Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies
Summary Background Cardiovascular risk factors are associated with dementia and cognitive decline. We investigated the effects of renin-angiotensin system blockade on cognitive function in patients aged 55 years and older with established atherosclerotic cardiovascular disease or diabetes with end-o...
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| Veröffentlicht in: | Lancet neurology 2011, Vol.10 (1), p.43-53 |
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| creator | Anderson, Craig, Prof Teo, Koon, MD Gao, Peggy, MSc Arima, Hisatomi, MD Dans, Antonio, MD Unger, Thomas, MD Commerford, Patrick, MD Dyal, Leanne, MSc Schumacher, Helmut, PhD Pogue, Janice, MSc Paolasso, Ernesto, MD Holwerda, Nicolaas, MD Chazova, Irina, MD Binbrek, Azan, MD Young, James, MD Yusuf, Salim, DPhil |
| description | Summary Background Cardiovascular risk factors are associated with dementia and cognitive decline. We investigated the effects of renin-angiotensin system blockade on cognitive function in patients aged 55 years and older with established atherosclerotic cardiovascular disease or diabetes with end-organ damage in two clinical trials. Methods In the main study, ONTARGET, a double-blind, double-dummy, randomised controlled trial, the effects on cardiovascular outcomes of standard doses of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), an angiotensin-receptor blocker (telmisartan), and a combination of the drugs were evaluated in 25 620 participants. In the parallel TRANSCEND trial, the effects of telmisartan were compared with those of placebo in 5926 participants intolerant to ACE inhibitors. Secondary outcomes included cognitive impairment (defined by investigator-reported diagnosis of dementia or significant cognitive dysfunction, or a score of ≤23 on the Mini-Mental State Examination [MMSE]) and cognitive decline (a decrease of ≤3 points on the MMSE from baseline during follow-up). Analyses were by intention to treat. We pooled data from these studies to identify baseline predictors of cognitive impairment and its frequency according to mean systolic blood pressure during follow-up. These studies were registered with ClinicalTrials.gov , number NCT00153101. Findings During a median duration of 56 months (IQR 51–64) of follow-up in ONTARGET, cognitive impairment occurred in 652 (8%) of 7865 patients allocated ramipril, 584 (7%) of 7797 allocated telmisartan, and 618 (8%) of 7807 allocated combination treatment (combination vs ramipril, odds ratio [OR] 0·95, 95% CI 0·85–1·07, p=0·39; telmisartan vs ramipril, OR 0·90, 0·80–1·01, p=0·06). Corresponding figures for cognitive decline were 1314 (17%), 1279 (17%), and 1240 (17%) in each of the groups, respectively (telmisartan vs ramipril, OR 0·97, 0·89–1·06, p=0·53; combination vs ramipril, OR 0·95, 0·88–1·04, p=0·28). In TRANSCEND, cognitive impairment occurred in 239 (9%) of 2694 participants allocated telmisartan compared with 245 (9%) of 2689 allocated placebo (OR 0·97, 0·81–1·17, p=0·76). The corresponding figures for cognitive decline were 454 (17%) and 412 (16%; OR 1·10, 0·95–1·27, p=0·22). Interpretation In patients with cardiovascular disease or diabetes, different approaches to blocking of the renin-angiotensin system had no clear effects on cognitive outcomes. Although patients with the |
| doi_str_mv | 10.1016/S1474-4422(10)70250-7 |
| format | Article |
