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

Zsofia D Drobni; Olivier Michielin; Thiago Quinaglia; Daniel A Zlotoff; Leyre Zubiri; Hannah K Gilman; Sama Supraja; Bela Merkely; Veronika Muller; Ryan J Sullivan; Kerry L Reynolds; Michael J Pittet; Rakesh K Jain; Tomas G Neilan

doi:10.1016/j.ejca.2021.12.024

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.

Authors

Affiliations

¹ Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Cardiovascular Imaging Research Center (CIRC), Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: drobni.zsofia@med.semmelweis-univ.hu.
² Oncology Department, Precision Oncology Center, Lausanne, Switzerland; Oncology Department, Lausanne University Hospital, Lausanne, Switzerland.
³ Cardiovascular Imaging Research Center (CIRC), Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Division of Oncology and Hematology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Cardiovascular Imaging Research Center (CIRC), Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: https://twitter.com/CIRC_MGH.
⁷ Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
⁸ Department of Pulmonology, Semmelweis University, Budapest, Hungary.
⁹ Division of Oncology and Hematology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: https://twitter.com/kreynoldsMD.
¹⁰ Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
¹¹ Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹² Cardiovascular Imaging Research Center (CIRC), Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: https://twitter.com/TomasNeilan.

Abstract

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

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding