{"id":771,"date":"2015-07-28T16:00:39","date_gmt":"2015-07-28T16:00:39","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=771"},"modified":"2017-08-21T11:36:40","modified_gmt":"2017-08-21T11:36:40","slug":"primary-care-corner-with-geoffrey-modest-md-extended-anticoag-for-pe","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/07\/28\/primary-care-corner-with-geoffrey-modest-md-extended-anticoag-for-pe\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Extended anticoag for PE"},"content":{"rendered":"

By: Dr. Geoffrey Modest<\/strong><\/p>\n

JAMA published the PADIS-PE trial of\u00a0patients having\u00a0a first unprovoked pulmonary embolism (PE), randomized to stopping anticoagulation\u00a0after 6 months\u00a0vs continuing an additional 18 months (see JAMA. 2015;314(1):31-40<\/strong>\u200b). <\/span><\/p>\n

Details:<\/span><\/p>\n

\u00a0<\/span>–371 patients (mean age 58, 40% >65yo, 50% women, mean BMI 27, 45% with high bleeding risk per the Am College of Chest Physicians rating) with a first episode of unprovoked, symptomatic PE, initially put on 6 months of a vitamin-K antagonist, who were then randomized from 2007-2014 in 14 French centers to continued warfarin vs placebo for 18 months. Target INR = 2.0-3.0. Patients with known major\u00a0thrombophilia were excluded. Blood was sent for thrombophilia workup on day 0.<\/span><\/p>\n

–minor thrombophilia (heterozygous factor V Leiden or heterozygous G20210A prothrombin mutation, or\u00a0factor VIII >90th %) was\u00a0found in 24% and major thrombophilia (antithrombin deficiency, anticardiolipin antibodies >99th %, or homozygous factor V Leiden or combined thrombophilia)\u00a0in 4%.<\/span><\/p>\n

–primary outcome: composite of recurrent venous thromboembolism (VTE) or major bleeding at 18 months; secondary outcome: this composite at 42 months, each component of the composite, and death unrelated to PE or bleeding at 18 and at 42\u00a0months (24 months after the end of the study).<\/span><\/p>\n

Results:<\/span><\/p>\n

–Mean % of time in the target INR range was 69.1%.<\/span><\/p>\n

–During the treatment period<\/span><\/span><\/p>\n

–primary outcome in 6\/184 patients in the warfarin group (3.3%, or 2.3 events per 100 person-years) vs 25\/187 in placebo (13.5%, or 10.6 events per 100 person-years), with HR 0.22 (0.09-0.55, p=0.001).\u00a0\u00a0<\/span><\/p>\n

–in the warfarin group, 3 patients (1.7%) had a symptomatic recurrent VTE, all after discontinuation of warfarin. in the placebo group, 25 patients (13.5%)\u00a0had symptomatic recurrence, only one of which was after stopping the placebo (p<0.001).<\/span><\/p>\n

—\u00a0major bleeding occurred in 4 patients in warfarin group and 1 in the placebo group (statistically\u00a0nonsignificant)<\/span><\/p>\n

–After treatment discontinuation<\/span><\/p>\n

–composite outcome in 27 warfarin-treated (17.7%; 10.0 events per 100 person-years) and 17 placebo-treated (10.3%, 5.7 events per 100 person-years)<\/span><\/p>\n

–in the warfarin group, 25 patients had symptomatic VTE (9.3 events per 100 person-years, all in the absence of anticoagulation, 4 of which were fatal). in the placebo group, symptomatic recurrence was in 14 patients (4.7 events per 100 person-years, all in the absence of anticoagulation)<\/span><\/p>\n

–major bleeding occurred in 2 patients on warfarin group (1 while taking warfarin and 1 fatal event happened after stopping it), and 4 in the placebo group (all nonfatal; 2 while on warfarin)<\/span><\/p>\n

–Review of the graphs showed a dramatic\u00a0difference during the 18 months after randomization, and a gradual reduction in warfarin protection over the next 24 months of observation when all were off warfarin (see below for the primary endpoint)<\/span><\/p>\n

\"Untitled2\"<\/p>\n

\u200b–After 42 months, composite outcome in 33 patients on warfarin (20.8%)\u00a0and 42 on placebo (24.0%)\u00a0 [HR 0.75 (0.47-1.18)] — \u00a0the\u00a0benefit of extended warfarin Rx was not maintained<\/span><\/strong><\/span><\/p>\n

–No difference in rate of recurrent VTE, major bleeding, and unrelated deaths<\/span><\/p>\n

–The risk of recurrent VTE was greatest in the first 6 months after stopping anticoagulation, then increased linearly by 4-5% per year. \u00a0the risk of major bleeding with continued warfarin was low, increasing by <2% per year<\/span><\/p>\n

So, a few issues:\u00a0<\/span><\/p>\n

–this study confirms that when anticoagulation is discontinued,\u00a0the patient at is at risk for recurrent VTE, whether anticoagulation\u00a0is for\u00a03-6 month or longer. Also that the risk of major bleeding with anticoagulation is pretty low (confirmed by other studies)<\/span><\/p>\n

–in the decision analysis of how long to anticoagulate, it is important to remember that the natural history of a venous thrombosis is different from a PE: the likelihood of a recurrent PE is much higher in the latter group, and the case-fatality rate is 4-fold higher than after a proximal DVT. <\/span>I<\/span>n the above study, 80% of the recurrent VTE events in both groups were from \u00a0symptomatic PEs.<\/span><\/p>\n

–if you and patient decide to stop anticoagulants, there are some potentially useful approaches:\u00a0for other articles, including one on different and safer ways to stop anticoagulation by checking d-dimer levels, see here\u00a0<\/a>and especially here<\/a>)<\/span><\/p>\n

–if you decide to stop the anticoagulation, 2 studies have found some efficacy of low dose aspirin (about 30% decreased risk of aspirin vs placebo — better than placebo but not as good as continuing the anticoagulation).<\/span><\/p>\n

–an (<\/span>unfortunately) untested hypothesis might be: check for underlying thrombophilia; 6 months of anticoagulation; check d-dimer; in those who are d-dimer negative, offer aspirin and discontinue anticoagulation (after discussing risks\/benefits with patient); also look to see if the underlying thrombophilia actually matters (and, if so, then preferentially continue life-long anticoagulation). Short of that, this study adds to other observational studies finding a high risk of recurrent PEs in those with initial symptomatic unprovoked PE, so my inclination (and what I have been doing) is to offer life-long anticoagulation (especially to low risk-of-bleeding patients), with a fallback to checking the d-dimer and changing to aspirin if all is okay.<\/span><\/span><\/p>\n

\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

By: Dr. Geoffrey Modest JAMA published the PADIS-PE trial of\u00a0patients having\u00a0a first unprovoked pulmonary embolism (PE), randomized to stopping anticoagulation\u00a0after 6 months\u00a0vs continuing an additional 18 months (see JAMA. 2015;314(1):31-40\u200b). Details: \u00a0–371 patients (mean age 58, 40% >65yo, 50% women, mean BMI 27, 45% with high bleeding risk per the Am College of Chest Physicians […]<\/p>\n

Read More…<\/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-771","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/771","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=771"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/771\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=771"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=771"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=771"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}