 60 newly detected drug naïve hypertensive patients were considered for the comparison, of which 30 patients were prescribed nebivolol and the other 30 were prescribed metoprolol succinate as per the recommended dosage. Based on the data, statistical analysis was carried out using GraphPad Prism 5 and MS Excel Spreadsheet 2007. RESULT: The cost of reducing 1 mm of Hg blood pressure per day with nebivolol was 0.60, 0.70, and 1.06 INR, whereas that of metoprolol succinate was 0.93, 1.18, and 1.25 INR at their respective equivalent doses, hence significantly lower with the nebivolol group as compared to the metoprolol group (P < 0.05). CONCLUSION: This pharmacoeconomic analysis shows that nebivolol is more cost-effective as compared to metoprolol when the cost per reduction in blood pressure per day is considered. This may affect the patients economically during their long-term use of these molecules for the treatment of hypertension.

Health and cost benefits associated with the use of metoprolol in heart attack patients.

Heart attack (myocardial infarction) is a highly prevalent entity worldwide. Widespread implementation of reperfusion strategies has dramatically reduced the mortality associated with infarction. Paradoxically, the mortality reduction has significantly increased the incidence of chronic heart failure (HF). Treatment of HF, once present, represents a huge socioeconomic burden on individuals and healthcare systems. The possibility of preventing rather than treating post-infarction HF would be of paramount importance. Given that infarct size is the main determinant of adverse post-infarction outcomes (including chronic HF), therapies able to reduce infarct size are needed. The single administration of intravenous metoprolol before reperfusion has been recently shown to reduce infarct size and reduce the cases of chronic HF in a proof-of-concept trial. If confirmed in larger trials, this low-cost therapy is expected to have a major health and socioeconomic impact.

Economic impact of switching from metoprolol to nebivolol for hypertension treatment: a retrospective database analysis.

OBJECTIVE: To estimate the real-world economic impact of switching hypertensive patients from metoprolol, a commonly prescribed, generic, non-vasodilatory ß1-blocker, to nebivolol, a branded-protected vasodilatory ß1-blocker. METHODS: Retrospective analysis with a pre-post study design was conducted using the MarketScan database (2007-2011). Hypertensive patients continuously treated with metoprolol for ≥6 months (pre-period) and then switched to nebivolol for ≥6 months (post-period) were identified. The index date for switching was defined as the first nebivolol dispensing date. Data were collected for the two 6-month periods pre- and post-switching. Monthly healthcare resource utilization and healthcare costs pre- and post-switching were calculated and compared using Wilcoxon test and paired t-test. Medical costs at different years were inflated to the 2011 dollar. RESULTS: In total, 2259 patients (mean age: 60 years; male: 52%; cardiovascular [CV] disease: 37%) met the selection criteria. Switching to nebivolol was associated with statistically significant reductions in the number of all-cause hospitalization (-33%; p < 0.01), CV-related hospitalizations (-60%; p < 0.01), and outpatient visits (-7%; p < 0.01). Monthly inpatient costs were reduced by $111 (p < 0.01), while monthly drug costs increased by $52 (p < 0.01). No statistically significant differences were found in overall costs and costs of outpatient or ER visits. Sensitivity analyses, conducted using various lengths of medication exposure, controlling for spill-over effect or excluding patients with compelling indications for metoprolol, all found some level of reduction in resource utilization and no significant difference in overall healthcare costs. CONCLUSIONS: This real-world study suggests that switching from metoprolol to nebivolol is associated with an increase in medication costs and significant reductions in hospitalizations and outpatient visits upon switching, resulting in an overall neutral effect on healthcare costs. These results may be interpreted with caution due to lack of a comparator group and confounding control caused by design and limitations inherent in insurance claims data.

Prevention of perioperative atrial fibrillation with betablockers in coronary surgery: betaxolol versus metoprolol.

