CVD Care Continuum in 2024: Metoprolol Revisited

Coronary artery disease (CAD) is a significant group within cardiovascular diseases (CVD) that results from decreased myocardial perfusion, leading to conditions such as angina, myocardial infarction (MI), and/or heart failure (1).

Hypertension and dyslipidemia are two major contributing risk factors for CVD. The reported prevalence of their co-existence ranges from 15% to 31%. This co-existence has an additive adverse impact on vascular endothelium, enhancing atherosclerosis and increasing the risk of CVD (2).

As per the World Health Organization, India accounts for one-fifth of cardiovascular (CV) deaths worldwide, especially in the younger population. Among all risks for cardiovascular diseases, high systolic blood pressure accounted for the largest proportion of disability-adjusted life years. Indians are liable to get hospitalized 2–4 times more frequently for complications of CAD. (3)

The ideal approach for CVD management is detecting and reducing risk, managing events, and preventing the progression of disease and recurrence of CVD (4). Therefore, the utmost importance is to manage hypertension and dyslipidemia to combat CVD risk. European Society of Hypertension Clinical Guidelines 2024 recommends the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), diuretics, and beta-blockers for the management of hypertension. (5)

Beta-blockers in CV Care:

Beta-blockers have been used for treating various CVDs. They act by inhibiting the effects of catecholamines via multiple pathways that affect myocardial chronotropy, inotropy, and renin release with anti-ischemic and anti-arrhythmic effects, therefore reducing myocardial oxygen consumption and decreasing heart rate and blood pressure. (6).

Beta‐1 selective blockers lowered systolic blood pressure (SBP) by a similar degree and lowered diastolic blood pressure (DBP) by a greater degree than diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. (6)

Metoprolol Use in Cardiovascular Disease Conditions:

Metoprolol is a cardioselective beta-blocker medication that acts on the beta-1 adrenergic receptors in the heart and reduces the effects of catecholamines (such as adrenaline and noradrenaline) on cardiac function. (7) The American Heart Association (AHA) guidelines recommend the use of agents, including beta-blockers, to prevent the progression of congestive heart failure. Three beta-blockers have been shown to reduce the risk of death in patients with congestive heart failure- metoprolol, bisoprolol, and carvedilol. (8) Based on a recently published 2024 expert opinion from Indian cardiologists, among beta-blockers, metoprolol is the first treatment choice for post-percutaneous coronary intervention (PCI) and heart failure patients. (9)

Considering Metoprolol in Hypertension:

European Society of Hypertension (ESH) clinical guidelines 2024 suggest the use of beta-blockers in hypertension associated with CAD and heart failure with poor ejection fraction as first-line therapy and in chronic kidney disease and true resistant hypertension as an add-on therapy. (5)

A systematic review including nine randomized controlled trials (RCTs) examined the blood pressure lowering efficacy of 25 mg to 400 mg per day metoprolol in 1004 hypertensive participants. All metoprolol doses significantly lowered SBP and DBP compared to placebo. The estimate of the blood pressure-lowering effect of metoprolol was ‐9/‐8 mmHg. (10)

Indian consensus as per the Journal of the Association of Physicians of India 2024, Beta-blockers can be considered in the treatment of hypertension and hypertension with comorbid disorders, such as MI, heart failure with reduced ejection fraction(HFrEF), and atrial fibrillation(AF). Patients with high resting heart rates who have hypertension, including younger hypertensives under 40, should be prescribed beta-blockers. (11)

A recent 2021 study comparing bisoprolol and metoprolol in hypertension highlights that both molecules are equally effective in controlling blood pressure and heart rate and were also similar with respect to efficacy and tolerability on Global Assessment by both doctors & patients. (12)

Use of Metoprolol in Left Ventricular Dysfunction:

Left-ventricular (LV) hypertrophy is often associated with arterial hypertension, impaired LV myocardial contractility, and LV diastolic dysfunction. Goldstein S et al. conducted a study including 60 patients with LV dysfunction were randomly assigned to either metoprolol succinate group or placebo for 6 months and concluded that treatment with metoprolol succinate is safe and well tolerated and associated with an increase in LV ejection fraction and a decrease in ventricular ectopic beats. (13)

The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial assessed the effects of adding metoprolol succinate or placebo to symptomatic heart failure patients who had received treatment with either an ACEi (enalapril), an ARB (candesartan), or both for 5 months (plus a diuretic in 84% of patients). After 24 weeks of treatment, patients randomized to metoprolol experienced a 53% decrease in mortality compared with a regimen that did not include a beta-blocker. Importantly, adding metoprolol to either enalapril, candesartan, or both resulted in significantly improved LV volumes and ejection fraction. (14)

