Withdrawal Of Antihypertensive Drugs Research Articles

Features of the arterial hypertension course and arterial stiffness in patients with ankylosing spondylitis who get infected COVID-19

Objective: to evaluate the features of development and course of arterial hypertension (AH) and changes in vascular stiffness in patients with ankylosing spondylitis (AS) who underwent COVID-19. Materials and methods: 60 patients with a reliable diagnosis of AS were included in the study. Patients were divided into 2 groups depending on the presence of COVID - 19 in anamnesis. The main group consisted of 30 patients with AS who had suffered COVID-19 of varying severity during the previous 12 months. The comparison group consisted of 30 patients with AS who had no laboratory and clinically confirmed COVID-19 infection within the last year. Patients were interviewed regarding the severity of their previous coronavirus infection and persisting symptoms in the post-COVID-19 period. AS activity was evaluated by ASDAS (CRB, BASDAI-index). BP measurement and study of arterial stiffness parameters by oscillographic method, evaluation of the results of ambulatory BP measurement were performed. Results: 6 (20%) patients had BP destabilization at the outpatient stage during home BP measurement early after COVID-19. After 12 months, BP elevation persisted in only 2 (7%) patients, the rest had BP stabilization with withdrawal of antihypertensive drugs. No correlation between BP level, arterial stiffness and AS activity was found. There was a weak inverse correlation between the severity of coronavirus infection and the level of systolic blood pressure, between age and pulse wave velocity. No significant differences in systolic, diastolic blood pressure, pulse wave velocity, aortic augmentation index were found in patients with AS with and without coronavirus infection. In the main group, 1 fatal outcome due to the development of acute ST-elevation myocardial infarction 6 months after COVID-19 was recorded, and no adverse cardiovascular events were registered among patients in the comparison group. Conclusion: it was hypothesized that patients with AS who underwent COVID-19 would be more likely to show BP elevation than those who did not undergo COVID-19. It was found that early after COVID-19 (first three months) a reversible increase in BP without significant changes in arterial stiffness is possible. However, no significant differences in the frequency of BP elevation, BP level, and arterial stiffness were found in patients with AS and COVID-19 or without COVID-19 in anamnesis.

Effects of Antihypertensive Deprescribing Strategies on Blood Pressure, Adverse Events, and Orthostatic Symptoms in Older Adults: Results From TONE.

The Trial of Nonpharmacologic Interventions in the Elderly (TONE) demonstrated the efficacy of weight loss and sodium reduction to reduce hypertension medication use in older adults. However, the longer-term effects of drug withdrawal (DW) on blood pressure (BP), adverse events, and orthostatic symptoms were not reported. TONE enrolled adults, ages 60-80 years, receiving treatment with a single antihypertensive and systolic BP (SBP)/diastolic BP <145/<85 mm Hg. Participants were randomized to weight loss, sodium reduction, both, or neither (usual care) and followed up to 36 months; ~3 months postrandomization, the antihypertensive was withdrawn and only restored if needed for uncontrolled hypertension. BP and orthostatic symptoms (lightheadedness, feeling faint, imbalance) were assessed at randomization and throughout the study. Two physicians independently adjudicated adverse events, masked to intervention, classifying symptomatic (lightheadedness, dizziness, vertigo), or clinical events (fall, fracture, syncope). Among the 975 participants (mean age 66 years, 48% women, 24% black), mean (±SD) BP was 128 ± 9/71 ± 7 mm Hg. Independent of assignment, DW increased SBP by 4.59 mm Hg (95% confidence interval [CI]: 3.89, 5.28) compared with baseline. There were 113 adverse events (84 symptomatic, 29 clinical), primarily during DW. Compared with usual care, combined weight loss and sodium reduction mitigated the effects of DW on BP (β = -4.33 mm Hg; 95% CI: -6.48, -2.17) and reduced orthostatic symptoms long term (odds ratio = 0.62; 95% CI: 0.41, 0.92), without affecting adverse events (hazard ratio = 1.81; 95% CI: 0.90, 3.65). In contrast, sodium reduction alone increased risk of adverse events (hazard ratio = 1.75; 95% CI: 1.04, 2.95), mainly during DW. In older adults, antihypertensive DW may increase risk of symptomatic adverse events, highlighting the need for caution in withdrawing their antihypertensive medications. Trial Number NCT00000535.

