Combination therapy for hypertension in patients with CKD: A subanalysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events trial

The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was a multicenter, randomized, three-arm comparative study (N=3293) undertaken to determine the optimal combination therapy, based on the occurrence of cardiovascular events in patients treated with an angiotensin II receptor blocker (ARB), a β-blocker (BB) or a thiazide diuretic (TD) in addition to the calcium antagonist benidipine as baseline medication. This subanalysis was conducted to compare the efficacy of three combination therapies in a subset of 834 patients with chronic kidney disease (CKD) (287 patients treated with benidpine-ARB, 283 patients treated with benidipine-BB and 264 patients treated with benidipine-TD). The incidence of composite cardiovascular events as the primary end point did not differ among these three groups. The incidence of hard end points and cerebrovascular events among these groups did not differ either, although the incidence among all patients in the COPE trial was lower in the benidipine-TD group than in the benidipine-BB group. The incidence of new-onset diabetes mellitus was higher in the benidipine-TD group than in the benidipine-ARB group among patients with CKD. The estimated glomerular filtration rate (eGFR) was maintained even after 12 months of treatment in patients with a baseline eGFR <60 ml min^-1 per 1.73 m² regardless of the treatment group, although the eGFR decreased over time in all patients in the three groups. In conclusion, in patients with CKD, all of the tested combination therapies demonstrated comparable efficacy in terms of prevention of cardiovascular events as well as maintenance of eGFR.