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Resistant or Difficult-to-Control Hypertension
Marvin Moser, M.D., and John F. Setaro, M.D.
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The articleends with the authors’ clinical recommendations.

A 70-year-old woman with a long-standing history of hypertension comes for follow-up. Her medications include atenolol (100 mg daily), hydrochlorothiazide (12.5 mg daily), lisinopril (40 mg daily), and ibuprofen (400 mg twice daily for osteoarthritis). She does not smoke or drink alcohol. Her body-mass index (the weight in kilograms divided bythe square of the height in meters) is 32. Her systolic and diastolic blood pressures (measured three times while she was seated) range from 164 to 170 mm Hg and 92 to 96 mm Hg, respectively, and the pulse rate is 72 per minute. Examination of her ocular fundi reveals arteriolar narrowing. The results of cardiovascular examination are normal. There are no abdominal bruits. The serum potassium levelis 3.8 meq per liter, and the serum creatinine level is 1.2 mg per deciliter (106 μmol per liter); there is no microalbuminuria. How should this patient be further evaluated and treated?

The Cl inic a l Probl e m
Resistant, or refractory, hypertension is defined by a blood pressure of at least 140/90 mm Hg or at least 130/80 mm Hg in patients with diabetes or renal disease (i.e., with acreatinine level of more than 1.5 mg per deciliter [133 μmol per liter] or urinary protein excretion of more than 300 mg over a 24-hour period), despite adherence to treatment with full doses of at least three antihypertensive medications, including a diuretic.1 Patients who have recently received a diagnosis of hypertension or who have not yet received treatment should not be considered to haveresistant hypertension, regardless of their blood-pressure level. Data on the prevalence of resistant hypertension are scant. In large clinical trials of hypertension2,3 in which protocols required drug titration until the blood pressure was below a predefined target, the diastolic blood pressure was below 90 mm Hg in approximately 90 percent of patients, but the systolic blood pressure was below 140 mmHg in only 60 percent of patients. However, patients who had no predefined response to treatment did not meet all of the criteria for resistant hypertension as cited above. In one specialty hypertension clinic, only 59 percent of patients whose hypertension was considered to be resistant had blood pressures below 140/90 mm Hg despite careful drug titration.4 These observations suggest thatblood-pressure goals may be difficult to achieve in as many as 40 percent of patients. Resistant or difficult-to-control systolic hypertension is more common in patients over the age of 60 years than in younger patients.5 Patients whose hypertension is uncontrolled are more likely to have target-organ damage and a higher long-term cardiovascular risk than are patients whose blood pressure is controlled.6Heart failure, stroke, myocardial infarction, and renal failure are related to the degree of the elevation in blood pressure. Other risk factors,
n engl j med 355;4 www.nejm.org july 27, 2006

From the Section of Cardiovascular Medicine and the Cardiovascular Disease Prevention Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn. Address reprintrequests to Dr. Moser at the Section of Cardiovascular Medicine, Yale University School of Medicine, Box 208017, 333 Cedar St., New Haven, CT 06520. N Engl J Med 2006;355:385-92.
Copyright © 2006 Massachusetts Medical Society.

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Downloaded from www.nejm.org by FLOR MIRANDA MD on April 12, 2010 . Copyright © 2006 Massachusetts Medical Society. All rights reserved.

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