Renin-angiotensin-aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors

Eur J Cancer. 2022 Mar:163:108-118. doi: 10.1016/j.ejca.2021.12.024. Epub 2022 Jan 19.


Background: Preclinical studies indicate that the concurrent use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) may improve outcomes in broad groups of patients with cancer. There are limited data on the association between the use of RAAS inhibitors and outcomes among patients treated with immune checkpoint inhibitors (ICIs).

Methods: We performed a retrospective study of all patients treated with an ICI in a single academic network. Of 10,903 patients, 5910 were on any anti-hypertensive medication. Of those on anti-hypertensive therapy, 3426 were prescribed a RAAS inhibitor during ICI treatment, and 2484 were prescribed other anti-hypertensive medications. The primary outcome was overall survival in the entire cohort and in sub-groups by cancer types.

Results: Thoracic cancer (34%) and melanoma (16%) were the most common types of cancer. Those prescribed a RAAS inhibitor were older, more frequently male, and had more cardiovascular risk factors. In a Cox proportional hazard model, the concurrent use of RAAS inhibitors was associated with better overall survival (hazard ratio (HR):0.92, [95% Confidence Interval (CI):0.85-0.99], P = .032). Patients with gastrointestinal (HR:0.82, [95% CI: 0.67-1.01], P = .057) and genitourinary cancer (HR:0.81, [95% CI:0.64-1.01], P = .067) had a non-statistically significant better overall survival.

Conclusions: In this large retrospective study, patients with hypertension who were concomitantly taking a RAAS inhibitor during ICI therapy had better overall survival. This benefit was primarily noted among patients with gastrointestinal and genitourinary cancers. Prospective randomized trials are warranted to further evaluate and specify the benefit of RAAS inhibitors in patients with cancer who receive ICI therapy.

Keywords: ACEI; ARB; Immune checkpoint inhibitors; Immune therapy; Renin–angiotensin–aldosterone system blocker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Humans
  • Hypertension* / chemically induced
  • Hypertension* / drug therapy
  • Immune Checkpoint Inhibitors / adverse effects
  • Male
  • Prospective Studies
  • Renin-Angiotensin System*
  • Retrospective Studies


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Immune Checkpoint Inhibitors