Can therapy be discontinued in well-controlled hypertension?

Can therapy be discontinued in well-controlled hypertension?
Hossam Kandil
Professor of Cardiology, Faculty of Medicine, Cairo University
INTRODUCTION—Among patients with mild hypertension who are well controlled for at least one year, it may be possible to gradually diminish or discontinue antihypertensive therapy once [1-3]. In a review of all published series of planned withdrawal, 42 percent of selected patients with mild hypertension (140-149/90-95 mmHg) were found to remain normotensive for 12 months or longer off medication [1]. In a more heterogeneous group of well-controlled hypertensives, only 18 percent remained normotensive after stopping therapy [4]. Patients who were more likely to tolerate cessation of antihypertensive therapy were those with milder hypertension, on fewer and lower doses of antihypertensive medications, and adherent to lifestyle modifications (eg, weight loss and sodium restriction). These findings suggest that full withdrawal may not be possible in patients on multiple drugs, but it may be possible to more gradually taper antihypertensive doses and agents [2].
The value of stopping successful drug therapy is uncertain, however lower doses are associated with a lower incidence of drug-induced side effects. It seems reasonable to reduce the
dose in well-controlled patients, and withdraw if tolerated, with continued close surveillance of the BP.
MECHANISM — The mechanism of persistent normotension with less intensive drug treatment is incompletely understood. Long-term blood pressure control may reverse hypertension-induced arteriolar hyperplasia thereby reducing vascular resistance directly and by reducing the sensitivity to vasoconstrictors such as angiotensin II and norepinephrine [5].
An alternate explanation was suggested by the Medical Research Council trial, which studied this issue in a controlled fashion [2]. Thiazide or beta blocker therapy was either continued or switched to placebo after five to six years of normotension. Within nine to twelve months, the patients switched to placebo had a rise in blood pressure to a level equivalent to that in a separate, mostly nontreated placebo group. However, up to 45 percent of patients in both groups were normotensive.
These findings suggest that effective therapy may not alter the course of the disease, but that many patients being treated for mild hypertension are in
fact normotensive or become normotensive by compliance with nonpharmacologic therapies. Several factors may contribute to this effect, particularly initial mislabeling and dietary modification. In addition, the ability to lower drug dosage in many patients may be due to the initial use of excessive dosing.
Mislabeling — Many patients who are at first diagnosed as having mild hypertension are actually normotensive, with the elevation in blood pressure representing an acute stress response induced by visiting the physician. This phenomenon, called «white-coat» hypertension, illustrates the importance of repeated blood pressure measurements over several months in the office or, preferably, by multiple home measurements before considering an asymptomatic patient with no end-organ damage to be truly hypertensive. Sequential studies have shown that the BP drops by an average of 10 to 15 mmHg between the first and third office visits in newly diagnosed patients with mild hypertension, with a stable value not being achieved until more than six visits in some cases [6].
Dietary modification— Patients who are initially hypertensive can, with dietary modification
alone, lower their BP into the normal range. . The triad of dietary sodium restriction, weight reduction in the obese, and avoidance of excess alcohol intake may be particularly important when step-down therapy is being considered [7-10]. Persistent normotension following drug withdrawal may be most likely among nonobese patients who restrict sodium, and overweight patients who lose weight [7]. One study, for example, evaluated the effect of these lifestyle changes following the discontinuation of antihypertensive medications after several years of excellent control. At four years, 39 percent of patients with dietary modification remained normotensive, compared to less than 5 percent of a control group[8].
Excessive doses — It is now clear that previous dosing recommendations for many antihypertensive drugs were too high, leading to an increased incidence of side effects while producing little if any further reduction in BP. In many patients treated with 50 to 100 mg of hydrochlorothiazide, for example, lowering the daily dose to 50, 25, and even 12.5 mg can be achieved without loss of blood pressure control [3,11]. Furthermore, 12.5 or 25 mg of hydrochlorothiazide (or its equivalent) as initial therapy is often as effective as 50 to 100 mg [12,13].
Although there is often a greater diuresis with the higher dose, the ensuing rise in renin and therefore angiotensin II leads to an increase in vascular resistance that may counteract the fall in blood volume. Low-dose therapy also minimizes the incidence of hypokalemia, hyperuricemia, and mild elevations in the plasma cholesterol and glucose concentrations [12,13].
WITHDRAWAL SYNDROMES
One last point must be emphasized. Abrupt cessation of therapy with a short-acting beta blocker (such as propranolol) or the short-acting alpha-2-agonist clonidine can lead to a potentially
fatal withdrawal syndrome [14]. This syndrome is characterized by increased sympathetic activity (due to adrenergic receptor upregulation during the period of decreased sympathetic activity), rebound hypertension, and possible accelerated angina or myocardial infarction. Gradual discontinuation of these agents over a period of weeks should prevent this problem.
SUMMARY
Among patients with mild hypertension (140-149/90-95 mmHg) who are well controlled for at least one year, it may be possible to gradually diminish or discontinue antihypertensive therapy. Patients who are more likely to tolerate cessation of antihypertensive therapy are those with milder hypertension, on fewer and lower doses of antihypertensive medications, and adherent to lifestyle modifications such as weight loss and sodium restriction.
The mechanism of persistent normotension with less intensive drug treatment is not completely understood. Long-term blood pressure control may reverse hypertension-induced arteriolar hyperplasia that contributes to the rise in blood pressure. Alternatively, many patients being treated for mild hypertension may have had «white-coat» hypertension or have successfully
lowered their BP into the normal range with dietary modification. In addition, previous dosing recommendations for many antihypertensive drugs were too high, allowing the step-down of medication.
Abrupt cessation of therapy with a short-acting beta blocker or the short-acting alpha-2-agonist clonidine can lead to a potentially fatal withdrawal syndrome. This syndrome is characterized by increased sympathetic activity, rebound hypertension, and possible accelerated angina or myocardial infarction. Gradual discontinuation of these agents over a period of weeks should prevent this problem.)