Withdrawal of antihypertensive drugs in older people.

Hypertension is an important risk factor for subsequent cardiovascular events, including ischaemic and haemorrhagic stroke, myocardial infarction, heart failure, chronic kidney disease, cognitive decline and premature death.Overall, the use of antihypertensive medications has led to reduction in cardiovascular disease, morbidity rates and mortality rates.However, the use of antihypertensive medications is also associated with harms, especially in older people, including the development of adverse drug reactions, drug-drug interactions and can contribute to increasing medication-related burden.As such, discontinuation of antihypertensives may be considered and appropriate in some older people. To investigate whether withdrawal of antihypertensive medications is feasible, and evaluate the effects of withdrawal of antihypertensive medications on mortality, cardiovascular outcomes, hypertension and quality of life in older people. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to April 2019: the Cochrane Hypertension Specialised Register, CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also conducted reference checking, citation searches and, when appropriate, contacted study authors to identify any additional studies. The searches had no language restrictions. We included randomised controlled trials (RCTs) of withdrawal versus continuation of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults (defined as 50 years and over). Participants were eligible if they lived in the community, residential aged care facilities, or were based in hospital settings. We sought to include trials looking at the complete withdrawal of the antihypertensive medication, and those focusing on a dose reduction of the antihypertensive medicine. We compared the intervention of discontinuing or reducing antihypertensive medication to usual treatment using mean differences (MD) and 95% confidence intervals (95% CIs) for continuous variables and we used Peto odds ratios (ORs) and 95% CI for binary variables. Our primary outcomes included: mortality, myocardial infarction, development of adverse drug reactions or adverse drug withdrawal reactions.Secondary outcomes included: blood pressure, hospitalisation, stroke, success of withdrawing from antihypertensives, quality of life, and falls.Two authors independently, and in duplicate,conducted all stages of study selection, data extraction and quality assessment. Six RCTs met the inclusion criteria and were included in the review (1073 participants). Study duration and follow-up ranged from 4 weeks to 56 weeks.Meta-analysis of studies showed that, in the discontinuation group compared to continuation, the odds for all-cause mortality were 2.08 (95% CI 0.79 to 5.46; low certainty of evidence), for myocardial infarction 1.86 (95% CI 0.19 to 17.98; very low certainty of evidence) and for stroke 1.44 (95% CI 0.25 to 8.35; low certainty of evidence). Blood pressure was higher in the discontinuation group than the continuation group (systolic blood pressure: MD = 9.75 mmHg, 95% CI 7.33 to 12.18; and diastolic blood pressure: MD = 3.5 mmHg, 95% CI 1.82 to 5.18; low certainty of evidence). For the development of adverse events, meta-analysis was not possible; antihypertensive discontinuation did not appear to increase the risk of adverse events and may lead to resolution of adverse drug reactions, although eligible studies had limited reporting of adverse effects of drug withdrawal (very low certainty of evidence).One study reported hospitalisation with an odds ratio of 0.83 for discontinuation compared to continuation (95% CI 0.33 to 2.10; low certainty of evidence). No studies were identified which reported falls. Between 10.5% and 33.3% of participants in the discontinuation group compared to 9% to 15% in the continuation group experienced raised blood pressure or other clinical criteria (as pre-defined by the studies) that would require restarting of therapy/removal from the study. The sources of bias included selective reporting (reporting bias), lack of blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and lack of blinding of participants and personnel (performance bias). There is no evidence of an effect of discontinuing compared with continuing antihypertensives used for hypertension or primary prevention of cardiovascular disease in older adults on all-cause mortality and myocardial infarction. The evidence was low to very low certainty mainly due to small studies and low event rates. These limitations mean that we cannot make any firm conclusions about the effect of deprescribing antihypertensives on these outcomes. Future research should focus on populations with the greatest uncertainty of the benefit:risk ratio for use of antihypertensive medications, such as those with frailty, older age groups and those taking polypharmacy, and measure clinically important outcomes such as falls, quality of life and adverse drug events.

