{"id":1049,"date":"2016-05-13T14:57:00","date_gmt":"2016-05-13T14:57:00","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1049"},"modified":"2017-08-21T10:54:35","modified_gmt":"2017-08-21T10:54:35","slug":"primary-care-corner-with-geoffrey-modest-md-warfarin-in-nonvalvular-atrial-fibrillation","status":"publish","type":"post","link":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/13\/primary-care-corner-with-geoffrey-modest-md-warfarin-in-nonvalvular-atrial-fibrillation\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Warfarin in Nonvalvular Atrial Fibrillation"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>Over the years,\u00a0I have sent out several blogs about the drug company shenanigans\/malfeasance in studies promoting\u00a0NOACs (non-vitamin K antagonist oral anticoagulants) &#8212; See link at bottom. Here is a large study suggesting the benefits of warfarin\u00a0(See doi:10.1001\/jamacardio.2016.0199\u00a0). The authors note that studies finding NOAC superiority\u00a0were in comparison to warfarin where the\u00a0times-in-therapeutic range (TTR) varied from 55.2% to 64.9%. In the current study researchers\u00a0looked at the relative effectiveness\u00a0of warfarin for patients with atrial fibrillation (AF)\u00a0as it varied with TTR. Data are\u00a0from a large Swedish registry.<\/p>\n<p>Details:<\/p>\n<ul>\n<li>Retrospective, multicenter cohort study of 40,449 patients<\/li>\n<li>40% women, mean age 73, mean CHA<sub>2<\/sub>DS<sub>2<\/sub>-VASc (see below)\u00a0score 3.3, TTR&lt;70% in 43%, hypertension\u00a060%, heart failure 30%, renal failure 4%, excessive alcohol use 2%, history of falls 8%, prior major bleed 6%, MI 21%, diabetes 18%, stroke 19%, TIA 8%<\/li>\n<li>4311\u00a0patients also on aspirin with the\u00a0warfarin, with the\u00a0concomitant\u00a0diseases\/risk factors about the same as the overall cohort except that 43% had a prior MI (vs 17% just on warfarin)<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>Annual all-cause mortality 2.19% (2.07-2.31), intracranial bleed 0.44% (0.39-0.49)<\/li>\n<li>Comparing those with TTR &lt;70% vs &gt;70% (all are annual rates)\n<ul>\n<li>All-cause mortality was 4.35% vs 1.29%<\/li>\n<li>Any major bleed was 3.81 vs 1.61%, with intracranial bleed 0.72 vs 0.34%;\u00a0GI bleed 1.26 vs 0.56%<\/li>\n<li>Any thromboembolism was 4.41 vs 2.37%,\u00a0MI 1.90 vs 0.98%, venous thromboembolism (VTE) 0.24 vs 0.09%, and arterial embolism 2.52 vs 1.41% [thromboembolism defined as: stroke, TIA, peripheral\u00a0arterial emboli, venous\u00a0thromboembolism, MI]<\/li>\n<\/ul>\n<\/li>\n<li>The role of INR variability (dividing those around the median of\u00a0higher vs lower variability in their cohort): comparing high vs low\n<ul>\n<li>All-cause mortality was 2.94% vs 1.50%<\/li>\n<li>Any major bleed was 3.04 vs 1.47%, with intracranial bleed 0.51\u00a0vs 0.38%;\u00a0GI bleed 1.05\u00a0vs 0.50%<\/li>\n<li>Any thromboembolism was 3.48 vs 2.46%, with MI 1.53\u00a0vs 0.96%, VTE 0.16 vs 0.11%, and arterial embolism 1.98 vs 1.51%<\/li>\n<\/ul>\n<\/li>\n<li><strong>For those with\u00a0TTR &gt;70%, INR variability did not matter<\/strong><\/li>\n<li>For those on aspirin\n<ul>\n<li>All-cause mortality was\u00a02.57% vs 2.13%<\/li>\n<li>Any major bleed was\u00a03.07\u00a0vs 2.04%, with intracranial bleed 0.62\u00a0vs 0.41%;\u00a0GI bleed 1.16\u00a0vs 0.67%<\/li>\n<li>Any thromboembolism was\u00a04.90\u00a0vs 2.12%, with MI 1.53\u00a0vs 0.96%,\u00a0VTE 0.19\u00a0vs 0.12%, and arterial embolism\u00a02.72\u00a0vs 1.54%<\/li>\n<\/ul>\n<\/li>\n<li>For those with renal failure, intracranial bleed more than twice as\u00a0common, with HR 2.25 (1.32-3.82)<\/li>\n<li>The strongest predictor of intracranial bleeding was renal failure<\/li>\n<\/ul>\n<p>So, a few issues:<\/p>\n<ul>\n<li>These\u00a0data, though not from a\u00a0prospective, randomized study, do\u00a0reflect more of a real-world community setting.<\/li>\n<li><strong>The results for patients in good control (TTR&gt;70%) is actually\u00a0better\u00a0than in the &#8220;pivotal NOAC studies&#8221;<\/strong>.