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The American Heart Association (AHA) has issued the first consensus statement dedicated to helping physicians undertake the challenges of resistant hypertension. In the new guidelines, published in the June 2008 issue of Hypertension, the importance of recognizing resistant hypertension as a condition is emphasized. This condition requires a special approach in terms of evaluation and treatment. Resistant hypertension is defined as blood pressure that remains elevated and uncontrolled despite the use of three antihypertensive agents from different drug classes. Uncontrolled hypertension, on the other hand, differs from resistant hypertension in that it may be caused by poor medication adherence and/or an inadequate treatment regimen. Although the prevalence of resistant hypertension is not specifically known, clinical trials suggest that it may affect between 20% and 30% of people with high blood pressure.

Risk Factors for Resistant Hypertension

Patients with resistant hypertension have a high cardiovascular risk and often suffer from multiple health problems that complicate blood pressure management. Physicians need to identify contributing factors in order to determine appropriate treatments. The two strongest risk factors associated with resistant hypertension are age and obesity. Successful treatment of resistant hypertension requires lifestyle changes (as appropriate) such as weight loss, exercise, and a low sodium diet. Other non-pharmacological recommendations include a high-fiber, low-fat diet and moderate consumption of alcohol.

Clinicians should recognize that there are many secondary causes of hypertension to consider when managing patients with resistant hypertension (Table). Patients must be screened and treated, if necessary, for these conditions. Furthermore, several medications may play a role in elevated blood pressure and can impede the effectiveness of antihypertensive medications, most notably NSAIDs and aspirin. Stimulants, oral contraceptives, licorice, and ephedra may also interfere in blood pressure management and should be withdrawn or reduced, if possible.

Value of Multi-Drug Regimens

The AHA guideline highlights the importance of using agents with different mechanisms of action to achieve greater benefits when treating resistant hypertension. A multi-drug regimen of an ACE inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a thiazide diuretic appears to be both effective and well-tolerated by patients. Published reports have demonstrated that mineralocorticoid receptor antagonists are effective in treating resistant hypertension by lowering blood pressure (on average) by an additional 25 mm Hg systolic and 12 mm Hg diastolic. Ultimately, a multi-drug regimen should be tailored to each individual patient. It’s important to note that treatment adherence worsens as patients take more pills, so the AHA statement recommends frequent clinic visits and having patients maintain a diary of home blood pressure values.

Patients whose blood pressure remains elevated after 6 months of evaluation and treatment or those with a specific secondary cause of hypertension should be referred to a specialist. Risk accumulates in hypertensive patients if their blood pressure remains uncontrolled for a long period, so including a specialist into the treatment paradigm is crucial. Currently, resistant hypertension remains understudied and additional knowledge is needed to better identify and treat patients with the condition. Efficacy assessments of specific multi-drug regimens are also needed to better guide therapy. The hope is that these guidelines will increase our understanding of resistant hypertension and motivate physicians to take specific steps to management it appropriately.

David A. Calhoun, MD, FAHA, has indicated to Physician’s Weekly that he has or has had the following financial interest: Novartis, AstraZeneca, National Institutes of Health/National Heart Lung and Blood Institute, American Heart Association, Merck, and Pfizer.