Discontinuation of Antihypertensive Medication, Cognitive Complaints, and Incident Dementia

ObjectivesTo evaluate whether discontinuation of antihypertensive medication in community-dwelling older people is associated with a reduction in memory complaints and/or incident dementia. DesignProspective observational cohort study within the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial. Setting and ParticipantsCommunity-dwelling participants (aged 70-78 years at baseline) who underwent 2-yearly assessments during 6-8 years of follow-up. MeasuresCox regression analyses of the relation between discontinuation of antihypertensive medication during the study and change in subjective memory complaints, incident dementia, and mortality. ResultsDementia occurred more often in participants discontinuing antihypertensive treatment (13.4% vs 6.2%, P = .02); mortality was similar (16.5% vs 13.9%, P = .52). Discontinuation of antihypertensive medication was associated with a double dementia hazard [hazard ratio (HR) (95% confidence interval) = 2.15 (1.15-4.03)], which somewhat attenuated after adjustment for sex, blood pressure, number of antihypertensives and other medications [HR = 1.92 (1.01-3.65)], and additionally for stroke, cardiovascular disease, diabetes, smoking, memory complaints, and MMSE score [HR = 1.79 (0.93-3.44)]. Antihypertensive discontinuation was associated with an approximately 50% higher hazard of dementia and/or mortality combined [HR = 1.58 (1.04-2.40); model 2: HR = 1.64 (1.07-2.51); model 3: HR = 1.49 (0.96-2.30)]. Antihypertensive discontinuation was not associated with change in memory complaints [odds ratio (95% confidence interval) = 0.96 (0.55-1.67)]. Subgroup and sensitivity analyses addressing possible sources of bias and confounding gave similar results. Conclusions/ImplicationsOur results suggest that antihypertensive withdrawal in community-dwelling older people does not preserve cognition and may in fact increase dementia risk. This is not due to reduced mortality as competing risk. Additional analyses suggest results are unlikely to be explainable by confounding, reverse causality, or observational biases. Studies with person-specific reasons for antihypertensive discontinuation may be able to exclude reverse causality completely. Given the beneficial effects of antihypertensive medication on cardiovascular risk, observational data may be the best currently obtainable on the pressing issue of when withdrawal of antihypertensives in older people is acceptable and what consequences need to be weighed.

Withdrawal of antihypertensive therapy in people with dementia: feasibility study

BackgroundThis study explored the feasibility of a randomised controlled withdrawal trial of antihypertensive medication in normotensive people with dementia. Feasibility aspects included response, recruitment, exclusion and drop-out rates, suitability of outcome measures, acceptability of study procedures and an indicative economic evaluation for a randomised controlled trial.MethodsA cohort study attempting the withdrawal of antihypertensive drugs where appropriate and a feasibility study of home-based blood pressure monitoring, in people with dementia treated for hypertension, was undertaken. Interviews with participants and carers and an indicative economic evaluation were also undertaken.ResultsThree hundred and sixty-two primary care practices in the East Midlands were contacted of which only 41 (11% (95%CI 8–15%)) agreed to support the study. These 41 practices posted 940 letters to potential participants. Thirty participants were enrolled in the cohort study of whom 9 were eligible for the antihypertensive withdrawal programme, 20 participated in a home blood pressure monitoring sub-group analysis and 12 took part in an interview study. Twenty-two of those enrolled in the cohort study were followed up at 6 months. The withdrawal programme was acceptable to participants and general practitioners (GPs). The study procedures including assessments and home blood pressure monitoring were acceptable to the participants and their carers. The economic evaluation was not possible.ConclusionA withdrawal trial of antihypertensive medication in normotensive people with dementia may not be feasible in the UK because of low recruitment rates.

Withdrawal of antihypertensive drugs in older people

Withdrawal of antihypertensive drugs in older people

A practical approach to the pharmacological management of hypertension in older people.

