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

Abstract

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=17190) were divided into three groups according to achieved blood pressure (BP): controlled (BP <140/90 mmHg on three or fewer drugs); uncontrolled (BP ≥ 40/90 mmHg on two or fewer drugs); or resistant (BP ≥ 40/90 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.

Figure 1

Flow diagram of participants included in this study. Controlled HTN indicates BP below 140/90 mmHg on three or fewer antihypertensive drugs. Res-HTN indicates BP at least 140/90 mmHg on at least three antihypertensive drugs (uncontrolled res-HTN) or BP below 140/90 on at least four antihypertensive drugs (controlled res-HTN). Uncontrolled HTN indicates BP at least 140/90 mmHg on two or fewer antihypertensive drugs. BP, blood pressure; ITT, intention to treat; res-HTN, resistant hypertension.

Figure 2

Mean SBP (top panel) and DBP (bottom panel) according to hypertension control group and study follow-up.

Figure 3

Percentage of patients according to total (study + nonstudy) number of antihypertensive drugs and hypertension control group.

Figure 4

Baseline predictors of increased risk for resistant hypertension. BB, β-blocker; CCB, calcium channel blocker; DM, diabetes mellitus; LVH, left-ventricular hypertrophy; PAD, peripheral artery disease; PCI, percutaneous coronary intervention; PVD, peripheral vascular disease; TIA, transient ischemic attack; Tx, treatment.

Figure 5

Prevalence of resistant hypertension according to total number of risk factors present. Risk factors represent those identified as independent baseline predictors of risk for resistant hypertension in multivariate logistic regression analyses and include presence of heart failure, diabetes, Black race, US residence, renal insufficiency, stroke/TIA, left-ventricular hypertrophy, peripheral artery disease, percutaneous coronary intervention, age, BMI, female sex, and treatment with β-blocker strategy. res-HTN, resistant hypertension; TIA, transient ischemic attack.

Figure 6

Rates and adjusted risk for composite and individual adverse outcomes risk according to hypertension control group. Composite outcome represents first occurrence of all-cause mortality, nonfatal stroke, or nonfatal MI. MI, myocardial infarction.

Figure 7

Cumulative event rate for the primary outcome according to hypertension control group.