Withdrawal Of Antihypertensive Drugs Research Articles

A systematic review of predictors of maintenance of normotension after withdrawal of antihypertensive drugs

Background: The identification and treatment of hypertension in the general community has contributed to the reduction in strokes and coronary heart disease observed during the past 30 years. However, concerns have arisen that some patients may be receiving unnecessary antihypertensive drug therapy leading to wasted resources and the potential for adverse drug effects. Once therapy has been started, treating physicians have difficulty in selecting patients for withdrawal and have concerns regarding patient safety and their own legal liability. Procedures: This study reviews and consolidates information from published studies to identify known predictors of the successful maintenance of normotension after antihypertensive drug withdrawal. The predictors were identified by determining the proportion of subjects with various baseline characteristics who remained normotensive while off medication for at least 12 months. From these data we have developed a clinical algorithm to help identify patients in whom antihypertensive drug withdrawal might be considered. This may assist primary care physicians in achieving successful withdrawal of antihypertensive therapy among selected hypertensive patients. Results: The most consistent predictors identified were blood pressure (BP) (lower pretreatment, on treatment, and after withdrawal), nature of pharmacotherapy (fewer agents and lower dose), and preparedness to accept dietary intervention (weight and sodium reduction). Conclusions: On the basis of this information, a trial of withdrawal of antihypertensive medication might be recommended for patients who have mildly elevated, uncomplicated BP that is well controlled on a single agent, and who are motivated and likely to accept lifestyle changes. Withdrawal, antihypertensive drugs, predictors.

Failure of L-arginine to induce hypotension in patients with a history of accelerated-malignant hypertension.

A profound elevation of blood pressure on exercises or after withdrawal of antihypertensive drugs has been reported in patients with a history of accelerated-malignant hypertension. We tested the hypothesis that severe endothelial dysfunction is responsible for the profound hypertensive response in these patients. Responses of blood pressure, heart rate and plasma cyclic guanosine monophosphate to intravenously infused L-arginine, a precursor of nitric oxide, was investigated in hypertensive patients with (group A) or without any history of accelerated-malignant hypertension (group B) in order to evaluate endothelial function. Casual blood pressure or severity of hypertension was not different between group A and B. Infusion of L-arginine decreased mean blood pressure in group B (97.4 +/- 8.7 to 81.7 +/- 6.9 mm Hg), but not in group A (99.0 +/- 10.2 to 101.5 +/- 8.7 mm Hg). Plasma levels of cyclic guanosine monophosphate were increased after infusion of L-arginine in group B (5.4 +/- 2.0 to 7. 7 +/- 1.7 pmol/ml, P< 0.01), while no significant changes were observed in group A (5.4 +/- 2.1 to 5.9 +/- 2.1 pmol/ml). There was a significant correlation between decrease in mean blood pressure and increase in plasma levels of cyclic guanosine monophosphate (r = 0.83, P < 0.001). The results indicated that much more severe endothelial dysfunction is present in hypertensive patients with a history of accelerated-malignant hypertension as compared to those without the history. The difference in the endothelial function may account for the different pressor responses to exercises or other stimuli observed in hypertensive patients with and without a history of accelerated-malignant hypertension. Journal of Human Hypertension (2000) 14, 485-488

Predictive value of ambulatory blood pressure shortly after withdrawal of antihypertensive drugs in primary care patients.

To determine whether ambulatory blood pressure eight weeks after withdrawal of antihypertensive medication is a more sensitive measure than seated blood pressure to predict blood pressure in the long term. Patients with previously untreated diastolic hypertension were treated with antihypertensive drugs for one year; these were withdrawn in patients with well controlled blood pressure, who were then followed for one year. Primary care. 29 patients fulfilling the criteria for withdrawal of antihypertensive drugs. Sensitivity, specificity, and positive and negative predictive value of seated and ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs. Eight weeks after withdrawal of medication, mean diastolic blood pressure returned to the pretreatment level on ambulatory measurements but not on seated measurements. One year after withdrawal of medication, mean diastolic blood pressure had returned to the pretreatment level both for seated and ambulatory blood pressure. For ambulatory blood pressure, the sensitivity and the positive predictive value eight weeks after withdrawal of medication were superior to those for seated blood pressure; specificity and negative predictive value were comparable for both types of measurement. Receiver operating characteristic curves showed that the results were not dependent on the cut off values that were used. Ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs predicts long term blood pressure better than measurements made when the patient is seated.

Withdrawal of antihypertensive therapy in the elderly. The issues.