Hypertension is the leading cause of cardiovascular (CV) morbidity and mortality in adults over the age of 65. The first part of this paper is an overview, summarizing the current guidelines on the pharmacological management of hypertension in older adults in Europe and the USA, and evidence from key trials that contributed to the guidelines. In the second part of the paper, we will discuss the major challenges of managing hypertension in the context of multimorbidity, including frailty, orthostatic hypotension (OH), falls and cognitive impairment that are associated with ageing. A novel 'BEGIN' algorithm is proposed for use by prescribers prior to initiating antihypertensive therapy to guide safe medication use in older adults. Practical suggestions are highlighted to aid practitioners in making rational decisions to treat and monitor hypertension, and for considering withdrawal of antihypertensive drugs in the complex older person.

Antihypertensive withdrawal for the prevention of cognitive decline.

Antihypertensive withdrawal for the prevention of cognitive decline.

Nebivolol withdrawal results in blood pressure returning toward pretreatment levels, but without rebound symptoms: phase IV randomized trial

Rapid withdrawal of antihypertensive drugs may lead to blood pressure (BP) increase above pretreatment values or symptoms such as palpitations, chest pain, and tremor. This phase IV trial assessed the consequences of abrupt and stepwise withdrawal of nebivolol, a β1-selective blocker, in individuals with stage I-II hypertension. After a 4- to 5-week placebo washout phase and 12-week single-blind nebivolol treatment (10–40 mg/day, titrated based on BP response), participants achieving BP control (systolic BP [SBP]/diastolic BP [DBP] <140/90 mm Hg) or response (SBP decrease ≥10 mm Hg or DBP decrease ≥5 mm Hg) entered a 4-week, randomized, double-blind phase of continued nebivolol treatment (n = 102) or withdrawal to placebo (n = 105). Primary and secondary efficacy measures were changes in mean sitting DBP and SBP, respectively, analyzed using an analysis of covariance model. Safety and tolerability were also assessed. In the withdrawal phase, nebivolol and placebo groups demonstrated mean DBP increases of 1.8 and 7.7 mm Hg, respectively (P < .001), and SBP increases of 3.5 and 7.6 mm Hg (P = .011). Twenty-three (22.5%) nebivolol-treated and 18 (17.1%) placebo-treated participants experienced a treatment-emergent adverse event. No adverse events associated with β-blocker withdrawal and considered causally related to nebivolol were reported. Nebivolol withdrawal resulted in a mean BP increase near pretreatment levels and was not associated with rebound hypertension.

Epidemiology of Interdialytic Ambulatory Hypertension and the Role of Volume Excess

Background: The epidemiology of hypertension among hemodialysis (HD) patients is difficult to describe accurately because of difficulties in the assessment of blood pressure (BP). Methods: Using 44-hour interdialytic ambulatory BP measurements, we describe the epidemiology of hypertension in a cohort of 369 patients. To seek correlates of hypertension control, antihypertensive agents were withdrawn among patients with controlled hypertension and ambulatory BP monitoring was repeated. Results: Hypertension (defined as an average ambulatory systolic BP ≧135 mm Hg or diastolic BP ≧85 mm Hg, or the use of antihypertensive medications) was prevalent in 82% of the patients and independently associated with epoetin use, lower body mass index and fewer years on dialysis. Although 89% of the patients were being treated, hypertension was controlled adequately in only 38%. Poor control was independently associated with greater antihypertensive drug use. Inferior vena cava (IVC) diameter in expiration was associated with increased risk of poorly controlled hypertension both in cross-sectional analysis and after withdrawal of antihypertensive drugs. Conclusions: Interdialytic hypertension is highly prevalent and difficult to control among HD patients. End-expiration IVC diameter is associated with poor control of hypertension in cross-sectional analyses as well as after washout of antihypertensive drugs. Among HD patients, an attractive target for improving hypertension control appears to be the reduction of extracellular fluid volume.

