resistant hypertension; refractory hypertension
Jump to navigation
Jump to search
Introduction
blood pressure that remains above goal despite treatment with optimal doses of 3 antihypertensives of different classes, including a diuretic (also see secondary hypertension) or uncontrolled blood pressure on >= 4 drugs[20]
Etiology
- primary hyperaldosteronism (22% of patients with resistant hypertension)[20]
- renovascular hypertension (renal artery stenosis)
- chronic kidney disease (ESRD)
- pheochromocytoma[1]
- obstructive sleep apnea[8][9][17] (up to 83%)
- medication non-compliance
- consumption of substances that aggravate hypertension
Epidemiology
- 20% of patients with chronic hypertension[20]
Laboratory
- plasma aldosterone/plasma renin activity
- serum K+: hypokalemia inconsistently associated with primary hyperaldosteronism
- angiotensin-2 in plasma
- captopril-renin stimulation test
- plasma free metanephrines &/or 24 hour urine metanephrines
Diagnostic procedures
- ambulatory blood pressure monitoring (distinguishes from white-coat hypertension)[1][4]
- renal ultrasound for renal artery stenosis
- sleep study (polysomnography) for obstructive sleep apnea
* note BP goals for ambulatory blood pressure may differ from those of office blood pressure[1]
Complications
- disease interaction(s) of primary hyperaldosteronism, chronic renal failure & resistant hypertension
- disease interaction(s) of obstructive sleep apnea with resistant hypertension
Differential diagnosis
- white-coat hypertension (1/3 of cases)[2]
- secondary hypertension
Management
- see treatment of chronic hypertension
- patient presumably on ACE inhibitor or ARB, calcium channel blocker & a thiazide diuretic or loop diuretic
- if patient not on diuretic, prescribe one unless ESRD
- if patient not on a calcium channel blocker, prescribe one
- general
- confirm out-of-office BP measurement[1]
- life-style modifications
- low sodium diet (< 2400 mg/day)
- achieve ideal body weight
- ensure adequate sleep hygiene, at least 6 hours/night[15]
- aerobic exercise reduces 24-hour & daytime ambulatory blood pressure & office systolic systolic blood pressure[21]
- discontinue offending medications include OTC[1][5]
- correct underlying cause(s)
- pharmaceuticals
- if medication noncompliance suspected, discontinue medications dosed > QD
- pre-packaging patient's pills in a blister pack less important than once a day dosing & including a dihydropyridine calcium channel blocker
- addition of antihypertensive of a new class may be of benefit[14]
- consider switching HCTZ to chlorthalidone or indapamide[15]
- chlorthalidone more effective than hydrochlorothiazide[17]
- switch thiazide diuretic to loop diuretic if eGFR < 20 mL/min
- mineralocorticoid receptor antagonist if hyperaldosteronism[20]
- spironolactone as add on[11]
- spironolactone not inferior to clonidine & it is QD[13]
- inferior to renal artery angioplasty with fibromuscular dysplasia[1]
- if medication noncompliance suspected, discontinue medications dosed > QD
- renal sympathetic denervation[3]
- renal denervation device in the SYMPLICITY HTN-3 trial failed to lower systolic BP by > 10 mm Hg[3]
- of no benefit[7]
- arterial-venous Coupler device that mechanically lowers systolic blood pressure via AV anastomosis shows promise[10]
Notes
- 29% of patients claiming complete adherence to therapy showed a marked blood pressure response when treatment was observed[18]
More general terms
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012. 2015, 2018, 2021.
