Resistant hypertension is associated with an increased cardiovascular risk compared to patients controlled on a similar multi-drug regimen

The long-term risk associated with resistant hypertension compared to other phenotypes of hypertension is still unclear. We aimed to assess cardiovascular and renal outcomes over 10 years of follow-up of patients with uncontrolled resistant hypertension (uRH) compared to a similarly treated (≥ 3 medication classes including a diuretic) and adherent group whose blood pressure is under control. This retrospective cohort study utilized the computerized database of Maccabi Healthcare Services, a state-mandated health provider covering 25% of the Israeli population. Clinical outcomes were assessed using Cox regression multivariable analyses. A total of 1487 patients (50% males, mean age at baseline = 68.3 ± 10.4 years) were included in the uRH cohort and 1343 patients (50% males, 66.2 ± 10.6 years) in the controlled hypertension reference group (Controlled hypertension on multi drug regimen- CH-MDR). After adjusting for age, sex, BMI and patients’ comorbidities, uRH was associated with a Hazard Ratio of 1.35 (95% CI: 1.08–1.69) for incidence of ischemic heart disease, 1.51 (1.06–2.16) for secondary cardiovascular events, and 1.36 (1.00–1.86) for risk of stroke or transient ischemic attack compared to the reference group. Patients with uRH were found to have more hospitalization days (mean, 4.2 vs. 3 days per year, p < 0.001), and more emergency room visits (83.3% vs. 77%, p < 0.001). Overall, uRH was associated with a 19% (95% CI 11% to 29%) increase in direct healthcare expenditures during the first year of follow-up. uRH is associated with a substantial increased risk of both cardiovascular and cerebrovascular events, when compared to similarly treated hypertensive patients whose blood pressure is under control.