Clinical Research Article
 

Betablockers in combination with other antihypertensives
RJ Manjuran MD,DM,PGDHRM,FCSI,FACC

Director, Pushpagiri Heart Institute Thiruvalla

ABSTRACT

Betablockers (BB) have been recognized as effective antihypertensive agents.  Recent meta analysis of various hypertension trials have brought to light the inferiority of BB compared to other antihypertensives as a first line monotherapy agent.  Combination of BB with dihydropyridine Calcium Channel Blocker (CCB) has been especially effective in smooth control of BP.  Combination  of diuretics with BB should be avoided in patients with dyslipidaemia and in those prone to develop diabetes.  BB can be combined with vasodilators and α blockers with good therapeutic benefit.  BB with angiotensin converting enzyme inhibitors/ angiotensin receptor blockers (ACEI/ARB) is not an ideal combination as both the drugs act in the renin – angiotensin system.    However, in hypertension with certain  specific clinical situation this combination is useful.  BB as a monotherapy agent is being less preferred in the treatment of hypertension based on recent evidence while in suitable combination it is a valuable antihypertensive. 

Introduction

Beta blockers along with diuretics were considered as first line antihypertensives based on the data from hypertension trials of 1980s1. However, in recent meta analysis beta blockers (BB) were found to be less effective in reducing stroke, myocardial infarction and death compared to other antihypertensives2,3. Proper understanding of effectiveness of BB as antihypertensive requires systematic analysis of the available data. Eventhough BB as a first line antihypertensive has fallen out of repute, it is still useful in combination with other antihypertensives. Kahn and
Mc Alister2 has suggested that the inferiority of BB is limited to the elderly. However at present, there are inadequate data to make valid comparison of BB in the young versus elderly patients. BB induced reduction in blood pressure was less compared to calcium channel blockers4 or angiotensin receptor blockers5. The BB lower brachial systolic blood pressure while central aortic systolic pressure may remain the same. This is because of the arterial wave returning from periphery during systole itself because of longer ejection time and reduced heart rate. This can play a major role in BB not able to bring down stroke and myocardial infarction.

Many drugs have been approved for the treatment of hypertension like diuretics, BB, Calcium Channel Blockers (CCB) angiotensin converting enzyme inhibitors (ACEI) angiotensin receptor blockers (ARB), direct vasodilators and centrally acting drugs. These drugs are effective as monotherapy in mild hypertension, but most of the patients whose target for reduction in blood pressure is equal to or more than 20/10 mm of Hg, require combination treatment6.

Why combination treatment in Systemic hypertension?

Majority of patients of hypertension will require more than one drug for the control of blood pressure (BP) to the desired level. The combination therapy has many advantages.
1. In combination treatment, lower dose of each drug can achieve good BP control with very little or no side effects.
2. All patients do not respond to same drugs and hence combination treatment is more effective.
3. Combination medications can be synergestic in BP reduction.
4. The drugs with varying modes of action can result in longer and smoother control of BP.
5. In properly selected drug combinations side effects of one can be neutralized by the other.
6. Combination therapy is more organ protective because of smooth blood pressure control.
7. Blood pressure reduction to target levels can be achieved more frequently.
8. Cost of treatment can be brought down by accepted fixed dose combinations,
9. Less frequent administration along with lower side effects leads to better patient compliance to combination medication.
BBs have a number of advantages as a combination antihypertensive.It combines well with diuretics, dihydropyridine calcium channel blockers or vasodilators and in combination can nullify the tachycardia induced by CCB and vasodilators.

Betablockers and Diuretics
It is one of the earliest antihypertensive drug combinations. Diuretics can stimulate

Correspondence:Dr.R.J. Manjuran, Director, Pushpagiri Heart Institute, Thiruvalla, Kerala, India
Email: [email protected]

Indian Heart J. 2010; 62:146-147
 
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Betablockers in Combination with other Anithypertension
 
 

rennin release while BB helps to reduce renin levels. BB are potassium sparing while most diuretics cause potassium depletion. However, this combination has few disadvantages like rise in peripheral resistance, unfavorable alteration in lipid fractions and higher risk of inducing diabetes mellitus. Hence in patients with dyslipidaemia and high risk of developing diabetes, this combination is to be avoided7.

Value of this combination has been proved in various clinical trials8,9. However in the recently concluded trial, BB in combination with diuretics was found to be inferior to CCB + ACEI combination4. BB with diuretic combination is most effective in patients with systolic hypertension with anxiety and sinus tachycardia.

Betablockers and Calcium Channel Blockers

BB can be effectively combined with dihydropyridine CCB like amlodipine or nifedipine or felodipine with synergestic effect on blood pressure reduction10. BB in combination with CCB is ideal combination in patients of hypertension with chronic stable angina11.

Dihydropyridine CCB can cause reflex tachycardia which can be counteracted by BB. Suppression of rennin secretion by BBs can potentiate the vasodilatory effect of dihydropyridine CCB10. The theoretical benefits of combining BB and CCB have been confirmed in clinical investigation12.

Non dyhydropyridine CCB like verapamil and diltiazem in combination with BB can cause symptomatic bradycardia and hence should be used with caution or better avoided.

Betablockers and Vasodilators

Beta blockers in combination with vasodilators like hydralazine and α blockers is beneficial in treating hypertension. BB can abolish the reflex tachycardia of vasodilators and α blockers and can have synergestic BP reducing effect.

Beta blockers in combination with ACEI/ARB

BB in combination with ACEI/ARB is not recommended as the preferred initial antihypertensive drug combination13. This is because both BB and ACEI/ARB inhibit the renin – angiotensin system. BB in combination with ACEI/ARB is beneficial in patients of systemic hypertension with:

 


a. Ischaemic heart disease and ventricular dilatation.
b. Atrial fibrillation, and
c. Ventricular dilatation and heart failure

Treatment with ACEI/ARB can result in upregulation of renin which can be prevented by the concomitant use of BB.

References:-

1. The Sixth report of the Joint National Committee on Prevention, Detection, Evaluation and
Treatment of High Blood Pressure. Arch. Intern.Med 1997;157:2413-46
2. Khan N, McAlister FA. Re examining the efficiency of betablockers for the treatment of hypertension. A meta – analysis. CMAJ 2006;174: 1737 – 42
3. Lindholm LH, Carlberg B, Samuelsson O; Should betablockers remain first choice in the treatment of primary hypertension? A meta-anyalysis . Lancet 2005;366:1545-53
4. Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, et al.Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA): A multicentre randomized controlled trial. Lancet 2005;366:895-06
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8. Ekbom T, Dahlof B, Hansson L, Lindholm L, Schersten B, WEester P-O, Antihypertensive
efficacy and side effects of three beta blockers and a diuretic in elderly hypertensives: a
report from the STOP Hypertension study. J Hypetens 1992;10:1525-30.
9. Medical Research Council Working Party. MRC trial of treatment of mild hypertension: Principal results. Br Med J 1985;291:97-04.
10. Dahlof B et al. Improved antihypertensive efficacy of the felodipine metoprolol extended release tablet compared to each drug alone. Blood Press 1993;2 (Suppl 1):37-45.
11. Gibbons RJ, Chatterjee K, Daley J, et al. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina. J Am Coll Cardiol. 1999;33:2092-2197
12. Geddes JS. Calcium antagonists and beta blockade-a useful combination, Postgrad Med J. 1983;59 Suppl 2:62-9
13. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): Summary. BMJ 2004;328:634-40

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Indian Heart J. 2010; 62:146-147