Raiza Gandola, Mercer University College of Pharmacy
Indication for oral anticoagulation therapy (OAC) in patients with left ventricular dysfunction is considered controversial as the risk of hemorrhage, drug interactions, and close monitoring of international normalized ratio (INR) increases. 
The amount of time patients’ stay within therapeutic INR range is 55%.  This is considered problematic as subtherapeutic anticoagulation can lead to insufficient protection while supratherapeutic anticoagulation can lead to life-threatening bleeds. It is suggested that common factors for fluctuating therapeutic ranges include age, genetics, gender, smoking, and co-morbid conditions. However, the influence of left ventricular systolic dysfunction (LVSD) on warfarin dose remains to be evaluated. 
|Title: Effect of Left Ventricular Systolic Dysfunction on Response to Warfarin|
|Design||Prospective cohort study; N= 1,354|
|Objective||To assess the influence of left ventricular systolic dysfunction (LVSD) on warfarin dose, anticoagulation control (percent time in target range-PTTR), risk of over-anticoagulation (international normalized ratio-INR >4), and major hemorrhage|
|Study Groups||LSVD absent (n= 1,140); LVSD present (n= 214) defined as left ventricular ejection fraction (LVEF) < 40%|
|Methods||Participants greater than 20 years of age initiating warfarin therapy with a target INR of two to three, managed at an anticoagulation clinic were followed up for two years, or for the duration of therapy if less than two years.|
|Primary Outcome Measure||Warfarin dose, anticoagulation control (PTTR), risk of over-anticoagulation (INR >4), and major hemorrhage|
|Baseline Characteristics||LVSD absent||LVSD present|
|Average age, y||61||61|
|Female, n (%)||595 (52)||58 (27)|
|Indication for warfarin therapy, n (%)|
|521 (46)||30 (14)|
|57 (5)||16 (7.5)|
|Atrial fibrillation||483 (42)||109 (51)|
|12 (1.1)||10 (4.7)|
|Other||66 (5.8)||49 (22.9)|
|Results||Dose requirements (4.9 mg and 5.7 mg/day) for patients with LVSD and no LVSD, respectively; p <0.001|
|PTTR was similar in patients with and without LVSD in subtherapeutic (p=0.55), therapeutic (p=0.21), and supratherapeutic (p=0.54) ranges|
|Patients with LVSD were not an increased risk for over-anticoagulation [HR 0.98, CI (0.81 – 1.18) p= 0.82]; this association remain unchanged even after accounting for clinical, demographic, and genetic factors [HR 1.01, CI (0.82–1.25) p= 0.91)|
|Incidence of hemorrhage was similar among patients with LVSD compared with those without LVSD (9.3/100 person-years vs. 8.4/100 person-years; incidence rate ratio= 1.10, CI (0.72-1.64) p= 0.63)|
|Adverse Events||Common Adverse Events: N/A|
|Serious Adverse Events: N/A|
|Percentage that Discontinued due to Adverse Events: N/A|
|Study Author Conclusions||Patients with LVSD require lower doses of warfarin. The risk of over-anticoagulation was not different in patients with LVSD, and those with LVSD are not at an increased risk of major hemorrhage.|
This study reveals that LVSD may be useful in predictive dose models, thus improving time spent in therapeutic INR range. However, there are several other variables to consider, such as elevated INR levels associated with liver damage and exaggerated responses to warfarin associated with reduced vitamin K intake, that may have warranted lower doses of warfarin in these patients. It is still unclear whether warfarin-dosing algorithms integrating LVSD in determining initial doses will improve outcomes.
- Avellana P, Segovia J, Ferrero A, et al. Anticoagulation Therapy in Patients with Heart Failure Due to Systolic Dysfunction and Sinus Rhythm, Analysis of REDINSCOR Registry. Rev Esp Cardiol 2012;65:705-12.
- Baker WL, Cios DA, Sander SD, Coleman CI. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm. 2009;15(3):244-52.
- Ather S, Shendre A, Beasley TM, et al. Effect of Left Ventricular Systolic Dysfunction on Response to Warfarin. Am J Cardiol. 2016;118(2):232-6.