- ↑ 2.0 2.1 de la Sierra A et al. Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension 2011 May; 57:898. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21444835
- ↑ 3.0 3.1 3.2 Krum H et al. Catheter-based renal sympathetic denervation for resistant hypertension: A multicentre safety and proof-of-principle cohort study. Lancet 2009 Mar 30; [e-pub ahead of print] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19332353 <Internet> http://dx.doi.org/10.1016/S0140-6736(09)60566-3
Doumas M and Douma S. Interventional management of resistant hypertension. Lancet 2009 Mar 30; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19332354 <Internet> http://dx.doi.org/10.1016/S0140-6736(09)60624-3
Symplicity HTN-2 Investigators Renal sympathetic denervation in patients with treatment- resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 2010 Dec 4; 376:1903 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21093036 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62039-9/fulltext
Doumas M, Douma S. Renal sympathetic denervation: the jury is still out. Lancet 2010 Dec 4; 376:1878 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21093037
Brandt MC et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol 2012 Mar 6; 59:901. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22381425
Zile MR and Little WC. Effects of autonomic modulation: More than just blood pressure. J Am Coll Cardiol 2012 Mar 6; 59:910. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22381426
Krum H et al. Percutaneous renal denervation in patients with treatment- resistant hypertension: Final 3-year report of the Symplicity HTN-1 study. Lancet 2013 Nov 7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24210779
ClinicalTrials.gov Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN-3) http://clinicaltrials.gov/ct2/show/record/NCT01418261
Meditronic News Release. Jan 9, 2014 Medtronic Announces U.S. Renal Denervation Pivotal Trial Fails to Meet Primary Efficacy Endpoint While Meeting Primary Safety Endpoint. http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=1889335&highlight= - ↑ 4.0 4.1 Calhoun DA, Jones D, Textor S et al Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008 Jun;51(6):1403-19. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18391085
- ↑ 5.0 5.1 5.2 Spence JD. Physiologic tailoring of treatment in resistant hypertension. Curr Cardiol Rev. 2010 May;6(2):119-23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21532778
- ↑ Calhoun DA, Jones D, Textor S et al Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008 Jun 24;117(25):e510-26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18574054
- ↑ 7.0 7.1 Bhatt DL et al. A clinical trial of renal denervation for resistant hypertension. N Engl J Med 2014 Mar 29 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24678939 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1402670
- ↑ 8.0 8.1 Moser M, Setaro JF. Clinical practice. Resistant or difficult-to-control hypertension. N Engl J Med 2006 Jul 28; 355:385. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16870917
- ↑ 9.0 9.1 Myat A et al. Resistant hypertension. BMJ 2012 Nov 22; 345:e7473. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23169802
- ↑ 10.0 10.1 Lobo MD et al Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial. Lancet. Jan 22, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25620016 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962053-5/abstract
- ↑ 11.0 11.1 Williams B et al Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. Sept 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26414968 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2900257-3/abstract http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2900257-3/fulltext
- ↑ Vongpatanasin W. Resistant hypertension: a review of diagnosis and management. JAMA. 2014 Jun 4;311(21):2216-24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24893089
- ↑ 13.0 13.1 Krieger EM, Drager LF, Giorgi DMA et al. Spironolactone versus clonidine as a fourth-drug therapy for resistant hypertension: The ReHOT randomized study (Resistant Hypertension Optimal Treatment). Hypertension 2018 Apr; 71:681 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29463627 <Internet> http://hyper.ahajournals.org/content/71/4/681
- ↑ 14.0 14.1 Markovitz AA, Mack JA, Nallamothu BK, Ayanian JZ, Ryan AM. Incremental effects of antihypertensive drugs: Instrumental variable analysis. BMJ 2017 Dec 22; 359:j5542 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29273586 Free PMC Article <Internet> http://www.bmj.com/content/359/bmj.j5542
- ↑ 15.0 15.1 15.2 Carey RM, Calhoun DA, Bakris GL et al Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. Sept 13, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30354828 https://www.ahajournals.org/doi/10.1161/HYP.0000000000000084
- ↑ Braam B, Taler SJ, Rahman M et al Recognition and Management of Resistant Hypertension. Clin J Am Soc Nephrol. 2017 Mar 7;12(3):524-535. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27895136 Free PMC Article
- ↑ 17.0 17.1 17.2 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 18.0 18.1 Ruzicka M, Leenen FHH, Ramsay T et al. Use of directly observed therapy to assess treatment adherence in patients with apparent treatment-resistant hypertension. JAMA Intern Med 2019 Jun 17; PMID: https://www.ncbi.nlm.nih.gov/pubmed/31206124 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2735985
- ↑ Khawaja Z, Wilcox CS. Role of the kidneys in resistant hypertension. Int J Hypertens 2011 Apr 5; 2011:143471 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21461391 Free PMC Article
- ↑ 20.0 20.1 20.2 20.3 20.4 Cohen JB, Cohen DL, Herman DS et al. Testing for primary aldosteronism and mineralocorticoid receptor antagonist use among U.S. veterans: A retrospective cohort study. Ann Intern Med 2020 Dec 29 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33370170 https://www.acpjournals.org/doi/10.7326/M20-4873
- ↑ 21.0 21.1 Lopes S, Mesquita-Bastos J, Garcia C et al Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension. A Randomized Clinical Trial. JAMA Cardiol. Published online August 4, 2021. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34347008 https://jamanetwork.com/journals/jamacardiology/fullarticle/2782554
- ↑ Acelajado MC, Hughes ZH, Oparil S et al. Treatment of resistant and refractory hypertension. Circ Res. 2019;124(7):1061-1070 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30920924 PMCID: PMC6469348 Free PMC article https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.118.312156
- ↑ NEJM Knowledge+ Endocrinology