Therapieresistente und ‑refraktäre Hypertonie

AbstractHypertension is defined as resistant to treatment when treatment fails to lower office systolic and diastolic blood pressure values to < 140/90 mmHg. The treatment strategy should include lifestyle measures and appropriate doses of three or more drugs acting by different mechanisms including a diuretic. An updated definition of treatment resistance includes all patients with ≥ 4 antihypertensive agents of different classes irrespective of their on-treatment blood pressure. The term “refractory” hypertension has been suggested for patients with uncontrolled blood pressure on ≥ 5 antihypertensive drugs including the thiazide-like diuretic chlorthalidone and the mineralocorticoid receptor antagonist spironolactone. “Pseudo resistance” especially due to white coat hypertension and non-adherence with the prescribed medication has to be ruled out to be able to identify patients with “true” treatment resistance. Therefore, before distinguishing true from pseudo resistance, the term “apparent” resistance should be used. While the prevalence of apparent resistance may be in the range of 10–15 % of treated patients, the exact prevalence of true resistance remains unknown due to the lack of appropriate studies but is likely to be rather small including a high proportion of patients with secondary forms of hypertension. Once identified most patients with true treatment resistance should receive intensified drug treatment primarily by expanded diuretic usage. Thus, resistant hypertension is primarily a diagnostic challenge: identifying patients with true resistance and those with secondary hypertension.

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The Road to Better Management in Resistant Hypertension–Diagnostic and Therapeutic Insights

Pharmaceutics ◽

10.3390/pharmaceutics13050714 ◽

2021 ◽

Vol 13 (5) ◽

pp. 714

Author(s):

Elisabeta Bădilă ◽

Cristina Japie ◽

Emma Weiss ◽

Ana-Maria Balahura ◽

Daniela Bartoș ◽

...

Keyword(s):

Blood Pressure ◽

Resistant Hypertension ◽

Renin Angiotensin System ◽

Drug Regimen ◽

Secondary Hypertension ◽

Adverse Outcomes ◽

Uncontrolled Hypertension ◽

White Coat Hypertension ◽

Mineralocorticoid Receptor Antagonist ◽

Mortality And Morbidity

Resistant hypertension (R-HTN) implies a higher mortality and morbidity compared to non-R-HTN due to increased cardiovascular risk and associated adverse outcomes—greater risk of developing chronic kidney disease, heart failure, stroke and myocardial infarction. R-HTN is considered when failing to lower blood pressure below 140/90 mmHg despite adequate lifestyle measures and optimal treatment with at least three medications, including a diuretic, and usually a blocker of the renin-angiotensin system and a calcium channel blocker, at maximally tolerated doses. Hereby, we discuss the diagnostic and therapeutic approach to a better management of R-HTN. Excluding pseudoresistance, secondary hypertension, white-coat hypertension and medication non-adherence is an important step when diagnosing R-HTN. Most recently different phenotypes associated to R-HTN have been described, specifically refractory and controlled R-HTN and masked uncontrolled hypertension. Optimizing the three-drug regimen, including the diuretic treatment, adding a mineralocorticoid receptor antagonist as the fourth drug, a β-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when failing to achieve target blood pressure values are current recommendations regarding the correct management of R-HTN.

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Identification and management of resistant hypertension

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20212333 ◽

2021 ◽

Author(s):

Abass Mahamoud Ahmed ◽

Xiaochen Yuan

Keyword(s):

Blood Pressure ◽

Resistant Hypertension ◽

Antihypertensive Drugs ◽

Blood Pressure Measurement ◽

Optimal Dose ◽

Secondary Hypertension ◽

White Coat ◽

Clinical Inertia ◽

White Coat Hypertension ◽

Hypertension Detection

Resistant hypertension is defined as blood pressure being higher than the patient's target blood pressure despite the use of three or more different types of antihypertensive drugs at the optimal dose, and one of them should be a diuretic. The evaluation of patients with resistant hypertension should first confirm that they have true resistant hypertension. By eliminating or correcting false resistance factors, such as white coat hypertension, poor blood pressure measurement technique, poor drug compliance, improper dosage or combination of antihypertensive drugs, and white coat effects and clinical inertia. Resistant hypertension therapy includes improved compliance with the use of drugs, secondary hypertension detection and treatment, use of lifestyle measures and treatment of obesity, and other comorbidities. switching to a long-acting diuretic type of thiazide like chlorthalidone could improve the BP from the patients taking hydrochlorothiazide. This review paper illustrates briefly the identification of the underlying causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

