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Resistant Hypertension A Review of Diagnosis and Management

Wanpen Vongpatanasin, MD1
[+] Author Affiliations
1Hypertension Section, Cardiology Division, University of Texas Southwestern Medical Center, Dallas
JAMA. 2014;311(21):2216-2224. doi:10.1001/jama.2014.5180.
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Resistant hypertension—uncontrolled hypertension with 3 or more antihypertensive agents—is increasingly common in clinical practice. Clinicians should exclude pseudoresistant hypertension, which results from nonadherence to medications or from elevated blood pressure related to the white coat syndrome. In patients with truly resistant hypertension, thiazide diuretics, particularly chlorthalidone, should be considered as one of the initial agents. The other 2 agents should include calcium channel blockers and angiotensin-converting enzyme inhibitors for cardiovascular protection. An increasing body of evidence has suggested benefits of mineralocorticoid receptor antagonists, such as eplerenone and spironolactone, in improving blood pressure control in patients with resistant hypertension, regardless of circulating aldosterone levels. Thus, this class of drugs should be considered for patients whose blood pressure remains elevated after treatment with a 3-drug regimen to maximal or near maximal doses. Resistant hypertension may be associated with secondary causes of hypertension including obstructive sleep apnea or primary aldosteronism. Treating these disorders can significantly improve blood pressure beyond medical therapy alone. The role of device therapy for treating the typical patient with resistant hypertension remains unclear.

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Figure 1.
Diagram of Study Selectiona

aOnly randomized clinical trials with a minimum sample size of 40 for a 2-group parallel design or prospective observational studies with a minimum sample size of 80 in patients with resistant hypertension were included. Priority was given to randomized clinical trials over observational studies. Review articles, retrospective studies, nonrandomized clinical trials, and studies that failed to include patients who met the definition of resistant hypertension were excluded.bThe sample size of 40 will have adequate statistical power to detect a clinically meaningful difference of more than 9/10 mm Hg66,67 between the treated and control group with a standard deviation of 10 and 80% to 86% power at a 2-sided .05 significance level for the 2-group parallel design. This level of blood pressure difference between the treated and control groups has been used to calculate the sample size in previous clinical trials of resistant hypertension.66,67 For a prospective observational study, the sample size of 80 patients and a standard deviation of 10 mm Hg for systolic blood pressure allows detection of a relationship between systolic blood pressure and the dependent variables at a 2-sided .05 significance level with power of 80% assuming that the correlation coefficient between the 2 variables is at least 0.3 or more. Because the correlation coefficient of between 0.2 and 0.4 is generally considered to be weak,71 this sample size would allow detection of at least modest predictors of blood pressure elevation.

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Figure 2.
Proposed Algorithm for Management of Resistant Hypertension

eGFR indicates estimated glomerular filtration.aBlood pressure should be measured after patients are resting quietly for 3 to 5 minutes with the upper arm supported at heart level, using appropriate sized arm cuffs. Three readings should be obtained in each sitting, separated by at least 1 minute. The average of the 3 readings should be used as the blood pressure reading. Home blood pressure measurements should be obtained in the early morning and the evening.72 The list of validated home blood pressure monitors can be found at http://www.dableducational.org.

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