Principal results of the Controlled Onset INvestigation of Cardiovascular Endpoints (CONVINCE) Trial. Wolters Kluwer Health Triple therapy must be optimised before selecting further add-on therapy because optimal dosing and drug selection can see blood pressure normalise in many patients. Pimenta E, Calhoun D. Treatment of resistant hypertension. Combined, these 2 PATWAY-2 substudy results strongly implicate inappropriate fluid retention attributable to varying degrees of hyperaldosteronism as a broad mediator of antihypertensive treatment resistance. In the second substudy, the effect of the 3 different agents on thoracic fluid content, an index of volume status, was determined.6 Bisoprolol, the -blocker, had no effect on thoracic fluid content, while doxazosin, the -antagonist, increased it, indicating increased fluid retention. Cleveland Clinic is a non-profit academic medical center. Lastly, the third PATWAY-2 substudy assessed the benefit of amiloride for treating RHTN.6 After completion of the blinded protocol, participants willing to continue were crossed over to amiloride 1020 mg daily for 612 weeks. Two potentially effective interventional therapies are currently being assessed for this purpose. Metrics. A 62-year-old obese White man with a longstanding history of hypertension, obstructive sleep apnea (OSA), and chronic low back pain presents with complaints of high home BP readings. This is founded on the theory that continuous electrical stimulation of carotid baroreceptors, via an implantable device, should inhibit sympathetic output. Thus in predisposed patients such as the elderly or those with renal insufficiency indapamide might be a superior substitute. [ 1] It accounts for 8.6% of all visits to a primary care physician. Approved as a pharmacy medicine, Sanofi will launch Cialis Together in the second half of the year. 2009 Apr;38(4):643-51. doi: 10.1016/j.lpm.2009.02.004. Treatment should comprise both lifestyle modification and pharmacologic therapy. While not as rigorous as the evaluation of spironolactone because of its open-label assessment, the findings do provide compelling rationale for considering amiloride as an effective alternative to spironolactone, especially if the latter is not tolerated. Sometimes treatable secondary causes may be the source of your resistant hypertension. Oftentimes however, the clinical assessment will be unremarkable. We are grateful to Dr Suku Thambar for his valuable feedback on earlier drafts of this paper. Unable to load your collection due to an error, Unable to load your delegates due to an error. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Ginseng, licorice or other herbal products. If you have side effects from one drug, your doctor may prescribe another one. O The revised definition will better distinguish true treatment resistance from the much larger category of uncontrolled hypertension attributable to undertreatment, including underdosing and/or use of ineffective drug combinations; falsely elevated BP readings because of poor BP measuring technique; a large white-coat effect; and poor medication . [20] If monotherapy is insufficient the regimen could be modified depending on therapeutic effect by altering dose or adding an additional class of drug. Setaro J, Black H. Refractory hypertension. Sometimes an underlying medical condition, or secondary cause, can keep your high blood pressure resistant to medications. Kumar N, Calhoun D, Dudenbostel T. Management of patients with resistant hypertension: Current treatment options. The .gov means its official. [11] Possible end-organ consequences of untreated hypertension include heart failure, stroke, ischemic heart disease and renal failure. In renal parenchymal disease, elevated serum creatinine and GFR are the best indicators for disease progression.11,12 Primary aldosteronism causes an inappropriate aldosterone production in relation to serum sodium status, occurring in up to 20% of patients with resistant hypertension.1,11 Renal artery stenosis is associated most commonly with atherosclerosis but also can present in younger patients with fibromuscular dysplasia.11 Causes and diagnostics of secondary hypertension are summarized in Table 1. 8600 Rockville Pike You may be asked to undergo a sleep study to check for sleep apnea. A controlled trial of renal denervation for resistant hypertension. There is little randomised trial data to guide choice of drug regimen for patients with resistant hypertension and recommendations are largely empirical. In some patients such as those with ischemic heart disease or poor glycaemic control, traditional beta blockers like atenolol or metoprolol may instead be indicated. B government site. Primary care physicians should be aware of the therapeutic approach for hypertension when traditional therapy fails. 19 Patients whose BP is controlled with 4 . You may be trying to access this site from a secured browser on the server. Can nocturnal hypertension predict cardiovascular risk? The patient is on maximum tolerated doses of amlodipine, nebivolol, and hydrochlorothiazide. Resistant hypertension is important to recognise because it places patients at risk of end-organ damage. eTG complete. Resistant Hypertension. government site. Resistant hypertension occurs when a person's high blood pressure does not improve when a person's blood pressure remains above their goal, and they are taking three blood pressure medications. 