Pharmacists’ influence on adverse reactions to warfarin: a randomised controlled trial in elderly rural patients

  • Slaven FalamićEmail author
  • Marko Lucijanić
  • Maja Ortner-Hadžiabdić
  • Srećko Marušić
  • Vesna Bačić-Vrca
Research Article


Background Adverse reactions to warfarin may be serious and can lead to hospitalisation or death. Minimising the risk of adverse drug reactions through the intervention of community pharmacists is important for patients receiving warfarin, especially for elderly (≥ 65 years) patients living in rural areas. Objective To evaluate the impact of an intervention by community pharmacists on the risk of adverse drug reactions in elderly rural patients receiving warfarin. Setting: A community pharmacy in a rural area of Croatia. Method We conducted a prospective randomised trial. Eligible patients were recruited at the pharmacy and randomised into one of two groups. The participants were followed up every month for 6 months. Main outcome measure: The incidence and type of adverse drug reactions caused by warfarin and the time-to-event. Results In total, 140 patients were randomized and 131 patients completed the study; 65 patients were in the intervention group. The median age of patients was 73 years of age. The cumulative incidence of adverse drug reactions was significantly lower in the intervention group (6-months rate 29% vs. 85% for intervention and control, respectively; hazard ratio = 0.17, p < 0.001) than in the control group. Factors multivariately associated with the development of adverse drug reactions related to warfarin (p < 0.05) were the absence of pharmaceutical intervention, higher time in therapeutic range, change of warfarin dose, changes in dietary vitamin K intake, and marital status other than married. Conclusion Overall, the pharmacist’s intervention significantly prolonged the time to occurrence of adverse drug reactions and reduced their incidence.


Adverse drug reactions Croatia Elderly Pharmacists’ intervention Rural population Warfarin 



This study is a part of the Ph.D. thesis of the first author. The authors would like to acknowledge all the general practitioners responsible for the study participants for the provision of the required data.


This study was self-funded.

Conflicts of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Pharmacy Branka MarušićDonji MiholjacCroatia
  2. 2.Hematology DepartmentUniversity Hospital DubravaZagrebCroatia
  3. 3.Centre for Applied Pharmacy, Faculty of Pharmacy and BiochemistryUniversity of ZagrebZagrebCroatia
  4. 4.Department of Clinical PharmacologyUniversity Hospital DubravaZagrebCroatia
  5. 5.Department of Clinical PharmacyUniversity Hospital DubravaZagrebCroatia

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