<\/li>\n<li>In terms of\u00a0the issue of using the combo of warfarin and aspirin:\n<ul>\n<li>I am very concerned about the increased serious adverse events with this combination (see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2014\/11\/20\/primary-care-corner-with-geoffrey-modest-md-aspirin-plus-warfarin-for-afib-and-cad\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2014\/11\/20\/primary-care-corner-with-geoffrey-modest-md-aspirin-plus-warfarin-for-afib-and-cad\/<\/a> , which\u00a0looks at several observational studies on aspirin plus warfarin for patients with AF and CAD, all showing much higher risks (e.g.,\u00a0bleeding) without any clear benefit. The PREFER trial (see De Caterina, R. Heart 2014;\u00a0100: 1625) looked at a large European registry of patients with AF\u00a0and found that 95% of those on dual antiplatelet and anticoagulation therapy did NOT have an\u00a0&#8220;accepted indication&#8221; (i.e.: acute coronary syndrome or stenting &#8211;and, this is the current recommendation of the European Society of Cardiology\u00a0guidelines in AF: anticoagulant therapy only except in these indications).<\/li>\n<li>In the above Swedish study, only 2.6% of those on additional aspirin had a clear indication for this therapy. And this study really supported NOT using aspirin, given the\u00a0higher mortality, higher MI\/VTE\/arterial embolism, and much higher bleeding risk (though, as noted, this was not an RCT, had many more patients with prior MI, so\u00a0it is\u00a0not so surprising that there was an increase in these thrombotic events. But twice the level of major bleeds??? \u00a0And 50% more thrombotic events??? Is aspirin really useful?? I personally have stopped aspirin in my patients on warfarin, based on the prior blog)<\/li>\n<\/ul>\n<\/li>\n<li>So, my bottom line: this Swedish\u00a0study confirms the utility of warfarin in patients with nonvalvular AF, though clearly differentiates its advantages in\u00a0those in good control (INR in range &gt;70% of the time) vs not. I do have trouble with the NOACs overall, given the noted drug company issues\u00a0in my prior blogs and the lingering concern that if they are in an accident, reversal agents are not widely\u00a0available. But I have occasionally used NOACs\u00a0in patients who are leaving the country and cannot get their INR checked, or it is just too difficult to get the INR in range\u00a0despite best efforts all around, often\u00a0including home-based nursing care\/checking the INR at home. That being said, the clear majority of my patients on warfarin are definitely in the &gt;70% TTR category and seem to be doing just fine&#8230;. (though I do need to monitor them frequently, but, then again, most of them have significant cardiac and other morbidities, and my guess is that the increased monitoring\/health system contact is actually a positive thing)<\/li>\n<\/ul>\n<p><strong>CHA2DS2-VASc<\/strong> (cardiac failure or dysfunction, hypertension, age 75 years [doubled], diabetes mellitus, stroke [doubled]\u2013vascular disease, age 65-74 years, and sex category [female])<\/p>\n<p>For older blogs, see:\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/01\/19\/primary-care-corner-with-geoffrey-modest-md-antithrombotic-therapy-guidelines\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/01\/19\/primary-care-corner-with-geoffrey-modest-md-antithrombotic-therapy-guidelines\/<\/a> goes through the antithrombotic therapy guidelines but also reviews the history of drug company malfeasance with the NOACs, which really make me uneasy about using them&#8230;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Warfarin in Nonvalvular Atrial Fibrillation  [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/13\/primary-care-corner-with-geoffrey-modest-md-warfarin-in-nonvalvular-atrial-fibrillation\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1049","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1049","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1049"}],"version-history":[{"count":0,"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1049\/revisions"}],"wp:attachment":[{"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1049"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1049"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1049"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}