30

Everyday PracticeTHE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 7, NO. I, 1994

Antihypertensive therapy in the elderlyA. K. KAPOOR, V. C. SAKSENA

INTRODUCfIONThe incidence of hypertension, both systolic and diastolic,increases with age. More than half the elderly populationmay be hypertensive. However, the reluctance to treathypertension in these patients is based on the notion that thetreatment may prove to be harmful. Recent research hashighlighted that one of the general principles in treatinghypertension in the elderly should be to concentrate ondiastolic blood pressure (DBP), as sustained DBP may causeend-organ damage. Cumulative data over several years hasunderlined the fact that the nature and prognostic impor-tance of elevation of DBP v. systolic blood pressure (SBP)may be incorrect. This article attempts to focus on some ofthese issues and impart guidelines on the treatment of hyper-tension in the elderly.

RISKS AND BENEFITSThe main aim of controlling hypertension is to reducemorbidity and mortality from cerebrovascular and cardio-vascular diseases, without increasing morbidity and mortalityfrom other causes.The questions which confront the practitioner are: (i) Is

antihypertensive therapy beneficial in the elderly, (ii) is oneform of therapy better than another, and (iii) does treatmentlower the risks of cardiovascular or cerebrovascular compli-cations in these patients? Several well-known studies such asthe Medical Research Council (MRC) Trial (UK), Veterans'Administrative Cooperative Study (USA) and the NationalBlood Pressure Study (Australia) have provided answers tothese questions.It seems that therapy reduces cardiovascular morbidity

and mortality and the incidence of stroke by one-third inthose with diastolic hypertension. However, several recentstudies show that in persons aged 45 or more, a raised SBPmay be a greater risk factor for subsequent morbidity andmortality due to cardiovascular diseases than an elevatedDBP. Two studies-Systolic Hypertension in ElderlyProgramme (SHEP) and the Medical Research Council Trialon Hypertension in the Elderly-have clearly demonstratedthat drug treatment of isolated systolic hypertension (ISH)in the elderly reduces cerebrovascular, coronary artery andtotal cardiovascular morbidity and mortality.

M. L. N. Medical College, Allahabad. Uttar Pradesh, IndiaA. K. KAPOOR, V. C. SAKSENA Department of Pharmacology

Correspondence to A. K. KAPOOR, 891, Dropdai Bhawan,Kalyani Devi , Allahabad 211003, Uttar Pradesh. India

© The National Medical Journal of India 1994

DEFINITION OF HYPERTENSIONCombined systolic and diastolic hypertension in the elderlyhas been defined as a sustained systolic pressure of> 160 mmHg with a diastolic pressure >90 mmHg. ISH isdefined as a systolic pressure of > 160 mmHg with a diastolicpressure of <90 mmHg. Readings should be taken on severaloccasions before deciding on treatment. The posture of thepatient at the time of recording the blood pressure is impor-tant, since elderly patients may have a considerably lowerblood pressure while standing than while lying down.

INDICATIONS FOR TREATMENTThe available evidence suggests that treatment should beinitiated if DBP is persistently >90 mmHg. The initial treat-ment modality should preferably be non-pharmacological.Similarly, treatment should be considered for patients up to80 years of age with ISH> 160 mmHg. The evidence is notsufficient to recommend treatment in patients over 80.

INITIAL ASSESSMENTIt is important to perform a complete physical examinationand to assess the function of various end-organs with the helpof laboratory tests. In addition, it is desirable to estimate thelevels of serum uric acid and glucose and perform a lipidprofile as these may be abnormal in patients with hyper-tension and are affected adversely by some antihypertensivedrugs.

FOLLOW UPIt is good practice to review the patient every 15 days till thetarget blood pressure is achieved, and later at 3-monthlyintervals. The initial screening investigations should berepeated annually to look for end-organ damage and adversereactions to antihypertensive medication.

NON-PHARMACOLOGICAL THERAPYNon-pharmacological therapy in elderly patients should beadvised with caution, as it may be difficult for them to give uplife-long habits. However, the following measures may betried:

1. weight reduction in obese patients to within 15% of thedesirable weight

2. reduction of dietary sodium to 2-3 g (5 g of sodiumchloride) per day

3. gradual increase in physical activity and regular aerobicexercises (subject to medical fitness)

4. cessation of smoking and the reduction of daily alcoholconsumption to no more than 30 ml

5. practice of relaxation techniques such as yoga andmeditation.

DRUG THERAPY AND ADVERSE REACfIONSThe response to antihypertensive drugs may be modified inelderly patients on account of several factors. These are:

1. lower stroke volume and cardiac output

KAPOOR. SAKSENA : ANTIHYPERTENSIVE TIlERAPY IN TIlE ELDERLY

2. decreased intravascular volume3. higher peripheral vascular resistance4. impaired baroreceptor function5. left ventricular hypertrophy6. subclinical cerebrovascular disease7. reduction of renal function.

