Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden
BACKGROUND AND PURPOSE—Cerebral microbleeds (CMBs) are a risk factor for intracranial hemorrhage. Whether intravenous thrombolysis (IVT) improves functional outcome in acute ischemic stroke patients with CMBs is unknown. We aimed to estimate the treatment effect of IVT in patients with acute ischemi...
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Veröffentlicht in: | Stroke (1970) 2020-01, Vol.51 (1), p.232-239 |
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description | BACKGROUND AND PURPOSE—Cerebral microbleeds (CMBs) are a risk factor for intracranial hemorrhage. Whether intravenous thrombolysis (IVT) improves functional outcome in acute ischemic stroke patients with CMBs is unknown. We aimed to estimate the treatment effect of IVT in patients with acute ischemic stroke and a high burden (>10) of CMBs.
METHODS—We devised a multistep algorithm to model 90-day modified Rankin Scale scores in patients with ≤10 versus >10 CMBs who do or do not receive IVT. Parameters were extracted from recently published meta-analyses and included pairwise relationships between CMBs, IVT, 3-month functional outcome, and intracranial hemorrhage. Uncertainty was quantified in probabilistic sensitivity analyses.
RESULTS—In patients with >10 CMBs as compared with ≤10 CMBs, point estimates of the odds ratios for favorable outcome (modified Rankin Scale ≤2) associated with IVT were 7% to 10% lower but still >1 (range, 1.03–1.51). On the other hand, IVT in patients with >10 CMBs significantly increased the odds of mortality. The point estimates for the net treatment effect of IVT (change in the utility-weighted modified Rankin Scale score) in patients with >10 CMBs were in favor of withholding IVT in older patients with more severe strokes and longer treatment delays. However, because the general pretest probability of >10 CMBs is low (0.6%–2.7%), pretreatment magnetic resonance imaging to quantify CMB burden would be justified only if it delayed IVT by 10 CMBs, IVT is associated with higher mortality and, in older patients with severe strokes and longer treatment delays, a net utility loss. Patients with higher-than-average pretest probability of >10 CMB might profit from magnetic resonance imaging screening if it does not increase the treatment time. |
doi_str_mv | 10.1161/STROKEAHA.119.027633 |
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METHODS—We devised a multistep algorithm to model 90-day modified Rankin Scale scores in patients with ≤10 versus >10 CMBs who do or do not receive IVT. Parameters were extracted from recently published meta-analyses and included pairwise relationships between CMBs, IVT, 3-month functional outcome, and intracranial hemorrhage. Uncertainty was quantified in probabilistic sensitivity analyses.
RESULTS—In patients with >10 CMBs as compared with ≤10 CMBs, point estimates of the odds ratios for favorable outcome (modified Rankin Scale ≤2) associated with IVT were 7% to 10% lower but still >1 (range, 1.03–1.51). On the other hand, IVT in patients with >10 CMBs significantly increased the odds of mortality. The point estimates for the net treatment effect of IVT (change in the utility-weighted modified Rankin Scale score) in patients with >10 CMBs were in favor of withholding IVT in older patients with more severe strokes and longer treatment delays. However, because the general pretest probability of >10 CMBs is low (0.6%–2.7%), pretreatment magnetic resonance imaging to quantify CMB burden would be justified only if it delayed IVT by <10 minutes.