In this study, we tried to compare the efficacy and safety of betaxolol vs. metoprolol immediately postoperatively in coronary artery bypass grafting (CABG) patients and to determine whether prophylaxy for atrial fibrillation (AF) with betaxolol could reduce hospitalization and economic costs after cardiac surgery. Our trial was open-label, randomized, multicentric enrolling 1352 coronary surgery patients randomized to receive betaxolol or metoprolol. The primary endpoints were the composites of 30-day mortality, in-hospital AF (safety endpoints), duration of hospitalization and immobilization, quality of life, and the above endpoint plus in-hospital embolic event, bradycardia, gastrointestinal symptoms, sleep disturbances, cold extremities (efficacy plus safety endpoint). At the end of the study the incidence and probability of early postoperative AF with betaxolol was lower than with metoprolol in coronary surgery (P<0.0001). In the two study groups minor side effects were similar and no major complication was reported (P<0.001). Patient compliance was good and the general condition improved due to shortened hospitalization and immobilization with subsequent improvement in the psychological status, less arrhythmias and lack of significant side effects. In conclusion, because of its efficacy and safety, betaxolol was superior to metoprolol for the prevention of the early postoperative AF in coronary surgery.

Medication costs as a primary cause of nonadherence in the elderly.

Many elderly enrolling in the Medicare Part D prescription drug benefit, which began January 1, 2006, have low annual incomes and few countable assets. Although some are eligible for special assistance to pay for prescription medications, many others will still have significant out-of-pocket expenses while enrolled. The inability to pay for medications is an important cause of nonadherence in the elderly and has been associated with an increase in adverse drug events, acute hospitalizations, and nursing home admissions. This case describes a 77-year-old woman residing in a retirement community who was failing to respond to drug therapy for her hypertension and diabetes. The physician was unaware of her inability to pay for medications, and the patient was too embarrassed to discuss the issue. The case demonstrates some of the techniques that a pharmacist can use to adjust a patient's medication regimen to reduce the cost load, improve adherence, and maintain treatment goals.

Use of natural gums and cellulose derivatives in production of sustained release metoprolol tablets.

Metoprolol tartrate sustained-release tablets (100 mg) were prepared using xanthan/guar gums and also hydroxypropyl methyl cellulose (HPMC) carboxymethyl-Cellulose (CMC) polymers by direct compression method. Physical characteristics of the tablets and water uptake in addition to their dissolution profiles were compared with standard (Lopressor SR) tablets. Dissolution test was performed in the phosphate buffer solution (pH 6.8) and the samples were analyzed spectrophotometerically in 275.7 nm. Dissolution studies showed that formulations containing 100 and 80% of HPMC, 100% of guar, and 20% of xanthan followed the Higuchi model, while those containing 60 and 40% HPMC and 100 and 80% xanthan followed a zero-order model. The tablets with 40% xanthen followed a Hixon-Crowell model. In cellulose derivatives the highest MDT and dissolution efficiency until 8 hr (DE8%) belonged to tablets with 40% HPMC, increasing the amount of CMC decreased the drug release rate, and formulations containing 60 and 40% of HPMC had the USP dissolution standards. While, in the gum formulations, the highest mean dissolution time and the lowest DE(8)% belonged to tablets with 100% xanthan, increasing the xanthan decreased the release rate of metoprolol, and formulations containing 80 and 100% xanthan had the USP dissolution standards. Results showed that natural gums are suitable for production of sustained-release tablets of metoprolol.

Economic implications of extended-release metoprolol succinate for heart failure in the MERIT-HF trial: a US perspective of the MERIT-HF trial.

BACKGROUND: The MERIT-HF trial demonstrated improved survival and fewer hospitalizations for worsening heart failure with extended-release (ER) metoprolol succinate in patients with heart failure. This study sought to estimate the economic implications of this trial from a US perspective. METHODS AND RESULTS: A discrete event simulation was developed to examine the course of patients with heart failure. Characteristics of the population modeled, probabilities of hospitalization and death with standard therapy, and risk reductions with ER metoprolol succinate were obtained from Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) and evaluated in weekly cycles. Direct medical costs were estimated from US databases in 2001 US dollars. Uncertainty in inputs was incorporated and analyses were carried out to estimate events prevented total and net costs. The model predicts that ER metoprolol succinate will prevent approximately 7 deaths and 15 hospitalizations from heart failure per 100 patients over 2 years. Compared with standard therapy alone, this translates to a cost reduction between $395 and $1112 per patient, depending on whether the costs of hospitalizations for other causes are included. Savings were maintained in 90% of the simulations. CONCLUSION: This analysis predicts that the positive effect of ER metoprolol succinate on mortality and morbidity demonstrated in MERIT-HF leads to substantial savings.

[Congestive heart failure in Spain: cost-effectiveness and cost-benefit analyses of treatment with beta-blockers]. / Análisis coste-efectividad y coste-beneficio del tratamiento con bloqueadores beta de la insuficiencia cardíaca congestiva en España.

