Insulin-Requiring Versus Noninsulin-Requiring Diabetes and Thromboembolic Risk in Patients With Atrial Fibrillation: PREFER in AF.

Published on Jan 31, 2017in Journal of the American College of Cardiology20.589
· DOI :10.1016/J.JACC.2016.10.069
Giuseppe Patti50
Estimated H-index: 50
(Sapienza University of Rome),
Markus Lucerna8
Estimated H-index: 8
(Daiichi Sankyo)
+ 8 AuthorsRaffaele De Caterina90
Estimated H-index: 90
Abstract Background Diabetes is a known risk predictor for thromboembolic events in patients with atrial fibrillation (AF), but no study has explored the prognostic weight of insulin in this setting. Objectives This study evaluated the differential role of insulin versus no insulin therapy on thromboembolic risk in patients with diabetes and AF. Methods We accessed individual patient data from the prospective, real-world, multicenter, PREFER in AF (European Prevention of thromboembolic events-European Registry in Atrial Fibrillation). We compared the rates of stroke/systemic embolism at 1 year according to diabetes status (no diabetes, diabetes without insulin therapy, diabetes on insulin therapy). Results In an overall population of 5,717 patients, 1,288 had diabetes, 22.4% of whom were on insulin. For patients with diabetes who were on insulin, there was a significantly increased risk of stroke/systemic embolism at 1 year versus either no diabetes (5.2% vs. 1.9%; hazard ratio: 2.89; 95% confidence interval: 1.67 to 5.02; p = 0.0002) or diabetes without insulin treatment (5.2% vs. 1.8%; hazard ratio: 2.96; 95% confidence interval: 1.49 to 5.87; p = 0.0019). Notably, rates of stroke/embolism were similar in patients with diabetes not receiving insulin versus patients without diabetes (hazard ratio: 0.97; 95% confidence interval: 0.58 to 1.61; p = 0.90). The selective predictive role of insulin-requiring diabetes was independent of potential confounders, including diabetes duration, and was maintained in various subpopulations, including the subgroup receiving anticoagulant therapy. Conclusions In this cohort of anticoagulated patients with AF, the sole presence of diabetes not requiring insulin did not imply an increased thromboembolic risk. Conversely, insulin-requiring diabetes contributed most, if not exclusively, to the overall increase of thromboembolic risk in AF.
📖 Papers frequently viewed together
53 Citations
4,324 Citations
4,312 Citations
#2Alan S. Go (Stanford University)H-Index: 124
Last. Daniel E. Singer (Harvard University)H-Index: 132
view all 7 authors...
Abstract Background Diagnosed diabetes mellitus (DM) is a consistently documented risk factor for ischemic stroke in patients with atrial fibrillation (AF). Objectives The purpose of this study was to assess the association between duration of diabetes and elevated hemoglobin A1c (HbA1c) with risk of stroke among diabetic patients with AF. Methods We assessed this association in the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) California community-based cohort of AF patients (...
53 CitationsSource
#1Michel Komajda (UPMC: Pierre-and-Marie-Curie University)H-Index: 90
#2Luigi TavazziH-Index: 131
Last. Karl Swedberg (NIH: National Institutes of Health)H-Index: 146
view all 7 authors...
Aims: To evaluate clinical profiles and outcomes in patients with systolic heart failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (heart rate-lowering agent) with respect to diabetic status. Methods and results: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with systolic HF, left ventricular ejection fraction ≤35%, and resting heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 m...
43 CitationsSource
Aims To provide insights on the antiarrhythmic management of atrial fibrillation among patients enrolled in the Antithrombotic Agents in Atrial Fibrillation (ATA-AF) study, and to assess the adherence of the Italian cardiologists and internists to guidelines recommendations. Methods and results The ATA-AF study is a multicenter, observational study with prospective data collection on the management and treatment of patients with atrial fibrillation. From March to July 2010, 6910 patients with at...
2 CitationsSource
#1Paulus Kirchhof (University of Birmingham)H-Index: 108
#2B. Ammentorp (Daiichi Sankyo)H-Index: 5
Last. José Luis ZamoranoH-Index: 82
view all 8 authors...