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We investigated the effects of renin-angiotensin system blockade on cognitive function in patients aged 55 years and older with established atherosclerotic cardiovascular disease or diabetes with end-organ damage in two clinical trials. Methods In the main study, ONTARGET, a double-blind, double-dummy, randomised controlled trial, the effects on cardiovascular outcomes of standard doses of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), an angiotensin-receptor blocker (telmisartan), and a combination of the drugs were evaluated in 25 620 participants. In the parallel TRANSCEND trial, the effects of telmisartan were compared with those of placebo in 5926 participants intolerant to ACE inhibitors. Secondary outcomes included cognitive impairment (defined by investigator-reported diagnosis of dementia or significant cognitive dysfunction, or a score of ≤23 on the Mini-Mental State Examination [MMSE]) and cognitive decline (a decrease of ≤3 points on the MMSE from baseline during follow-up). Analyses were by intention to treat. We pooled data from these studies to identify baseline predictors of cognitive impairment and its frequency according to mean systolic blood pressure during follow-up. These studies were registered with ClinicalTrials.gov , number NCT00153101. Findings During a median duration of 56 months (IQR 51–64) of follow-up in ONTARGET, cognitive impairment occurred in 652 (8%) of 7865 patients allocated ramipril, 584 (7%) of 7797 allocated telmisartan, and 618 (8%) of 7807 allocated combination treatment (combination vs ramipril, odds ratio [OR] 0·95, 95% CI 0·85–1·07, p=0·39; telmisartan vs ramipril, OR 0·90, 0·80–1·01, p=0·06). Corresponding figures for cognitive decline were 1314 (17%), 1279 (17%), and 1240 (17%) in each of the groups, respectively (telmisartan vs ramipril, OR 0·97, 0·89–1·06, p=0·53; combination vs ramipril, OR 0·95, 0·88–1·04, p=0·28). In TRANSCEND, cognitive impairment occurred in 239 (9%) of 2694 participants allocated telmisartan compared with 245 (9%) of 2689 allocated placebo (OR 0·97, 0·81–1·17, p=0·76). The corresponding figures for cognitive decline were 454 (17%) and 412 (16%; OR 1·10, 0·95–1·27, p=0·22). Interpretation In patients with cardiovascular disease or diabetes, different approaches to blocking of the renin-angiotensin system had no clear effects on cognitive outcomes. Although patients with the lowest systolic blood pressure had the greatest preservation of cognitive function, meta-regression analyses did not show any benefits of blood-pressure lowering on cognition over several years of treatment. Funding Boehringer-Ingelheim.</description><identifier>ISSN: 1474-4422</identifier><identifier>EISSN: 1474-4465</identifier><identifier>DOI: 10.1016/S1474-4422(10)70250-7</identifier><identifier>PMID: 20980201</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Aged ; Aged, 80 and over ; Alzheimer's disease ; Angiotensin Receptor Antagonists - adverse effects ; Angiotensin Receptor Antagonists - therapeutic use ; Angiotensin-Converting Enzyme Inhibitors - adverse effects ; Angiotensin-Converting Enzyme Inhibitors - therapeutic use ; Arteriosclerosis ; Benzimidazoles - adverse effects ; Benzimidazoles - therapeutic use ; Benzoates - adverse effects ; Benzoates - therapeutic use ; Blood pressure ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - drug therapy ; Clinical trials ; Cognition Disorders - chemically induced ; Cognitive ability ; Data processing ; Dementia ; Dementia disorders ; Diabetes ; Diabetes mellitus ; Disease prevention ; Double-Blind Method ; Drug development ; Drug dosages ; Drug Therapy, Combination ; Endocrine system ; Enzymes ; Female ; Follow-Up Studies ; Heart failure ; Humans ; Hypotheses ; Male ; Mental Status Schedule ; Motivation ; Neurology ; Neuropsychological Tests ; Odds Ratio ; Peptidyl-dipeptidase A ; Preservation ; Ramipril - adverse effects ; Ramipril - therapeutic use ; Renin-Angiotensin System - drug effects ; Renin-Angiotensin System - physiology ; Risk factors ; Stroke ; Treatment Outcome</subject><ispartof>Lancet neurology, 2011, Vol.10 (1), p.43-53</ispartof><rights>Elsevier Ltd</rights><rights>2011 Elsevier Ltd</rights><rights>Copyright Elsevier Limited Jan 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-980492d978c4f15cc7c1f967cdf5a789b017bf6e2fdb013a98087ead0ef387833</citedby><cites>FETCH-LOGICAL-c478t-980492d978c4f15cc7c1f967cdf5a789b017bf6e2fdb013a98087ead0ef387833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/818448403?