title: Inadequate anticoagulation by Vitamin K Antagonists is associated with Major Adverse Cardiovascular Events in patients with atrial fibrillation.
abstract: BACKGROUND
  Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients.
  
  
  METHODS
  We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8 months (1755 patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death.
  
  
  RESULTS
  Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13-58%, 59-74%, and 75-100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177-0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067-0.402), age (p<0.001, HR 1.094, CI 95% 1.042-1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172-4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532-7.769) predicted MACE.
  
  
  CONCLUSIONS
  TTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE.
authors: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Daniele
authors: D
authors: Pastori
authors: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Pasquale
authors: P
authors: Pignatelli
authors: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Mirella
authors: M
authors: Saliola
authors: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
authors: Roberto
authors: R
authors: Carnevale
authors: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Tommasa
authors: T
authors: Vicario
authors: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Maria
authors: M
authors: Del Ben
authors: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors: Roberto
authors: R
authors: Cangemi
authors: Department of the Heart and Great Vessels Attilio Reale, "Sapienza" University of Rome, Rome, Italy.
authors: Francesco
authors: F
authors: Barillà
authors: University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK.
authors: Gregory Y H
authors: GY
authors: Lip
authors: I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy. Electronic address: francesco.violi@uniroma1.it.
authors: Francesco
authors: F
authors: Violi
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D063868:Patient Outcome Assessment; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012044:Regression Analysis; D020521:Stroke / Q000188:drug therapy; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin; D000074:Acenocoumarol
keywords: Anticoagulant drugs; Atrial fibrillation; Cardiovascular diseases; Myocardial infarction; Warfarin