Tapering and discontinuing antihypertensive medications

INTRODUCTION — The majority of patients with hypertension will require lifelong antihypertensive drug therapy to control their blood pressure. However, a minority of patients are able to achieve normotension with a consistent low-sodium diet; others have well-controlled blood pressures with a single medication. When blood pressure in these patients is consistently at or below target blood pressure, many wonder whether antihypertensive drug therapy can be gradually diminished or even discontinued. The issue of discontinuation of drug therapy also arises in patients who develop symptoms related to low blood pressure.

The discontinuation of antihypertensive drug therapy in patients with controlled blood pressure is discussed in this topic. A general approach to drug deprescribing is presented elsewhere. (See "Deprescribing".)

CANDIDATES FOR ANTIHYPERTENSIVE TAPERING — Patients experiencing adverse effects from antihypertensive therapy, including symptomatic hypotension, should have their medication tapered regardless of their history of hypertension-related complications. These patients may also warrant a more rapid and carefully monitored taper of medications. (See 'Approach to tapering antihypertensives' below.)

Among patients without adverse effects from their antihypertensive regimen, candidacy for medication tapering depends upon the presence or absence of hypertension-mediated organ damage:

●Patients without hypertension-mediated organ damage who are consistently at their blood pressure goal are candidates for antihypertensive tapering.

●Conversely, patients who have hypertension-mediated organ damage should not have antihypertensive therapy tapered, even if they are consistently at their blood pressure goal, due to the risk of worsening existing disease [1]. Such patients include those with hypertensive cardiomyopathy, past history of hypertensive emergency, and others. (See "Overview of hypertension in adults", section on 'Complications of hypertension'.)

PREDICTORS OF SUCCESS WHEN TAPERING ANTIHYPERTENSIVES — Most studies find that only a limited proportion of patients with hypertension can maintain normal blood pressure during long-term follow-up without medication [2]. In one study, approximately 40 percent of patients on stable medication remained free from antihypertensive drugs at one year after discontinuation [3,4], and approximately 25 percent remained off therapy at two years [4]. A larger fraction can successfully decrease the number and/or dose of medications taken [3,5,6].

Predictors of success when discontinuing or reducing antihypertensive drug therapy include the following [3-5,7]:

●Lower pretreatment blood pressure – Patients with lower blood pressures prior to initiation of antihypertensive medication are more likely to maintain normal blood pressure when therapy is reduced or withdrawn [7,8].

●Adherence to lifestyle modifications – Lifestyle modifications, including dietary sodium, weight reduction in patients with obesity, regular exercise, and avoidance of excess alcohol intake, are fundamental components of antihypertensive treatment that may reduce medication requirements and support sustained discontinuation over time [9].

One trial evaluated the effect of lifestyle changes following the discontinuation of antihypertensive medications after several years of excellent control. At four years, 39 percent of patients assigned lifestyle modifications remained normotensive, compared with less than 5 percent of those in the control group [10]. In another trial of older adults undergoing antihypertensive drug discontinuation, the composite endpoint of cardiovascular event-free survival plus persistent normotension (off of medications) at two years was twice as likely among those assigned to weight loss and sodium reduction compared with those assigned usual care (50 versus 24 percent) [11].

Recommended lifestyle modifications in the treatment of hypertension are discussed separately. (See "Diet in the treatment and prevention of hypertension" and "Salt intake and hypertension" and "Overweight, obesity, and weight reduction in hypertension".)

●Younger age – Successful discontinuation of antihypertensive medication is more likely in younger adults [3]. However, an attempt at tapering antihypertensive therapy is still appropriate in older patients. In one study, 18 percent of patients aged 65 to 84 years successfully stopped antihypertensive medication and maintained normotension [6]. In a separate randomized, nonblinded trial of 569 patients aged 80 and older treated with multiple antihypertensive medications, patients who reduced their antihypertensive regimen by one medication had similar systolic blood pressure at 12 weeks when compared with patients who continued all antihypertensives [12].

