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

Eirik Olsen; Kenneth Jamerson; Roland E Schmieder; Camilla L Søraas; Julian E Mariampillai; Giuseppe Mancia; Sverre E Kjeldsen; Sondre Heimark; Maria H Mehlum; Knut Liestøl; Anne C K Larstorp; Lene V Halvorsen; Aud Høieggen; Michel Burnier; Morten Rostrup; Stevo Julius; Michael A Weber

doi:10.1016/j.ejim.2024.12.021

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

Eur J Intern Med. 2024 Dec 17:S0953-6205(24)00516-8. doi: 10.1016/j.ejim.2024.12.021. Online ahead of print.

Authors

Eirik Olsen¹, Kenneth Jamerson², Roland E Schmieder³, Camilla L Søraas⁴, Julian E Mariampillai⁵, Giuseppe Mancia⁶, Sverre E Kjeldsen⁷, Sondre Heimark⁸, Maria H Mehlum⁸, Knut Liestøl⁹, Anne C K Larstorp⁴, Lene V Halvorsen⁴, Aud Høieggen⁴, Michel Burnier¹⁰, Morten Rostrup⁴, Stevo Julius², Michael A Weber¹¹

Affiliations

¹ The Norwegian University of Science and Technology, Trondheim, Norway; St. Olav´s University Hospital, Trondheim, Norway.
² University of Michigan, Ann Arbor, MI, USA.
³ University of Erlangen, Erlangen, Germany.
⁴ Oslo University Hospital, Ullevaal, Oslo, Norway; University of Oslo, Oslo, Norway.
⁵ Akershus University Hospital, Lørenskog, Norway.
⁶ University of Milan-Bicocca, Milan, Italy.
⁷ University of Michigan, Ann Arbor, MI, USA; Oslo University Hospital, Ullevaal, Oslo, Norway; University of Oslo, Oslo, Norway. Electronic address: [email protected].
⁸ Oslo University Hospital, Ullevaal, Oslo, Norway.
⁹ University of Oslo, Oslo, Norway.
¹⁰ University of Lausanne, Lausanne, Switzerland.
¹¹ SUNY Downstate College of Medicine, New York, NY, USA.

PMID: 39694747
DOI: 10.1016/j.ejim.2024.12.021

Abstract

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.

Keywords: Amlodipine; Blood pressure; Cardiovascular disease; Hypertension; Kidney failure; Valsartan.