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Predictors and outcomes of resistant hypertension among patients with coronary artery disease and hypertension

Smith, Steven M.a; Gong, Yanb; Handberg, Eileenc; Messerli, Franz H.d; Bakris, George L.e; Ahmed, Alif; Bavry, Anthony A.c; Pepine, Carl J.c; Cooper-DeHoff, Rhonda M.b,c

doi: 10.1097/HJH.0000000000000051
ORIGINAL PAPERS: Resistant hypertension

Objective: Resistant hypertension (res-HTN) is a challenging problem, but little is known of res-HTN in patients with coronary artery disease (CAD). In this post-hoc INternational VErapamil SR-Trandolapril STudy (INVEST) analysis, we assessed prevalence, predictors, and impact on outcomes of res-HTN in CAD patients with hypertension.

Methods: Participants (n = 17 190) were divided into three groups according to achieved blood pressure (BP): controlled (BP <140/90 mmHg on three or fewer drugs); uncontrolled (BP ≥140/90 mmHg on two or fewer drugs); or resistant (BP ≥140/90 mmHg on three drugs or any patient on at least four drugs).

Results: The prevalence of res-HTN was 38%: significant predictors of res-HTN included heart failure [odds ratio (OR) 1.73], diabetes (OR 1.63), Black race (OR 1.50), and US residence (OR 1.50). Compared with controlled HTN, res-HTN had multivariate-adjusted association with higher risk of adverse outcomes {first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke [hazard ratio 1.27, 95% confidence interval (CI) 1.13–1.43], and individual outcomes of all-cause death (hazard ratio 1.29, 95% CI 1.13–1.48), cardiovascular mortality (hazard ratio 1.47, 95% CI 1.21–1.78), and nonfatal stroke (hazard ratio 1.61, 95% CI 1.17–2.22), but not nonfatal myocardial infarction (hazard ratio 0.98, 95% CI 0.72–1.34)}. Adverse outcomes, except nonfatal stroke, did not differ in patients with res-HTN compared to uncontrolled HTN.

Conclusions: Res-HTN is common in patients with CAD and hypertension, associated with poor prognosis, and linked with a number of conditions. Emphasis should be placed on recognizing those at risk for res-HTN and future studies should examine whether more aggressive treatment of res-HTN improves outcomes.

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aDepartment of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado

bDepartment of Pharmacotherapy and Translational Research, College of Pharmacy

cDivision of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida

dDivision of Cardiology, St. Luke's-Roosevelt Hospital, New York

eDepartment of Preventive Medicine, Rush University, Chicago, Illinois

fDepartments of Medicine and Epidemiology, Schools of Medicine and Public Health, University of Alabama Birmingham, Birmingham, Alabama, USA

Correspondence to Rhonda M. Cooper-DeHoff, PharmD, MS, Associate Professor, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL 32610, USA. Tel: +1 352 273 6184; fax: +1 352 273 6121; e-mail:

Abbreviations: BP, blood pressure; CAD, coronary artery disease; INVEST, INternational VErapamil SR-Trandolapril Study; res-HTN, resistant hypertension

Received 25 July, 2013

Accepted 15 October, 2013

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