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Impact of hospitalization for checking medication adherence due to resistant and refractory hypertension suspicious on short and mid-term blood pressure control

European Heart Journal ◽

10.1093/ehjci/ehaa946.2800 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Pio-Abreu ◽

F Trani-Ferreira ◽

G.V Silva ◽

L.A Bortolotto ◽

L Drager

Keyword(s):

Blood Pressure ◽

Hospital Discharge ◽

Outpatient Clinic ◽

Antihypertensive Drugs ◽

Outpatient Visit ◽

Target Organ Damage ◽

Refractory Hypertension ◽

Gold Standard Method ◽

Medication Intake

Abstract Background Resistant (HR) and refractory hypertension (HRef) are associated with increased cardiovascular events and target-organ damage. However, appropriate HR and HRef diagnosis require good drug adherence. In this context, the “gold standard” method for assessing adherence is supervised medication intake. However, it is not clear the real utility of supervised medication intake in clinical practice. Purpose To evaluate whether hospitalization for confirming anti-hypertensive adherence in patients with HR and HRef may impact blood pressure (BP) control after hospital discharge in patients with HR or HRef suspicious at a tertiary outpatient clinic. Methods We recruited consecutive patients with HR or HRef suspicious admitted to the Hospital for confirming treatment adherence. HR was defined as uncontrolled office BP (≥140 and/or ≥90mmHg) despite using ≥3 classes at optimal doses (one of them being diuretic) or controlled BP using ≥4 classes. HRef was defined as no BP control despite using ≥5 antihypertensive drugs. Patients with suspected HRef who did not meet the criteria but full field the HR definition were named HRNoRef. During hospitalization, all patients used low sodium diet and had supervised taking of prescribed drugs by the medical team aiming BP control. We defined not only the rate of adherence and HF/HRef status but also BP and number of antihypertensive drugs at hospital discharge and in the two first return outpatient's visits. Results We studied a total of 83 patients with suspected HR/HRef (age 53±14 years; 76% females; pre-hospitalization systolic and diastolic BP: 177±28 and 106±21mmHg, respectively). Of these, 68.7% (57 patients) had suspected HRef in the outpatient clinic. The average number of antihypertensive drugs on admission was 5.3±1.3 classes. After hospitalization, the overall frequency of HR fell to 80% (66 patients). The average number of antihypertensive drugs at hospital discharge as well as systolic and diastolic BP was 4.5±1.3 classes, 131±17mmHg and 80±12mmHg, respectively (p<0.001 vs. pre-hospitalization for all comparisons). Among the HR types, HRef was confirmed in only 27 patients (32.5%). During the outpatient follow-up, the patients remained with lower number of antihypertensive drugs as well as lower systolic and diastolic BP at first outpatient visit (mean returned time: 2.1±1.7months) and second outpatient visit post-discharge (mean returned time 7.1±2.6months) as compared to pre-hospitalization data: First visit: 4.3±1.2 classes, systolic: 152±24mmHg, diastolic BP: 89±17mmHg; second visit: 4.5±1.3 classes, systolic: 150±26mmHg, diastolic BP: 89±15mmHg; (p<0.001 vs. pre-hospitalization for all comparisons). Conclusion Supervised medication intake during hospitalization may help not only to define the HR and HRef status but also to have impact on the number of antihypertensive drugs and lower BP values at short and mid-term follow-up. Funding Acknowledgement Type of funding source: None

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Blood Pressure Control: Stroke and Stroke Prevention