OBJECTIVE: Beta-blockers (BB) have proven to be effective in the treatment of congestive heart failure (CHF). This study is an economic analysis for the addition of BB to standard treatment of CHF. PATIENTS AND METHOD: Randomized, double-blinded controlled studies are included, with 1,647 patients treated with bisoprolol, 3,034 treated with carvedilol, 2,432 treated with metoprolol, and 6,807 treated with placebo. Direct costs of BB treatment and of every hospitalization episode are assessed. Cost-effectiveness is assessed as cost in euros by prevented death, and cost-benefit as the difference between hospitalization costs and BB costs. The study is conducted from the perspective of a third-party payer. RESULTS: Two studies with bisoprolol, six with carvedilol, and five with metoprolol are included, with an average follow-up of 13.5 months. Carvedilol prevents 5.07% of deaths per year of treatment and is more effective than bisoprolol (3.82% of avoided deaths) and metoprolol (3.03%). Cost-effectiveness ratio (cost for every prevented death and year) was 10,832 euros for bisoprolol, 17,516 euros for carvedilol and 16,664 euros for metoprolol. Incremental cost-effectiveness ratio for carvedilol ranges between 12,631 euros and 86,610 euros for life saved. All BB generate costs saving for hospitalization but only bisoprolol provides a net profit. Benefit-cost index is 1.13 for bisoprolol, 0.26 for carvedilol and 0.59 for metoprolol. CONCLUSIONS: Use of BB in the treatment of CHF is an effective and cost-effective alternative. Carvedilol is the most effective alternative, and bisoprolol the most cost-effective alternative and the drug with greater benefit-cost index.

Cost-effectiveness of differing perioperative beta-blockade strategies in vascular surgery patients.

OBJECTIVES: To determine the incremental value of different strategies of both oral and intravenous beta-blockade during the perioperative period in high-risk vascular patients in reducing costs and improving outcomes. DESIGN: Decision analytic model incorporating costs from provider's perspective INTERVENTIONS: Five perioperative strategies in patients undergoing abdominal aortic aneurysm surgery: (1). no routine beta-blockade, (2). preoperative oral bisoprolol for 7 days followed by perioperative intravenous metoprolol and oral bisoprolol based on preoperative titration, (3). immediate preoperative atenolol with postoperative intravenous then oral atenolol, (4). intraoperative esmolol and postoperative intravenous then oral atenolol, and (5). intraoperative and 18 hours of postoperative esmolol then atenolol. MEASUREMENTS AND MAIN RESULTS: Perioperative death was associated with a net increase of US dollars 21909 in charges to Medicare, whereas sustaining a perioperative myocardial infarction was associated with a net increase in charges of US dollars 15000. There is a net hospital saving of US dollars 500 using a strategy of titration of an oral beta-blocker medication for a minimum of 7 days, with a net increase in efficacy of 0.0304. All of the strategies involving acute perioperative blockade were associated with a net cost savings and increase in efficacy, although less than the strategy involving preoperative oral titration. CONCLUSION: Perioperative beta-blockade is both cost effective as well as efficacious from a short-term provider perspective. The optimal strategy of treatment for patients who do not present to surgery already on beta-blockers requires further study, although all strategies save money even accounting for pharmaceutical costs.

In heart failure, all beta-blockers are not necessarily equal.

The Carvedilol or Metoprolol European Trial (COMET; Lancet 2003; 362:7-13) found that in patients with heart failure, survival appears to be better with carvedilol than with immediate-release metoprolol tartrate. Whether the target doses used were equivalent (carvedilol 25 mg twice daily vs metoprolol tartrate 50 mg twice daily) has been debated, but the COMET trial shows that drugs in the same class do not necessarily have the same effects. Given the overwhelming evidence of the benefit of carvedilol, metoprolol succinate, and bisoprolol in patients with heart failure, we should all strive to increase the use of these drugs in appropriate doses.

Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: the beta-Blocker Length Of Stay (BLOS) study.