WEIGHING RISK AND BENEFIT OF TAPERING ANTIHYPERTENSIVES

Potential benefits — Tapering and discontinuing antihypertensive medication simplifies a patient's medication list, thereby reducing the risk of adverse drug effects and polypharmacy.

There may be a cost benefit. However, this should be considered alongside the indirect costs of frequent follow-up after discontinuation. This is an opportunity for shared decision making, as some patients are eager to reduce and/or discontinue medication and are willing to undertake home blood pressure monitoring and/or more frequent office visits [12]. (See "Deprescribing", section on 'Shared decision-making'.)

Potential risks — Risks of tapering antihypertensives include the following:

●Adverse cardiovascular outcomes – Withdrawing antihypertensive therapy may lead to adverse cardiovascular outcomes. In a subgroup analysis of the Hypertension in the Very Elderly Trial (HYVET), for example, withdrawing antihypertensive therapy in already treated individuals was associated with an increase in total death (59 versus 42 per 1000 patient-years; HR 0.71, 95% CI 0.58-0.87), cardiovascular death, and nonfatal cardiovascular events [13,14].

●Return of hypertension – Hypertension can occur when tapering antihypertensive medications over the course of days to weeks, sometimes exceeding the pretreatment levels. (See 'Patients with return of hypertension' below.)

●Withdrawal syndromes – Acute, potentially life-threatening withdrawal syndromes can occur, especially when tapering alpha-2 agonists (eg, clonidine) and moderate to high doses of beta blockers. Extra caution must be taken with monitoring these patients while tapering medications. (See 'Withdrawal syndromes' below.)

●Psychologic distress – Patients may experience anxiety with medication tapering. In one study of antihypertensive medication withdrawal, increased psychologic distress and anxiety was a primary reason why participants dropped out of the study, underscoring the importance of regular follow-up and reassurance when withdrawing antihypertensive therapy [15].

APPROACH TO TAPERING ANTIHYPERTENSIVES — Discontinuation of antihypertensive therapy requires shared decision making in appropriately selected patients, with an understanding of risks and benefits.

Timing of taper initiation — Patients experiencing adverse effects from antihypertensives, including rebound hypertension, should undergo medication taper under clinician guidance as soon as the adverse effect is identified. (See 'Rapid tapering for patients experiencing adverse effects from antihypertensives' below.)

Other patients should be on a stable antihypertensive medication regimen with blood pressure at goal for at least one year. Optimal timing of medication discontinuation should be discussed with the patient, as safe discontinuation requires frequent home and in-office blood pressure monitoring for several months to ensure sustained normotension. (See 'Weighing risk and benefit of tapering antihypertensives' above and 'Potential risks' above.)

Tapering schedule

Stable patients on antihypertensive monotherapy — Patients on antihypertensive monotherapy should be instructed to halve the daily dose of their medication, either with a new prescription or by using a pill cutter. Patients on amlodipine, chlorthalidone, or other monotherapy with a long serum elimination half-life may be offered the option of taking the usual dose every other day, if preferred. In patients without adverse effects from the medication, a dose change should be made no more frequently than every five to seven days; although, patients may find that a dose change with each monthly refill may be most practical.

Nonsynchronous, uncontrolled observational studies suggest that "step-down therapy" with close follow-up is associated with less cardiovascular risk than unsupervised stopping of antihypertensive agents, especially in people with diabetes [16,17].

A slower taper may be prudent in patients with a history of complications from hypertension.

Additional, as noted earlier, precautions are necessary for patients on clonidine or beta blockers who are at risk of a life-threatening withdrawal syndrome. Tapering these medications should be accompanied with additional anticipatory guidance and monitoring. (See 'Withdrawal syndromes' below.)

Stable patients on combination antihypertensive regimens — Studies on reducing antihypertensive medications in patients on multidrug therapy are lacking. We follow a similar approach to patients on antihypertensive monotherapy, stepping down therapy by one component at a time. (See 'Stable patients on antihypertensive monotherapy' above.)