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/14703203050060010301 ◽

2005 ◽

Vol 6 (1_suppl) ◽

pp. S8-S11

Author(s):

Hans-Christoph Diener

Keyword(s):

Blood Pressure ◽

Stroke Prevention ◽

Antihypertensive Drugs ◽

Angiotensin Receptor Blockers ◽

Antihypertensive Agents ◽

Pressure Control ◽

Angiotensin Receptor ◽

Risk Of Death ◽

Pressure Lowering ◽

Receptor Blockers

Hypertension is the most important modifiable risk factor for primary and secondary stroke prevention. All antihypertensive drugs are effective in primary prevention: the risk reduction for stroke is 30—42%. However, not all classes of drugs have the same effects: there is some indication that angiotensin receptor blockers may be superior to other classes of antihypertensive drugs in stroke prevention. Seventy-five percent of patients who present to hospital with acute stroke have elevated blood pressure within the first 24—48 hours. Extremes of systolic blood pressure (SBP) increase the risk of death or dependency. The aim of treatment should be to achieve and maintain the SBP in the range 140—160 mmHg. However, fast and drastic blood pressure lowering can have adverse consequences. The PROGRESS trial of secondary prevention with perindopril + indapamide versus placebo + placebo showed a decrease in numbers of stroke recurrences in patients given both active antihypertensive agents, more impressive for cerebral haemorrhage.There were also indications that active treatment might decrease the development of post-stroke dementia.

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Clinical Practice Patterns of Hypertensive Disease in Pregnancy among Korean Obstetricians

JOURNAL OF THE KOREAN SOCIETY OF MATERNAL AND CHILD HEALTH ◽

10.21896/jksmch.2021.25.3.221 ◽

2021 ◽

Vol 25 (3) ◽

pp. 221-229

Author(s):

Tae Gyu Ahn ◽

Yeon Hee Kim ◽

Yun Sook Kim ◽

Jae Eun Shin ◽

Young-Lim Oh ◽

...

Keyword(s):

Blood Pressure ◽

Clinical Practice ◽

Practice Patterns ◽

Antihypertensive Drugs ◽

Antihypertensive Agents ◽

Delivery Method ◽

Hypertensive Disease ◽

Clinical Practice Patterns ◽

Elevated Liver Enzymes ◽

Prophylactic Aspirin

Purpose: The purpose of this study was to investigate the clinical practice patterns of Korean obstetricians and gynecologists the diagnosis and management of hypertensive disease in pregnant women. Methods: From April 2015 to October 2015, questionnaire was distributed via email to obstetricians who were members of the Society for Maternal and Fetal Medicine. The survey consisted of 37 questions in 6 categories. Responses to the questions on the management of hypertensive disorders of pregnancy, from diagnosis to treatment, were evaluated. Results: A total of 93 obstetricians and gynecologists responded to the survey. High blood pressure was allocated the highest priority as an index mainly used when deciding to hospitalize patients with hypertensive disease during pregnancy, followed by pregnancy symptoms, proteinuria, and blood test results. Calcium channel blocker (CCB) for oral administration and hydralazine for injection were preferred as antihypertensive drugs mainly used to control severe hypertension. Regarding the delivery method for hypertensive disease during pregnancy, in cases of preeclampsia, 63% of the respondents chose the delivery method according to the cervical status, and in cases of hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and eclampsia, which increased in severity, 52% and 31% responded that the delivery method was determined according to the cervical status, respectively. In cases of mild preeclampsia, the 70% of respondents preferred 37–38 weeks of gestation for the delivery time. Regarding the use of aspirin in patient with hypertension during pregnancy, 52% of the respondents occasionally administered aspirin, and in patients with a history of hypertensive disease during pregnancy, only 43% were administered prophylactic aspirin. Conclusion: Domestic obstetricians regarded blood pressure as the most meaningful factor when treating women with hypertension during pregnancy and considered blood pressure control as important. The preferred antihypertensive agents were oral CCB and hydralazine injections, and the choice of delivery method was determined according to the condition of the cervix and severity of the disease. Even in women with high risk factors for preeclampsia, prophylactic aspirin was administered in as low as 50%, of patients, possibly may due to the absence of domestic guidelines for aspirin use during pregnancy. Korean guidelines for prophylactic aspirin administration during pregnancy is needed based on additional research on the efficacy of aspirin for domestic women in the future.