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,776,780,3536,4009,27902,27903,27904,64361,64363,64365,65309,72215</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20980201$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anderson, Craig, Prof</creatorcontrib><creatorcontrib>Teo, Koon, MD</creatorcontrib><creatorcontrib>Gao, Peggy, MSc</creatorcontrib><creatorcontrib>Arima, Hisatomi, MD</creatorcontrib><creatorcontrib>Dans, Antonio, MD</creatorcontrib><creatorcontrib>Unger, Thomas, MD</creatorcontrib><creatorcontrib>Commerford, Patrick, MD</creatorcontrib><creatorcontrib>Dyal, Leanne, MSc</creatorcontrib><creatorcontrib>Schumacher, Helmut, PhD</creatorcontrib><creatorcontrib>Pogue, Janice, MSc</creatorcontrib><creatorcontrib>Paolasso, Ernesto, MD</creatorcontrib><creatorcontrib>Holwerda, Nicolaas, MD</creatorcontrib><creatorcontrib>Chazova, Irina, MD</creatorcontrib><creatorcontrib>Binbrek, Azan, MD</creatorcontrib><creatorcontrib>Young, James, MD</creatorcontrib><creatorcontrib>Yusuf, Salim, DPhil</creatorcontrib><creatorcontrib>for the ONTARGET and TRANSCEND Investigators</creatorcontrib><creatorcontrib>ONTARGET and TRANSCEND Investigators</creatorcontrib><title>Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies</title><title>Lancet neurology</title><addtitle>Lancet Neurol</addtitle><description>Summary Background Cardiovascular risk factors are associated with dementia and cognitive decline. We investigated the effects of renin-angiotensin system blockade on cognitive function in patients aged 55 years and older with established atherosclerotic cardiovascular disease or diabetes with end-organ damage in two clinical trials. Methods In the main study, ONTARGET, a double-blind, double-dummy, randomised controlled trial, the effects on cardiovascular outcomes of standard doses of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), an angiotensin-receptor blocker (telmisartan), and a combination of the drugs were evaluated in 25 620 participants. In the parallel TRANSCEND trial, the effects of telmisartan were compared with those of placebo in 5926 participants intolerant to ACE inhibitors. Secondary outcomes included cognitive impairment (defined by investigator-reported diagnosis of dementia or significant cognitive dysfunction, or a score of ≤23 on the Mini-Mental State Examination [MMSE]) and cognitive decline (a decrease of ≤3 points on the MMSE from baseline during follow-up). Analyses were by intention to treat. We pooled data from these studies to identify baseline predictors of cognitive impairment and its frequency according to mean systolic blood pressure during follow-up. These studies were registered with ClinicalTrials.gov , number NCT00153101. Findings During a median duration of 56 months (IQR 51–64) of follow-up in ONTARGET, cognitive impairment occurred in 652 (8%) of 7865 patients allocated ramipril, 584 (7%) of 7797 allocated telmisartan, and 618 (8%) of 7807 allocated combination treatment (combination vs ramipril, odds ratio [OR] 0·95, 95% CI 0·85–1·07, p=0·39; telmisartan vs ramipril, OR 0·90, 0·80–1·01, p=0·06). Corresponding figures for cognitive decline were 1314 (17%), 1279 (17%), and 1240 (17%) in each of the groups, respectively (telmisartan vs ramipril, OR 0·97, 0·89–1·06, p=0·53; combination vs ramipril, OR 0·95, 0·88–1·04, p=0·28). In TRANSCEND, cognitive impairment occurred in 239 (9%) of 2694 participants allocated telmisartan compared with 245 (9%) of 2689 allocated placebo (OR 0·97, 0·81–1·17, p=0·76). The corresponding figures for cognitive decline were 454 (17%) and 412 (16%; OR 1·10, 0·95–1·27, p=0·22). Interpretation In patients with cardiovascular disease or diabetes, different approaches to blocking of the renin-angiotensin system had no clear effects on cognitive outcomes. Although patients with the lowest systolic blood pressure had the greatest preservation of cognitive function, meta-regression analyses did not show any benefits of blood-pressure lowering on cognition over several years of treatment. Funding Boehringer-Ingelheim.