Getting to Goal Blood Pressure: Why Reserpine Deserves a Second Look

THE JOURNAL OF CLINICAL HYPERTENSION 591 In this editorial, we review data from several hypertension trials in which reserpine therapy was used with good results. We present new data from the Multiple Risk Factor Intervention Trial (MRFIT) that also demonstrate the positive effects of reserpine. We believe that reserpine deserves reconsideration as an effective antihypertensive medication, especially in combination therapy in difficult-to-control hypertensive patients. The prevalence of hypertension in the United States has increased, mainly as a result of the increased prevalence of obesity and the increasing age of the population. At the same time, blood pressure (BP) control rates have improved. For example, data from the National Health and Nutrition Examination Survey (NHANES) indicate that between 1999–2000 and 2003–2004, the prevalence of hypertension increased from 27% to 29%, while BP control rates (BP <140/90 mm Hg) improved from 29% to 37%.1 Recent survey data suggest further improvement in control rates.2 Despite this recent success, BP control rates may still remain below the Healthy People 2010 goal of 50%.3 Reasons for this include not using specific treatment algorithms; lack of careful follow-up; failure to control systolic BP, especially in older patients; and therapeutic inertia (ie, failure to increase the dose of medication or add another medication when BP is not at goal). Until recently, even in the best clinical trials, BP control rates of only 66% to 70% have been achieved,4,5 although the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial6 reported that with a 2-drug combination as initial therapy, a 73% control rate was achieved in a hypertensive population. One antihypertensive medication that could be used to improve BP control, especially systolic BP, is reserpine, a centrally acting adrenergic antagonist. Its use fell into disfavor years ago, and it has been labeled a relic from the past and an obsolete medication.7,8 While its use in westernized countries has fallen precipitously in the past decades8,9 despite its proven efficacy,10–15 reserpine is still used extensively in nonwesternized countries, where health care expenditures are more costconstrained. In South Africa, for example, it is a second-step hypertension medication after diuretic therapy.10,16,17 In India, low-dose reserpine, in combination with diuretics and hydralazine, is used effectively to prevent renal disease.18 Several adverse effects attributed to reserpine in the 1950s and 1960s led to its near demise. These included depression, gastric bleeding, and breast cancer. Early in its use, recommended dosages of reserpine varied from 0.25 mg 3 times a day to as much as 10 mg/d. With the recognition that the halflife of reserpine is several days and that its clinical effect may last even longer, much smaller dosages were recommended (0.05–0.25 mg/d). Studies in which low dosages (0.05–0.1 mg/d) of reserpine are used (usually in combination with diuretics) show www.lejacq.com ID: 7229 E d i t o r i a l