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The first Russian national multicenter study - ROBLS (Russian Optimal Blood pressure Lowering Study)

Arterial’naya Gipertenziya (Arterial Hypertension) ◽

10.18705/1607-419x-2003-9-5-151-154 ◽

2003 ◽

Vol 9 (5) ◽

pp. 151-154

Author(s):

Yu. N. Belenkov ◽

I. Ye. Chazova

Keyword(s):

Blood Pressure ◽

Intensive Care ◽

Treatment Group ◽

Multicenter Study ◽

Antihypertensive Drugs ◽

Antihypertensive Agents ◽

Fixed Dose ◽

Care Group ◽

Routine Treatment ◽

Optimal Blood Pressure

ROBIS is the first large multicenter study performed in Russia. The Objective of the study was to compare the efficiency, safely, and impact of two treatment policies (the application of an algorithm to the stepwise use of 4 classes of antihypertensive agents in an intensive care group and random antihypertensive therapy in a routine treatment group) on the incidence of cardiovascular events in patients with arterial hypertension. Design: This is a national multicenter open consecutive prospective study. The patients meeting the criteria of inclusion were randomly divided into two equal groups, one of them (an intensive care group) received therapy with a nifedipine retard in Fixed dose for 4 weeks. In patients who failed to achieve the target level of blood pressure (BP), the therapy was supplemented by enalapril, 20 mg, hydrochlorothiazide, 25 mg, and metoprolol, 50 mg, at a 4-week interval. After achieving the target BP level, the patients continued the treatment with which the level had been attained. If the antihypertensive effect of therapy was found to disappear, the above drugs were successively supplemented. The other group (a routine treatment group) continued to be treated with the antihypertensive drugs prescribed in the polyclinic (Fig. 1). BP and heart rate were monitored and the patients' complaints and adverse reactions were recorded on repeated visits 4, 8, 12, 16, 24, 52, 64, 70, 88, and 104 weeks after the initiation of therapy. Control blood and urine analyses and ECG studies were made 12, 16, 52, and 104 weeks after therapy.

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Hypertension Subtypes among Thai Hypertensives: An Analysis of Telehealth-Assisted Instrument in Home Blood Pressure Monitoring Nationwide Pilot Project

International Journal of Hypertension ◽

10.1155/2020/3261408 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Sakolwat Montrivade ◽

Pairoj Chattranukulchai ◽

Sarawut Siwamogsatham ◽

Yongkasem Vorasettakarnkij ◽

Witthawat Naeowong ◽

...

Keyword(s):