Aims We sought to describe the management of patients with atrial fibrillation (AF) in Europe after the release of the 2010 AF Guidelines of the European Society of Cardiology. Methods and results The PREFER in AF registry enrolled consecutive patients with AF from January 2012 to January 2013 in 461 centres in seven European countries. Seven thousand two hundred and forty-three evaluable patients were enrolled, aged 71.5 ± 11 years, 60.1% male, CHA2DS2VASc score 3.4 ± 1.8 (mean ± standard devia...
307 CitationsSource
#1Robert P. Giugliano (Partners HealthCare)H-Index: 91
#2Christian T. RuffH-Index: 46
Last. Abstr ActH-Index: 53
view all 21 authors...
The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P = 0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.8...
3,044 CitationsSource
#1Ralph L. SaccoH-Index: 157
#2Scott E. KasnerH-Index: 77
Last. Harry V. VintersH-Index: 126
view all 20 authors...
Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term “stroke” is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated d...
1,394 CitationsSource
#1Abderrahim Nemmar (United Arab Emirates University)H-Index: 50
#2Deepa Subramaniyan (United Arab Emirates University)H-Index: 9
Last. Badreldin H. Ali (Sultan Qaboos University)H-Index: 52
view all 4 authors...
Background Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear.
25 CitationsSource
#1Laura Oggianu (CUA: The Catholic University of America)H-Index: 3
#2Stefano Lancellotti (CUA: The Catholic University of America)H-Index: 18
Last. Raimondo De Cristofaro (CUA: The Catholic University of America)H-Index: 28
view all 8 authors...
The thrombogenic activity of Von Willebrand factor (VWF) is proportional to its molecular size and inversely related to its proteolysis by ADAMTS-13. Oxidation of VWF severely impairs its proteolysis by the metalloprotease. This study was aimed at assessing in patients with type 1 and type 2 diabetes whether protein carbonyls, marker of oxidative stress, are associated with both the level and oxidation status of VWF as well as with micro- and macroangiopathic complications. Eighty-three diabetic...
27 CitationsSource
#3A. John Camm (St George's, University of London)H-Index: 114
#4Gregory Y.H. Lip (St George's, University of London)H-Index: 195
Last. Freek W.A. VerheugtH-Index: 92
view all 53 authors...
ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American–Australian–African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association ANDROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific ...
2,453 CitationsSource
#2A. John Camm (St George's, University of London)H-Index: 114
#3Jeroen J. BaxH-Index: 164
Last. Isabelle C. Van GelderH-Index: 83
view all 17 authors...
2012 focused update of the ESC Guidelines for the management of atrial fibrillation : An update of the 2010 ESC Guidelines for the management of atrial fibrillation: Developed with the special contribution of the European Heart Rhythm Association
3,466 CitationsSource
Cited By48
#1Sian Bradley (UNSW: University of New South Wales)H-Index: 4
#2Kevin Spring (UNSW: University of New South Wales)H-Index: 31
view all 6 authors...
The increasing prevalence of diabetes and stroke is a major global public health concern. Specifically, acute stroke patients, with pre-existing diabetes, pose a clinical challenge. It is established that diabetes is associated with a worse prognosis after acute stroke and the various biological factors that mediate poor recovery profiles in diabetic patients is unknown. The level of association and impact of diabetes, in the setting of reperfusion therapy, is yet to be determined. This article ...
#1Laurent Fauchier (François Rabelais University)H-Index: 58
#2Giuseppe Boriani (University of Modena and Reggio Emilia)H-Index: 83
Last. A. John Camm (St George's, University of London)H-Index: 114
view all 6 authors...
Atrial fibrillation (AF), type 2 diabetes mellitus (DM), and chronic kidney disease (CKD) are three global epidemics with significant effects on morbidity and mortality. Diabetes is a risk factor for AF, and a risk factor for thromboembolism, comorbidity, and mortality when AF is present. The pathophysiology of diabetes-related AF and interrelationships with cardiovascular events and renal events is not fully understood but is in part related to structural, electrical, electromechanical, and aut...
