{"id":138126,"date":"2023-11-11T12:51:31","date_gmt":"2023-11-11T17:51:31","guid":{"rendered":"https:\/\/cardiologynownews.org\/?p=138126"},"modified":"2023-11-13T12:32:57","modified_gmt":"2023-11-13T17:32:57","slug":"dapa-mi-dapagliflozin-improves-clinical-and-cardiometabolic-outcomes-in-post-ami-patients-with-impaired-lv-function-versus-placebo","status":"publish","type":"post","link":"https:\/\/cardiologynownews.org\/?p=138126","title":{"rendered":"DAPA-MI: Dapagliflozin improves clinical and cardiometabolic outcomes in post-AMI patients with impaired LV function versus placebo\u00a0"},"content":{"rendered":"<p><span data-contrast=\"auto\">Key Points<\/span><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/p>\n<ul>\n<li data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"2\" data-list-defn-props=\"{&quot;335552541&quot;:1,&quot;335559684&quot;:-2,&quot;335559685&quot;:360,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;\uf0b7&quot;,&quot;469777815&quot;:&quot;hybridMultilevel&quot;}\" aria-setsize=\"-1\" data-aria-posinset=\"1\" data-aria-level=\"1\"><span data-contrast=\"auto\">This trial of patients with acute myocardial infarction (AMI) and impaired left ventricular (LV) systolic function found that dapagliflozin significantly improved clinical and cardiometabolic outcomes compared with placebo.<\/span><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/li>\n<li data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"2\" data-list-defn-props=\"{&quot;335552541&quot;:1,&quot;335559684&quot;:-2,&quot;335559685&quot;:360,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;\uf0b7&quot;,&quot;469777815&quot;:&quot;hybridMultilevel&quot;}\" aria-setsize=\"-1\" data-aria-posinset=\"2\" data-aria-level=\"1\"><span data-contrast=\"auto\">There was no significant difference in clinical events rates, which were low in both groups.<\/span><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/li>\n<li data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"2\" data-list-defn-props=\"{&quot;335552541&quot;:1,&quot;335559684&quot;:-2,&quot;335559685&quot;:360,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;\uf0b7&quot;,&quot;469777815&quot;:&quot;hybridMultilevel&quot;}\" aria-setsize=\"-1\" data-aria-posinset=\"3\" data-aria-level=\"1\"><span data-contrast=\"auto\">The innovative registry-based clinical trial design helped facilitate efficient patient recruitment and outcomes ascertainment.\u00a0<\/span><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/li>\n<\/ul>\n<p><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><!--more--><\/p>\n<p><span data-contrast=\"auto\">Patients with AMI are at higher risk for subsequent adverse cardiometabolic events.\u00a0\u00a0 SGLT2 inhibitors (SGLT2i) have demonstrated benefit in prior randomized control trials in reducing major adverse cardiovascular and renal events in patients with diabetes or heart failure, irrespective of left ventricular ejection fraction (LVEF).\u00a0\u00a0\u00a0 Whether the SGLT2i dapagliflozin might prevent the development of subsequent clinical heart failure or other adverse cardiometabolic events in patients with recent AMI and newly impaired LVEF is unknown.<\/span><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/p>\n<p><span data-contrast=\"auto\">On November 11, 2023 the results of Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure <a href=\"https:\/\/evidence.nejm.org\/doi\/full\/10.1056\/EVIDoa2300286\">(DAPA-MI)<\/a> were presented at AHA Scientific Sessions 2023 with simultaneous publication in the <\/span><i><span data-contrast=\"auto\">NEJM Evidence<\/span><\/i><span data-contrast=\"auto\">.\u00a0\u00a0 This industry-sponsored, multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial (R-RCT), compared dapagliflozin 10mg with placebo among patients who with recent AMI (within 10 days) and impaired LV systolic function (but without cardiogenic shock) on the primary hierarchical composite of death, heart failure hospitalization, non-fatal MI, atrial fibrillation or flutter, new onset diabetes, NYHA functional class, and weight loss.\u00a0 Patients with known diabetes, heart failure, or eGFR &lt;20 mL\/min\/1.73m<\/span><span data-contrast=\"auto\">2<\/span><span data-contrast=\"auto\"> were excluded. The innovative pragmatic R-RCT design integrated existing national clinical registries in Sweden and the UK with the trial database to facilitate recruitment, randomization, blinding, and data collection (both baseline demographics as well as outcome ascertainment).<\/span><span data-contrast=\"auto\">1<\/span><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/p>\n<p><span data-contrast=\"auto\">It should be noted that the initial endpoint chosen for the study was a composite of cardiovascular death or heart failure, however during the trial the number of outcome was substantially lower than anticipated and so in February 2023 it was modified to a hierarchal (win ratio) composite outcome approach including the cardiometabolic metrics listed above.