Blood Pressure ◽

Blood Pressure Monitoring ◽

Demographic Data ◽

Real Life ◽

Antihypertensive Agents ◽

Home Blood Pressure ◽

White Coat ◽

White Coat Hypertension ◽

Routine Practice ◽

White Coat Effect

Background. White-coat hypertension (HT), masked HT, HT with white-coat effect, and masked uncontrolled HT are well-recognized problems of over- and undertreatment of high blood pressure in real-life practice. However, little is known about the true prevalence in Thailand. Objectives. To examine the prevalence and characteristics of each HT subtype defined by mean home blood pressure (HBP) and clinic blood pressure (CBP) using telemonitoring technology in Thai hypertensives. Methods. A multicenter, observational study included adult hypertensives who had been diagnosed for at least 3 months based on CBP without the adoption of HBP monitoring. All patients were instructed to manually measure their HBP twice a day for the duration of at least one week using the same validated automated, oscillometric telemonitoring devices (Uright model TD-3128, TaiDoc Corporation, Taiwan). The HBP, CBP, and baseline demographic data were recorded on the web-based system. HT subtypes were classified according to the treatment status, CBP (≥or <140/90 mmHg), and mean HBP (≥or <135/85 mmHg) into the following eight subtypes: in nonmedicated hypertensives, there are four subtypes that are normotension, white-coat HT, masked HT, and sustained HT; in treated hypertensives, there are four subtypes that are well-controlled HT, HT with white-coat effect, masked uncontrolled HT, and sustained HT. Results. Of the 1,184 patients (mean age 58 ± 12.7 years, 59% women) from 46 hospitals, 1,040 (87.8%) were taking antihypertensive agents. The majority of them were enrolled from primary care hospitals (81%). In the nonmedicated group, the prevalence of white-coat and masked HT was 25.7% and 7.0%, respectively. Among the treated patients, the HT with white-coat effect was found in 23.3% while 46.7% had uncontrolled HBP (a combination of the masked uncontrolled HT (9.6%) and sustained HT (37.1%)). In the medicated older subgroup (n = 487), uncontrolled HBP was more prevalent in male than in female (53.6% vs. 42.4%, p=0.013). Conclusions. This is the first nationwide study in Thailand to examine the prevalence of HT subtypes. Almost one-fourth had white-coat HT or HT with white-coat effect. Approximately half of the treated patients especially in the older males had uncontrolled HBP requiring more intensive interventions. These results emphasize the role of HBP monitoring for appropriate HT diagnosis and management. The cost-effectiveness of utilizing THAI HBPM in routine practice needs to be examined in the future study.

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Reserpine Substantially Lowers Blood Pressure in Patients With Refractory Hypertension: A Proof-of-Concept Study

American Journal of Hypertension ◽

10.1093/ajh/hpaa042 ◽

2020 ◽

Vol 33 (8) ◽

pp. 741-747 ◽

Cited By ~ 3

Author(s):

Mohammed Siddiqui ◽

Hemal Bhatt ◽

Eric K Judd ◽

Suzanne Oparil ◽

David A Calhoun

Keyword(s):

Blood Pressure ◽

Antihypertensive Treatment ◽

Proof Of Concept ◽

Open Label ◽

Refractory Hypertension ◽

Antihypertensive Medications ◽

Mineralocorticoid Receptor Antagonist ◽

Antihypertensive Regimen ◽

Automated Office Blood Pressure ◽

Current Clinical Trial

Abstract BACKGROUND Refractory hypertension (RfHTN), a phenotype of antihypertensive treatment failure, is defined as uncontrolled automated office blood pressure (AOBP) ≥130/80 mm Hg and awake ambulatory blood pressure (ABP) ≥130/80 mm Hg on ≥5 antihypertensive medications, including chlorthalidone and a mineralocorticoid receptor antagonist. Previous studies suggest that RfHTN is attributable to heightened sympathetic tone. The current study tested whether reserpine, a potent sympatholytic agent, lowers blood pressure (BP) in patients with RfHTN. METHODS Twenty-one out of 45 consecutive patients with suspected RfHTN were determined to be fully adherent with their antihypertensive regimen. Seven patients agreed to participate in the current clinical trial with reserpine and 6 patients completed the study. Other sympatholytic medications, such as clonidine or guanfacine, were tapered and discontinued before starting reserpine. Reserpine 0.1 mg daily was administered in an open-label fashion for 4 weeks. All patients were evaluated by AOBP and 24-hour ABP at baseline and after 4 weeks of treatment. RESULTS Reserpine lowered mean systolic and diastolic AOBP by 29.3 ± 22.2 and 22.0 ± 15.8 mm Hg, respectively. Mean 24-hour systolic and diastolic ABPs were reduced by 21.8 ± 13.4 and 15.3 ± 9.6 mm Hg, mean awake systolic and diastolic ABPs by 23.8 ± 11.8 and 17.8 ± 9.2 mm Hg, and mean asleep systolic and diastolic ABPs by 21.5 ± 11.4 and 13.7 ± 6.4 mm Hg, respectively. CONCLUSIONS Reserpine, a potent sympatholytic agent, lowers BP in patients whose BP remained uncontrolled on maximal antihypertensive therapy, lending support to the hypothesis that excess sympathetic output contributes importantly to the development of RfHTN.

