Renin‐Angiotensin System Inhibitors: Do They Have the Same Impact at All Ages?

To the Editor: We read with real interest the study by Schmieder and colleagues, which provides important data on the efficacy of the angiotensin receptor blocker (ARB) azilsartan over the angiotensin-converting enzyme (ACE) inhibitor ramipril in blood pressure (BP) reduction in patients with hypertension. Furthermore, the authors showed greater decreases in BP in the patients with newly diagnosed hypertension vs the group with established hypertension, while target BP control was achieved more frequently in the first aforementioned group. The potency of ACE inhibitors and ARBs in decreasing BP has been sufficiently proven; however, results from various studies have provided contradictory results on the efficacy of these agents in older vs younger patients. We therefore believe that a subgroup analysis according to age would provide significant information about the management of hypertensive patients in real-life everyday clinical practice. In a study of young adults, aged 22 to 51 years, patients sequentially received one of each of the four main drug groups: ACE inhibitors, b-blockers, diuretics, and calcium channel blockers (CCBs). Results indicated significantly greater responses to either the ACE inhibitor or the b-blocker than to the CCB or the diuretic. Another study rotated young patients (aged 28–55 years) with hypertension in a crossover fashion through 6 weeks of treatment each with amlodipine, doxazosin, lisinopril, bisoprolol, bendrofluazide, and placebo. At the end of the study, the majority of patients responded better to a drug that suppressed the renin system (either an ACE inhibitor or a b-blocking agent) than to a CCB or a diuretic. In addition, the authors noted a high correlation between the responses to pairs of ACE inhibitors and b-blockers. On the other hand, another randomized crossover study sought to determine which of the common groups of antihypertensive drugs is most effective in lowering systolic BP (SBP) in elderly patients (aged 65–86) with previously untreated hypertension. The decrease in SBP with ACE inhibitors and b-blocking drugs was less than the decrease achieved with the other two drug classes, while the percentage of patients who achieved the target SBP was higher during treatment with diuretics or CCBs. All the previous data suggest that the inhibitors of the renin-angiotensin system are an optimal choice for the optimization of hypertension in younger patients, while they may not be the first favorable choice for the elderly. In fact, the guidelines for the treatment of hypertension by the British Hypertension Society in collaboration with the National Institute for Health and Care Excellence suggest that physicians administer either an ACE inhibitor or an ARB in patients younger than 55 years with newly diagnosed hypertension. In contrast, patients older than 55 years should receive either a CCB or a diuretic. In contrast to the findings of the aforementioned small clinical studies, a large meta-analysis of 31 trials and 96,466 hypertensive patients revealed that there were no differences between the effects of different classes of drugs in older compared with younger adults in BP reduction and cardiovascular outcomes. The same was true for all drug comparisons, while some variations were not present with a systematic pattern. In conclusion, available data do not equivocally support a similar effect of renin-angiotensin system inhibitors in younger and older patients. Considering the large number of patients in the present study, it would be interesting to determine the effect of the agents in each age subgroup of the study population, and we would be obliged to the authors if they could provide us with relevant data.