Is Azilsartan More Effective in Younger Than in Older Patients? An Explorative Analysis of the Prospective EARLY Registry

To the Editor:

We read the letter by Imprialos and colleagues1 with great interest. The authors hypothesized that a subgroup analysis of the Treatment With Azilsartan Compared to ACE Inhibitors in Antihypertensive Therapy (EARLY) study population2 according to age would provide significant insight into the efficacy/effectiveness of renin angiotensin blockers in younger vs older patients. This was based on our published observation that BP control was more frequently achieved in patients with newly diagnosed hypertension compared with patients with established hypertension.

There are a number of design characteristics of the EARLY registry that need to be considered when analyzing the efficacy of RAS‐blocking agents by age: (1) patients (≥18 years) were assigned to treatment groups at their physician's discretion targeting the documentation of seven patients receiving azilsartan vs three patients receiving an angiotensin‐converting enzyme (ACE) inhibitor, which mostly proved to be ramipril; (2) there was no control cohort that received only non–RAS‐blocking agents, which did not allow for the assessment of the relative efficacy of RAS blockers vs β‐blockers, diuretics, and calcium channel blockers in young vs old patients; and (3) patients received either no antihypertensive drugs or non–RAS‐based treatments prior to baseline, at which time they were switched to azilsartan or any ACE inhibitor, suggesting a pronounced response in angiotensin‐dependent hypertension.

Based on these design specifications, we decided to focus on the patient group who received azilsartan by age in an attempt to explore the hypothesis raised by Imprialos and colleagues. We decided not to consider patients in the ACE inhibitor group because of the potential heterogeneity and unknown bias this would introduce into the analysis. Azilsartan patients were grouped into age quartiles: 50 years and younger (n=674), 51 to 60 years (n=728), 61 to 69 years (n=668), and 70 years and older (n=739).

The results in Figure 1 illustrate that systolic blood pressure (SBP) readings were fairly uniform across age groups, while diastolic blood pressure (DBP) values where higher in the youngest age group. There was a slightly stronger SBP lowering in young (− 27.0 mm Hg) than in older patients (− 24.6 mm Hg). DBP reductions were substantially more pronounced in the young (− 15.3 mmHg) than in older patients (− 10.2 mm Hg). Our observation that blood pressure reduction tended to be greater for DBP in young vs older patients resulted in more patients having a normal blood pressure reading at 12 months (Figure 2).

Figure 1.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure by age at baseline and 12‐month follow‐up (FU).

Figure 2.

Blood pressure normalization (<140/90 mm Hg) at 12‐month follow‐up (FU).

These results, although potentially confirming the hypothesis raised, should be interpreted with caution. There was an imbalance in sex, duration of hypertension, mean body mass index, and the proportion of patients with concomitant disease conditions such as heart failure, coronary artery disease, prior stroke, diabetes mellitus, and chronic kidney disease. Therefore, our results are of explorative nature and need confirmation in a randomized clinical study.

In conclusion, the treatment of hypertensive patients using azilsartan appears to be more effective in younger than in older patients. Furthermore, more elaborate analyses are needed to adjust for potential confounding variables and to confirm or falsify the hypothesis.