Patients on single-pill combination regimens (table 1) should transition to separate dosing of individual antihypertensive drug components to facilitate step down of therapy.

Rapid tapering for patients experiencing adverse effects from antihypertensives — Patients experiencing symptoms related to low blood pressure or other adverse effects warrant a shorter taper to provide relief from medication side effects. As an example, an interval of four to seven days between dose adjustment may be reasonable. Most drugs have half-lives that allow this duration; although, commonly used drugs like amlodipine have longer effects and may last longer by one to two weeks, even with a taper.

Patients should be monitored closely for withdrawal syndromes during shorter tapers, especially with alpha-2 agonists and beta blockers. (See 'Withdrawal syndromes' below.)

Monitoring during tapering — We closely monitor blood pressure (eg, every two to four weeks) after each dose change. Patients may self-monitor their blood pressure at home. More frequent monitoring is advised in patients with a history of hypertensive emergency or past history of hypertension-related complications and those at risk of withdrawal syndrome. (See "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring".)

If home monitoring is not feasible, due to access or patient preference, office visits with a medical assistant, nurse, or clinician may be required. Telephone communication and electronic mechanisms of relaying blood pressure logs for staff review are equally viable.

SUBSEQUENT MANAGEMENT

Patients with sustained normotension — If blood pressure remains well controlled for at least three months, then we fully discontinue the medication. Blood pressure should be monitored via home or in-office monitoring for another one to three months to ensure stability of target blood pressure, after which usual monitoring may be resumed.

Patients with return of hypertension — Most commonly, discontinuation of antihypertensive therapy leads to a gradual rise in the blood pressure to pretreatment levels over a period of days to as long as six months [7]. Patients may experience relatively rapid, asymptomatic return of hypertension or a slower return over several weeks. Occasionally, the return of hypertension may exceed pretreatment levels.

If hypertension recurs, we resume the previous dose of antihypertensive medication if the patient experienced no adverse effects from the medication.

If the antihypertensive was tapered due to medication-related adverse effects, a different antihypertensive class should be prescribed. Selection of antihypertensive therapy is discussed separately. (See "Choice of drug therapy in primary (essential) hypertension".)

Patients with rebound hypertension/withdrawal syndrome — Some patients may develop a potentially fatal withdrawal syndrome characterized by acute rebound of blood pressure with symptoms and signs of sympathetic overactivity. This pattern of blood pressure response is most common with alpha-2 agonists and short-acting beta blockers. (See 'Withdrawal syndromes' below.)

WITHDRAWAL SYNDROMES — Withdrawal syndromes reflect a rapid return of catecholamine secretion or receptor sensitivity that had been suppressed during therapy [18-21]. The extent of sympathetic overactivity depends upon the relationship between the rate at which the antihypertensive agent wears off and the rate at which the receptors downregulate; these receptors have half-lives of 24 to 36 hours [22]. Thus, a hyperadrenergic state is most likely with short-acting antihypertensive drugs (eg, clonidine or propranolol) since receptor upregulation will persist after the antihypertensive effect has disappeared [18,22]. By comparison, withdrawal syndromes are relatively unusual with longer-acting agents (such as guanfacine and nadolol) [18,22].

Alpha-2 agonists — Abrupt cessation of therapy with an alpha-2 agonist (eg, clonidine, guanfacine, guanabenz) can lead to a potentially fatal withdrawal syndrome characterized by increased sympathetic activity and acute rebound hypertension above the pretreatment level [18]. Rebound hypertension usually occurs after abrupt cessation of fairly large oral doses and has also been noted with transdermal clonidine [21].

To avoid precipitating an alpha-2 agonist withdrawal syndrome, clonidine should be weaned over least a 6- to 10-day interval, cutting the dose by one-half every two to three days; though, rebound hypertension has been reported even with gradual clonidine withdrawal [20,23]. Patients who are not experiencing adverse effects from the medication may find that a taper over several weeks is more practical [18,24].

