Incidence and prognosis of apparent-treatment resistant hypertension: a multi-state analysis using real world evidence

Background: There is limited evidence regarding the incidence and prognosis of apparent resistant hypertension (aRHT) in hypertensive patients. This study aimed to estimate the incidence of aRHT and assess the risk of cardiovascular and kidney complications in patients with aRHT compared to those without aRHT, using a multi-state analysis. Methods: This retrospective cohort study utilized real-world data from hypertensive patients treated at Ramathibodi Hospital, Bangkok, Thailand, between January 2010 and June 2024. aRHT was defined as having uncontrolled blood pressure (BP), while using ≥ 3 antihypertensive medications or having controlled BP with using ≥ 4 antihypertensive medications. The outcomes of interest were cardiovascular and kidney complications including coronary artery disease (CAD), stroke, heart failure (HF), and chronic kidney disease (CKD), and all-cause mortality. A multi-state analysis was applied to estimate the risk of disease progression from hypertension without complications to aRHT, CAD, stroke, HF, CKD, and all-cause death. Kaplan-Meier estimates with a clock-reset approach were used to calculate transition probabilities for each progression. Multivariate Cox regression analysis was applied to assess the risk factors of aRHT and assess the prognosis of aRHT. Results: Among 114,364 hypertensive patients, the incidence of aRHT was 2.61 per 100 person-years (95% confidence interval [CI], 2.56-2.65). Results from multivariate Cox regression analysis found that the independent risk factors of aRHT were increasing age, males, obesity, type 2 diabetes mellitus, dyslipidemia, and having cardiovascular and kidney complications including CAD, stroke, CKD, and HF. Regarding the prognosis of aRHT, compared to non-aRHT patients, those with aRHT had significant higher risk of CAD, CKD, HF, and all-cause mortality with hazard ratios (95% CI) of 1.80 (1.56-2.08), 1.93 (1.79-2.08), 4.24 (3.54-5.08), and 2.84 (1.89-4.27), respectively. Conclusions: The risk of aRHT was higher in hypertensive patients with cardiovascular and kidney complications compared to those without. Patients with aRHT had a worse prognosis than hypertensive patients without aRHT, as evidenced by higher risks of CAD, CKD, HF, and all-cause death.