The Short Treatment with the Angiotensin Receptor Blocker Candesartan Surveyed by Telemedicine (STAR CAST) Study: Rationale and Study Design

Previous studies have shown that transient treatment of animal models of hypertension with an angiotensin receptor blocker (ARB) causes a sustained decrease in blood pressure values that persists even after the drug treatment is discontinued (J Am Soc Nephrol 12: 659-666, 2001; Nephron 91: 710-718, 2002; Hypertens Res 30: 63-75, 2007). These results have been shown to be clinically relevant by the recent TROPHY study (N Engl J Med 354: 1685-1697, 2006). We have recently found that transient treatment with an ARB may also cause regression of established hypertension in hypertensive rats (J Am Soc Nephrol 18: 157A, 2007). The Short Treatment with the Angiotensin Receptor Blocker Candesartan Surveyed by Telemedicine (STAR CAST) study is a prospective, randomized, open, blinded end-point study in patients aged 30-59 with a positive family history of hypertension that will be conducted in several centers in Japan. The aim of the study is to evaluate the antihypertensive drug withdrawal success rate, the median duration of drug withdrawal, and the changes in home and office blood pressure values in patients with mild hypertension after tapering and withdrawal of antihypertensive treatment following treatment for 1 year with the ARB candesartan or the calcium channel blocker (CCB) nifedipine slow-release. A unique feature of this study is the use of a home blood pressure monitoring telemedicine system (i-TECHO) to allow frequent evaluation of the changes in blood pressure in the trial patients. This study will be the first clinical study to examine if regression from stage 1 (mild) hypertension to prehypertension (high-normal blood pressure) is possible using an ARB or CCB.

Misoprostol Effects on Diclofenac‐Induced Cardiorenal Changes in Salt‐Sensitive Patients with Hypertension: The MEDIC Study

To determine whether coadministration of misoprostol with the nonsteroidal antiinflammatory drug diclofenac lessens the increase in blood pressure and improves the alterations in renal hemodynamics induced by diclofenac. Prospective, randomized, double-blind, placebo-controlled, crossover study. Two university research centers. Nineteen senior (mean age 62 yrs [range 55-73 yrs]), salt-sensitive patients with stage 1 or 2 hypertension. After a 3-week antihypertensive withdrawal lead-in phase, patients received either diclofenac 75 mg alone or diclofenac 75 mg plus misoprostol 200 microg twice/day for 14 days. After a 10-day washout period, patients received the alternate treatment. Blood pressure was measured by 24-hour ambulatory blood pressure monitoring, effective renal plasma flow (ERPF) rate was determined by para-aminohippurate clearance, and glomerular filtration rate (GFR) was measured by iothalamate clearance. Mean arterial pressure (MAP = diastolic blood pressure + 0.33[systolic - diastolic blood pressure]) and rate-pressure product (RPP = systolic blood pressure x heart rate x 10(-2)) were also used to compare treatment groups. Diclofenac alone increased MAP by a mean +/- SEM of 5.0 +/- 1.0 mm Hg and RPP by 337 +/- 181 units compared with baseline. The ERPF rate and GFR decreased by 40.5 +/- 26.9 ml/minute and 14.1 +/- 6.5 ml/minute, respectively. Diclofenac plus misoprostol decreased the diclofenac-induced increase in MAP by 3.3 +/- 1.0 mm Hg (95% confidence interval [CI] 1.1-5.3 mm Hg, p=0.004) and decreased the RPP by 724 +/- 238 units (95% CI 225-1223 units, p=0.007). The ERPF rate increased by 56.1 +/- 35.0 ml/minute (95% CI -24.7-137.0 ml/min, p=0.15) and GFR by 18.1 +/- 7.1 ml/minute (95% CI 1.9-34.5 ml/min, p=0.03). Diclofenac alone was relatively well tolerated; no adverse effects were reported with diclofenac plus misoprostol. In senior salt-sensitive patients with hypertension, coadministration of misoprostol with diclofenac attenuated the blood pressure elevation and renal vasoconstrictive effects of diclofenac and was well tolerated.

Consequences of the discontinuation of antihypertensive treatment in successfully treated patients

Hypertension is probably the most important public health problem in developed countries. Over the last 40 years, an increasing number of hypertensive patients have been treated with various antihypertensive drugs. If the blood pressure (BP) is controlled, the discontinuation of the antihypertensive drug may result either in a relapse of the disease or in the maintenance of normal BP for a long time. In this study, we discuss the available data regarding the consequences of antihypertensive drug withdrawal in successfully treated patients and we suggest guidelines for the application in clinical practice.