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer's disease</subject><subject>Angiotensin Receptor Antagonists - adverse effects</subject><subject>Angiotensin Receptor Antagonists - therapeutic use</subject><subject>Angiotensin-Converting Enzyme Inhibitors - adverse effects</subject><subject>Angiotensin-Converting Enzyme Inhibitors - therapeutic use</subject><subject>Arteriosclerosis</subject><subject>Benzimidazoles - adverse effects</subject><subject>Benzimidazoles - therapeutic use</subject><subject>Benzoates - adverse effects</subject><subject>Benzoates - therapeutic use</subject><subject>Blood pressure</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - drug therapy</subject><subject>Clinical trials</subject><subject>Cognition Disorders - chemically induced</subject><subject>Cognitive ability</subject><subject>Data processing</subject><subject>Dementia</subject><subject>Dementia disorders</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Disease prevention</subject><subject>Double-Blind Method</subject><subject>Drug development</subject><subject>Drug dosages</subject><subject>Drug Therapy, Combination</subject><subject>Endocrine system</subject><subject>Enzymes</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Heart failure</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Male</subject><subject>Mental Status Schedule</subject><subject>Motivation</subject><subject>Neurology</subject><subject>Neuropsychological Tests</subject><subject>Odds Ratio</subject><subject>Peptidyl-dipeptidase A</subject><subject>Preservation</subject><subject>Ramipril - adverse effects</subject><subject>Ramipril - therapeutic use</subject><subject>Renin-Angiotensin System - drug effects</subject><subject>Renin-Angiotensin System - physiology</subject><subject>Risk factors</subject><subject>Stroke</subject><subject>Treatment Outcome</subject><issn>1474-4422</issn><issn>1474-4465</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkcFuEzEQhlcIREvhEUAWF-AQsL3e2NsDKAqhIFWplIaz5diziZuNHWxvpDwQ74k3CTn00pNH1jffaOYvircEfyaYDL_cE8bZgDFKPxL8iWNa4QF_VlyevofV83NN6UXxKsYHjClhgrwsLiiuBaaYXBZ_Z-CsGyi3tD6Bi9ahuI8JNmjRer1WBpByBmm_dDbZHaCmczpZ71AmtypZcCkildDKLlco2LhGvkFaBWP9TkXdtSogYyOoCNdZpdp9tLFnjEoKNcFvUFoBupvOR7ObyfwwbT4bTe_Hk-l3FFNnLMTXxYtGtRHenN6r4vePyXz8c3B7d_NrPLodaMZFGuSlWE1NzYVmDam05po09ZBr01SKi3qBCV80Q6CNyWWpMi84KIOhKQUXZXlVfDh6t8H_6SAmubFRQ9sqB76LUlQlE6Kq6dMkpWUlaiwy-f4R-eC7kA-RISIYEwz3g6sjpIOPMUAjt8FuVNhLgmWftzzkLfsw-69D3pLnvncnebfYgDl3_Q84A9-OAOSz7SwEGXXOTIOxAXSSxtsnR3x9ZNCtdVardg17iOdliIxU4qOkdxB8MPDyHySVz5o</recordid><startdate>2011</startdate><enddate>2011</enddate><creator>Anderson, Craig, Prof</creator><creator>Teo, Koon, MD</creator><creator>Gao, Peggy, MSc</creator><creator>Arima, Hisatomi, MD</creator><creator>Dans, Antonio, MD</creator><creator>Unger, Thomas, MD</creator><creator>Commerford, Patrick, MD</creator><creator>Dyal, Leanne, MSc</creator><creator>Schumacher, Helmut, PhD</creator><creator>Pogue, Janice, MSc</creator><creator>Paolasso, Ernesto, MD</creator><creator>Holwerda, Nicolaas, MD</creator><creator>Chazova, Irina, MD</creator><creator>Binbrek, Azan, MD</creator><creator>Young, James, MD</creator><creator>Yusuf, Salim, DPhil</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><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>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>2011</creationdate><title>Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies</title><author>Anderson, Craig, Prof ; Teo, Koon, MD ; Gao, Peggy, MSc ; Arima, Hisatomi, MD ; Dans, Antonio, MD ; Unger, Thomas, MD ; Commerford, Patrick, MD ; Dyal, Leanne, MSc ; Schumacher, Helmut, PhD ; Pogue, Janice, MSc ; Paolasso, Ernesto, MD ; Holwerda, Nicolaas, MD ; Chazova, Irina, MD ; Binbrek, Azan, MD ; Young, James, MD ; Yusuf, Salim, DPhil</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-980492d978c4f15cc7c1f967cdf5a789b017bf6e2fdb013a98087ead0ef387833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer's disease</topic><topic>Angiotensin Receptor Antagonists - adverse effects</topic><topic>Angiotensin Receptor Antagonists - therapeutic use</topic><topic>Angiotensin-Converting Enzyme Inhibitors - adverse effects</topic><topic>Angiotensin-Converting Enzyme Inhibitors - therapeutic use</topic><topic>Arteriosclerosis</topic><topic>Benzimidazoles - adverse effects</topic><topic>Benzimidazoles - therapeutic use</topic><topic>Benzoates - adverse effects</topic><topic>Benzoates - therapeutic use</topic><topic>Blood pressure</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - drug therapy</topic><topic>Clinical trials</topic><topic>Cognition Disorders - chemically induced</topic><topic>Cognitive ability</topic><topic>Data processing</topic><topic>Dementia</topic><topic>Dementia disorders</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Disease prevention</topic><topic>Double-Blind Method</topic><topic>Drug development</topic><topic>Drug dosages</topic><topic>Drug Therapy, Combination</topic><topic>Endocrine system</topic><topic>Enzymes</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Heart failure</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Male</topic><topic>Mental Status Schedule</topic><topic>Motivation</topic><topic>Neurology</topic><topic>Neuropsychological Tests</topic><topic>Odds Ratio</topic><topic>Peptidyl-dipeptidase A</topic><topic>Preservation</topic><topic>Ramipril - adverse effects</topic><topic>Ramipril - therapeutic use</topic><topic>Renin-Angiotensin System - drug effects</topic><topic>Renin-Angiotensin System - physiology</topic><topic>Risk factors</topic><topic>Stroke</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anderson, Craig, Prof</creatorcontrib><creatorcontrib>Teo, Koon, MD</creatorcontrib><creatorcontrib>Gao, Peggy, MSc</creatorcontrib><creatorcontrib>Arima, Hisatomi, MD</creatorcontrib><creatorcontrib>Dans, Antonio, MD</creatorcontrib><creatorcontrib>Unger, Thomas, MD</creatorcontrib><creatorcontrib>Commerford, Patrick, MD</creatorcontrib><creatorcontrib>Dyal, Leanne, MSc</creatorcontrib><creatorcontrib>Schumacher, Helmut, PhD</creatorcontrib><creatorcontrib>Pogue, Janice, MSc</creatorcontrib><creatorcontrib>Paolasso, Ernesto, MD</creatorcontrib><creatorcontrib>Holwerda, Nicolaas, MD</creatorcontrib><creatorcontrib>Chazova, Irina, MD</creatorcontrib><creatorcontrib>Binbrek, Azan, MD</creatorcontrib><creatorcontrib>Young, James, MD</creatorcontrib><creatorcontrib>Yusuf, Salim, DPhil</creatorcontrib><creatorcontrib>for the ONTARGET and TRANSCEND Investigators</creatorcontrib><creatorcontrib>ONTARGET and TRANSCEND Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Lancet neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anderson, Craig, Prof</au><au>Teo, Koon, MD</au><au>Gao, Peggy, MSc</au><au>Arima, Hisatomi, MD</au><au>Dans, Antonio, MD</au><au>Unger, Thomas, MD</au><au>Commerford, Patrick, MD</au><au>Dyal, Leanne, MSc</au><au>Schumacher, Helmut, PhD</au><au>Pogue, Janice, MSc</au><au>Paolasso, Ernesto, MD</au><au>Holwerda, Nicolaas, MD</au><au>Chazova, Irina, MD</au><au>Binbrek, Azan, MD</au><au>Young, James, MD</au><au>Yusuf, Salim, DPhil</au><aucorp>for the ONTARGET and TRANSCEND Investigators</aucorp><aucorp>ONTARGET and TRANSCEND Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies</atitle><jtitle>Lancet neurology</jtitle><addtitle>Lancet Neurol</addtitle><date>2011</date><risdate>2011</risdate><volume>10</volume><issue>1</issue><spage>43</spage><epage>53</epage><pages>43-53</pages><issn>1474-4422</issn><eissn>1474-4465</eissn><coden>LANCAO</coden><abstract>Summary Background Cardiovascular risk factors are associated with dementia and cognitive decline. We investigated the effects of renin-angiotensin system blockade on cognitive function in patients aged 55 years and older with established atherosclerotic cardiovascular disease or diabetes with end-organ damage in two clinical trials. Methods In the main