journal o$ Internal Medicine 1994; 235: 577-579

EDITORIAL

Stopping antihypertensive drug therapy in elderly people-a dangerous experiment ?

Introduction The indications for starting drug treatment in hy- pertension are still the subject of lively discussion. During the last few years new guidelines have been suggested both by the International Society of Hypertension (ISH)/World Health Organization (WHO) [l] and by the Joint National Committee of the United States [2]. Different expert groups have suggested different cut-off points for when to start drug treatment if changes in lifestyle have failed. In particular, there has been considerable debate about the treatment of hypertension in elderly people, but during the last 2 years several well-controlled studies have suggested that elderly hypertensive people benefit greatly from well-selected and cautious antihypertensive drug treatment [ 1-31. The number of elderly hypertensives people in whom drug treat- ment is proposed has increased, particularly after the results from the SHEP study where it was shown that elderly people with isolated systolic hypertension (SAP > 160 mmHg) also seem to benefit consider- ably from drug treatment [3].

At the same time the expenses for health care have increased, and in those countries where social welfare has paid for most of the cost of the antihypertensive drugs, difficulties in the economy have increased the share to be paid by the patients themselves. Thus, for obvious reasons unnecessary drug treatment should be avoided.

Over the years several trials have been performed in order to elucidate the risk and success rate of withdrawing antihypertensive treatment in patients of different ages with different degrees of hyper- tension, treated with different drugs over different periods of time.

In most of these studies-usually carried out in middle-aged subjects-withdrawal of treatment was rarely successful, and blood pressure increased to cut-off points for restarting treatment in more than 80% of the patients within 1 year [4-61.

There have been few withdrawal studies in elderly people, and therefore the study from Sweden

published in this issue of the Journal-a 5-year prospective study of withdrawal of antihypertensive treatment-is of greater interest [ 71.

Hypertensive patients aged 70-84 years were recruited for a multicentre trial (the STOP pilot trial). In total, 367 patients (from 22 health centres) were planned to start a withdrawal phase: Of these, 3 4 did not fulfill the complete withdrawal programme for various reasons thus 3 3 3 patients were candidates for the present study. Of these 333 patients, data for follow-up were incomplete in 1 5 patients, but data on survival were complete for all. Thus, the report contains 333 patients followed for 5 years.

During this study period, 74 (22.2%) died. In total there were three fatal and 16 nonfatal strokes, and 33 fatal and nonfatal myocardial infarctions. The death-rate was compared in the various types of patients for: (i) those who remained without antihypertensive treatment, (ii) those who had to restart treatment because of hypertension, and (iii) those who restarted treatment for other reasons such as palpitations, angina pectoris, anxiety, headache, unwillingness to remain without drugs, oedema and congestive heart failure.

The results showed that with respect to hazard of cardiovascular events and death, the risk in (i) was not higher than in (ii) or in (iii). For the total number of cardiovascular events, the risk ratio in (i) was significantly lower than in (ii) and (iii).

The majority of the patients had to restart treat- ment, 60% within 1 year. In order to find the predictors of restarting the treatment, a test closely related to Gehan's test was applied. By this test it was shown that age did not have any correlation with the duration of the unmedicated period, nor did the duration of drug treatment before withdrawal. The authors were able to demonstrate significant correlations for four variables: mono- or combined therapy, dose level, systolic blood pressure and diastolic blood pressure before withdrawal of treat- ment. As expected, patients on low-dose monotherapy and those with low blood pressure had a greater chance of remaining untreated over a

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longer period. The authors conclude that during the state of no treatment (after treatment withdrawal), the patients had a lower total mortality risk than the general Swedish population matched for age and sex. They also had a lower risk of cardiovascular events than those in the treated states. The results suggest that with frequent check-ups, withdrawal of anti- hypertensive therapy in elderly people can be tried without increased risk of cardiovascular events.

Ideally, studies on the benefit and risks of stopping antihypertensive treatments should be undertaken in well-defined patient groups treated with one type of antihypertensive drug during a defined period of time, and then randomized to stopping or to con- tinuing. The event rates in the two groups should then be followed closely. It appears that no such large study in elderly people exists. In the present study [ 71 the original inclusion criteria imply that patients with different types of other diseases or very high blood pressures (systolic pressure > 230 mmHg or diastolic > 120 mmHg), were not included. Therefore, the patients in the present study were fairly healthy and during the inclusion period able to cope on their own. The patients were followed at fixed visits and often with frequent check-ups the first few months after withdrawal of antihypertensive medication. Before withdrawal most of the patients (n = 218) had been on single-drug diuretics (in- cluding potassium supplementation or potassium sparing agents). Only 39 were on single-drug beta blockers and the rest were on drug combinations. The incidence of target organ damage before with- drawal is not presented. Thus, the results of the trial appear to be largely valid for elderly subjects (70-84 years) mainly on low-dose diuretic monotherapy for a certain time and with rather low blood pressure (mean value on drugs about 170/90 mmHg).