Short-term predictors of maintenance of normotension post withdrawal of antihypertensive drugs in the second Australian national blood pressure study (ANBP2)

Short-term predictors of maintenance of normotension post withdrawal of antihypertensive drugs in the second Australian national blood pressure study (ANBP2)

Short-term predictors of maintenance of normotension after withdrawal of antihypertensive drugs in the second Australian National Blood Pressure Study (ANBP2)

BackgroundAntihypertensive drug therapy is considered lifelong but in the family practice environment drug cessation may provide an opportunity to attempt nonpharmacologic strategies for blood pressure (BP) control with a clear outcome, maintaining drug-free status. The identification of simple predictors would assist the family physician to select who may or may not have their medication ceased. MethodsTo monitor a drug cessation program in currently treated hypertensive patients in Australian family practice, 25,826 patients aged 65 to 84 years currently receiving antihypertensive medication, were offered drug withdrawal as part of the run-in phase of a large clinical trial. Outcomes investigated were the proportion of patients completing drug withdrawal and maintaining short-term BP control and factors that predicted these patients. ResultsA total of 18,993 patients did not enter the withdrawal program; 6291 (92% of those who entered) completed drug withdrawal. In comparison to patients who did not complete drug withdrawal, they were younger and more likely male. A total of 1,228 (18% of those who entered) ceased medication and maintained adequate BP control for 0 to 76 weeks (median, 4 weeks). Cox regression analysis identified lower on therapy systolic and diastolic BP, younger age, type of agent, and monotherapy as predictors of successful drug withdrawal and maintenance of BP control. ConclusionsCessation of antihypertensive drug therapy is possible in a substantial proportion (18%) of patients attending family practice who are willing to do so and is most successful in those who are younger with BP controlled on monotherapy. Where this strategy is initiated, use of such predictors, effective behavioral change, and systematic follow-up is recommended.

An innovative program for changing health behaviours.

Health-related behaviours affecting diet, weight control and physical activity are important for long-term cardiovascular health but behaviour change is difficult to initiate and even more difficult to maintain. We have developed a health promotion program, in which social support has a key role, to encourage a prudent diet, weight control and physical activity. Behaviour change is based on evaluating initial behaviour, weighing up costs and benefits, assessing barriers to change and goal-setting. We first evaluated the program in couples beginning to live together, a group chosen because of the risk of weight gain and decreased physical activity after marriage, readiness to change behaviour at that time in the life course and the opportunity to use partner's support in achieving behaviour change. In an initial short-term study with 39 couples, intake of fat and take-away foods decreased and consumption of fruit, vegetables and reduced fat foods increased. Physical activity increased and there was a 6% fall in blood cholesterol. Further evaluation in 137 couples included assessment after 12 months. A decrease in fat intake and increase in physical activity and fitness seen at the end of the program persisted 1 year later. Lower cholesterol and a trend to lower weight gain and lower blood pressure were also maintained after 12 months. We have modified the program aiming for weight loss, improved dietary habits and increased physical activity in overweight treated hypertensives, supported by their partners. Decreased intake of energy, total and saturated fat, and weight loss seen at the end of the 16 week program was significantly greater in the intervention group than with usual care. Blood pressure fell in the program group at the end of intervention and, in men, withdrawal of antihypertensive drugs was significantly associated with the intervention. Weight loss and a decrease in waist circumference were maintained in the program group up to 16 months after entering the study. This program has the potential for wider application in other at-risk groups.

Predictors of normotension on withdrawal of antihypertensive drugs in elderly patients: prospective study in second Australian national blood pressure study cohort

Objectives: To identify simple long term predictors of maintenance of normotension after withdrawal of antihypertensive drugs in elderly patients in general practice.Design: Prospective cohort study.Setting: 169 general practices in Victoria,...

Successful withdrawal of antihypertensive drugs can be predicted

Successful withdrawal of antihypertensive drugs can be predicted

Predictors of normotension after antihypertensive drug withdrawal

Predictors of normotension after antihypertensive drug withdrawal

Withdrawal of Antihypertensive Drugs Before Anesthesia

Withdrawal of Antihypertensive Drugs Before Anesthesia