Poor Adherence Is a Crucial Poor Prognosis Factor in Resistant Hypertension: Results From a Nationwide Cohort Study

Objective: Poor adherence is one of the most common causes of hypertension treatment failure. However, the prognostic significance of medication adherence in resistant hypertension is unknown. Design and method: We sampled 25% of hypertensive patients from the Korean National Health Insurance Service Database from 2013 to 2018 and selected patients without a history of cardiovascular disease who met the definition of resistant hypertension with a target blood pressure of 140/90 mm Hg. Adherence was calculated as the proportion of days covered (PDC) for one year after the index date and divided into the poor (PDC <0.6), suboptimal (0.6<= PDC <0.8), and optimal (PDC >=0.8) groups. The primary outcome was a composite of all-cause of death, myocardial infarction (MI), stroke, and heart failure during follow-up. Secondary outcomes were individual events of the primary outcome, end-stage renal disease (ESRD), and atrial fibrillation. Results: The poor group, suboptimal group, and optimal group were 3,852 (5.7%), 11,667 (17.3%), and 51,879 (77%), respectively. Compared to other groups, the poor group was younger, had a higher proportion of smokers and alcohol drinkers, exercised less, and had a lower prevalence of comorbidities. During 5.6 years of median follow-up, the incidence of the primary outcome in the poor group, suboptimal group, and optimal group were 30.7, 26.6, and 28.9/1,000 person-years, respectively. In a multivariable Cox proportional hazard model, the risk of the primary outcome was 1.47 times higher in the poor group and 1.31 times higher in the suboptimal group compared to the optimal group (all P values <0.001). In the poor group, the risk was 1.37 to 1.52 times higher for all-cause death, MI, and stroke and 1.9 times higher for hemorrhagic stroke. The suboptimal group showed similar results but with a lower increased risk than the poor group. Conclusions: Even in resistant hypertension, poor adherence is strongly associated with an increased risk of clinical events. Based on this study, prospective studies are warranted to see if improving medication adherence can lower the risk of clinical events in patients with resistant hypertension.