These factors may be present individually or in combination,and the dose and regimen of antihypertensive drugs shouldbe modified accordingly.In addition, unnecessary treatment may be started in

patients with 'white coat' hypertension (elevated bloodpressure in the presence of a doctor), and 'pseudohyper-tension' (elevated blood pressure as recorded by asphygmomanometer, while the actual intra-arterial pressure islower). The latter condition is widely prevalent in the elderlydue to atherosclerosis.It is important to observe the following guidelines while

initiating drug therapy:

1. Start with half the normal dose of one drug, preferablyusing it once a day to improve compliance.

2. Control the blood pressure gradually to facilitateautoregulation.

3. The goal of therapy is to reduce blood pressure to160 mmHg systolic and 90 mmHg diastolic and not belowthese levels.

4. Encourage home monitoring of blood pressure to ensurethat treatment is neither inadequate nor excessive.

5. Look out for side-effects. They may reduce complianceand interfere with the quality of life.

6. When selecting the target blood pressure take intoaccount the standing blood pressure.

7. Tailor therapy to individual needs because elderlypatients have poor physical and psychological reserves.

8. Keep the number of pills and their daily dose to a minimum,using once-a-day and slow-release formulations wheneverpossible.

9. Assess the function of vital organs from time to time tomodify the drug regime and dose.

DiureticsDiuretics are the drugs of choice in elderly hypertensivesbecause when used alone they control blood pressure in 80%of the cases. Other advantages are their low cost, convenientdosage regimes, a low incidence of side-effects and thepotentiation of other antihypertensive agents. They reduceintravascular volume and intracellular calcium, therebyinhibiting vasoconstriction. They contribute to the reductionof mortality and complications of hypertension such as heartfailure, renal failure and stroke.The MRC trial concluded that bendrofluazide had a

greater antihypertensive effect, provided better bloodpressure control and greater reduction in the incidence ofstroke than a beta-blocker. Moreover, diuretics are also usedin combination therapy because the majority of antihyper-tensive agents cause sodium and water retention and thisresults in a progressive loss of their antihypertensive effect.By depleting sodium and water, diuretics counter theseadverse effects and potentiate practically all antihyper-tensive drugs.Thiazides have potentially serious side-effects such as

hypokalaemia, hyponatraemia, azotaemia, hyperlipidaemia,

31

glucose intolerance, hypercalcaemia, hyperuricaemia, skinrashes, muscle cramps and impotence. Recently, otheradverse effects of diuretics have been described, particularlytheir interference with glucose and cholesterol metabolism.However, several workers regard these as clinically un-important if diuretics are used as long term treatment.Thiazides reduce urinary calcium excretion, and this maybe beneficial in lowering the incidence of osteoporoticfractures. To minimize these side-effects, thiazides areoften combined with potassium-sparing diuretics such astriamterene. It is advisable to use the lowest effective dose ofthiazides, usually 12.5 mg/day of hydrochlorothiazide or itsequivalent, as adverse reactions are frequent when the doseexceeds 50 mg/day.

Beta-blockersIn general only 20% of elderly patients respond tomonotherapy with beta-blockers because their beta-adrenoceptor responsiveness is decreased and levels of reninare low. However, these drugs may be particularly useful inthose who have resting tachycardia. There has been a reduc-tion in the overall mortality from coronary artery disease andstroke after treatment with metoprolol (a beta-l-selectiveblocker). Beta-blockers may also ameliorate associatedangina and reduce the incidence of cardiac arrhythmias.Metoprolol should be prescribed for mild to moderatehypertension. Of late, labetalol, a combined alpha- andbeta-blocker, has been found to bring about quicker controlof blood pressure with a less negative inotropic effect eventhough it has a tendency to cause orthostatic hypotension.Other side-effects of beta-blockers include fatigue, insomnia,depression, bradycardia, conduction defects, bronchospasmand exacerbation of heart failure.

Calcium channel blockersThese drugs lower blood pressure by blocking slow calciumchannels thereby reducing the inward flux of calcium ionsinto the vascular smooth muscle. The dihydropyridines(nicardipine and nifedepine) are the most potent agents inthis category with a low negative inotropic effect andatrioventricular nodal activity. Even though they are effec-tive in the treatment of mild to moderate hypertension in theelderly, their efficacy in long term management needsfurther evaluation.A single daily dose of calcium channel blockers is slightly

more effective than beta-blockers or angiotensin convertingenzyme (ACE) inhibitors. Calcium channel blockers are alsoindicated if coronary artery disease and arrhythmiasco-exist, because they have few contraindications. They donot alter the levels of the serum electrolytes, lipids orhormones and rarely cause orthostatic hypotension orsymptoms related to the central nervous systems. Theirdisadvantages are their relatively high cost, tendency toprecipitate congestive heart failure due to their negativeinotropic and chronotropic effects and their side-effects ofheadache and oedema. The constipation they cause may beparticularly difficult to manage in the elderly.