Studies of antihypertensive drug withdrawal suggest that at least 20% of selected older patients with hypertension can remain normotensive without drug treatment for periods of up to 5 years. Success of drug withdrawal is greater in those patients controlled on low dose monotherapy who have low on-treatment blood pressure (BP), are not overweight and who have no ECG evidence of left ventricular hypertrophy. Compliance with lifestyle advice may increase the chance of successful drug withdrawal. Unfortunately, many older hypertensive patients have poorly controlled BP despite treatment with antihypertensive drugs, and are overweight. These factors limit opportunities for drug withdrawal although they may not be so much of a problem in the very elderly. Patient who could be considered for a trial of antihypertensive drug withdrawal are those unhappy with such therapy who also: (a) have well controlled BP on monotherapy with no significant target organ damage, (b) have 'white-coat' hypertension, or (c) are very elderly (> 80 years). The withdrawal of antihypertensive drugs can improve drug-induced metabolic abnormalities and symptoms, and appears safe providing there is a gradual reduction in drug dosages and close follow-up to detect a return to hypertension.

Safe discontinuation of antihypertensive therapy.

We summarize herein the clinical and pathophysiological features of antihypertensive withdrawal syndrome and its risk factors, management, and prevention. Antihypertensive withdrawal syndrome occurs most frequently with beta-blocking agents and centrally acting antihypertensives such as clonidine hydrochloride. This syndrome resembles a state of sympathetic nervous system hyperactivity. In the most critical case, it can be severe and life threatening. Antihypertensive dosages, particularly for beta-blockers and clonidine, should be tapered slowly rather than discontinued abruptly.

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

Journal of Internal MedicineVolume 235, Issue 6 p. 577-579 Free Access Stopping antihypertensive drug therapy in elderly people—a dangerous experiment? Professor P. Lund-Johansen, Corresponding Author Professor P. Lund-Johansen Department of Heart Disease, Haukeland Hospital, University of Bergen, Bergen, NorwayDepartment of Heart Disease, 5021 Haukeland Hospital, Bergen, Norway.Search for more papers by this author Professor P. Lund-Johansen, Corresponding Author Professor P. Lund-Johansen Department of Heart Disease, Haukeland Hospital, University of Bergen, Bergen, NorwayDepartment of Heart Disease, 5021 Haukeland Hospital, Bergen, Norway.Search for more papers by this author First published: June 1994 https://doi.org/10.1111/j.1365-2796.1994.tb01264.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure: the Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNCV). Arch Int Med 1993: 153: 154– 83. 2 Zanchetti A., Chalmers JP, Arakawa K.. Gyarfas I., Hamet P., Hansson L., Julius S., MacMahon S., Mancia G., Menard J., Omae T., Reid J., Safar M. The 1993 guidelines for the management of mild hypertension: memorandum from a WHO/ISH meeting. Blood Pressure 1993: 2: 86– 100. 3 SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA 1991: 265: 3255– 64. 4 Veterans Administration cooperative study group. Return of elevated blood pressure after withdrawal of antihypertensive drugs. Circulation 1975: 51: 1107– 13. 5 Medical research council working party on mild hypertension. Course of blood pressure in mild hypertensives after withdrawal of long term antihypertensive treatment. Br Med J 1986: 293: 988– 92. 6 Levinson PD, Khatri IM, Freis ED. Persistence of normal BP after withdrawal of drug treatment in mild hypertension. Arch Intern Med 1982: 142: 2265– 8. 7 Ekblom T., Lindholm LH, Odén A. Dahlöf B., Hansson L., Wester P-O. et al. A 5-year prospective, observational study of withdrawal of antihypertensive treatment in elderly. J Intern Med 1994: 235: 581– 8. 8 Straand J., Fugelli P., Laake K. Withdrawing long-term diuretic treatment among elderly patients in general practice. Family Practice 1993; 10: 38– 42. 9 Langford HG, Blaufox D., Oberman A., Hawkins M., Curb JD, Cutter GR et al. Dietary therapy slows the return of hypertension after stopping prolonged medication. JAMA 1985: 253: 657– 64. 10 Devereux R., Alderman MH. Role of preclinical cardiovascular disease in the evolution from risk factor exposure to development of morbid events. Circulation 1993; 88 (Part 1): 1444– 55. 11 Lund-Johansen P., Omvik P. Hemodynamic patterns of untreated hypertensive disease. In: JH Laragh, B. Brenner, eds. Hypertension: Pathophysiology, Diagnosis and Management. New York: Raven Press, 1990: 305– 27. Citing Literature Volume235, Issue6June 1994Pages 577-579 ReferencesRelatedInformation

2 Year Follow-Up of Anti-Hypertensive Drug Withdrawal in the Elderly

2 Year Follow-Up of Anti-Hypertensive Drug Withdrawal in the Elderly

Yohimbine-precipitated clonidine withdrawal: an experimental model of the antihypertensive drug withdrawal syndrome.