\u00a0\u00a0<\/span><\/p>\n<p><span data-contrast=\"auto\">The trial enrolled 4017 patients, of whom 2019 were assigned to dapagliflozin and 1998 to placebo. The two groups were well balanced in key demographic and baseline characteristics. \u00a0The median time from hospital admission to random assignment was 3\u2009days. The mean age was\u00a0 62,9 years in both groups, with approximately 20% of the patients being female and the majority (~70%) from Sweden with the rest from UK.\u00a0 About 9% had a prior MI.\u00a0 The majority of the patients (72%) presented with ST elevation MI and LV ejection fraction was below 50% in the majority of participants (73.2%).\u00a0 More than 90%\u00a0 received aspirin, P2Y12 inhibitors, ACE inhibitors, beta blockers, and statins, indicating appropriate background guideline directed medical therapy, though only 23% were treated with aldosterone receptor antagonists.\u00a0 <\/span><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/p>\n<p><span data-contrast=\"none\">The analysis of the primary hierarchical composite outcome resulted in significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval [CI], 1.20 to 1.50; P&lt;0.001). The win ratio outcome was mainly driven by the added cardiometabolic outcomes. <\/span><span data-contrast=\"auto\">When the weight loss outcome was removed from the primary endpoint, the benefits of dapagliflozin were attenuated but still statistically significant (win ratio 1.20 (95% CI 1.01,1.40; p = 0.015).\u00a0 <\/span><span data-contrast=\"none\">The composite of time to cardiovascular death\/hospitalization for heart failure occurred in 50\/2019 (2.5%) patients assigned to dapagliflozin and 52\/1998 (2.6%) patients assigned to placebo (hazard ratio, 0.95; 95% CI, 0.64 to 1.40). The rates of other cardiovascular events were low, with differences between the groups not reaching nominal statistical significance. No safety concerns were identified. <\/span><span data-contrast=\"auto\">Patients on dapagliflozin had greater weight loss and lower rates of incident diabetes. There was no difference in the secondary outcomes of time to first occurrence of cardiovascular death or hospitalization for heart failure or major adverse cardiovascular events (MI, stroke, or CV death).\u00a0 The benefits were consistent across subgroups and no new safety concerns were identified.<\/span><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/p>\n<p><span data-contrast=\"auto\">Professor Stefan James of Uppsala University, Sweden, concluded: \u201cIn patients with AMI and impaired LV systolic function, without prior diabetes or chronic heart failure, dapagliflozin demonstrated significant benefit with regards to improvement in cardiometabolic outcomes compared with placebo\u2026Clinical event rates were low with no significant difference between randomized groups.\u201d<\/span><\/p>\n<p><b><span data-contrast=\"auto\">References<\/span><\/b><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/p>\n<ol>\n<li><span data-contrast=\"auto\"> James S, Erlinge D, Storey RF, et al. Rationale and design of the DAPA-MI trial: Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction. <\/span><i><span data-contrast=\"auto\">Am Heart J<\/span><\/i><span data-contrast=\"auto\">. 2023. Published onlineAugust 25, 2023. https:\/\/doi.org\/10.1016\/j.ahj.2023.08.008.<\/span><\/li>\n<\/ol>\n<p><span data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:480}\">\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Key Points\u00a0 This trial of patients with acute myocardial infarction (AMI) and impaired left ventricular (LV) systolic function found that dapagliflozin significantly improved clinical and cardiometabolic outcomes compared with placebo.\u00a0 There was no significant difference in clinical events rates, which were low in both groups.\u00a0 The innovative registry-based clinical trial design helped facilitate efficient patient [&hellip;]<\/p>\n","protected":false},"author":40603,"featured_media":138127,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[883,8],"tags":[885,45,47,185],"ppma_author":[1029],"class_list":{"0":"post-138126","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-aha-2023","8":"category-news","9":"tag-aha-2023","10":"tag-conference","11":"tag-featured","12":"tag-news","13":"author-leah-kosyakovsky"},"authors":[{"term_id":1029,"user_id":40603,"is_guest":0,"slug":"leah-kosyakovsky","display_name":"Leah Kosyakovsky","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/864bde69f6f1f80e91e4a97f0a0ba8daa64c2bb702be09ed787444c7dfa045bb?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138126","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40603"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=138126"}],"version-history":[{"count":3,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138126\/revisions"}],"predecessor-version":[{"id":138154,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138126\/revisions\/138154"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/138127"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=138126"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=138126"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=138126"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=138126"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}