{"id":47746,"date":"2015-04-02T17:11:57","date_gmt":"2015-04-02T21:11:57","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=voices&#038;p=47746"},"modified":"2015-05-15T18:11:15","modified_gmt":"2015-05-15T22:11:15","slug":"liberal-changes-to-rt-pa-contraindications-for-acute-ischemic-stroke","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2015\/04\/02\/liberal-changes-to-rt-pa-contraindications-for-acute-ischemic-stroke\/","title":{"rendered":"Liberal Changes to rt-PA Contraindications for Acute Ischemic Stroke"},"content":{"rendered":"<p><em>This post was originally published on <a href=\"http:\/\/blogs.nejm.org\/cardioexchange\/members\/ccocchio\/\">Craig Cocchio<\/a>&#8216;s blog, <a href=\"http:\/\/empharmd.blogspot.com\/2015\/03\/liberal-changes-to-rt-pa.html\">Emergency Medicine PharmD<\/a>.<\/em><\/p>\n<p>Flying in under the radar recently were the changes to the Alteplase (rt-PA) prescribing information. These changes pertain to the contraindications to use of the drug in acute ischemic stroke. It&#8217;s hard to find anything\u2014and puzzlingly so\u2014on the particulars about why the FDA authorized such changes.<\/p>\n<p>The updated contraindications now read as follows:\u00a0<a href=\"http:\/\/www.gene.com\/download\/pdf\/activase_prescribing.pdf\">Link<\/a><br \/>\nDo not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit:<\/p>\n<ul>\n<li>Current intracranial hemorrhage<\/li>\n<li>Subarachnoid hemorrhage<\/li>\n<li>Active internal bleeding<\/li>\n<li>Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma<\/li>\n<li>Presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms)<\/li>\n<li>Bleeding diathesis<\/li>\n<li>Current severe uncontrolled hypertension<\/li>\n<\/ul>\n<p>Without the old contraindications to compare to side by side, the changes may not be obvious. From a 2013 package insert, the contraindications read as follows (changes\u00a0<i>italicized<\/i>):<\/p>\n<p>Activase therapy in patients with acute ischemic stroke is contraindicated in the following situations because of an increased risk of bleeding,\u00a0<i>which could result in significant disability or death<\/i>:<\/p>\n<ul>\n<li>Evidence of intracranial hemorrhage on pretreatment evaluation<\/li>\n<li>Suspicion of subarachnoid hemorrhage on pretreatment evaluation<\/li>\n<li>Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke<\/li>\n<li><i>History of intracranial hemorrhage<\/i><\/li>\n<li><i>Uncontrolled hypertension at time of treatment (e.g., &gt; 185 mm Hg systolic or &gt; 110 mm Hg diastolic)<\/i><\/li>\n<li><i>Seizure at the onset of stroke<\/i><\/li>\n<li>Active internal bleeding<\/li>\n<li>Intracranial neoplasm, arteriovenous malformation, or aneurysm<\/li>\n<li><i>Known bleeding diathesis including but not limited to:<\/i>\n<ul>\n<li><i>Current use of oral anticoagulants (e.g., warfarin sodium) or an International Normalized Ratio (INR) &gt; 1.7 or a prothrombin time (PT) &gt; 15 seconds<\/i><\/li>\n<li><i>Administration of heparin within 48 hours preceding the onset of stroke and have an elevated activated partial thromboplastin time (aPTT) at presentation.<\/i><\/li>\n<li><i>Platelet count &lt; 100,000\/mm3<\/i><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>The changes can be significant, particularly the language introducing the contraindications. The consequences which were previously &#8220;significant disability or death&#8221; are now simply &#8220;situations in which the risk of bleeding is greater than the potential benefit.&#8221; If you didn&#8217;t catch the specific changes, rt-PA is no longer contraindicated in patients with:<\/p>\n<ul>\n<li>History of intracranial hemorrhage<\/li>\n<li>Seizure at the onset of stroke<\/li>\n<\/ul>\n<p>Furthermore, the language describing specific bleeding diatheses (drugs: warfarin, diabigatran, rivaroxaban, etc.; thrombocytopenia or prolonged bleeding times) and describing what constitutes &#8220;uncontrolled hypertension&#8221; are now very vague.<\/p>\n<p>At this point the guidelines have not updated their list of contraindications&#8230; for now.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Dr. Craig Cocchio discussing changes to the contraindications for acute ischemic stroke, about which the FDA has been curiously silent.<\/p>\n","protected":false},"author":1021,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[1497,514,196,595,1334,1407],"class_list":["post-47746","post","type-post","status-publish","format-standard","hentry","category-general","tag-acute-ischemic-stroke","tag-drug-labels","tag-fda","tag-guidelines","tag-ischemic-stroke","tag-pharmaceutical-industry"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/47746","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/1021"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=47746"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/47746\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=47746"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=47746"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=47746"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}