ACE inhibitorsIn this group, captopril, enalapril, ramipril and lisinopril arevery useful in the treatment of mild to moderate hyperten-sion, particularly in those with a high plasma renin activity.

32 THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 7, NO.1, 1994

TABLEI. Appropriate antihypertensive drug selection in elderly patients with co-existingdisease

Co-existing disease Diuretics Beta-blockers Calcium ACEchannel blockers inhibitors

None ++ + + +Congestive heart failure ++ ++Angina + ++ ++ +Asthma/chronic obstructive ++ + +pulmonary disease

Peripheral vascular disease + ++Gout + + +Diabetes + +Hyperlipidaemias + + +Hypokalaemia + + ++

+ + first line drug + Suitable alternative - Usually contraindicated • A high proportion of patientswith peripheral vascular disease will have occult renovascular disease

They are usually well tolerated. Some of them have beenshown to reverse left ventricular hypertrophy. Unlikebeta-blockers, ACE inhibitors do not disturb short termmemory and are safe for use in asthmatics and in patientswith congestive heart failure. In diabetic patients, ACEinhibitors are effective, reduce proteinuria and can be usedwithout altering daily insulin requirements. The secondgeneration ACE inhibitors-ramipril and lisinopril-combine well with diuretics and calcium antagonists, con-serve potassium and cause no postural hypotension oradverse metabolic effects.In some elderly patients, ACE inhibitors may cause a

dangerous fall in blood pressure, particularly in those withcardiac failure and those taking diuretics. All ACE inhibitorscan cause cough, angioneurotic oedema and rashes. Otheradverse effects include renal damage (particularly in patientswith decreased renal function, bilateral renal artery stenosisor stenosis in a solitary functioning kidney), bone marrowsuppression and altered taste. They may cause dangeroushyperkalaeroia if concomitantly administered with potassium-sparing diuretics.

Other agentsCentrally acting alpha-2 agonists. Other agents are advisable

if a drug such as a beta-blocker is contraindicated (e.g.in asthmatics). These include methyldopa, clonidine,'guanabenz and guanfacine which act by decreasing thesympathetic outflow. Methyldopa and clonidine are stillbeing used in elderly hypertensive patients but they fre-quently cause drowsiness and fatigue. Due to their adversecentral nervous system side-effects the use of centrally actingsympatholytics such as reserpine has declined.

Alpha-I-blockers. The two currently available selectivealpha-I-receptor antagonists, prazosin and terazocin, evokevasodilatation and lower blood pressure without reflextachycardia or compromise of cerebral blood flow. Thesehave favourable effects on plasma lipids. They reduce bothpreload and afterload and benefit patients in congestiveheart failure. However, they may cause severe orthostatichypotension and should be used with caution in patients withcoronary artery or cerebrovascular disease. Initially, it ispreferable to use small doses of alpha-l-blockers at bed time.

Direct acting vasodilators. Hydrallazine , which waspreviously used as a third step drug, can effectively bringdown blood pressure in the elderly. Even though it is welltolerated and does not cause orthostatic hypotension, thelack of regression of left ventricular hypertrophy makes it aless attractive option than other drugs. It elicits less reflextachycardia in the elderly than in younger patients and hencethe concomitant use of a beta-blocker may not be required.Since it causes sodium retention, it should be used incombination with a diuretic.

Drug combinationsIn elderly patients with systolic and diastolic hypertensionfailing to respond to a single drug, a combination of drugsmay be tried. Those frequently used include: diuretics andbeta-blockers, diuretics and ACE inhibitors, alpha- andbeta-blockers, and beta-blockers and calcium channelblockers. However, it should be stressed that optimaltherapy should be individualized and the quality of lifeshould be assessed frequently while evaluating the riskand benefits of therapy. The choice of an appropriateantihypertensive agent for various co-existing diseasesis listed in Table I.

CONCLUSIONS1. Strong evidence suggests that raised diastolic and systolicblood pressures constitute risk factors for the develop-ment of cardiovascular complications. Therapy results inlowering cardiovascular morbidity and mortality.

2. Drug treatment in elderly hypertensive patients should bestarted with low doses, and increased only when indicated,keeping in mind adverse reactions such as orthostatichypotension and end-organ dysfunction.

3. Current evidence favours diuretics as the first line of treat-ment. The use of other agents is guided by the presence ofco-existing disease. The absence of metabolic adversereactions makes calcium channel blockers and ACEinhibitors attractive antihypertensive agents.

4. Combination drug therapy is required in almost half of thepatients and it should be selected on the basis of diseaseprofile, complementary mode of action, adverse reactionsand drug interactions.