9 May 2008 - The American Heart Association has issued new statement for the treatment of resistant hypertension, which are published online in Hypertension.

The new statement zeroes in on a group it says may make up 20% to 30% of patients with hypertension but has received only limited attention in formal guidelines, probably because they have been targeted in few clinical trials. The document defines the group, patients with "resistant" hypertension, as those whose blood pressure remains above goal despite concurrent therapy with three distinct agents or who need at least four such drugs to achieve control.

David A Calhoun, MD (University of Alabama at Birmingham), Writing Committee chair, observed that the document, the first of its kind, is "based largely on expert consensus, mainly because as a group, these patients have not been studied separately." He and his colleagues hope that it will, among other things, encourage the development of clinical trials specifically for resistant hypertension.

Evaluation of patients who don't respond to a regimen consisting of three agents from different drug classes, such as a diuretic, an ACE inhibitor or angiotensin receptor blocker, and a calcium-channel blocker, should be directed at "confirming true treatment resistance." It usually has multiple causes, according to the statement, and requires the exclusion of "pseudoresistance," managing lifestyle-related causes, and looking for possible underlying etiologies.

Pseudoresistance, the document says, involves the perception of treatment resistance due to such causes as poor patient adherence to therapy (one of the leading causes of uncontrolled blood pressure), incorrect blood-pressure readings (the result, usually, of poor BP-measurement technique on the provider's part), or a "white-coat" effect.

"White-coat hypertension is as common in these patients as it is in the general population," Calhoun said, and is behind about one-fifth of cases of apparent resistant hypertension. Ambulatory blood-pressure monitoring may be necessary for an accurate diagnosis, according to the document.

Modifiable "lifestyle factors" that can be associated with resistant hypertension, it says, include obesity, dietary salt intake, and alcohol use.

Similarly, a number of noncardiac drugs and similar substances can raise blood pressure and "should be avoided or withdrawn." They include selective COX-2 inhibitors and traditional nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin; amphetamines; oral contraceptives; erythropoietin; and even natural licorice and some herbal medications such as ephedra.

Then there should be a search for underlying secondary causes of treatment resistance, which as a workup strategy "is probably not as common as it should be," Calhoun said. Such causes can include obstructive sleep apnea, diabetes, pheochromocytoma, Cushing's syndrome, renal parenchymal disease, renal artery stenosis, and primary aldosteronism.

Primary aldosteronism, in particular, "seems to be particularly common in patients with resistant hypertension," according to Calhoun; the document says it is present in perhaps 20% of cases. But interestingly, "we and others have shown that even in the absence of true primary aldosteronism, aldosterone blockade can often be effective," he said. "We feel it is important to screen for classic primary aldosteronism, and if that evaluation is negative, the patient may still benefit from aldosterone antagonists," even if aldosterone levels are normal, Calhoun said.

Measures related to drug therapy include determining whether diuretic dosing is optimal, "maximizing adherence," and encouraging patients to take at least one of their antihypertensives at bedtime, and then making any necessary changes. A "lack of or underuse of diuretic therapy," the document says, has been a consistent finding in studies of patients seen at hypertension specialty clinics. And, as complex dosing regimens are associated with poor compliance, "prescribed regimens should be simplified as much as possible."

Hypertension 2008; Available at http://hyper.ahajournals.org