How could these results be applied to 'daily life ' general practice? In a recent study from Bergen, Norway, Straand et al. [8] followed 33 hypertensive subjects aged 75 years or more recruited from general practice. After with- drawal of diuretics the patients were followed for 6 months. Diuretic treatment had to be reinstituted in 1 5 patients despite very high limits for restarting treatment: 230/120 mmHg. In this small group of patients (n = 33) there were six sudden, severe cardiovascular events, four of which were life- threatening : one patient suffered an ischaemic

cerebrovascular stroke and had to be cared for in a nursing home, one patient was found lying on the floor with hemiparesis caused by a cerebrovascular accident 4 months after diuretic discontinuation and was referred to a nursing home, one patient de- veloped heart failure with pulmonary congestion and another patient developed acute heart failure. This study was started before the STOP trial results were published, and it is reported that eight patients had blood pressures in the withdrawal period that exceeded the threshold values of 180/105 mmHg used in the STOP study. The authors also emphasize that three of the four life-threatening cardiovascular events occurred 4 months or later after the diuretic withdrawal. The patients had been examined several times between withdrawal and the event without showing increases either in blood pressure or in body weight.

Is it possible to increase the success rate after stopping drug treatment by improvement of lifestyle ?

Langford et al. [9] followed patients from the Hyper- tension Follow-up Programme (HDFP) study who were randomized into a control group and dis- continued medication groups with and without delivery intervention. At 56 weeks. 50% of those who were no longer receiving medication remained normotensive according to the study criteria. Ran- domization either to a weight-loss group or to a sodium-restriction group increased the probability of remaining without drug therapy. Thus, these results emphasized the importance of weight control and a low-salt diet when antihypertensive drugs are with- drawn.

Conclusions Based on the Swedish study published in this issue of the Journal [7] and a few other studies of withdrawal of antihypertensive treatment in elderly people, the following conclusions seem appropriate.

In elderly patients with uncomplicated hyper- tension who have been on low-dose monotherapy with diuretics and who after months or years have achieved good blood pressure control, a gradual reduction in dose could be tried provided the patients have no signs of angina pectoris, heart failure or oedema. Moderate reduction in salt intake and a reduction in body weight in overweight patients will

EDITORIAL 579

probably increase the success rate with respect to remaining without antihypertensive treatment.

It is most important that such subjects are followed very carefully and that special arrangements are made to make sure that the patients will arrive for follow-up control. If the blood pressure increases-which it most probably will do in the majority of the patients-the cut-off point for restarting should be defined according to the STOP hypertension and SHEP studies. A permanently increased diastolic arterial pressure of 2 105 mmHg or a permanently increased systolic arterial pressure of 2 180 mmHg would seem reasonable guidelines for restarting in patients 70 + years old. In subjects aged 60-70 years, 100 mmHg diastolic and 170 mmHg systolic would seem reasonable cut-off points El-31. If a patient develops preclinical car- diovascular disease (i.e. left ventricular hypertrophy) treatment should be restarted [lo]. However, a serious problem is that perhaps the most tragic outcome-a severe but nonfatal stroke-usually appears without warning, and the question remains: could a low dose of a cheap diuretic have prevented it? It should be noted that 1-year therapy with a thiazide diuretic plus potassium will cost about 150 Nkr. The cost of hospitalization and nursing home care after a severe stroke is about 0.3 to 0.5 mn Nkr per year.

Why normalization of blood pressure is obtained in a small subgroup of patients is not known. Perhaps the most probable explanation is that the diagnosis has initially been made on shaky grounds and might have been incorrect [7]. Another possibility, of course, is that the treatment has reversed structural changes in the arterioles, because elderly hyper- tensive people, from a haemodynamic point of view, suffer from increased total peripheral resistance with a low cardiac output [ll]. Assuming that the patient has not developed myocardial infarction, it is im- probable that diuretic therapy should have induced a reduction in cardiac output that also would remain after drug withdrawal [1 I ] .

A depressing conclusion from the withdrawal studies is that in the vast majority of hypertensive patients temporary drug treatment will not cure the hypertension. Nevertheless, in some patients with relatively low blood pressures, therapy may be withdrawn. If this is done because of minor side- effects or for other reasons, withdrawal should be gradual, and it is vital that the patient is followed very closely in the following weeks and months and

that proper antihypertensive therapy is reinstituted if the blood pressure increases. If a close follow-up of the patient is not possible, then withdrawal will be a risky gamble and should not be attempted.

PROFESSOR P. LUND-JOHANSEN Department of Heart Disease

Haukeland Hospital University of Bergen

Bergen, Norway

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1444-55.

Received 26 November 1993, accepted 6 December 1993.

Correspondence: Professor Per Lund-Johansen, Department of Heart Disease. 5021 Haukeland Hospital. Bergen, Norway.