In this study, a model of the clonidine withdrawal syndrome in normotensive rats was used to investigate the mechanisms and sites of the cardiovascular responses associated with this withdrawal. Clonidine (400 micrograms.kg-1.day-1), an alpha 2-adrenergic receptor agonist, was administered to rats via indwelling osmotic minipumps for 7 days. Withdrawal was precipitated by an intravenous injection of the alpha 2-adrenergic receptor antagonist yohimbine under alpha-chloralose anaesthesia, and the blood pressure and heart rate responses were recorded. Yohimbine (0.25, 0.50, and 1.0 mg/kg i.v.) in clonidine-treated rats provoked an immediate rise in blood pressure and heart rate. Similar injections in saline-treated rats produced slight hypotension and modestly increased the heart rate. Intracerebroventricular (i.c.v.) yohimbine injection (30 or 120 micrograms/kg in 10 microL volume) failed to elicit signs of withdrawal in clonidine-treated animals, but a subsequent intravenous injection of yohimbine (0.5 mg/kg) provoked brisk signs of withdrawal. hexamethonium (2 mg/kg) pretreatment did not abolish the increase in the heart rate, but it delayed the blood pressure increase. Pretreatment with atropine sulfate (1 mg/kg) did not block the yohimbine-induced increase in heart rate or blood pressure. This study demonstrates that yohimbine can effectively produce cardiovascular signs of withdrawal in rats chronically exposed to clonidine. The lack of i.c.v. yohimbine suggests that the antagonist-precipitated withdrawal may not have a central origin.(ABSTRACT TRUNCATED AT 250 WORDS)

The likelihood of remaining normotensive following antihypertensive drug withdrawal.

To determine the proportion and characteristics of mild hypertensives who remain normotensive after withdrawal from drug treatment. Longitudinal descriptive study. A university family practice unit (FPU) and a large steel company (DOFASCO) in Hamilton, Ontario. Participants were 107 of 125 (86%) eligible hypertensives at the two sites; 103 (96%) subjects completed the study. Subjects discontinued antihypertensive medication and were followed until blood pressure (BP) became elevated or for 12 months, whichever was shorter. BPs were monitored according to a predefined schedule and before, during, and after mental and physical stress tests. Thirty-eight (37%, 95% confidence interval [CI] 27-46%) subjects remained normotensive at 12 months. Predictors of remaining normotensive included lower medicated standing diastolic blood pressure (DBP) (87.6 versus 91.8 mm Hg, 95% CI for the difference 2.2-6.2, p less than 0.001) and longer duration of normotension on drugs (12.6 months versus 8.7, 95% CI for the difference 0.9-6.9, p = 0.012). There was no significant relationship between maintenance of normotension and age, medication potency, duration of hypertension, weight, lying BP, change in heart rate, or BP during mental or physical stress tests; the power to detect a clinically important difference in lying DBP was 99% but for other variables was lower (21-75%). The probability of hypertensives' remaining normotensive for one year after drug withdrawal increases as the medicated standing DBP decreases and as the number of months of BP control while on medication increases. Studies with larger sample sizes are warranted to determine whether other variables may be significant predictors.

Symptoms in hypertensive patients

We have evaluated the effect of withdrawal of antihypertensive drugs on the frequency of symptoms over a 2-week period in 11,710 hypertensive patients. Previously untreated patients complained most frequently of headache, dizziness and chest pain, whereas most other symptoms occurred more often in previously treated patients. With the exception of headache, which rose in frequency, most symptoms showed a significant reduction following therapy withdrawal. The burden of symptoms reported by treated hypertensive patients is probably the result of a combination of their disease, drug-related adverse effects and inappropriate use of drugs in certain patient groups.

Withdrawal of antihypertensive drugs and its relation to pre-treatment blood pressure

Withdrawal of antihypertensive drugs and its relation to pre-treatment blood pressure

Effects of monotherapy and withdrawal of antihypertensive drugs in the treatment of hypertension.

The final number of antihypertensive drugs used in the long-term treatment of a given patient is not always predictable at the start of therapy. By reviewing clinical records, we retrospectively examined the relationship between pretreatment blood pressure and the final number of drugs administered in 282 patients with mild to moderate hypertension who had been treated for 5 years or more (average 9.7 years). After years of treatment approximately one third and one half of 137 patients with a pretreatment diastolic blood pressure of between 90 and 104 mmHg were well controlled with combined therapy and monotherapy, respectively. The drugs had been withdrawn in the remaining 17% for 12 months or more. Lower pretreatment systolic blood pressure and lower pretreatment QRS voltage were signs favorable for withdrawal of the drugs. Combined therapy was required in more than half the patients with higher pretreatment diastolic blood pressure.

Recent trend in the research of hypertension in Japan. Problems on the long-term treatment of hypertension--withdrawal of antihypertensive drugs and regression of cardiac hypertrophy

Recent trend in the research of hypertension in Japan. Problems on the long-term treatment of hypertension--withdrawal of antihypertensive drugs and regression of cardiac hypertrophy

Antihypertensive drug withdrawal syndrome.

