Metoprolol scientific update |
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Kidney Int. 2006 Oct 4;
Bakris GL, Hart P, Ritz E.
Department of Medicine, Hypertension Center, Endocrine Division, University of Chicago School of Medicine, Chicago, Illinois, USA.
Beta blockers in the management of chronic kidney disease.
The sympathetic nervous system modulates renal function through its receptors namely beta(1) (cardiac output and renin release), alpha(1) (systemic and renovascular constriction), and beta(2) renovascular dilation. Sympathetic overactivity is commonly seen in chronic kidney disease (CKD) and is an important contributor to increasing the risk of cardiovascular events as well as increasing renal disease progression. Recent evaluations of drug use in people with CKD shows a remarkably low percentage of patients receiving beta-blockers, especially in more advanced stage CKD when cardiovascular risk is higher. This is in large part due to tolerability of these agents. Moreover, water-soluble beta-blockers such as atenolol and metoprolol are dialyzable and require supplementation to avoid exacerbation of arrhythmias following dialysis. Newer vasodilating beta-blockers have better tolerability and different effects on renal hemodynamics as well as metabolic variables. These effects are related to the relative alpha(1)-blocking effect of agents such as carvedilol and labetolol, with carvedilol having relatively greater alpha-blocking effects. Few studies evaluate beta-blockers on cardiovascular risk in CKD patients. Studies with carvedilol demonstrate attenuated increases in albuminuria as well as reduction in cardiovascular events in CKD patients with hypertension. This paper reviews the animal and clinical trial data that evaluate beta-blockers in CKD highlighting the vasodilating beta-blockers. It is apparent that greater use of this drug class for blood pressure control would further enhance reduction of risk of heart failure, the most common cause of death in the first year of starting dialysis.Kidney International advance online publication, 4 October 2006; doi:10.1038/sj.ki.5001835.
Clin Pharmacol Ther. 2005 Mar;77(3):189-201.
Tu W, Morris AB, Li J, Wu J, Young J, Brater DC, Murray MD.
Association between adherence measurements of metoprolol and health care utilization in older patients with heart failure.
Objective Data from electronic dosing monitors and published pharmacokinetic parameters were used to derive medication adherence measures for immediate-release metoprolol and examine their association with health care utilization of outpatients aged 50 years or older with heart failure. Methods We used a 1-compartment model and published population pharmacokinetic parameters to estimate mean plasma metoprolol concentrations for patients treated for 6 to 12 months. In the absence of directly measured plasma concentrations, we calculated the intended mean plasma concentration (Cp' ave ) under the assumption of perfect adherence to the prescribed dose and frequency of administration. Projected mean plasma concentrations (Cp ave ) were estimated by use of data from recorded dosing times. In addition to taking adherence (percentage of dose taken) and scheduling adherence (percentage of doses taken on schedule), we calculated the deviation from the intended exposure (DeltaCp ave = Cp' ave - Cp ave ) and the proportion of intended exposure achieved by the patient (Cp ave /Cp' ave ). We assessed the association between the adherence measures and the numbers of emergency department visits and hospital admissions experienced by the patients. Results Patients (N = 80) were aged 62 +/- 8 years. Mean DeltaCp ave and Cp ave /Cp' ave were 7.9 ng/mL (SD, 10.7) and 0.6 (SD, 0.3), respectively. Log-linear models adjusted for patient functional status indicated that greater deviation from the intended metoprolol exposure (DeltaCp ave ) was associated with increased numbers of emergency department visits ( P < .0001) and hospital admissions ( P < .0001). A higher proportion of intended exposure (Cp ave /Cp' ave ) corresponded to a reduced number of emergency department visits ( P = .0204) and hospital admissions ( P = .0093). Taking adherence was univariately associated with both emergency department visits and hospital visits ( P < .0001 and P = .0010, respectively). Scheduling adherence was associated with the number of emergency department visits ( P = .0181) but not with the number of hospital admissions ( P = .1602). Model selection procedures consistently chose the proposed measures over taking adherence and scheduling adherence. Conclusion Deviation from the intended exposure and proportion of intended exposure achieved by the patient are valid adherence measures for immediate-release metoprolol and are associated with health care utilization. The potential utility of these measures for other beta-adrenergic antagonists and perhaps other cardiovascular drugs should be investigated.
Am Heart J. 2005 Jan;149(1):159-67.
Jeedwania PC, Giles TD, Klibaner M, Ghali JK, Herlitz J, Hildebrandt P, Kjekshus J, Spinar J, Vitovec J, Stanbrook H, Wikstrand J;
Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF.
BACKGROUND: The objective of the current study was to examine the efficacy and tolerability of the beta-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF). METHODS: The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI). RESULTS: The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%). Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37% in the diabetic group (95% CI 53% to 15%), and by 35% in the non-diabetic group (95% CI 48% to 19%). Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II), MERIT-HF, and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed similar survival benefits in patients with diabetes (25%; 95% CI 40% to 4%) and without diabetes (36%; 95% CI 44% to 27%); test of diabetes by treatment interaction was non-significant. Adverse events were reported more often on placebo than on metoprolol CR/XL. CONCLUSIONS: Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes. Regardless of diabetic status, a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy, which was very well tolerated also by patients with diabetes. Furthermore, the pooled data showed a statistically significant survival benefit in patients with diabetes.
Am Heart J. 2005 Feb;149(2):370-6.
Torp-Pedersen C, Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lutiger B, Metra M, Remme WJ, Scherhag A,
Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark.
Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET.
BACKGROUND: Beta-blockers with different receptor bindings reduce mortality in patients with chronic heart failure. We compared the effects of the beta1-blocker metoprolol tartrate and the beta1-, beta2-, and alpha1-blocker carvedilol. METHODS: In a randomized double-blind design, 3029 patients with chronic congestive heart failure requiring diuretic therapy and with left ventricular dysfunction were randomized to treatment with carvedilol (n = 1511) or metoprolol tartrate (n = 1518) and titrated to target doses of 25 mg of carvedilol twice daily or 50 mg of metoprolol tartrate twice daily. The main outcome measures were total mortality and the combination of mortality or hospitalization for any cause. Secondary end points were cardiovascular death, combinations of morbidity and mortality, New York Heart Association class, worsening of heart failure, hospitalizations, and discontinuation of study therapy. RESULTS: A total of 512 and 600 patients in the carvedilol group and metoprolol group, respectively, died (hazard ratio [HR] 0.83, 95% CI 0.74-0.93, P = .0017). Cardiovascular death was reduced by carvedilol (HR 0.80, 95% CI 0.70-0.90, P = .0004). There were fewer sudden deaths and deaths caused by circulatory failure or by stroke in the carvedilol group. There was no difference in all-cause hospitalizations or in worsening heart failure between treatment groups. The incidence of fatal or nonfatal acute myocardial infarction was significantly lower in the carvedilol group (HR 0.71, 95% CI 0.52-0.97, P = .03). Discontinuations of study therapy were similar in the 2 groups. CONCLUSION: Compared with metoprolol tartrate, carvedilol reduced cardiovascular mortality, sudden death, death caused by circulatory failure, death caused by stroke, as well as fatal and nonfatal myocardial infarctions.
Metoprolol description...
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Drug category:Hypotensive agents
 Metoprolol scientific update
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