Application of Metoprolol Post-Acute Myocardial Infarction:

Metoprolol has become part of recommended therapy in acute myocardial infarction in recognition of its significant effect on mortality reduction with less risk of worsening heart failure. In a study published in Frontiers of Cardiovascular Medicine 2021, patients receiving metoprolol treatment following PCI-related periprocedural myocardial infarction decreased subsequent risk of major cardiovascular adverse events (MACE) by 7.1% and revascularization by nearly 5.5%. (15)

Scope of Metoprolol in Congestive Heart Failure:

As per the metoprolol randomized intervention trial in congestive heart failure (MERIT-HF), 34% reduction in total mortality in the metoprolol controlled/extended release group compared with the placebo group. Total mortality or hospitalization for worsening heart failure was reduced by 31%. (16)

Summary:

• As per ESH 2024, Beta-blockers can be considered in the treatment of hypertension with comorbid disorders, such as MI, HFrEF & AF.
• Metoprolol is a widely accepted and safe cardio-selective beta blocker in use for more than 40 years. (18)
• Metoprolol is as effective as bisoprolol in the management of hypertension, with reportedly similar efficacy and tolerability.
• Metoprolol treatment may lead to a significant reduction in the risk of HF, increase LVEF, improve post-PCI outcomes, and reduce major cardiovascular risk events.

References:

1. Edgardo Olvera Lopez et al. Cardiovascular Disease. Stat Pearls Publishing 2024. Bookshelf ID: NBK535419PMID: 30571040

2. MUTHUSAMY, V.V.. BR 08-3 MANAGEMENT OF DYSLIPIDEMIA IN HYPERTENSION. Journal of Hypertension 34():p e545, September 2016. | DOI: 10.1097/01.hjh.0000501492.32355.c5

3. A Sreenivas kumar et al. Cardiovascular disease in India: A 360-degree overview. Med J Armed Forces India 2020; 76(1); PMC6994761

4. Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. Washington (DC): National Academies Press (US); 2010. ISBN-13: 978-0-309-14774-3

5. 2024 European Society of Hypertension clinical practice guidelines for the management of arterial hypertensionEndorsed by the European Federation of Internal Medicine (EFIM), European Renal Association (ERA), and International Society of Hypertension (ISH).

6. Saumrita Ray et al. Role of β-blockers in the cardiovascular disease continuum: a collaborative Delphi survey-based consensus from Asia-Pacific. Current Medical Research and Opinion 2023; 39(12), 1671–1683.

7. Jason Morris et al. Metoprolol. Stat Pearls Publishing 2024. Bookshelf ID: NBK532923PMID: 30422518

8. Writing Committee Members. and ACC/AHA Joint Committee Members. “2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.” Journal of cardiac failure vol. 28,5 (2022): e1-e167. doi:10.1016/j.cardfail.2022.02.010

9. Kumar, Arram Sreenivas; Kumar, Viveka; Shah, Chetan P; Kasturi, Sridhar; Birla, Ashish; Revankar, Santosh; Yadav, Neeraj Kumar. Hypertension Management in Pre- and Post-Percutaneous Coronary Intervention Patients: An Expert Opinion of Cardiologists from India. Journal of the Practice of Cardiovascular Sciences. 2024;10(1):18-24.

10. Gavin WK Wong et al. Blood pressure lowering efficacy of beta‐1 selective beta blockers for primary hypertension. Cochrane Database Syst Rev. 2016 Mar; 2016(3): CD007451.

11. J C Mohan et al. Position of Beta-blockers in the Treatment of Hypertension Today: An Indian Consensus. J of the Asso of Phy of India 2024; 72(10): 83-90.

12. A Dasbiswas et al. Efficacy & tolerability of bisoprolol in comparison to metoprolol in Indian patients with stage-1 hypertension: a multicentre, parallel-group, open-labeled, randomized noninferiority clinical study. European Heart Journal 2021. 42(suppl 1).

13. Sidney Goldstein et al. Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction. Am H Jour 1999; 138(6): 1158-65.

14. R E Willams. Early Initiation of β Blockade in Heart Failure: Issues and Evidence. J Clin Hypertens (Greenwich) 2005; 7(9); PMC8109715

15. Duanbin Li et al. Effects of Metoprolol on Periprocedural Myocardial Infarction After Percutaneous Coronary Intervention (Type 4a MI): An Inverse Probability of Treatment Weighting Analysis. Fron Cardiovas Med 2021;8: 746988

16. O D Freitas et al. The use of metoprolol CR/XL in the treatment of patients with diabetes and chronic heart failure. Vasc Health Risk Manag 2006;2(2):139-44