study, ONTARGET, a double-blind, double-dummy, randomised controlled trial, the effects on cardiovascular outcomes of standard doses of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), an angiotensin-receptor blocker (telmisartan), and a combination of the drugs were evaluated in 25 620 participants. In the parallel TRANSCEND trial, the effects of telmisartan were compared with those of placebo in 5926 participants intolerant to ACE inhibitors. Secondary outcomes included cognitive impairment (defined by investigator-reported diagnosis of dementia or significant cognitive dysfunction, or a score of ≤23 on the Mini-Mental State Examination [MMSE]) and cognitive decline (a decrease of ≤3 points on the MMSE from baseline during follow-up). Analyses were by intention to treat. We pooled data from these studies to identify baseline predictors of cognitive impairment and its frequency according to mean systolic blood pressure during follow-up. These studies were registered with ClinicalTrials.gov , number NCT00153101. Findings During a median duration of 56 months (IQR 51–64) of follow-up in ONTARGET, cognitive impairment occurred in 652 (8%) of 7865 patients allocated ramipril, 584 (7%) of 7797 allocated telmisartan, and 618 (8%) of 7807 allocated combination treatment (combination vs ramipril, odds ratio [OR] 0·95, 95% CI 0·85–1·07, p=0·39; telmisartan vs ramipril, OR 0·90, 0·80–1·01, p=0·06). Corresponding figures for cognitive decline were 1314 (17%), 1279 (17%), and 1240 (17%) in each of the groups, respectively (telmisartan vs ramipril, OR 0·97, 0·89–1·06, p=0·53; combination vs ramipril, OR 0·95, 0·88–1·04, p=0·28). In TRANSCEND, cognitive impairment occurred in 239 (9%) of 2694 participants allocated telmisartan compared with 245 (9%) of 2689 allocated placebo (OR 0·97, 0·81–1·17, p=0·76). The corresponding figures for cognitive decline were 454 (17%) and 412 (16%; OR 1·10, 0·95–1·27, p=0·22). Interpretation In patients with cardiovascular disease or diabetes, different approaches to blocking of the renin-angiotensin system had no clear effects on cognitive outcomes. Although patients with the lowest systolic blood pressure had the greatest preservation of cognitive function, meta-regression analyses did not show any benefits of blood-pressure lowering on cognition over several years of treatment. Funding Boehringer-Ingelheim.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>20980201</pmid><doi>10.1016/S1474-4422(10)70250-7</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1474-4422 |
| ispartof | Lancet neurology, 2011, Vol.10 (1), p.43-53 |
| issn | 1474-4422 1474-4465 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_853488592 |
| source | MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland |
| subjects | Aged Aged, 80 and over Alzheimer's disease Angiotensin Receptor Antagonists - adverse effects Angiotensin Receptor Antagonists - therapeutic use Angiotensin-Converting Enzyme Inhibitors - adverse effects Angiotensin-Converting Enzyme Inhibitors - therapeutic use Arteriosclerosis Benzimidazoles - adverse effects Benzimidazoles - therapeutic use Benzoates - adverse effects Benzoates - therapeutic use Blood pressure Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - drug therapy Clinical trials Cognition Disorders - chemically induced Cognitive ability Data processing Dementia Dementia disorders Diabetes Diabetes mellitus Disease prevention Double-Blind Method Drug development Drug dosages Drug Therapy, Combination Endocrine system Enzymes Female Follow-Up Studies Heart failure Humans Hypotheses Male Mental Status Schedule Motivation Neurology Neuropsychological Tests Odds Ratio Peptidyl-dipeptidase A Preservation Ramipril - adverse effects Ramipril - therapeutic use Renin-Angiotensin System - drug effects Renin-Angiotensin System - physiology Risk factors Stroke Treatment Outcome |
| title | Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies |
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