Renin–angiotensin–aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors
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 im...
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| Veröffentlicht in: | European journal of cancer (1990) 2022-03, Vol.163, p.108-118 |
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| creator | Drobni, Zsofia D. Michielin, Olivier Quinaglia, Thiago Zlotoff, Daniel A. Zubiri, Leyre Gilman, Hannah K. Supraja, Sama Merkely, Bela Muller, Veronika Sullivan, Ryan J. Reynolds, Kerry L. Pittet, Michael J. Jain, Rakesh K. Neilan, Tomas G. |
| description | 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).
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.
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.
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.
•We evaluated the effect of RAAS inhibitors among 5910 patients with cancer on an ICI.•Patients taking a RAAS inhibitor during ICI therapy had better overall survival.•The effect of RAAS inhibitors was similar among patients on an ACE inhibitor and an ARB.•The benefit was not noted among patients with melanoma and lung cancer.•Benefit was principally seen in patients with gastrointestinal and genitourinary cancers. |
| doi_str_mv | 10.1016/j.ejca.2021.12.024 |
| format | Article |
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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.
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.
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.
•We evaluated the effect of RAAS inhibitors among 5910 patients with cancer on an ICI.•Patients taking a RAAS inhibitor during ICI therapy had better overall survival.•The effect of RAAS inhibitors was similar among patients on an ACE inhibitor and an ARB.•The benefit was not noted among patients with melanoma and lung cancer.•Benefit was principally seen in patients with gastrointestinal and genitourinary cancers.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2021.12.024</identifier><identifier>PMID: 35065368</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>ACEI ; Aldosterone ; Angiotensin ; Angiotensin Receptor Antagonists - pharmacology ; Angiotensin Receptor Antagonists - therapeutic use ; Angiotensin-Converting Enzyme Inhibitors - therapeutic use ; Antihypertensive Agents - pharmacology ; Antihypertensive Agents - therapeutic use ; Antihypertensives ; ARB ; Cancer ; Cardiovascular diseases ; Clinical trials ; Confidence intervals ; Health hazards ; Health risks ; Humans ; Hypertension ; Hypertension - chemically induced ; Hypertension - drug therapy ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors - adverse effects ; Immune therapy ; Inhibitors ; Lung cancer ; Male ; Melanoma ; Patients ; Prospective Studies ; Renin ; Renin-Angiotensin System ; Renin–angiotensin–aldosterone system blocker ; Retrospective Studies ; Risk analysis ; Risk factors ; Statistical analysis ; Statistical models ; Survival ; Therapy ; Thorax</subject><ispartof>European journal of cancer (1990), 2022-03, Vol.163, p.108-118</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Mar 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-8a601c2994898a62dca10b3eae54f94d757703e09d46c553c6951bfb37bb1ba63</citedby><cites>FETCH-LOGICAL-c483t-8a601c2994898a62dca10b3eae54f94d757703e09d46c553c6951bfb37bb1ba63</cites><orcidid>0000-0001-7571-3548 ; 0000-0002-1398-3187 ; 0000-0001-5344-6645 ; 0000-0002-1355-5318 ; 0000-0001-9099-3007</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejca.2021.12.024$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35065368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Drobni, Zsofia D.</creatorcontrib><creatorcontrib>Michielin, Olivier</creatorcontrib><creatorcontrib>Quinaglia, Thiago</creatorcontrib><creatorcontrib>Zlotoff, Daniel A.</creatorcontrib><creatorcontrib>Zubiri, Leyre</creatorcontrib><creatorcontrib>Gilman, Hannah K.</creatorcontrib><creatorcontrib>Supraja, Sama</creatorcontrib><creatorcontrib>Merkely, Bela</creatorcontrib><creatorcontrib>Muller, Veronika</creatorcontrib><creatorcontrib>Sullivan, Ryan J.</creatorcontrib><creatorcontrib>Reynolds, Kerry L.</creatorcontrib><creatorcontrib>Pittet, Michael J.</creatorcontrib><creatorcontrib>Jain, Rakesh K.</creatorcontrib><creatorcontrib>Neilan, Tomas G.</creatorcontrib><title>Renin–angiotensin–aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>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).
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.
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.
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.
•We evaluated the effect of RAAS inhibitors among 5910 patients with cancer on an ICI.•Patients taking a RAAS inhibitor during ICI therapy had better overall survival.•The effect of RAAS inhibitors was similar among patients on an ACE inhibitor and an ARB.•The benefit was not noted among patients with melanoma and lung cancer.•Benefit was principally seen in patients with gastrointestinal and genitourinary cancers.</description><subject>ACEI</subject><subject>Aldosterone</subject><subject>Angiotensin</subject><subject>Angiotensin Receptor Antagonists - pharmacology</subject><subject>Angiotensin Receptor Antagonists - therapeutic use</subject><subject>Angiotensin-Converting Enzyme Inhibitors - therapeutic use</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Antihypertensive Agents - therapeutic use</subject><subject>Antihypertensives</subject><subject>ARB</subject><subject>Cancer</subject><subject>Cardiovascular diseases</subject><subject>Clinical trials</subject><subject>Confidence intervals</subject><subject>Health hazards</subject><subject>Health risks</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - chemically induced</subject><subject>Hypertension - drug therapy</subject><subject>Immune checkpoint inhibitors</subject><subject>Immune Checkpoint Inhibitors - adverse effects</subject><subject>Immune therapy</subject><subject>Inhibitors</subject><subject>Lung cancer</subject><subject>Male</subject><subject>Melanoma</subject><subject>Patients</subject><subject>Prospective Studies</subject><subject>Renin</subject><subject>Renin-Angiotensin System</subject><subject>Renin–angiotensin–aldosterone system blocker</subject><subject>Retrospective Studies</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Statistical analysis</subject><subject>Statistical models</subject><subject>Survival</subject><subject>Therapy</subject><subject>Thorax</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS1ERYfCC7BAkVgn-CdObAkhoQooUiWkCtaW49xpHCZ2sJ2pZseSPW_Ik9RDSlU2rHzte-7no3sQekFwRTBpXo8VjEZXFFNSEVphWj9CGyJaWWLB6WO0wZLLUuBanqKnMY4Y41bU-Ak6ZRw3nDVig35egbPu949f2l1bn8DF9bbrfUwQvIMiHnI1FdYNtrPJh1ho1xdxCXu717v8Xsw6WXApFjc2DcVwmCH8IXlXpAA6Qb927DQtGWgGMN9mb116AH2GTrZ6F-H53XmGvn54_-X8orz8_PHT-bvL0tSCpVLoBhNDpayFzDXtjSa4Y6CB11tZ9y1vW8wAy75uDOfMNJKTbtuxtutIpxt2ht6u3HnpJuhN9h30Ts3BTjoclNdW_dtxdlDXfq9kQwQVPANe3QGC_75ATGr0S3DZs6JNjZnkjOCsoqvKBB9jgO39DwSrY3pqVMf01DE9RajK6eWhlw-93Y_8jSsL3qwCyBvaWwgqmrx5A70NYJLqvf0f_xaaY7LU</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Drobni, Zsofia D.</creator><creator>Michielin, Olivier</creator><creator>Quinaglia, Thiago</creator><creator>Zlotoff, Daniel A.</creator><creator>Zubiri, Leyre</creator><creator>Gilman, Hannah K.</creator><creator>Supraja, Sama</creator><creator>Merkely, Bela</creator><creator>Muller, Veronika</creator><creator>Sullivan, Ryan J.</creator><creator>Reynolds, Kerry L.</creator><creator>Pittet, Michael J.</creator><creator>Jain, Rakesh K.</creator><creator>Neilan, Tomas G.</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7571-3548</orcidid><orcidid>https://orcid.org/0000-0002-1398-3187</orcidid><orcidid>https://orcid.org/0000-0001-5344-6645</orcidid><orcidid>https://orcid.org/0000-0002-1355-5318</orcidid><orcidid>https://orcid.org/0000-0001-9099-3007</orcidid></search><sort><creationdate>20220301</creationdate><title>Renin–angiotensin–aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors</title><author>Drobni, Zsofia D. ; Michielin, Olivier ; Quinaglia, Thiago ; Zlotoff, Daniel A. ; Zubiri, Leyre ; Gilman, Hannah K. ; Supraja, Sama ; Merkely, Bela ; Muller, Veronika ; Sullivan, Ryan J. ; Reynolds, Kerry L. ; Pittet, Michael J. ; Jain, Rakesh K. ; Neilan, Tomas G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-8a601c2994898a62dca10b3eae54f94d757703e09d46c553c6951bfb37bb1ba63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>ACEI</topic><topic>Aldosterone</topic><topic>Angiotensin</topic><topic>Angiotensin Receptor Antagonists - pharmacology</topic><topic>Angiotensin Receptor Antagonists - therapeutic use</topic><topic>Angiotensin-Converting Enzyme Inhibitors - therapeutic use</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Antihypertensive Agents - therapeutic use</topic><topic>Antihypertensives</topic><topic>ARB</topic><topic>Cancer</topic><topic>Cardiovascular diseases</topic><topic>Clinical trials</topic><topic>Confidence intervals</topic><topic>Health hazards</topic><topic>Health risks</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - chemically induced</topic><topic>Hypertension - drug therapy</topic><topic>Immune checkpoint inhibitors</topic><topic>Immune Checkpoint Inhibitors - adverse effects</topic><topic>Immune therapy</topic><topic>Inhibitors</topic><topic>Lung cancer</topic><topic>Male</topic><topic>Melanoma</topic><topic>Patients</topic><topic>Prospective Studies</topic><topic>Renin</topic><topic>Renin-Angiotensin System</topic><topic>Renin–angiotensin–aldosterone system blocker</topic><topic>Retrospective Studies</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Statistical analysis</topic><topic>Statistical models</topic><topic>Survival</topic><topic>Therapy</topic><topic>Thorax</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Drobni, Zsofia D.</creatorcontrib><creatorcontrib>Michielin, Olivier</creatorcontrib><creatorcontrib>Quinaglia, Thiago</creatorcontrib><creatorcontrib>Zlotoff, Daniel A.</creatorcontrib><creatorcontrib>Zubiri, Leyre</creatorcontrib><creatorcontrib>Gilman, Hannah K.</creatorcontrib><creatorcontrib>Supraja, Sama</creatorcontrib><creatorcontrib>Merkely, Bela</creatorcontrib><creatorcontrib>Muller, Veronika</creatorcontrib><creatorcontrib>Sullivan, Ryan J.</creatorcontrib><creatorcontrib>Reynolds, Kerry L.</creatorcontrib><creatorcontrib>Pittet, Michael J.</creatorcontrib><creatorcontrib>Jain, Rakesh K.</creatorcontrib><creatorcontrib>Neilan, Tomas G.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Drobni, Zsofia D.</au><au>Michielin, Olivier</au><au>Quinaglia, Thiago</au><au>Zlotoff, Daniel A.</au><au>Zubiri, Leyre</au><au>Gilman, Hannah K.</au><au>Supraja, Sama</au><au>Merkely, Bela</au><au>Muller, Veronika</au><au>Sullivan, Ryan J.</au><au>Reynolds, Kerry L.</au><au>Pittet, Michael J.</au><au>Jain, Rakesh K.</au><au>Neilan, Tomas G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Renin–angiotensin–aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>163</volume><spage>108</spage><epage>118</epage><pages>108-118</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>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).
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.
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.
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.
•We evaluated the effect of RAAS inhibitors among 5910 patients with cancer on an ICI.•Patients taking a RAAS inhibitor during ICI therapy had better overall survival.•The effect of RAAS inhibitors was similar among patients on an ACE inhibitor and an ARB.•The benefit was not noted among patients with melanoma and lung cancer.•Benefit was principally seen in patients with gastrointestinal and genitourinary cancers.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>35065368</pmid><doi>10.1016/j.ejca.2021.12.024</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7571-3548</orcidid><orcidid>https://orcid.org/0000-0002-1398-3187</orcidid><orcidid>https://orcid.org/0000-0001-5344-6645</orcidid><orcidid>https://orcid.org/0000-0002-1355-5318</orcidid><orcidid>https://orcid.org/0000-0001-9099-3007</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0959-8049 |
| ispartof | European journal of cancer (1990), 2022-03, Vol.163, p.108-118 |
| issn | 0959-8049 1879-0852 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | ACEI Aldosterone Angiotensin Angiotensin Receptor Antagonists - pharmacology Angiotensin Receptor Antagonists - therapeutic use Angiotensin-Converting Enzyme Inhibitors - therapeutic use Antihypertensive Agents - pharmacology Antihypertensive Agents - therapeutic use Antihypertensives ARB Cancer Cardiovascular diseases Clinical trials Confidence intervals Health hazards Health risks Humans Hypertension Hypertension - chemically induced Hypertension - drug therapy Immune checkpoint inhibitors Immune Checkpoint Inhibitors - adverse effects Immune therapy Inhibitors Lung cancer Male Melanoma Patients Prospective Studies Renin Renin-Angiotensin System Renin–angiotensin–aldosterone system blocker Retrospective Studies Risk analysis Risk factors Statistical analysis Statistical models Survival Therapy Thorax |
| title | Renin–angiotensin–aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors |
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