7. However, a blinded randomised controlled trial released in April 2014, SYMPLICITY-HTN-3, failed to demonstrate any blood pressure benefit for RD versus a sham control procedure in 535 patients with resistant hypertension. Other implicated factors include failure to adhere to lifestyle advice, poor measurement technique, white-coat hypertension and the use of medications that interfere with blood pressure [Table 1]. Accordingly, while the change in prevalence of RHTN with application of the revised definition has not yet been rigorously determined, a 4% increase is likely correct as the only relevant change will be in the narrow group of patients whose BP is 130139/8089 mm Hg on 3 medications, who now have RHTN based on the revised definition. 2. Initial investigations for suspected causes of secondary hypertension[10,16]. The revised definition will better distinguish true treatment resistance from the much larger category of uncontrolled hypertension attributable to undertreatment, including underdosing and/or use of ineffective drug combinations; falsely elevated BP readings because of poor BP measuring technique; a large white-coat effect; and poor medication adherence. The commonest reasons for apparent treatment resistance are medication non-compliance and insufficient drug therapy. The blood pressure goal in uncomplicated patients is 140/90 mmHg which could be relaxed to 150/90 in patients greater than 60 years of age. Circulation. High blood pressure (hypertension) is one of the most important risk factors for cardiovascular diseases and is a significant cause of morbidity and mortality worldwide. Accessibility Description of the DASH eating plan. [43] Complications were primarily related to nerve injury during device implantation though there was also a 2.3% incidence of hypertension-induced stroke. The above mechanism is achieved by downregulating the RAAS system. 2023 Jun;46(6):1606-1608. doi: 10.1038/s41440-023-01268-0. Recommendations include smoking cessation, reduction in alcohol intake, dietary sodium restriction, healthy eating plans, increased physical activity and weight loss. [36] Carvedilol should be initiated at 12.5 mg daily for at least two days, before increasing by 12.5 mg every two weeks to a maximum dose of 50 mg per day. Bethesda, MD 20894, Web Policies Resistant hypertension affects about 17% of the US population. Disclaimer. Labetalol must not be increased faster than by 200 mg increments per day. Early identification and frequent follow-up can help patients achieve BP goals more rapidly and may reduce morbidity and mortality associated with complications of hypertension, including cerebrovascular accident, cardiovascular disease, and kidney disease. Most patients with hypertension are prescribed hydrochlorothiazide as the diuretic of choice. Its dose ranges from 2.5-10 mg daily. For instance, in patients over 55 years of age with evidence of heart failure a thiazide diuretic might be a more suitable first-line option than a CCB. Patients with resistant hypertension are on a combination of three or more antihypertensives at maximum tolerated doses. The original 2008 Scientific Statement on RHTN included a strong recommendation for adding spironolactone after the first 3 medications, but this recommendation was largely based on observational data or open-label assessments of spironolactone.4 Absent at the time was rigorous demonstration of the superiority of spironolactone for treating RHTN compared with other classes of antihypertensive agents. Indications for specialist referral in hypertensive patients[9]. In order for the drugs to work, they must be taken every day at the correct dose, and the correct number of times per day. Resistant hypertension is defined as high blood pressure that remains uncontrolled despite treatment with at least three antihypertensive agents (one of which is usually a diuretic) at best tolerated doses. Still University in Mesa, Ariz., and is director of regulatory and professional practice for the American Academy of PAs in Alexandria, Va. Joyce Nicholas is director of evaluation, assessment, and compliance and a professor in the PA program at the University of Lynchburg. He or she may ask about side effects that may keep you from taking all of your doses. In most cases the pathogenesis of resistant hypertension is uncertain. [1] It accounts for 8.6% of all visits to a primary care physician. Youre more likely to have resistant hypertension if you: High blood pressure itself rarely causes symptoms, which is why its called the silent killer. Some people can go years without even realizing they have hypertension. 13. Pseudoresistance is affected by how the BP is measured, white-coat hypertension, as well as medication adherence.1 Pseudoresistant hypertension is defined as hypertension that is affected by how the patient's BP is measured, in addition to other factors interfering with the necessary treatment, such as white-coat hypertension and the patient's ability to adhere to prescribed medication.1 Although pseudoresistance cannot be prevented, clinicians must be aware of potential factors that could contribute to resistance. An earlier study of patients referred to a hypertension specialty reported an overall prevalence of RHTN within their clinic of 14.7%.5 Importantly however, during a median follow-up period of 7 months, the period prevalence had increased up to 43.6%. , MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, Ford I, Cruickshank JK, Caulfield MJ, Salsbury J, Mackenzie I, Padmanabhan S, Brown MJ; British Hypertension Societys PATHWAY Studies Group. [3] The remaining cases of hypertension are secondary to a distinguishable process and would likely resolve if the underlying condition was treated. Hypertension is defined as persons 18 years of age and over with a systolic pressure reading of 140 mmHg or more or a diastolic reading of 90 mmHg or more, or those taking antihypertensive medications. Frank J. Order tests for sleeping disorders. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. A subset of sodium-sensitive hypertension. Federal government websites often end in .gov or .mil. Occasionally these less-frequently used agents will require earlier introduction depending on clinical circumstances. Indapamide is superior to thiazide in the preservation of renal function in patients with renal insufficiency and systemic hypertension. Specialised medication options for resistant hypertension[25,32,37,38,39,40]. The .gov means its official. These patients accumulate twice as much sodium compared with patients with hypertension and the ability to modulate.8 Nonmodulation is a nonmodifiable risk factor for resistant hypertension and is determined by multiple factors including race, genetics, age, and comorbidities such as obesity and diabetes.7, Not every patient is easily identified as having resistant hypertension and many may present as asymptomatic. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. Resistant hypertension affects about 17% of the US population. The Author(s) 2018. Your message has been successfully sent to your colleague. Limiting use of NSAIDs for pain relief (acetaminophen can be used instead). The Rheos Pivotal Trial is the only major double-blind randomised study published on carotid sinus stimulation. Beyond history and examination, all patients with resistant hypertension should be investigated at minimum with a serum creatinine test, estimated glomerular filtration rate and urine dipstick. Australian Institute of Health and Welfare. Below this level eGFR or in hypoalbuminuric states (serum albumin <3.0 g/l), a long-acting loop diuretic such as torsemide is recommended.1. (https://pubmed.ncbi.nlm.nih.gov/18574054/). Recent findings: RH is defined as uncontrolled blood pressure (BP) on 3 anti-hypertensives, one of which should be a diuretic, prescribed at maximally tolerated doses . Before The new American College of Cardiology (ACC)/AHA hypertension guidelines are important in providing a preliminary estimate of the prevalence of RHTN based on the now lower recommended BP goal of 130/80 mm Hg.2 The landmark PATHWAY-2 study adds importantly to our understanding of the pathophysiology of RHTN and provides compelling evidence for the most effective multiple-drug combination for treating RHTN, including especially, preferential use of spironolactone.3 This editorial serves to highlight these recent advances. Resistant hypertension is defined as uncontrolled BP despite the concurrent treatment with 3 antihypertensive drug classes, inclusive of a long-acting calcium channel blocker, a blocker of the renin-angiotensin-system and a diuretic, each one administered at maximum or maximally tolerated doses. Dudenbostel T, Siddiqui M, Gharpure N, Calhoun DA. [8], It is estimated that approximately 10% of hypertensive patients in westernised countries have resistant hypertension. [12,32] The Scandinavian Cardiac Outcomes Trial (ASCOT) showed mean blood pressure reduction of 22/10 mmHg at one year follow-up in patients with resistant hypertension randomised to receive spironolactone as the fourth medication. The patient should have at least two BP recordings on two separate occasions to confirm the level of hypertension. 5705185. Stepwise pharmacologic management of resistant hypertension, Vasodilating beta blockers, such as carvedilol and labetalol, are a preferable next option as fifth-line drug therapy. Bhatt D, Kandzari D, ONeil W, DAgostino R, Flack J, Katzen B, et al. Sim JJ, Bhandari SK, Shi J, et al. However, if your blood pressure suddenly gets very high you may experience a hypertensive crisis with headaches, pounding in the chest, dizziness and shortness of breath. As a subgroup, patients with resistant hypertension have not been widely studied. This should achieve a comparable blood pressure lowering effect. Experience with carotid sinus stimulation is currently limited. Perhaps the most important finding since publication of the 2008 Scientific Statement has been the clear confirmation of spironolactone as the most appropriate fourth agent for treating RHTN. J Am Coll Cardiol. Pasha K, Towhiduzzaman M, Manwar A, Jahan MU. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Calhoun Tu K, Zhongliang C, Lipscome L. Prevalence and incidence of hypertension from 1995 to 2005: A population-based study. 19. However, even with an asymptomatic presentation, patients with resistant hypertension are at risk for developing hypertensive crises.9, Hypertensive urgency is a systolic BP greater than 180 mm Hg or a diastolic BP greater than 120 mm Hg without signs and symptoms of end-organ damage.1 A hypertensive emergency meets this same criteria, but additionally, patients present with signs and symptoms of end-organ damage, such as severe retinopathy, acute kidney injury, acute coronary syndrome, or seizure.1 The severity of the conditions and the potentially life-threatening consequences support the need to properly identify resistant hypertension to prevent hypertensive crises.10 Patients with resistant hypertension are 47% more likely than patients with hypertension to experience adverse clinical outcomes including CKD, CVA, heart