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Emerging Drug Classes and Their Potential Use in Hypertension

Hypertension ◽

10.1161/hypertensionaha.119.12676 ◽

2019 ◽

Vol 74 (5) ◽

pp. 1075-1083 ◽

Cited By ~ 10

Author(s):

Michel Azizi ◽

Patrick Rossignol ◽

Jean-Sébastien Hulot

Keyword(s):

Blood Pressure ◽

Antihypertensive Drugs ◽

Generic Drugs ◽

Antihypertensive Agents ◽

Uncontrolled Hypertension ◽

Blood Pressure Lowering ◽

Receptor Antagonists ◽

Drug Classes ◽

Pressure Lowering ◽

Potential Use

Despite the availability of multiple antihypertensive drugs targeting the different pathways implicated in its pathophysiology, hypertension remains poorly controlled worldwide, and its prevalence is increasing because of the aging of the population and the obesity epidemic. Although nonadherence to treatment contributes to uncontrolled hypertension, it is likely that not all the pathophysiological mechanisms are neutralized by the various classes of antihypertensive treatment currently available, and, the counter-regulatory mechanisms triggered by these treatments may decrease their blood pressure–lowering effect. The development of new antihypertensive drugs acting on new targets, with different modes of action, therefore, remains essential, to improve blood pressure control and reduce the residual burden of cardiovascular risks further. However, the difficulties encountered in the conception, development, costs, and delivery to the market of new classes of antihypertensive agents highlights the hurdles that must be overcome to release and to evaluate their long-term safety and efficacy for hypertension only, especially because of the market pressure of cheap generic drugs. New chemical entities with blood pressure–lowering efficacy are thus being developed more for heart failure or diabetic kidney disease, 2 diseases pathophysiologically associated with hypertension. These include dual angiotensin II receptor-neprilysin inhibitors, soluble guanylate cyclase stimulators, nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists, as well as sodium-glucose cotransporter 2 inhibitors. However, centrally acting aminopeptidase A inhibitors and endothelin receptor antagonists have a dedicated program of development for hypertension. All these emergent drug classes and their potential use in hypertension are reviewed here.

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Unilateral renal sympathetic denervation may reduce blood pressure in patients with refractory hypertension

Italian Journal of Medicine ◽

10.4081/itjm.2015.544 ◽

2015 ◽

Vol 9 (4) ◽

pp. 362

Author(s):

Aurelio Negro ◽

Rosaria Santi ◽

Antonio Manari ◽

Franco Perazzoli

Keyword(s):

Blood Pressure ◽

Renal Artery ◽

Renal Denervation ◽

Antihypertensive Drugs ◽

Renal Sympathetic Denervation ◽

Caucasian Woman ◽

Left Renal Artery ◽

Refractory Hypertension ◽

The Mean

A 52-year-old Caucasian woman with essential resistant and refractory hypertension despite optimal medical therapy, including 6 different antihypertensive drugs was referred for the catheter-based renal denervation. Due to unfavourable anatomy because of non-critical fibromuscular dysplasia on the right renal artery, renal denervation of only the left renal artery was performed. Before and after the renal denervation, the patient’s blood pressure was monitored by office measurements and ambulatory blood pressure measurements (ABPM). Before the procedure, the mean office blood pressure was 157/98 mmHg; at ABPM, the mean blood pressure values were 145/94 mmHg. At 6 months of follow-up, the mean office blood pressure was 134/90 mmHg and 121/76 mmHg at ABPM. In latest 12 months of follow-up, office and ABPM blood pressure were 125/80 and 127/80 mmHg respectively. This unique case suggests that unilateral renal denervation may be effective in lowering blood pressure in patients with refractory hypertension and unfavorable renal arteries anatomy.

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