#1Francis E. Ugowe (Duke University)H-Index: 4
#2Anne S. Hellkamp (Duke University)H-Index: 57
Last. Jonathan P. Piccini (Duke University)H-Index: 81
view all 15 authors...
Background Insulin use may be a better predictor of stroke risk and morbidity and mortality than diabetes in patients with atrial fibrillation (AF). Objectives Determine if the increased risk of stroke observed in patients with AF and diabetes is restricted to those treated with insulin. Methods We analyzed the association between diabetes and treatment and the occurrence of stroke/systemic embolism, myocardial infarction (MI), all-cause death, vascular death, composite outcomes, and bleeding ri...
#1Dimitrios A. Vrachatis (UoA: National and Kapodistrian University of Athens)H-Index: 14
#2Konstantinos A. Papathanasiou (UoA: National and Kapodistrian University of Athens)
Last. Georgios GiannopoulosH-Index: 25
view all 13 authors...
Atrial fibrillation (AF) and diabetes mellitus (DM) are commonly encountered in clinical practice. Although, the long term macrovascular and microvascular sequela of DM are well validated, the association between the less prevalent type 1 DM (T1DM) and atrial arrhythmogenesis is poorly understood. In the present review we highlight the current experimental and clinical data addressing this complex interaction. Animal studies support that T1DM, characterized by insulin deficiency and glycemic var...
#1Emily P. Zeitler (Dartmouth–Hitchcock Medical Center)H-Index: 13
#2Jonathan P. Piccini (Duke University)H-Index: 81
#1Ilaria Cavallari (Università Campus Bio-Medico)H-Index: 13
#2Ernesto Maddaloni (Sapienza University of Rome)H-Index: 19
Last. Rossella Marcucci (UniFI: University of Florence)H-Index: 57
view all 12 authors...
The risk of ischemic events carried by different clusters of type 2 diabetes mellitus (DM) in the setting of secondary prevention is not definite and the association between DM and bleeding complications is controversial. We explored these issues in the START-ANTIPLATELET, a multicenter Italian registry including acute coronary syndrome (ACS) patients. Study outcome was 1-year incidence of the net composite endpoint including major adverse cardiovascular events (MACE) or any bleeding and its ind...
3 CitationsSource
#1Andreas S Papazoglou (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 3
#2Anastasios Kartas (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 5
Last. George Giannakoulas (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 19
view all 17 authors...
BACKGROUND There are limited data on the association of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) with outcomes in patients with atrial fibrillation (AF). METHODS This retrospective cohort study included patients who were recently hospitalized with a primary or secondary diagnosis of AF from December 2015 through June 2018. Kaplan-Meier curves and Cox-regression adjusted hazard ratios (aHR) were calculated for the primary outcome of all-cause mortality and for the secondar...
3 CitationsSource
#1Ting Wei Lee (TMU: Taipei Medical University)H-Index: 7
#2Ting I. Lee (TMU: Taipei Medical University)H-Index: 14
Last. Yi Jen Chen (TMU: Taipei Medical University)H-Index: 30
view all 6 authors...
Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia and is associated with substantial morbidity and mortality. Advanced glycation end product and its receptor activation, cardiac energy dysmetabolism, structural and electrical remodeling, and autonomic dysfunction are implicated in AF pathophysiology in diabetic hearts. Antidiabetic drugs have been demonstrated to possess therapeutic potential for AF. However, clinical...
2 CitationsSource
#1Thomas Jensen (Aarhus University Hospital)H-Index: 13
#2Kevin Kris Warnakula Olesen (Aarhus University Hospital)H-Index: 8
Last. Michael Maeng (Aarhus University Hospital)H-Index: 52
view all 6 authors...
Abstract Background Diabetes mellitus (DM) and atrial fibrillation (AF) are known risk factors for ischemic stroke. Recent data, however, suggest that only insulin-treated DM is a risk factor for ischemic stroke among AF patients. Objectives To evaluate the risk of stroke in patients with insulin and noninsulin treated DM. Methods We included AF patients undergoing coronary angiography in Western Denmark between 2003 and 2016. Patients were categorized as 1) insulin treated DM, 2) noninsulin tre...
2 CitationsSource