CONCLUSIONS—High CMB burden modifies the treatment effect of IVT. In patients with >10 CMBs, IVT is associated with higher mortality and, in older patients with severe strokes and longer treatment delays, a net utility loss. Patients with higher-than-average pretest probability of >10 CMB might profit from magnetic resonance imaging screening if it does not increase the treatment time.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/STROKEAHA.119.027633</identifier><identifier>PMID: 31739772</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Acute Disease ; Administration, Intravenous ; Brain Ischemia - diagnostic imaging ; Brain Ischemia - drug therapy ; Cerebral Hemorrhage - diagnostic imaging ; Cerebral Hemorrhage - drug therapy ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Models, Cardiovascular ; Stroke - diagnostic imaging ; Stroke - drug therapy ; Thrombolytic Therapy</subject><ispartof>Stroke (1970), 2020-01, Vol.51 (1), p.232-239</ispartof><rights>American Heart Association, Inc.</rights><rights>2020 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4473-f7aeae899d28b7b2a8ce511995298c346bc723db1bb5f1ad77a57b5f026c40463</citedby><cites>FETCH-LOGICAL-c4473-f7aeae899d28b7b2a8ce511995298c346bc723db1bb5f1ad77a57b5f026c40463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3674,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31739772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schlemm, Ludwig</creatorcontrib><creatorcontrib>Endres, Matthias</creatorcontrib><creatorcontrib>Werring, David J.</creatorcontrib><creatorcontrib>Nolte, Christian H.</creatorcontrib><title>Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>BACKGROUND AND PURPOSE—Cerebral microbleeds (CMBs) are a risk factor for intracranial hemorrhage. Whether intravenous thrombolysis (IVT) improves functional outcome in acute ischemic stroke patients with CMBs is unknown. We aimed to estimate the treatment effect of IVT in patients with acute ischemic stroke and a high burden (>10) of CMBs.
METHODS—We devised a multistep algorithm to model 90-day modified Rankin Scale scores in patients with ≤10 versus >10 CMBs who do or do not receive IVT. Parameters were extracted from recently published meta-analyses and included pairwise relationships between CMBs, IVT, 3-month functional outcome, and intracranial hemorrhage. Uncertainty was quantified in probabilistic sensitivity analyses.
RESULTS—In patients with >10 CMBs as compared with ≤10 CMBs, point estimates of the odds ratios for favorable outcome (modified Rankin Scale ≤2) associated with IVT were 7% to 10% lower but still >1 (range, 1.03–1.51). On the other hand, IVT in patients with >10 CMBs significantly increased the odds of mortality. The point estimates for the net treatment effect of IVT (change in the utility-weighted modified Rankin Scale score) in patients with >10 CMBs were in favor of withholding IVT in older patients with more severe strokes and longer treatment delays. However, because the general pretest probability of >10 CMBs is low (0.6%–2.7%), pretreatment magnetic resonance imaging to quantify CMB burden would be justified only if it delayed IVT by <10 minutes.
CONCLUSIONS—High CMB burden modifies the treatment effect of IVT. In patients with >10 CMBs, IVT is associated with higher mortality and, in older patients with severe strokes and longer treatment delays, a net utility loss. Patients with higher-than-average pretest probability of >10 CMB might profit from magnetic resonance imaging screening if it does not increase the treatment time.</description><subject>Acute Disease</subject><subject>Administration, Intravenous</subject><subject>Brain Ischemia - diagnostic imaging</subject><subject>Brain Ischemia - drug therapy</subject><subject>Cerebral Hemorrhage - diagnostic imaging</subject><subject>Cerebral Hemorrhage - drug therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Models, Cardiovascular</subject><subject>Stroke - diagnostic imaging</subject><subject>Stroke - drug therapy</subject><subject>Thrombolytic Therapy</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1P3DAQtSpQWaD_oKp85BLqr8TxcVnR7qogKtiqx8h2Jo3BSajtFPHvMVrgSA-jmSe9Nx9vEPpMySmlFf16s72--nG-XC8zVKeEyYrzD2hBSyYKUbF6Dy0I4apgQqkDdBjjLSGE8br8iA44lVxJyRbo9gxG6FzCU4c3Ywr6H4zTHPG2D9NgJv8YXcRuxEs7J8CbaHsYnMU3KUx3gH_q5GBMEf92qcdr96fHKwhggvb40tkwGQ_Q4rM5tDAeo_1O-wifXvIR-vXtfLtaFxdX3zer5UVhhZC86KQGDbVSLauNNEzXFsp8oiqZqi0XlbGS8dZQY8qO6lZKXcpcElZZQUTFj9DJru99mP7OEFMzuGjBez1CPq1hnJZK0pI8U8WOmleNMUDX3Ac36PDYUNI8u9y8uZyhanYuZ9mXlwmzGaB9E73amgn1jvAw-QQh3vn5AULTg_ap_19v8Y40v5DISpKCEUYIzajIwSv-BDBnm0E</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Schlemm, Ludwig</creator><creator>Endres, Matthias</creator><creator>Werring, David J.