Effects of valsartan vs amlodipine and achieved lower blood pressure on the incidence of end-stage kidney disease: The VALUE Trial.

Background: There is a paucity of data investigating the impact of antihypertensive drug classes and blood pressure (BP) treatment targets on the incidence of end-stage kidney disease (ESKD). In patients with high-risk hypertension aged 50-80 years or above, we aimed to, 1) compare effects of valsartan, an angiotensin receptor blocker, with amlodipine, a calcium channel blocker and, 2) assess the effect of achieving systolic BP <135 vs ≥135 mmHg on the ESKD incidence.

Methods: The VALUE Trial was a multicenter prospective double-blinded randomized clinical trial in patients with essential hypertension and high cardiovascular risk including known coronary disease, left ventricular hypertrophy and previous stroke, in which ESKD was a secondary endpoint defined as progression to kidney transplant and/or dialysis. Patients were randomized to either valsartan or amlodipine, with other anti-hypertensive medications as add-on if needed to reach the systolic BP target of <140 mmHg. Cox proportional hazards ratio (HR) was used to compare different treatment groups and achieved systolic BP <135 with ≥135 mmHg, during 3-6 years of follow-up.

Results: 15,245 patients were randomized and followed until 63,631 patient-years with only 90 patients lost to follow-up. The primary outcome, a composite of cardiac morbidity and mortality, was neutral between valsartan and amlodipine. On valsartan 47 patients (0.61 %) and on amlodipine 50 patients (0.66 %) developed ESKD (HR=1.02, 95 % CI 0.68-1.52, p =0.94). Achieved SBP <135 mmHg was strongly related to less ESKD (n =9/5036 patients, 0.2 %) compared with achieved SBP ≥135 mmHg (n =73/8766 patients, 0.8 %) (HR=0.28, CI 0.14-0.58, p <0.001).

Conclusions: In hypertensive patients with a high cardiovascular risk, valsartan and amlodipine have a similar impact on the incidence of end-stage kidney disease. Achieving SBP <135 mmHg, averaging 128.8/77.3 mm, is highly efficacious in kidney protection.