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Predictors and Mediators of Successful Long-term Withdrawal From Antihypertensive Medications
Mark A. Espeland, PhD;
Paul K. Whelton, MD;
John B. Kostis, MD;
Judy L. Bahnson;
Walter H. Ettinger, MD;
Jeffrey A. Cutler, MD;
Larry J. Appel, MD;
Shiriki Kumanyika, PhD;
Deborah Farmer, PhD;
Jan Elam;
Alan C. Wilson, PhD;
William B. Applegate, MD;
for the TONE Cooperative Research Group
Arch Fam Med. 1999;8:228-236.
Background National guidelines recommend consideration of step down or withdrawal of medication in patients with well-controlled hypertension, but knowledge of factors that predict or mediate success in achieving this goal is limited.
Objective To identify patient characteristics associated with success in controlling blood pressure (BP) after withdrawal of antihypertensive medication.
Design The Trial of Nonpharmacologic Interventions in the Elderly tested whether lifestyle interventions designed to promote weight loss or a reduced intake of sodium, alone or in combination, provided satisfactory BP control among elderly patients (aged 60-80 years) with hypertension after withdrawal from antihypertensive drug therapy. Participants were observed for 15 to 36 months after attempted drug withdrawal.
Main Outcome Measures Trial end points were defined by (1) a sustained BP of 150/90 mm Hg or higher, (2) a clinical cardiovascular event, or (3) a decision by participants or their personal physicians to resume BP medication.
Results Proportional hazards regression analyses indicated that the hazard (±SE) of experiencing an end point among persons assigned to active interventions was 75%±9% (weight loss), 68%±7% (sodium reduction), and 55%±7% (combined weight loss/sodium reduction) that of the hazard for those assigned to usual care. Lower baseline systolic BP (P<.001), fewer years since diagnosis of hypertension (P<.001), fewer years of antihypertensive treatment (P<.001), and no history of cardiovascular disease (P=.01) were important predictors of maintaining successful nonpharmacological BP control throughout follow-up, based on logistic regression analysis. Age, ethnicity, baseline level of physical activity, baseline weight, medication class, smoking status, and alcohol intake were not statistically significant predictors. During follow-up, the extent of weight loss (P=.001) and urinary sodium excretion (P=.04) were associated with a reduction in the risk of trial end points in a graded fashion.
Conclusions Withdrawal from antihypertensive medication is most likely to be successful in patients with well-controlled hypertension who have been recently (within 5 years) diagnosed or treated, and who adhere to lifestyle interventions involving weight loss and sodium reduction. More than 80% of these patients may have success in medication withdrawal for longer than 1 year.
From the Section on Biostatistics (Dr Espeland and Ms Bahnson) and the Department of Medicine (Drs Ettinger and Farmer), Wake Forest University School of Medicine, Winston-Salem, NC; Tulane University School of Public Health and Tropical Medicine, New Orleans, La (Dr Whelton); Department of Medicine, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick (Drs Kostis and Wilson); National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Cutler); Welch Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins University School of Hygiene and Public Health and School of Medicine, Baltimore, Md (Dr Appel); Department of Human Nutrition and Dietetics, University of Illinois at Chicago (Dr Kumanyika); Department of Medicine, University of Tennessee–Memphis (Ms Elam and Dr Applegate). A complete list of members of the TONE Cooperative Research Group was previously published (JAMA. 1998;279:839-846).
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