BACKGROUND: Atrial fibrillation (AF) is a common complication of heart surgery. Previous studies have shown that there is an association between postoperative AF and prolongation of hospital length of stay. No previous trials have been primarily directed at demonstrating that the use of drugs that prevent AF would shorten length of stay and reduce the costs of postoperative care. METHODS: A randomized, double-blind, placebo-controlled trial of metoprolol was performed in patients immediately after nonemergent heart surgery. Metoprolol was given orally at a dose of 100 mg per day after the patient's arrival in the intensive care unit until hospital discharge or 14 days, whichever was sooner. This dose was increased to 150 mg per day after the enrollment of 411 patients. The primary outcome measure of the study was hospital length of stay from admission to intensive care unit until hospital discharge. There were 1000 patients enrolled, evenly distributed to the metoprolol and placebo groups. RESULTS: There was a 20% reduction in the risk of AF developing with metoprolol, from 39% of patients to 31% of patients (P =.01). There was no effect of treatment on hospital length of stay, which was 152 +/- 61 hours for placebo and 155 +/- 90 hours for metoprolol (P = 0.79). The cost of postoperative care in the 2 treatment groups was similar. CONCLUSION: Prophylactic metoprolol reduces the risk of AF after heart surgery. It does not reduce hospital length of stay. Although it is cost effective for the reduction of AF, it did not reduce the overall cost of care.

Reimbursement claims analysis of outcomes with carvedilol and metoprolol.

OBJECTIVE: To compare resource use and costs in heart failure (HF) patients receiving metoprolol, a selective beta1-receptor blocker, with carvedilol, which blocks beta1-, beta2-, and alpha1-adrenergic receptors, by use of a retrospective reimbursement-claims analysis. METHODS: Resource use and cost data were extracted for patients diagnosed with HF and treated with carvedilol or metoprolol for 6 months after the initiation of the respective therapy, by use of claims submitted to 6 healthcare plans. A modified Charlson index was used to assess comorbidity. Stepwise logistic regression was used to measure the influence of treatment on hospitalization. RESULTS: Claims from 139 carvedilol and 106 metoprolol patients showed that carvedilol patients experienced significantly fewer total hospitalizations (36.0% vs. 62.3%, respectively; p < 0.001) and emergency department visits (23.7% vs. 42.5%, respectively; p = 0.002) and a trend for fewer HF-related (7.9% vs. 14.2%, respectively; NS) and cardiac-related hospitalizations (15.1% vs. 24.5%, respectively; NS). Treatment with carvedilol was associated with a significant decrease in the risk of any hospitalization (adjusted odds ratio 0.35, 95% CI 0.20 to 0.63; p <0.001). Higher pharmacy costs (mean $1677 vs. $1322; p <0.001) and lower total costs (mean $8100 vs. $14475; p = 0.025) were observed in carvedilol-treated compared with metoprolol-treated patients, respectively. CONCLUSIONS: Compared with metoprolol, the more comprehensive adrenergic blockade achieved with carvedilol may translate into greater clinical benefits in patients with HF. Despite higher pharmacy costs, lower total costs were observed in carvedilol-treated patients.

Cost-effectiveness of beta-blocker therapy with metoprolol or with carvedilol for treatment of heart failure in Canada.

OBJECTIVE: The purpose of this study was to estimate the cost-effectiveness of beta-blocker therapy with either metoprolol or carvedilol in addition to conventional therapy for patients with heart failure (HF) in Canada. DESIGN: A Markov simulation was used to estimate the costs and life expectancy for treating patients with conventional therapy alone and with the addition of metoprolol or carvedilol. Although carvedilol has been marketed in Canada since 1999, metoprolol succinate has yet to be marketed there, so the price is unknown. Therefore we input a Canadian price based on the price ratio of the 2 drugs in the United States. RESULTS: For subjects aged 60 years at HF onset, the expected years of life are 4.53 years for those treated with conventional therapy alone, 5.70 years for those who receive conventional therapy plus metoprolol, and 6.21 years for those who receive conventional therapy plus carvedilol. The expected costs (in 1999 Canadian dollars) are $8,989, $13,833, and $18,114, respectively. This yields incremental cost-effectiveness ratios (ICERs) for metoprolol relative to conventional therapy alone of $4,140 per life-year gained, and for carvedilol relative to metoprolol, the ICER is $8,394 per life-year gained. CONCLUSIONS: In addition to conventional therapy with furosemide and angiotensin converting enzyme inhibitors, treatment with either metoprolol or carvedilol confers a survival benefit that is attractive from a cost-effectiveness point of view. Until better information becomes available, it is not possible to distinguish between the two beta-blockers on the basis of cost-effectiveness. This means that the choice of beta-blockers for HF should be based largely on clinical considerations because both beta-blockers prolong life at relatively low cost.