Treatment with β‐blockers—the value of an even plasma concentration over 24 h

Abstract

SUMMARYThe aim of this paper was to examine if there were clinical studies supporting a beneficial effect of an even plasma concentration over 24 h for the most frequently prescribed 1-blockers in clinical practice, metoprolol CR/ZOK and atenolol. There are several studies showing that metoprolol CR/ZOK has a more even plasma concentration compared with atenolol and conventional metoprolol tablets when administered once daily. There are also studies showing that metoprolol CR/ZOK produces a more even 1-blockade over 24 h. This is determined by expressing the percentage reduction in exercise heart rate in relation to placebo at intervals throughout the 24-h period and comparing the results with those of atenolol and conventional metoprolol tablets. Clinical studies indicate that the low peak plasma concentration produced by metoprolol CR/ZOK leads to more 1 selectivity than atenolol and conventional metoprolol tablets. The loss of 1 selectivity at peak plasma concentrations may cause unwanted side-effects. The peak plasma concentration of atenolol coincides with increased general and leg fatigue, problems less evident when patients are on metoprolol CR/ZOK. The frequency and severity of other central nervous system related side-effects are comparable with metoprolol CR/ZOK and atenolol. In conclusion, there are several clinical studies supporting a beneficial effect of the even plasma concentration over 24 h achieved with metoprolol CR/ZOK.

Atenolol Is Inferior to Metoprolol in Improving Left Ventricular Function and Preventing Ventricular Remodeling in Dogs with Heart Failure

“…Atenolol was chosen because of the high prescription rate of this agent in large HF registries in clinical practice [10, 11]. In order to avoid potential bias related to choice of doses, we selected doses and frequency of administration of atenolol and metoprolol CR/XL commonly recommended in treatment guidelines [1,2,3, 8, 9], accepted to be equivalent [25] and previously used in comparative studies [30]. Current recommendations for the use of atenolol in hypertension and chronic stable angina is once daily [8, 9] and metoprolol CR/XL for HF is also once daily [1,2,3].…”

“…Current recommendations for the use of atenolol in hypertension and chronic stable angina is once daily [8, 9] and metoprolol CR/XL for HF is also once daily [1,2,3]. Comparisons in healthy volunteers and hypertensive or stable patients after myocardial infarction have been performed between metoprolol CR/XL 100 mg once daily and atenolol 50 mg once daily or metoprolol CR/XL 200 mg once daily and atenolol 100 mg once daily [30]. These studies provide compelling evidence to support the appropriateness of the selection of the doses of both metoprolol CR/XL and atenolol used in the present study.…”

“…When compared to atenolol (50 mg once daily) over a 24-hour interval, metoprolol CR/XL (100 mg once daily) shows a more even plasma concentration, with lower fluctuation ratio and longer time period of concentration higher than 50% of maximum concentration [36]. In addition, the low peak plasma concentration produced by metoprolol CR/XL may lead to higher β 1 -selectivity than equivalent doses of atenolol [30], while cardioselectivity is maintained up to dosages of 200 mg of metoprolol CR/XL [37, 38]. …”

β-Blockers in Chronic Heart Failure: Considerations for Selecting an Agent

“…25 The more even plasma concentration achieved with ER metoprolol succinate, however, ensures consistent 24-hour β 1blockade. 58 Patients who generally should not receive a β-blocker for heart failure therapy include those with bronchial asthma and chronic obstructive pulmonary disease requiring β-agonist therapy, symptomatic hypotension, resting heart rate of less than 60 beats/min, or advanced heart block without a pacemaker and those with general contraindications to β-blocker therapy. 1 Additionally, volumeoverloaded patients should not receive β-blockers until fluid retention has been treated effectively.…”

Metoprolol CR/XL in the Treatment of Chronic Heart Failure

“…Therapy with ␤-blockers in patients with COPD can be challenging, particularly in those with severe disease. A ␤ 1 -selective agent is preferred in this population 30,31 Patients with bronchospastic disease may not be able to tolerate ␤-blocker therapy, even with a ␤ 1selective agent. Patients not requiring ␤-agonist therapy and who do not experience worsening of pulmonary status should be treated with a ␤blocker, and as with diabetes, the mere presence of COPD is not an absolute contraindication to their use.…”