Causes of Death in Anticoagulated Patients With Atrial Fibrillation
Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. Objectives The authors sought to analyze and compar...
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| Veröffentlicht in: | Journal of the American College of Cardiology 2016-12, Vol.68 (23), p.2508-2521 |
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| creator | Gómez-Outes, Antonio, MD, PhD Lagunar-Ruíz, Julián, MD Terleira-Fernández, Ana-Isabel, MD, PhD Calvo-Rojas, Gonzalo, MD, PhD Suárez-Gea, Maria Luisa, PharmD, PhD Vargas-Castrillón, Emilio, MD, PhD |
| description | Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. Objectives The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. Methods The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. Results 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings. Conclusions In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF. |
| doi_str_mv | 10.1016/j.jacc.2016.09.944 |
| format | Article |
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Objectives The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. Methods The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. Results 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings. Conclusions In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/j.jacc.2016.09.944</identifier><identifier>PMID: 27931607</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Administration, Oral ; Aged ; Anticoagulants ; Anticoagulants - therapeutic use ; apixaban ; atrial fibrillation ; Atrial Fibrillation - complications ; Atrial Fibrillation - drug therapy ; Atrial Fibrillation - mortality ; Cardiac arrhythmia ; Cardiology ; Cardiovascular ; Cause of Death - trends ; Clinical trials ; dabigatran ; Embolisms ; Female ; Follow-Up Studies ; Humans ; Internal Medicine ; Male ; Meta-analysis ; Mortality ; Patients ; Quality ; Registries ; Retrospective Studies ; rivaroxaban ; Software ; Stroke ; Stroke - etiology ; Stroke - mortality ; Stroke - prevention & control ; Studies ; Survival Rate - trends ; United States - epidemiology ; warfarin</subject><ispartof>Journal of the American College of Cardiology, 2016-12, Vol.68 (23), p.2508-2521</ispartof><rights>American College of Cardiology Foundation</rights><rights>2016 American College of Cardiology Foundation</rights><rights>Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Dec 13, 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-4c2b2ad87f1c88264b09bb494a1c8feb86b540e47773151d3895633afc07b2d63</citedby><cites>FETCH-LOGICAL-c516t-4c2b2ad87f1c88264b09bb494a1c8feb86b540e47773151d3895633afc07b2d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jacc.2016.09.944$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27931607$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gómez-Outes, Antonio, MD, PhD</creatorcontrib><creatorcontrib>Lagunar-Ruíz, Julián, MD</creatorcontrib><creatorcontrib>Terleira-Fernández, Ana-Isabel, MD, PhD</creatorcontrib><creatorcontrib>Calvo-Rojas, Gonzalo, MD, PhD</creatorcontrib><creatorcontrib>Suárez-Gea, Maria Luisa, PharmD, PhD</creatorcontrib><creatorcontrib>Vargas-Castrillón, Emilio, MD, PhD</creatorcontrib><title>Causes of Death in Anticoagulated Patients With Atrial Fibrillation</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. Objectives The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. Methods The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. Results 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings. Conclusions In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.</description><subject>Administration, Oral</subject><subject>Aged</subject><subject>Anticoagulants</subject><subject>Anticoagulants - therapeutic use</subject><subject>apixaban</subject><subject>atrial fibrillation</subject><subject>Atrial Fibrillation - complications</subject><subject>Atrial Fibrillation - drug therapy</subject><subject>Atrial Fibrillation - mortality</subject><subject>Cardiac arrhythmia</subject><subject>Cardiology</subject><subject>Cardiovascular</subject><subject>Cause of Death - trends</subject><subject>Clinical trials</subject><subject>dabigatran</subject><subject>Embolisms</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Meta-analysis</subject><subject>Mortality</subject><subject>Patients</subject><subject>Quality</subject><subject>Registries</subject><subject>Retrospective Studies</subject><subject>rivaroxaban</subject><subject>Software</subject><subject>Stroke</subject><subject>Stroke - etiology</subject><subject>Stroke - mortality</subject><subject>Stroke - prevention & control</subject><subject>Studies</subject><subject>Survival Rate - trends</subject><subject>United States - epidemiology</subject><subject>warfarin</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk2L1TAUhoMoznX0D7iQghs3rfn-ABEuV0eFAQUVlyFJTzW1tx2TVJh_b8odFWYhrpKQ5z2c874HoccEdwQT-XzsRhdCR-u9w6YznN9BOyKEbpkw6i7aYcVES7BRZ-hBziPGWGpi7qMzqgwjEqsdOhzcmiE3y9C8Ale-NXFu9nOJYXFf18kV6JsPrkSYS26-xPq_Lym6qbmIPsWpAnGZH6J7g5syPLo5z9Hni9efDm_by_dv3h32l20QRJaWB-qp67UaSNCaSu6x8Z4b7up7AK-lFxwDV0oxIkjPtBGSMTcErDztJTtHz051r9LyY4Vc7DHmALWLGZY1W6KFwMoQLv4D5UobLKmp6NNb6Lisaa6DbJRWRklCK0VPVEhLzgkGe5Xi0aVrS7Dd0rCj3dKwWxoWG1vTqKInN6VXf4T-j-S3_RV4cQKg2vYzQrI5VK8D9DFBKLZf4r_rv7wlD1OcY3DTd7iG_HcOm6nF9uO2D9s6EMkkN4axX-korUE</recordid><startdate>20161213</startdate><enddate>20161213</enddate><creator>Gómez-Outes, Antonio, MD, PhD</creator><creator>Lagunar-Ruíz, Julián, MD</creator><creator>Terleira-Fernández, Ana-Isabel, MD, PhD</creator><creator>Calvo-Rojas, Gonzalo, MD, PhD</creator><creator>Suárez-Gea, Maria Luisa, PharmD, PhD</creator><creator>Vargas-Castrillón, Emilio, MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20161213</creationdate><title>Causes of Death in Anticoagulated Patients With Atrial Fibrillation</title><author>Gómez-Outes, Antonio, MD, PhD ; Lagunar-Ruíz, Julián, MD ; Terleira-Fernández, Ana-Isabel, MD, PhD ; Calvo-Rojas, Gonzalo, MD, PhD ; Suárez-Gea, Maria Luisa, PharmD, PhD ; Vargas-Castrillón, Emilio, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c516t-4c2b2ad87f1c88264b09bb494a1c8feb86b540e47773151d3895633afc07b2d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Administration, Oral</topic><topic>Aged</topic><topic>Anticoagulants</topic><topic>Anticoagulants - therapeutic use</topic><topic>apixaban</topic><topic>atrial fibrillation</topic><topic>Atrial Fibrillation - complications</topic><topic>Atrial Fibrillation - drug therapy</topic><topic>Atrial Fibrillation - mortality</topic><topic>Cardiac arrhythmia</topic><topic>Cardiology</topic><topic>Cardiovascular</topic><topic>Cause of Death - trends</topic><topic>Clinical trials</topic><topic>dabigatran</topic><topic>Embolisms</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Meta-analysis</topic><topic>Mortality</topic><topic>Patients</topic><topic>Quality</topic><topic>Registries</topic><topic>Retrospective Studies</topic><topic>rivaroxaban</topic><topic>Software</topic><topic>Stroke</topic><topic>Stroke - etiology</topic><topic>Stroke - mortality</topic><topic>Stroke - prevention & control</topic><topic>Studies</topic><topic>Survival Rate - trends</topic><topic>United States - epidemiology</topic><topic>warfarin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gómez-Outes, Antonio, MD, PhD</creatorcontrib><creatorcontrib>Lagunar-Ruíz, Julián, MD</creatorcontrib><creatorcontrib>Terleira-Fernández, Ana-Isabel, MD, PhD</creatorcontrib><creatorcontrib>Calvo-Rojas, Gonzalo, MD, PhD</creatorcontrib><creatorcontrib>Suárez-Gea, Maria Luisa, PharmD, PhD</creatorcontrib><creatorcontrib>Vargas-Castrillón, Emilio, MD, PhD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gómez-Outes, Antonio, MD, PhD</au><au>Lagunar-Ruíz, Julián, MD</au><au>Terleira-Fernández, Ana-Isabel, MD, PhD</au><au>Calvo-Rojas, Gonzalo, MD, PhD</au><au>Suárez-Gea, Maria Luisa, PharmD, PhD</au><au>Vargas-Castrillón, Emilio, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Causes of Death in Anticoagulated Patients With Atrial Fibrillation</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2016-12-13</date><risdate>2016</risdate><volume>68</volume><issue>23</issue><spage>2508</spage><epage>2521</epage><pages>2508-2521</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><abstract>Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. Objectives The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. Methods The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. Results 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings. Conclusions In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27931607</pmid><doi>10.1016/j.jacc.2016.09.944</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Administration, Oral Aged Anticoagulants Anticoagulants - therapeutic use apixaban atrial fibrillation Atrial Fibrillation - complications Atrial Fibrillation - drug therapy Atrial Fibrillation - mortality Cardiac arrhythmia Cardiology Cardiovascular Cause of Death - trends Clinical trials dabigatran Embolisms Female Follow-Up Studies Humans Internal Medicine Male Meta-analysis Mortality Patients Quality Registries Retrospective Studies rivaroxaban Software Stroke Stroke - etiology Stroke - mortality Stroke - prevention & control Studies Survival Rate - trends United States - epidemiology warfarin |
| title | Causes of Death in Anticoagulated Patients With Atrial Fibrillation |
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