AHA updates definition of resistant hypertension, addresses management in new scientific statement

Issue: October 2018

The American Heart Association has released an updated scientific statement on resistant hypertension that focuses on changes to the definition, approaches to diagnosis and recommendations for treatment of the disease.

This statement is designed to bring recommendations for resistant hypertension in line with the 2017 American College of Cardiology/AHA clinical practice guideline for adults with hypertension as well as reflect new scientific evidence published during the past decade, according to Robert M. Carey, MD, MACP, chair of the statement writing committee.

“There has been a tremendous amount of new, excellent research on all aspects of resistant hypertension — from definition to prognosis to diagnosis to treatment — that has emerged since the last scientific statement was published in 2008,” Carey, who is dean emeritus and professor of medicine at the University of Virginia, told Cardiology Today.

Updated definition

One important update in this scientific statement concerns the definition of resistant hypertension, which has changed in several ways, according to Carey.

First, the new BP threshold for treatment (130/80 mm Hg) and treatment targets are now consistent with the 2017 ACC/AHA clinical practice guideline. There is also an emphasis on accurate BP measurement through minimizing errors, such as preparation of the patient, environmental conditions, cuff size and technique, he said.

Second, for patients to be diagnosed with resistant hypertension, they must have BP levels above target while taking at least antihypertensive agents — which are commonly limited to diuretics, long-acting calcium channel blockers and blockers of the renin-angiotensin system such as ACE inhibitors or angiotensin receptor blockers — at maximally tolerated doses, according to the statement.

Third, to diagnose true resistant hypertension, Carey said, the white-coat effect must be excluded by not only measuring out-of-office BP using ambulatory or home BP monitoring.

Fourth, diagnosis of resistant hypertension now requires the exclusion of nonadherence to antihypertensive medications, according to Carey. Nonadherence can be detected through several methods, including “frank and nonjudgmental clinician-patient discussion, monitoring of prescription refills and pill counts, and, if available, biochemical assays of drugs or their metabolites in urine or plasma,” the committee wrote. However, none of these methods are perfect and it may be best to use a combination to assess patient nonadherence, according to Carey.

“With these four changes, the definition of resistant hypertension is more rigorous,” he said. “The idea is to make the diagnosis only when true resistant hypertension is present so as not to include false or pseudo-resistant hypertension.”

Importance of sleep

Although the scientific statement includes many updates, one major focus in terms of lifestyle factors that contribute to resistant hypertension is the role of sleep disorders, according to Carey.

“When people think of sleep disorders, they often think of obstructive sleep apnea, but we’ve actually expanded this area to cover sleep deprivation as well,” he told Cardiology Today. “If a patient is not getting a sufficient amount of sleep, particularly less than 6 hours of sleep at night, or if they’re getting up or waking up multiple times during the night, they’re not getting enough REM sleep. In turn, this can elevate BP and contribute to or actually cause resistant hypertension.”

Next steps in treatment

With the statement’s updated definition of resistant hypertension requiring patients to be on at least three different classes of antihypertensive medications, the question is how should physicians proceed with treatment when BP remains uncontrolled, according to Carey.

The committee, he noted, said it feels that scientific research supports two critical next steps.

Most patients with resistant hypertension, Carey said, are taking a thiazide diuretic, which is usually hydrochlorothiazide. The updated statement, however, suggests adding or substituting a thiazide-like diuretic, such as chlorthalidone or amlodipine.

“We now have definitive evidence that this will have a major positive impact on decreasing BP to below target,” he told Cardiology Today.

If the BP is still not at target after addition or substitution of a thiazide-like medication, a mineralocorticoid receptor antagonist, such as spironolactone or eplerenone, should be added, according to the scientific statement.

“Mineralocorticoid receptor antagonists have been shown in randomized trials to be highly efficacious and better than adding any other drug class to the drug regimen,” Carey said.

The scientific statement also contains an algorithm recommending further steps if BP remains uncontrolled. However, Carey said these recommendations are based on expert opinion as opposed to randomized trials at this point.

Additionally, the committee created a table included in the statement that describe specific clinical issues in patients that are associated with resistance to treatment, such as low renin and aldosterone levels, and how to address them, Carey noted.

Further research

The scientific statement also identifies gaps in knowledge, according to Carey.

The causes of resistant hypertension, for instance, require further investigation. The pathophysiology, Carey said, is not always clear and the question is whether there are ways to better define the cause so as to improve treatment.

The actual prevalence of resistant hypertension also warrants more attention, Carey said. Currently, physicians and researchers have information about the prevalence of apparent treatment-resistant hypertension, but this number includes many patients with the white-coat effect and those who are nonadherent to their antihypertensive medication regimens.

“We need to determine the outcomes of patients with true resistant hypertension compared with these patients with what we used to call pseudo-resistant hypertension,” he said.

Further, more research is necessary with regards to what to do when BP is still uncontrolled after making changes to the medication regimen, such as the addition or substitution of a thiazide-like diuretic and the addition of a mineralocorticoid receptor, according to Carey.

“We’re also in limbo in terms of device-based therapy. We have carotid baroreceptor stimulation and renal denervation, among others, that don’t have a complete set of evidence supporting them. We need better evidence before we can make recommendations regarding their use,” he told Cardiology Today. – by Melissa Foster

Reference:

Carey RM, et al. Hypertension. 2018;doi:10.1161/HYP.0000000000000084.

For more information:

Robert M. Carey, MD, MACP, can be reached at RMC4C@hscmail.mcc.virginia.edu.

Disclosure: Carey reports no relevant financial disclosures.