After discontinuation of antihypertensive medications, patients may experience symptoms associated with catecholamine excess, with or without a rapid rise in blood pressure; this is referred to as antihypertensive drug withdrawal syndrome. Though most often associated with the discontinuation of clonidine, this syndrome has been reported to follow the withdrawal of many other antihypertensives. Proposed mechanisms for the syndrome, depending on the drug involved, include enhanced activity of (1) the sympathoadrenal system, (2) the renin-angiotensin-aldosterone system, and (3) the thyroid hormones. The typical patient at risk is a younger person with severe hypertension, who has been on multiple drugs in high doses for a long period. Guidelines are provided for minimizing the occurrence of the syndrome and for treating the reaction, should it occur.

Drug and dietary intervention in hypertension.

Antihypertensive drug treatment has been shown to be efficacious in reducing mortality, morbidity, and end-organ damage from hypertension. However, the health care consequences of providing continued antihypertensive therapy for approximately one-fourth of the adult population has led to inquiry into the potential of nutritional change as an alternative therapy. The relapse rate for the return of hypertension after withdrawal of antihypertensive drugs is greater in the obese than in the nonobese patient. The relapse rate is also much greater if the hypertension was severe before antihypertensive drugs were started. A programmed course of dietary instruction enabled participants to drop sodium excretion by 50%, and to lose approximately 5% of body weight in 32 weeks. Adequate large-scale trials to determine the therapeutic success rate of dietary modification in mild hypertension have yet to be done. Studies have been initiated in the United States and Finland to determine the feasibility of dietary modifications as a means of preventing the occurrence of hypertension. This endeavor deserves the highest priority, for the magnitude of the problem threatens to overwhelm conventional means of provision of medical care.

Withdrawal Syndromes and the Cessation of Antihypertensive Therapy

A review of the available literature concerning sudden withdrawal of antihypertensive drugs shows that withdrawal syndromes after cessation of such agents have occurred with beta-blockers, methyldopa, clonidine hydrochloride, guanabenz, and bethanidine sulfate. Most commonly, these syndromes are limited to nervousness, tachycardia, headache, and nausea 36 to 72 hours after cessation of the drug. In rare cases, serious exacerbation of myocardial ischemia (beta-blockers) or hypertension (clonidine, methyldopa) may occur in the posttreatment period. The withdrawal syndromes generally respond promptly to reinstitution of antihypertensive therapy. The infrequent occurrence of withdrawal syndromes should not discourage use of these efficacious agents.

Blood pressure elevation after withdrawal of antihypertensive drugs in the aged (author's transl)

老年者本態性高血圧で降圧剤治療中の65例に降圧剤を中断した後の血圧の推移を観察した. 降圧剤中断1カ月で血圧はほぼ一定値まで上昇し, 以後6カ月まで著変がなかった. 治療中血圧の低いものが6カ月後の血圧も比較的低値を示した. 治療中収縮期血圧149以下のものは, 160以上への上昇65%, 150台のものは85.7%であり, 160, 170台のものの中止後血圧上昇はそれぞれ56.3%, 57.1%, 180, 190台では血圧上昇は見られなかった. 降圧剤中断後も160未満の収縮期圧を示したものは26.5%であった. 拡張期血圧79以下のものは90以上への上昇13.6%, 80台のもの53.6%であった. 90台では血圧上昇41.7%, 100以上のものでは血圧上昇は見られなかった. 降圧剤中断後も90未満の拡張期圧を示したものは64.0%であり, 老年者高血圧の特微の1つと思われる. 服用中の降圧剤は thiazide 降圧利尿剤が大多数であり, 1剤群と2剤以上併用群で血圧上昇率には差を認めなかった.

Renal artery reconstruction in renovascular hypertension.

Over a period of 8 years, 52 patients (31 females and 21 males) between 12 and 59 years of age (mean age 40 years) underwent renal artery reconstruction for correction of renovascular hypertension. Five patients were operated on bilaterally. A thoracoretroperitoneal approach was chosen at 48 of 57 renal artery reconstructions. The most used types of arterial reconstruction were thrombendarterectomy and vein patch, resection of the stenosis and end-to-end anastomosis, vein patch only or aortorenal vein bypass. No early or late nephrectomies were performed. These was no operative mortality, but 3 late deaths occurred. Twenty-two patients were normotensive postoperatively, 20 were improved and there were 10 failures. The follow-up time as 1--8 years. The blood pressures were measured after withdrawal of antihypertensive drugs for at least 10 days. The best predictable criterion for normotension was a positive renin test with a renin ratio of 1.5 or more. The normotensive patients were in the younger age group with a shorter duration of known hypertension and had mainly fibromuscular hyperplasia.

Blood pressure and heart rate and withdrawal of antihypertensive drugs.

The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets.