Long term use of drugs affecting the renin‐angiotensin system and the risk of cancer: a population‐based case‐control study
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • A recent meta‐analysis has suggested an increased risk of cancer among users of angiotensin receptor blockers. WHAT THIS STUDY ADDS • Within the limitations of an observational study there is no difference in the cancer incidence between users of drugs affe...
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| Veröffentlicht in: | British journal of clinical pharmacology 2012-07, Vol.74 (1), p.180-188 |
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| creator | Hallas, Jesper Christensen, Rene Andersen, Morten Friis, Søren Bjerrum, Lars |
| description | WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• A recent meta‐analysis has suggested an increased risk of cancer among users of angiotensin receptor blockers.
WHAT THIS STUDY ADDS
• Within the limitations of an observational study there is no difference in the cancer incidence between users of drugs affecting the renin‐angiotensin system and users of other antihypertensives.
• No consistent dose or duration dependency could be demonstrated for angiotensin reeptor blockers and angiotensin converting enzyme inhibitors.
AIMS A recent meta‐analysis of clinical trials has demonstrated a small excess of cancers in persons who had been allocated to angiotensin receptor blockers (ARBs). We undertook this observational study to look at dose–response and dose–duration effects and look for specificity with respect to outcome. Use of angiotensin converting enzyme inhibitors (ACEIs) was included in the main analysis since ACEIs share pharmacological properties with ARBs.
METHODS We identified 149 417 incident cancer cases in Denmark during the period 2000–2005. Four controls, matched by age and gender, were selected for each case by a risk‐set sampling. Data on medication were retrieved from the Danish National Prescription Registry. We defined long term exposure as at least 1000 defined daily doses redeemed within the past 5 years. Confounders were controlled by conditional logistic regression.
RESULTS The odds ratio (OR) associating long term drug use with incident cancer was 1.12 (95% CI 1.06, 1.18), 1.17 (95% CI 1.14, 1.20), 1.23 (95% CI 1.20, 1.26), 1.18 (95% CI 1.14, 1.22), 1.25 (95% CI 1.22, 1.28), 1.37 (95% CI 1.21, 1.54), 1.29 (95% CI 1.22, 1.37) for ARBs, ACEIs, calcium channel blockers, β‐adrenoceptor blockers, thiazide diuretics and α‐adrenoceptor blockers. No consistent dose–duration or dose–response association could be demonstrated for ARBs or ACEIs.
CONCLUSIONS The indication or possibly threshold for prescribing antihypertensives appears to be related to a small increase in cancer risk. The ARB‐cancer association is probably too weak to be addressed in observational studies, given their limitations. |
| doi_str_mv | 10.1111/j.1365-2125.2012.04170.x |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_539623</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>BCP4170</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6580-e1e98249c97bf32476ddbab729b4a2ff50714a032e17bb58931ae0cc59da88b63</originalsourceid><addsrcrecordid>eNqNksmO1DAQQC0EYpqBX0C-cEzwmgUJJGixSS3BAc6W41R63JO2Izthpm_wB3wjX4JDenqYAxK-eKn3yraqEMKU5DSN57uc8kJmjDKZM0JZTgQtSX59D61OgftoRTgpMskkPUOPYtwRQjkt5EN0xhgTXAi2Qj823m3xCGGPpwjYd7gN0zZi3XVgRjvHLgAHcNb9-v5Tu631I7hoHY6HOMIea9cuiI2Xs260MxBeYI0HP0y9Hq2fzUZHaFMwQtoY78bgexzHqT08Rg863Ud4cpzP0dd3b7-sP2SbT-8_rl9vMlPIimRAoa6YqE1dNh1noizattFNyepGaNZ1kpRUaMIZ0LJpZFVzqoEYI-tWV1VT8HOULXnjFQxTo4Zg9zoclNdWHY8u0wqU5HXBeOLrf_JD8O2tdCPS9CpKJZXJfbW4CdhDayD9V_d3U9yJOHuhtv6b4rwWVMyXV0sCE3yMAbqTS4maW0Dt1FxpNVdazS2g_rSAuk7q07_vPok3NU_AsyOgo9F9F1LFbLzlCkJYJcrEvVy4K9vD4b8foN6sP88r_hs7NtRC</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Long term use of drugs affecting the renin‐angiotensin system and the risk of cancer: a population‐based case‐control study</title><source>MEDLINE</source><source>SWEPUB Freely available online</source><source>Wiley Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library All Journals</source><source>Alma/SFX Local Collection</source><creator>Hallas, Jesper ; Christensen, Rene ; Andersen, Morten ; Friis, Søren ; Bjerrum, Lars</creator><creatorcontrib>Hallas, Jesper ; Christensen, Rene ; Andersen, Morten ; Friis, Søren ; Bjerrum, Lars</creatorcontrib><description>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• A recent meta‐analysis has suggested an increased risk of cancer among users of angiotensin receptor blockers.
WHAT THIS STUDY ADDS
• Within the limitations of an observational study there is no difference in the cancer incidence between users of drugs affecting the renin‐angiotensin system and users of other antihypertensives.
• No consistent dose or duration dependency could be demonstrated for angiotensin reeptor blockers and angiotensin converting enzyme inhibitors.
AIMS A recent meta‐analysis of clinical trials has demonstrated a small excess of cancers in persons who had been allocated to angiotensin receptor blockers (ARBs). We undertook this observational study to look at dose–response and dose–duration effects and look for specificity with respect to outcome. Use of angiotensin converting enzyme inhibitors (ACEIs) was included in the main analysis since ACEIs share pharmacological properties with ARBs.
METHODS We identified 149 417 incident cancer cases in Denmark during the period 2000–2005. Four controls, matched by age and gender, were selected for each case by a risk‐set sampling. Data on medication were retrieved from the Danish National Prescription Registry. We defined long term exposure as at least 1000 defined daily doses redeemed within the past 5 years. Confounders were controlled by conditional logistic regression.
RESULTS The odds ratio (OR) associating long term drug use with incident cancer was 1.12 (95% CI 1.06, 1.18), 1.17 (95% CI 1.14, 1.20), 1.23 (95% CI 1.20, 1.26), 1.18 (95% CI 1.14, 1.22), 1.25 (95% CI 1.22, 1.28), 1.37 (95% CI 1.21, 1.54), 1.29 (95% CI 1.22, 1.37) for ARBs, ACEIs, calcium channel blockers, β‐adrenoceptor blockers, thiazide diuretics and α‐adrenoceptor blockers. No consistent dose–duration or dose–response association could be demonstrated for ARBs or ACEIs.
CONCLUSIONS The indication or possibly threshold for prescribing antihypertensives appears to be related to a small increase in cancer risk. The ARB‐cancer association is probably too weak to be addressed in observational studies, given their limitations.</description><identifier>ISSN: 0306-5251</identifier><identifier>ISSN: 1365-2125</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1111/j.1365-2125.2012.04170.x</identifier><identifier>PMID: 22243442</identifier><identifier>CODEN: BCPHBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; angiotensin converting enzyme inhibitors ; Angiotensin Receptor Antagonists - adverse effects ; angiotensin receptor blockers ; Angiotensin-Converting Enzyme Inhibitors - adverse effects ; Antihypertensive Agents - adverse effects ; antihypertensives ; Biological and medical sciences ; cancer ; Case-Control Studies ; case‐controls study ; Child ; Child, Preschool ; Denmark ; Female ; Humans ; Infant ; Logistic Models ; Male ; Medical sciences ; Medicin och hälsovetenskap ; Middle Aged ; Neoplasms - chemically induced ; Pharmacoepidemiology ; Pharmacology. Drug treatments ; Renin-Angiotensin System - drug effects ; Risk Factors ; Young Adult</subject><ispartof>British journal of clinical pharmacology, 2012-07, Vol.74 (1), p.180-188</ispartof><rights>2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society</rights><rights>2015 INIST-CNRS</rights><rights>2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.</rights><rights>2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6580-e1e98249c97bf32476ddbab729b4a2ff50714a032e17bb58931ae0cc59da88b63</citedby><cites>FETCH-LOGICAL-c6580-e1e98249c97bf32476ddbab729b4a2ff50714a032e17bb58931ae0cc59da88b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2125.2012.04170.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2125.2012.04170.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,552,780,784,885,1417,1433,27923,27924,45573,45574,46408,46832</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26002847$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22243442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:124711515$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Hallas, Jesper</creatorcontrib><creatorcontrib>Christensen, Rene</creatorcontrib><creatorcontrib>Andersen, Morten</creatorcontrib><creatorcontrib>Friis, Søren</creatorcontrib><creatorcontrib>Bjerrum, Lars</creatorcontrib><title>Long term use of drugs affecting the renin‐angiotensin system and the risk of cancer: a population‐based case‐control study</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• A recent meta‐analysis has suggested an increased risk of cancer among users of angiotensin receptor blockers.
WHAT THIS STUDY ADDS
• Within the limitations of an observational study there is no difference in the cancer incidence between users of drugs affecting the renin‐angiotensin system and users of other antihypertensives.
• No consistent dose or duration dependency could be demonstrated for angiotensin reeptor blockers and angiotensin converting enzyme inhibitors.
AIMS A recent meta‐analysis of clinical trials has demonstrated a small excess of cancers in persons who had been allocated to angiotensin receptor blockers (ARBs). We undertook this observational study to look at dose–response and dose–duration effects and look for specificity with respect to outcome. Use of angiotensin converting enzyme inhibitors (ACEIs) was included in the main analysis since ACEIs share pharmacological properties with ARBs.
METHODS We identified 149 417 incident cancer cases in Denmark during the period 2000–2005. Four controls, matched by age and gender, were selected for each case by a risk‐set sampling. Data on medication were retrieved from the Danish National Prescription Registry. We defined long term exposure as at least 1000 defined daily doses redeemed within the past 5 years. Confounders were controlled by conditional logistic regression.
RESULTS The odds ratio (OR) associating long term drug use with incident cancer was 1.12 (95% CI 1.06, 1.18), 1.17 (95% CI 1.14, 1.20), 1.23 (95% CI 1.20, 1.26), 1.18 (95% CI 1.14, 1.22), 1.25 (95% CI 1.22, 1.28), 1.37 (95% CI 1.21, 1.54), 1.29 (95% CI 1.22, 1.37) for ARBs, ACEIs, calcium channel blockers, β‐adrenoceptor blockers, thiazide diuretics and α‐adrenoceptor blockers. No consistent dose–duration or dose–response association could be demonstrated for ARBs or ACEIs.
CONCLUSIONS The indication or possibly threshold for prescribing antihypertensives appears to be related to a small increase in cancer risk. The ARB‐cancer association is probably too weak to be addressed in observational studies, given their limitations.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>angiotensin converting enzyme inhibitors</subject><subject>Angiotensin Receptor Antagonists - adverse effects</subject><subject>angiotensin receptor blockers</subject><subject>Angiotensin-Converting Enzyme Inhibitors - adverse effects</subject><subject>Antihypertensive Agents - adverse effects</subject><subject>antihypertensives</subject><subject>Biological and medical sciences</subject><subject>cancer</subject><subject>Case-Control Studies</subject><subject>case‐controls study</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Denmark</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Middle Aged</subject><subject>Neoplasms - chemically induced</subject><subject>Pharmacoepidemiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Renin-Angiotensin System - drug effects</subject><subject>Risk Factors</subject><subject>Young Adult</subject><issn>0306-5251</issn><issn>1365-2125</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqNksmO1DAQQC0EYpqBX0C-cEzwmgUJJGixSS3BAc6W41R63JO2Izthpm_wB3wjX4JDenqYAxK-eKn3yraqEMKU5DSN57uc8kJmjDKZM0JZTgQtSX59D61OgftoRTgpMskkPUOPYtwRQjkt5EN0xhgTXAi2Qj823m3xCGGPpwjYd7gN0zZi3XVgRjvHLgAHcNb9-v5Tu631I7hoHY6HOMIea9cuiI2Xs260MxBeYI0HP0y9Hq2fzUZHaFMwQtoY78bgexzHqT08Rg863Ud4cpzP0dd3b7-sP2SbT-8_rl9vMlPIimRAoa6YqE1dNh1noizattFNyepGaNZ1kpRUaMIZ0LJpZFVzqoEYI-tWV1VT8HOULXnjFQxTo4Zg9zoclNdWHY8u0wqU5HXBeOLrf_JD8O2tdCPS9CpKJZXJfbW4CdhDayD9V_d3U9yJOHuhtv6b4rwWVMyXV0sCE3yMAbqTS4maW0Dt1FxpNVdazS2g_rSAuk7q07_vPok3NU_AsyOgo9F9F1LFbLzlCkJYJcrEvVy4K9vD4b8foN6sP88r_hs7NtRC</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>Hallas, Jesper</creator><creator>Christensen, Rene</creator><creator>Andersen, Morten</creator><creator>Friis, Søren</creator><creator>Bjerrum, Lars</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Blackwell Science Inc</general><scope>IQODW</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>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>201207</creationdate><title>Long term use of drugs affecting the renin‐angiotensin system and the risk of cancer: a population‐based case‐control study</title><author>Hallas, Jesper ; Christensen, Rene ; Andersen, Morten ; Friis, Søren ; Bjerrum, Lars</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6580-e1e98249c97bf32476ddbab729b4a2ff50714a032e17bb58931ae0cc59da88b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>angiotensin converting enzyme inhibitors</topic><topic>Angiotensin Receptor Antagonists - adverse effects</topic><topic>angiotensin receptor blockers</topic><topic>Angiotensin-Converting Enzyme Inhibitors - adverse effects</topic><topic>Antihypertensive Agents - adverse effects</topic><topic>antihypertensives</topic><topic>Biological and medical sciences</topic><topic>cancer</topic><topic>Case-Control Studies</topic><topic>case‐controls study</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Denmark</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Middle Aged</topic><topic>Neoplasms - chemically induced</topic><topic>Pharmacoepidemiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Renin-Angiotensin System - drug effects</topic><topic>Risk Factors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hallas, Jesper</creatorcontrib><creatorcontrib>Christensen, Rene</creatorcontrib><creatorcontrib>Andersen, Morten</creatorcontrib><creatorcontrib>Friis, Søren</creatorcontrib><creatorcontrib>Bjerrum, Lars</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hallas, Jesper</au><au>Christensen, Rene</au><au>Andersen, Morten</au><au>Friis, Søren</au><au>Bjerrum, Lars</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long term use of drugs affecting the renin‐angiotensin system and the risk of cancer: a population‐based case‐control study</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>2012-07</date><risdate>2012</risdate><volume>74</volume><issue>1</issue><spage>180</spage><epage>188</epage><pages>180-188</pages><issn>0306-5251</issn><issn>1365-2125</issn><eissn>1365-2125</eissn><coden>BCPHBM</coden><abstract>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• A recent meta‐analysis has suggested an increased risk of cancer among users of angiotensin receptor blockers.
WHAT THIS STUDY ADDS
• Within the limitations of an observational study there is no difference in the cancer incidence between users of drugs affecting the renin‐angiotensin system and users of other antihypertensives.
• No consistent dose or duration dependency could be demonstrated for angiotensin reeptor blockers and angiotensin converting enzyme inhibitors.
AIMS A recent meta‐analysis of clinical trials has demonstrated a small excess of cancers in persons who had been allocated to angiotensin receptor blockers (ARBs). We undertook this observational study to look at dose–response and dose–duration effects and look for specificity with respect to outcome. Use of angiotensin converting enzyme inhibitors (ACEIs) was included in the main analysis since ACEIs share pharmacological properties with ARBs.
METHODS We identified 149 417 incident cancer cases in Denmark during the period 2000–2005. Four controls, matched by age and gender, were selected for each case by a risk‐set sampling. Data on medication were retrieved from the Danish National Prescription Registry. We defined long term exposure as at least 1000 defined daily doses redeemed within the past 5 years. Confounders were controlled by conditional logistic regression.
RESULTS The odds ratio (OR) associating long term drug use with incident cancer was 1.12 (95% CI 1.06, 1.18), 1.17 (95% CI 1.14, 1.20), 1.23 (95% CI 1.20, 1.26), 1.18 (95% CI 1.14, 1.22), 1.25 (95% CI 1.22, 1.28), 1.37 (95% CI 1.21, 1.54), 1.29 (95% CI 1.22, 1.37) for ARBs, ACEIs, calcium channel blockers, β‐adrenoceptor blockers, thiazide diuretics and α‐adrenoceptor blockers. No consistent dose–duration or dose–response association could be demonstrated for ARBs or ACEIs.
CONCLUSIONS The indication or possibly threshold for prescribing antihypertensives appears to be related to a small increase in cancer risk. The ARB‐cancer association is probably too weak to be addressed in observational studies, given their limitations.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22243442</pmid><doi>10.1111/j.1365-2125.2012.04170.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over angiotensin converting enzyme inhibitors Angiotensin Receptor Antagonists - adverse effects angiotensin receptor blockers Angiotensin-Converting Enzyme Inhibitors - adverse effects Antihypertensive Agents - adverse effects antihypertensives Biological and medical sciences cancer Case-Control Studies case‐controls study Child Child, Preschool Denmark Female Humans Infant Logistic Models Male Medical sciences Medicin och hälsovetenskap Middle Aged Neoplasms - chemically induced Pharmacoepidemiology Pharmacology. Drug treatments Renin-Angiotensin System - drug effects Risk Factors Young Adult |
| title | Long term use of drugs affecting the renin‐angiotensin system and the risk of cancer: a population‐based case‐control study |
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