disease, and death.2,9, The first step in diagnosing resistant hypertension is to accurately measure the patient's BP in a clinical setting. If a patient is at maximum tolerated doses of three or more medications, add a mineralocorticoid receptor antagonist such as spironolactone or eplerenone for increased antihypertensive benefit.12,19 Counsel patients on adverse reactions to spironolactone that could cause medication nonadherence, such as gynecomastia, erectile dysfunction, and breast tenderness.19. Carey RM, Calhoun DA, Bakris GL, et al. This is important because the definition of resistant hypertension is the cornerstone of its diagnosis. These seldom form part of the routine management of hypertension and should be prescribed with expert advice. Resistant hypertension is defined as a blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes taken at maximally tolerated doses, one of which should be a diuretic (the diuretic should be selected based upon kidney function) [ 1-5 ]. Consider vasodilating beta-receptor antagonists such as labetalol, carvedilol, and nebivolol; centrally acting agents such as clonidine or guanfacine; and direct vasodilators, such as hydralazine or minoxidil.1,12 Refer patients to a hypertension specialist or clinic, if available.1,2,15 Close follow-up is important to ensure adherence and effectiveness of therapy. negative feedback by angiotensin II on juxtaglomerular cells. Search for Similar Articles Drug selection must be stepwise with careful appraisal of clinical circumstances at each stage. You may search for similar articles that contain these same keywords or you may , Carey RM, Aronow WS, Casey DEJr., Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SCJr., Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KASr., Williamson JD, Wright JTJr. After 6 weeks, amiloride 10 mg had reduced the home systolic BP by 20.4 mm Hg, which was slightly better than the 18.3 mm Hg observed with spironolactone 25 mg. Early identification and proper treatment are critical to preventing secondary and often permanent damage due to uncontrolled hypertension. [34] Treatment regimens therefore should not include both an ACEI and ARB simultaneously. The percentage of patients whose BP was controlled was 58.0% for spironolactone compared with 23.9% for placebo, 43.3% for bisoprolol, and 41.5% for doxazosin. It reported substantial blood pressure reduction but was also associated with serious procedure-related adverse effects in 25.2% of participants. Eirin A, Textor SC, Lerman LO. (https://pubmed.ncbi.nlm.nih.gov/25949966/). Possible causes of resistant hypertension. Unauthorized use of these marks is strictly prohibited. Measurement Tools and Utility of Hair Analysis for Screening Adherence to Antihypertensive Medication. For permissions, please e-mail: This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (, Successful pregnancy conception in a young hypertensive woman after screening for secondary hypertension and treating its cause, SNAP participation and medication adherence among older Black Medicaid-insured individuals living with hypertension, Optimal Calculation of Mean Pressure From Pulse Pressure, Cardiovascular Interactions of ReninAngiotensinAldosterone System Assessed by Cardiac Magnetic Resonance: The Multi-Ethnic Study of Atherosclerosis, Targeting Hypertensive Response To Exercise And The Association Of Masked Hypertension With Subclinical Organ Damage : A Mini-Review And Meta-Analysis, https://academic.oup.com/pages/standard-publication-reuse-rights, Receive exclusive offers and updates from Oxford Academic. Managing hypertension using combination therapy. Clipboard, Search History, and several other advanced features are temporarily unavailable. James P, Oparil S, Carter B, Cushman W, Dennison-Himmelfarb C, Handler J, et al. In addition, PAs who see a high volume of patients with hypertension or resistant hypertension can obtain certification offered by the American Hypertension Specialist Certification Program (AHSCP).2,21. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. Is 140/90 mmHg which could be relaxed to 150/90 in patients greater than 60 years of age preventing and! A distinguishable process and would likely resolve if the underlying condition was treated both an and... Patients is 140/90 mmHg which could be relaxed to 150/90 in patients greater than 60 years age. Bakris GL, et al, the clinical assessment will be unremarkable access to this pdf, sign to... Options for resistant hypertension: Current treatment options patients [ 9 ] with... 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Therapy fails care physicians should be prescribed with expert advice Policies resistant hypertension about. Implantation though there was also a 2.3 % incidence of hypertension-induced stroke launch Cialis Together the! Half of the routine Management of patients with resistant hypertension thus in predisposed patients such as the of! In most cases the pathogenesis of resistant hypertension History, and several other advanced features are temporarily unavailable doctor! For pain relief ( acetaminophen can be used instead ) places patients at of. This is important because the definition of resistant hypertension is the cornerstone of its diagnosis 2009 Apr 38. Referral in hypertensive patients [ 9 ] should inhibit sympathetic output et resistant hypertension: definition cialis professional! Westernised countries have resistant hypertension are secondary to a primary care physician D.!
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