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CLINICAL RESEARCH: CHRONIC CORONARY ARTERY DISEASE

Predictors of Adverse Outcome Among Patients With Hypertension and Coronary Artery Disease

Carl J. Pepine, MD, MACC^_*,_*, Peter R. Kowey, MD, FACC, Stuart Kupfer, MD, Rainer E. Kolloch, MD, Athanase Benetos, MD, PhD^||, Giuseppe Mancia, MD, PhD^¶, Antonio Coca, MD^#, Rhonda M. Cooper-DeHoff, PharmD^_*, Eileen Handberg, PhD^_*, Efrain Gaxiola, MD, FACC^_**, Peter Sleight, MD, FACC, C. Richard Conti, MD, MACC^_*, Ann C. Hewkin, MSc, Luigi Tavazzi, MD, FACC for the INVEST Investigators

^_* Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida
Lankenau Hospital, Wynnewood, Pennsylvania
Abbott, Abbott Park, Illinois
University of Munster School of Medicine, Bielefeld, Germany
^|| University of Nancy, Vandoeuvre-les-Nancy, France
^¶ Department of Medicine, University of Milano-Bicocca, Milano, Italy
^# Hospital Clinic, Barcelona, Spain
^_** Instituto Cardiovascular de Guadalajara, Guadalajara, Mexico
University of Oxford, Oxford, United Kingdom
Prioario Division of Cardiology, Policlinico San Matteo, Pavia, Italy.

Manuscript received May 28, 2004; revised manuscript received September 2, 2005, accepted September 12, 2005.

^_* Reprint requests and correspondence: Dr. Carl J. Pepine, Division of Cardiovascular Medicine, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610-0277. (Email: pepincj{at}medicine.ufl.edu).

OBJECTIVES: We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD).

BACKGROUND: Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies.

METHODS: We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling.

RESULTS: Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk.

CONCLUSIONS: In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk.

Abbreviations and Acronyms   BMI = body mass index   BP = blood pressure   CAD = coronary artery disease   CI = confidence interval   DBP = diastolic blood pressure   HCTZ = hydrochlorothiazide   HR = hazard ratio   INVEST = INternational VErapamil-trandolapril STudy   MI = myocardial infarction   SBP = systolic blood pressure   SR = sustained release

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