Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis
To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients. Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hy...
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| creator | van der Pol, Karel H Wever, Kimberley E Verbakel, Mariette Visseren, Frank L J Cornel, Jan H Rongen, Gerard A |
| description | To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients.
Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT's a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT's and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved ( |
| doi_str_mv | 10.1371/journal.pone.0260844 |
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Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT's a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT's and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l).
Data from RCT's and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia.
PROSPERO registration CRD42018089744.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0260844</identifier><identifier>PMID: 34855873</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Allopurinol ; Allopurinol - therapeutic use ; Antimetabolites - therapeutic use ; Asymptomatic ; Bias ; Cardiology ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - mortality ; Cardiovascular Diseases - pathology ; Cardiovascular Diseases - prevention & control ; Cerebral infarction ; Clinical trials ; Cohort analysis ; Complications and side effects ; Dosage and administration ; Drug dosages ; Drug therapy ; Health risks ; Health sciences ; Heart attacks ; Humans ; Hyperuricemia ; Kidney diseases ; Medicine and Health Sciences ; Meta-analysis ; Morbidity ; Mortality ; Myocardial infarction ; Observational studies ; Patient outcomes ; Patients ; Physical Sciences ; Placebos ; Prevention ; Prognosis ; Research and Analysis Methods ; Rheumatism ; Risk factors ; Risk groups ; Risk management ; Stroke ; Survival Rate ; Systematic review ; Toxicology ; Uric acid</subject><ispartof>PloS one, 2021-12, Vol.16 (12), p.e0260844</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 van der Pol et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 van der Pol et al 2021 van der Pol et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6060ab288af8ea50600e5677f7958f39c59cbf8fcc012ebc8b933daeb0bcc1503</citedby><cites>FETCH-LOGICAL-c692t-6060ab288af8ea50600e5677f7958f39c59cbf8fcc012ebc8b933daeb0bcc1503</cites><orcidid>0000-0001-5345-9788 ; 0000-0002-3064-3192 ; 0000-0003-3635-3660</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638940/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638940/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34855873$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Pol, Karel H</creatorcontrib><creatorcontrib>Wever, Kimberley E</creatorcontrib><creatorcontrib>Verbakel, Mariette</creatorcontrib><creatorcontrib>Visseren, Frank L J</creatorcontrib><creatorcontrib>Cornel, Jan H</creatorcontrib><creatorcontrib>Rongen, Gerard A</creatorcontrib><title>Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients.
Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT's a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT's and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l).
Data from RCT's and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia.
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attacks</subject><subject>Humans</subject><subject>Hyperuricemia</subject><subject>Kidney diseases</subject><subject>Medicine and Health Sciences</subject><subject>Meta-analysis</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Myocardial infarction</subject><subject>Observational studies</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Physical Sciences</subject><subject>Placebos</subject><subject>Prevention</subject><subject>Prognosis</subject><subject>Research and Analysis Methods</subject><subject>Rheumatism</subject><subject>Risk factors</subject><subject>Risk groups</subject><subject>Risk management</subject><subject>Stroke</subject><subject>Survival Rate</subject><subject>Systematic review</subject><subject>Toxicology</subject><subject>Uric 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to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis</title><author>van der Pol, Karel H ; Wever, Kimberley E ; Verbakel, Mariette ; Visseren, Frank L J ; Cornel, Jan H ; Rongen, Gerard A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6060ab288af8ea50600e5677f7958f39c59cbf8fcc012ebc8b933daeb0bcc1503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Allopurinol</topic><topic>Allopurinol - therapeutic use</topic><topic>Antimetabolites - therapeutic use</topic><topic>Asymptomatic</topic><topic>Bias</topic><topic>Cardiology</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - etiology</topic><topic>Cardiovascular Diseases - mortality</topic><topic>Cardiovascular Diseases - pathology</topic><topic>Cardiovascular Diseases - prevention & control</topic><topic>Cerebral 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Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT's a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT's and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l).
Data from RCT's and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia.
PROSPERO registration CRD42018089744.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34855873</pmid><doi>10.1371/journal.pone.0260844</doi><tpages>e0260844</tpages><orcidid>https://orcid.org/0000-0001-5345-9788</orcidid><orcidid>https://orcid.org/0000-0002-3064-3192</orcidid><orcidid>https://orcid.org/0000-0003-3635-3660</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-12, Vol.16 (12), p.e0260844 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2605596758 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Allopurinol Allopurinol - therapeutic use Antimetabolites - therapeutic use Asymptomatic Bias Cardiology Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - etiology Cardiovascular Diseases - mortality Cardiovascular Diseases - pathology Cardiovascular Diseases - prevention & control Cerebral infarction Clinical trials Cohort analysis Complications and side effects Dosage and administration Drug dosages Drug therapy Health risks Health sciences Heart attacks Humans Hyperuricemia Kidney diseases Medicine and Health Sciences Meta-analysis Morbidity Mortality Myocardial infarction Observational studies Patient outcomes Patients Physical Sciences Placebos Prevention Prognosis Research and Analysis Methods Rheumatism Risk factors Risk groups Risk management Stroke Survival Rate Systematic review Toxicology Uric acid |
| title | Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T03%3A46%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Allopurinol%20to%20reduce%20cardiovascular%20morbidity%20and%20mortality:%20A%20systematic%20review%20and%20meta-analysis&rft.jtitle=PloS%20one&rft.au=van%20der%20Pol,%20Karel%20H&rft.date=2021-12-02&rft.volume=16&rft.issue=12&rft.spage=e0260844&rft.pages=e0260844-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0260844&rft_dat=%3Cgale_plos_%3EA684621162%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2605596758&rft_id=info:pmid/34855873&rft_galeid=A684621162&rft_doaj_id=oai_doaj_org_article_4677bfc6c5724f919b034d4faf8c67aa&rfr_iscdi=true |