Patients who experience adverse effects while on the medication should be tapered with close home blood pressure monitoring over five to seven days. This includes patients with rebound hypertension due to incomplete adherence. Such patients may appear to have resistant hypertension on clonidine but are actually experiencing rebound hypertension due to missed doses of clonidine. This inconsistency of medication adherence is also true in those taking short-acting drugs like immediate-release beta blockers and hydralazine. Patients who note increasing blood pressure on home monitoring as clonidine is tapered may warrant a temporary dose increase, followed by a slower taper to address acute rebound hypertension. Alternatively, additional antihypertensive agents may be indicated as the alpha-2 agonist is tapered [23,25]. Management of resistant hypertension is discussed separately. (See "Treatment of resistant hypertension".)

Beta blockers — Beta blocker withdrawal syndromes are due to increased sympathetic activity related to adrenergic receptor upregulation during the period of sympathetic blockade [18,19,26]. In addition to a rise in blood pressure and heart rate, beta blocker withdrawal in patients with underlying coronary disease can lead to angina, myocardial infarction, or sudden death [18,19,24,27,28]. This can occur even in patients who have no previous history of coronary symptoms [27].

To avoid withdrawal symptoms, these drugs should be slowly discontinued over at least 6 to 10 days; though, a taper over several weeks may be more practical.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in adults".)

SUMMARY AND RECOMMENDATIONS

●Candidates for antihypertensive tapering – Patients with stable blood pressure at goal on medication and no history of hypertension-mediated organ damage are candidates for tapering of antihypertensive therapy. In addition, tapering is appropriate in patients who are experiencing symptoms related to low blood pressure or other adverse effects.

Cessation is more likely to be successful in younger patients, those with lower pretreatment blood pressure, and those who adhere to lifestyle modifications. (See 'Candidates for antihypertensive tapering' above.)

●Weighing risk and benefit – Tapering antihypertensive medication offers the benefit of simplifying a patient's medication list, thereby reducing the risk of adverse effects from polypharmacy.

Withdrawing antihypertensive therapy may lead to negative cardiovascular outcomes, including increased cardiovascular death and total death, especially in older adults. In the absence of adverse drug effects, most patients with a history of hypertension-mediated organ damage should not have treatment withdrawn, due to the risk of worsening existing disease. Patients may also experience rebound hypertension, life-threatening withdrawal syndromes, and increased anxiety as medication is reduced. (See 'Weighing risk and benefit of tapering antihypertensives' above.)

●Approach to tapering antihypertensives – When attempting to reduce and then discontinue antihypertensive medication, we take the following approach, following shared decision making with the patient:

•Patients on antihypertensive monotherapy should be instructed to halve the dose of their medication, either with a new prescription or by using a pill cutter. Patients on amlodipine or chlorthalidone may be offered the option of taking the usual dose every other day, if preferred. A dose change should be made no more frequently than every five to seven days; though, patients may find that a dose change with each monthly refill is more practical. (See 'Stable patients on antihypertensive monotherapy' above.)

•Patients on combination antihypertensive regimens should step down therapy by one component at a time. (See 'Stable patients on combination antihypertensive regimens' above.)

•We closely monitor blood pressure (eg, every two to four weeks) after reducing or discontinuing antihypertensive medications for at least one to three months. Patients may self-monitor their blood pressure at home; though, office visits may be required if home monitoring is not feasible.

•If blood pressure consistently exceeds the target, then the previous dose of antihypertensive medication is resumed. If blood pressure remains well controlled after one to three months, we formally discontinue the medication and closely monitor the blood pressure for another one to three months, after which usual monitoring may resume.

●Antihypertensive withdrawal syndromes

•Abrupt cessation of therapy with a short-acting beta blocker (eg, propranolol) or an alpha-2 agonist (eg, clonidine, guanfacine, guanabenz) can lead to a potentially fatal withdrawal syndrome. (See 'Withdrawal syndromes' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Norman M Kaplan, MD, who contributed to an earlier version of this topic review.