Metoprolol: Applicability in Young Hypertensives in India

Hypertension affects 1 in 8 adults aged between 20 and 40 years. The prevalence of hypertension among adults in India is about 25 to 42% and three times more prevalent in young men. (1)

Hypertension is attributable to 10.8% of all deaths in India. Its prevalence has been on a steep rise over the past three decades both in urban and rural parts of the country. This burden is expected to rise two times from 118 million in 2000 to 213.5 million by 2025. It was estimated that 16% of coronary artery disease (CAD), 21% of peripheral vascular disease (PVD), 24% of acute myocardial infarction (AMI), and 29% of strokes are attributable to hypertension. (2)

The general treatment targets of blood pressure are aimed at least 130/80 mmHg for almost all patients. In patients younger than 65 years, systolic blood pressure should be aimed to be <130 mmHg. In most patients, a blood pressure goal of at least 130/80 mmHg is recommended. Lifestyle interventions are reinforced in all stages of hypertension. (1)

Pathophysiological Factors Contributing to Hypertension- Importance of Sympathetic Overdrive in Indian Context

Increased arterial stiffness due to renin angiotensin aldosterone system (RAAS) activation and increased sympathetic overactivity due to stress have been implicated as primary factors for hypertension. It is noteworthy that the prevalence of sympathetic overactivity (SO) in newly diagnosed hypertensive patients in India has been reported to be about 62.42%. (1)

Sympathetic overactivity (SO) plays an important role in the development of both hypertension and its related cardiovascular disorders. SO causes an increase in heart rate, cardiac output, peripheral vascular resistance, and sodium reabsorption in the kidney and a consequent elevation of systemic blood pressure. The reported symptoms of SO include restlessness, inappropriate sweating, tremors in hands, and fast speech (3)

Critical Relevance of Beta-Blockers in Hypertension:

Beta-blockers have the potential to have a special place in the management of hypertension in young adults in India because sympathetic over-activity is one of the factors implicated in the development of hypertension.

Beta-blockers are equally effective as compared to angiotensinconverting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), thiazides, and calcium channel blockers in reducing cardiovascular events in younger and older individuals over 65 years with hypertension. (4)

Metoprolol is a cardio-selective beta-1-adrenergic receptor inhibitor. Metoprolol competitively blocks beta1-receptors with minimal or no effects on beta-2 receptors. (1) In young patients, hypertension is characterized by a marked adrenergic overdrive that could be effectively treated with beta-1 selective beta-blockers like metoprolol. (5)

BetaBlockers in Hypertension: Look at National and International Guidelines:

ESH Guidelines:

Beta-blockers have been shown to be specifically useful for the treatment of hypertension in specific situations such as symptomatic angina, for heart rate control, post-myocardial infarction, heart failure with reduced ejection fraction (HFrEF), and as an alternative to ACEIs or ARBs in younger hypertensive women planning pregnancy or of child-bearing potential.(6)

Beta-blockers are used for controlling heart rate (>80beats/min) in young hypertensive adults. (7) Second-generation (cardio-selective) and third-generation (vasodilating) beta-blockers are preferred in all clinical scenarios. (6)

Metoprolol Use in Hypertension-Review of Literature:

As per a recent report, metoprolol succinate accounts for more than half of the beta-blockers dispensed in New Zealand for the management of hypertension and other cardiovascular conditions and was the eighth most prescribed medicine overall in 2023. (8)

A cross-sectional observational Indian survey using a structured questionnaire showed that Metoprolol was the preferred beta blocker by almost 64% of doctors in India. The objective for the selection of beta-blockers by the majority of clinicians was sympathetic overactivity. (1)

As per the Indian consensus published in 2024, beta-blockers can be considered in the treatment of Hypertension and hypertension with comorbid disorders, such as myocardial infarction (MI), HFrEF, and atrial fibrillation (AF). Patients with high resting heart rates who have hypertention, including younger hypertensives under 40, could be considered for the clinical application of beta-blockers. (9)

Metoprolol on the Therapeutic Landscape of Beta-Blockers

A recent study comparing bisoprolol and metoprolol in hypertension suggested 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 and patients. (10) Metoprolol is as effective as other beta1 selective blockers like nebivolol and bisoprolol. (11,10).

Metoprolol use also helps in reducing the risk of hospitalization in heart failure, one of the long-term complications of hypertension. Metoprolol is as effective as carvedilol and nebivolol in terms of prevention of future cardiovascular events in hypertensive patients. (11)

Another recent study demonstrated that metoprolol and nebivolol achieved comparable effects on the control of blood pressure during exercise among patients with hypertension. (12)

Summary:

• Beta-blockers are among the preferred antihypertensives in young patients with hypertension as well as among those associated with other comorbid conditions.
• Metoprolol is an effective and safe cardio-selective beta-blocker for the management of hypertension.
• Metoprolol is preferred by the majority of Indian clinicians in young hypertensive patients due to sympathetic overdrive, based on published literature. (1)
• Metoprolol treatment is also associated with a reduced risk of future CV events in hypertensive patients.

References:

1. Uday Jadhav et al. Hypertension in Young Adults in India: Perspectives and Therapeutic Options amongst Clinician’s in a Cross-Sectional Observational Study. Journal of The Association of Physicians of India 2021;69: 68-73

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

3. TNC Padmanabhan et al. Prevalence of sympathetic overactivity in hypertensive patients – A pan India, non-interventional, cross-sectional study. Indian Heart J. 2014; 66(6): 686–690.

4. Thomas C Hinton et al. Investigation and Treatment of High Blood Pressure in Young People: Too Much Medicine or Appropriate Risk Reduction? Hypertension 2019; 75(1).

5. 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, 39(12), 1671–1683.

6. 2024 European Society of Hypertension clinical practice guidelines for the management of arterial hypertension Endorsed by the European Federation of Internal Medicine (EFIM), European Renal Association (ERA), and International Society of Hypertension (ISH).

7. Giuseppe Mancia et al. Individualized Beta-Blocker Treatment for High Blood Pressure Dictated by Medical Comorbidities: Indications Beyond the 2018 European Society of Cardiology/European Society of Hypertension Guidelines. Hypertension 2022; 79 (6): 1153-1166.

8. Beta-blockers for cardiovascular conditions: one size does not fit all. BPAC nz Better Medicine 2024.

9. 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.

10. 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).

11. Seng Chan you et al. Comprehensive Comparative Effectiveness and Safety of First Line β-Blocker Monotherapy in Hypertensive Patients: A Large-Scale Multicentre Observational Study. Hypertension 2021; 77(5).

12. Huseyin Ugur Yazici et al. Effects of Metoprolol and Nebivolol on Exercise Blood Pressure in Patients with Mild Hypertension. The Scientific World Journal 2013.