Predictors of serious adverse events in < 65-year-aged hypertensive women: a sub-analysis of the SPRINT

Abstract

Introduction: Women are more likely to experience antihypertensive treatment‐related adverse effects in the management of hypertension. 1 Besides, intensive treatment approaches could increase the rates of serious adverse events (SAEs) during antihypertensive therapy. 2 We aimed to identify potential basal predictors of SAEs in middle‐aged hypertensive women managed with standard or intensive treatment. Method: Hypertensive patients in the SPRINT, a multicentre controlled trial, were randomized to receive either standard or intensive treatment approach to achieve a target systolic blood pressure of <140 mmHg or < 120 mmHg, respectively. In this sub‐analysis, we examined baseline characteristics of the <65‐year‐old hypertensive women in the standard‐ (n = 595) or intensive‐treatment groups (n = 652) to identify predictive factors of SAEs by Cox proportionalhazards model. Results: A total 341 SAEs were identified in the study population, which was observed in 27.6% and 27.1% of the standard‐ and intensive‐treatment groups, respectively. Most common SAEs were electrolyte abnormalities (3.5%) and acute kidney injury/failure (2.8%). Rates of all SAEs or its individual subclasses were similar in each treatment groups. The risk of overall SAEs was significantly higher in blacks vs. non‐blacks (HR 1.27, 95% CI: 1.01‐1.58), in current smokers vs. non‐smokers (HR 1.59, 95% CI: 1.23‐2.05), and those with vs. without chronic kidney disease (CKD) (HR 1.38, 95% CI: 1.08‐1.77). These characteristics were found to be associated with also higher risk in the standard‐treatment group, whereas this association was not detected in the intensive‐treatment group. The likelihood of SAEs significantly increased with age (HR 1.04, 95% CI: 1.01‐1.07), where the association was preserved in the standardtreatment group and lost in the intensive‐treatment group. The rate of hypotension SAE and syncope SAE were increased among CKD patients (HR 6.20, 95% CI: 2.02‐19.03) and active smokers (HR 4.54, 95% CI: 1.17‐17.57) at baseline. A reduced rate of electrolyte abnormalities was found in obese patients compared to that in under/normo‐weight hypertensive women (HR 0.33, 95% CI, 0.14‐0.77). Conclusion: Our sub‐analysis in middle‐aged hypertensive women shows increased risk of SAEs with age, black race, smoking, and CKD, especially in patients where standard treatment strategy was adopted. Consideration of these clinical features by clinicians during choosing a standard or aggressive blood pressure goal may improve rationality of the pharmacotherapy for middle‐aged hypertensive women.