</creator><creator>Nolte, Christian H.</creator><general>American Heart Association, Inc</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>7X8</scope></search><sort><creationdate>20200101</creationdate><title>Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden</title><author>Schlemm, Ludwig ; Endres, Matthias ; Werring, David J. ; Nolte, Christian H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4473-f7aeae899d28b7b2a8ce511995298c346bc723db1bb5f1ad77a57b5f026c40463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute Disease</topic><topic>Administration, Intravenous</topic><topic>Brain Ischemia - diagnostic imaging</topic><topic>Brain Ischemia - drug therapy</topic><topic>Cerebral Hemorrhage - diagnostic imaging</topic><topic>Cerebral Hemorrhage - drug therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Models, Cardiovascular</topic><topic>Stroke - diagnostic imaging</topic><topic>Stroke - drug therapy</topic><topic>Thrombolytic Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schlemm, Ludwig</creatorcontrib><creatorcontrib>Endres, Matthias</creatorcontrib><creatorcontrib>Werring, David J.</creatorcontrib><creatorcontrib>Nolte, Christian H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schlemm, Ludwig</au><au>Endres, Matthias</au><au>Werring, David J.</au><au>Nolte, Christian H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>51</volume><issue>1</issue><spage>232</spage><epage>239</epage><pages>232-239</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><abstract>BACKGROUND AND PURPOSE—Cerebral microbleeds (CMBs) are a risk factor for intracranial hemorrhage. Whether intravenous thrombolysis (IVT) improves functional outcome in acute ischemic stroke patients with CMBs is unknown. We aimed to estimate the treatment effect of IVT in patients with acute ischemic stroke and a high burden (>10) of CMBs.
METHODS—We devised a multistep algorithm to model 90-day modified Rankin Scale scores in patients with ≤10 versus >10 CMBs who do or do not receive IVT. Parameters were extracted from recently published meta-analyses and included pairwise relationships between CMBs, IVT, 3-month functional outcome, and intracranial hemorrhage. Uncertainty was quantified in probabilistic sensitivity analyses.
RESULTS—In patients with >10 CMBs as compared with ≤10 CMBs, point estimates of the odds ratios for favorable outcome (modified Rankin Scale ≤2) associated with IVT were 7% to 10% lower but still >1 (range, 1.03–1.51). On the other hand, IVT in patients with >10 CMBs significantly increased the odds of mortality. The point estimates for the net treatment effect of IVT (change in the utility-weighted modified Rankin Scale score) in patients with >10 CMBs were in favor of withholding IVT in older patients with more severe strokes and longer treatment delays. However, because the general pretest probability of >10 CMBs is low (0.6%–2.7%), pretreatment magnetic resonance imaging to quantify CMB burden would be justified only if it delayed IVT by <10 minutes.
CONCLUSIONS—High CMB burden modifies the treatment effect of IVT. In patients with >10 CMBs, IVT is associated with higher mortality and, in older patients with severe strokes and longer treatment delays, a net utility loss. Patients with higher-than-average pretest probability of >10 CMB might profit from magnetic resonance imaging screening if it does not increase the treatment time.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>31739772</pmid><doi>10.1161/STROKEAHA.119.027633</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Acute Disease Administration, Intravenous Brain Ischemia - diagnostic imaging Brain Ischemia - drug therapy Cerebral Hemorrhage - diagnostic imaging Cerebral Hemorrhage - drug therapy Female Humans Magnetic Resonance Imaging Male Models, Cardiovascular Stroke - diagnostic imaging Stroke - drug therapy Thrombolytic Therapy |
title | Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden |
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