Resistant hypertension: a frequent and ominous finding among hypertensive patients with atherothrombosis

Abstract

The effect of resistant hypertension on outcomes in patients with atherothrombotic disease is currently unknown. Accordingly, we sought to determine the prevalence and outcomes of resistant hypertension in stable hypertensive outpatients with subclinical or established atherothombotic disease enrolled in the international Reduction of Atherothrombosis for Continued Health (REACH) registry. Resistant hypertension was defined as a blood pressure ≥140/90 mmHg at baseline (≥130/80 mmHg if diabetes/renal insufficiency) with the use of ≥3 antihypertensive medications, including a diuretic. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke at 4 years. A total of 53 530 hypertensive patients were included. The prevalence of resistant hypertension was 12.7%; 6.2% on 3 antihypertensive agents, 4.6% on 4 agents, and 1.9% on ≥5 agents (mean: 4.7 ± 0.8). In addition to a diuretic, these patients were being treated mostly with ACE-inhibitors/angiotensin receptor blockers (90.1%), beta-blockers (67.0%), and calcium channel blockers (50.8%). Patients with resistant hypertension had a higher risk of the primary endpoint on multivariable analysis [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.02-1.20; P = 0.017], including an increased non-fatal stroke risk (HR: 1.26; 95% CI: 1.10-1.45; P = 0.0008). Hospitalizations due to congestive heart failure were higher (P < 0.0001). Patients on ≥5 agents had a higher adjusted risk for the primary endpoint when compared with those on ≤3 agents (P = 0.03). The presence of resistant hypertension identifies a subgroup of patients with hypertension and atherothrombosis who are at heightened risk for adverse long-term outcomes.