Preferable effects of olmesartan/calcium channel blocker to olmesartan/diuretic on blood pressure variability in very elderly hypertension: COLM study subanalysis.

Antihypertensive treatment for elderly hypertensive patients has been demonstrated to significantly reduce both the incidence of cardiovascular events and mortality [1]. However, many hypertensive patients require treatment with two or more antihypertensive agents to achieve the target blood pressure (BP) recommended by guidelines for the management of hypertension [2–4]. Although several trials have demonstrated the effectiveness of some combination therapies for elderly hypertensive individuals [5–7], it remains unclear what kinds of combinations are more suitable for elderly hypertensive patients. The Combination of OLMesartan and a calcium channel blocker (CCB) or a diuretic in Japanese elderly hypertensive patients (COLM) trial was a prospective, randomized, open-label, blinded-endpoint study that investigated the preferable combination therapy for high-risk elderly hypertensive patients by comparing treatment with an angiotensin II receptor blocker (ARB) along with a CCB or an ARB along with a diuretic. This study showed that there was no significant difference of the primary composite endpoint (cardiovascular morbidity and mortality) between the two treatment groups [8,9]. A prespecified subgroup analysis of the COLM trial [10] demonstrated that olmesartan along with CCB therapy may be preferable to olmesartan along with diuretic therapy for preventing cardiovascular events in very elderly patients (75–84 years), although there was no significant difference of BP between the two groups at the end of treatment. In contrast, there was no significant difference of the primary composite endpoint between elderly patients (65–74 years) from these two treatment groups. However, the mechanisms underlying the superiority of olmesartan along with CCB therapy for preventing cardiovascular events in very elderly hypertensive patients are unclear. The visit-to-visit variability (VVV) of BP was recently reported to show a significant correlation with atherosclerosis or the cardiovascular prognosis independently of BP or other risk factors [11–14]. Therefore, we hypothesized that VVV of BP could be a possible mechanism that explains the superiority of ARB along with CCB therapy over ARB along with diuretic therapy in very elderly hypertensive patients from the COLM trial [10]. To test this hypothesis, we compared VVV of SBP between elderly patients and very elderly patients, as well as between olmesartan along with CCB group and the olmesartan along with diuretic group, using data from the COLM trial. We also investigated whether these effects on VVV of BP were associated with preferable effect of the combination of olmesartan along with CCB vs. olmesartan along with diuretic on cardiovascular events in very elderly patients.