Adherence to guidelines for the prescribing of double and triple combinations of antithrombotic agents

Eur J Prev Cardiol. 2014 Feb;21(2):231-43. doi: 10.1177/2047487312451253. Epub 2012 Jun 8.


Background: To prevent cardiovascular complications, sometimes double and triple therapy with a vitamin K antagonist (VKA), clopidogrel and/or acetylsalicylic acid (ASA) are indicated. These combinations increase the patient's risk of serious bleeding events. Therefore, adherence to clinical guidelines is of the utmost importance when these high-risk therapies are prescribed.

Methods: We performed a retrospective cohort study of 238 cases in a community pharmacy that were treated with a combination of VKA, clopidogrel and/or ASA between January 2006 and December 2009. Hospital records and community pharmacy records were used to obtain the indication(s), the duration of combination therapy, the presence of risk-increasing and risk-decreasing co-medications and any relevant co-morbidities. The cardiologists' attitudes towards the prescribing of antithrombotic combinations and their self-reported adherence to guidelines were assessed by a brief questionnaire.

Results: We found there was no guideline-based indication for 22 of the 146 cases (14%) on ASA plus clopidogrel and 19 of the 82 cases (23%) on VKA plus ASA. Of the 238 cases given antithrombotic combination therapies, 77 (32%) were placed at an additional increased risk of serious gastrointestinal events, yet 43 (56%) of these did not receive adequate gastric protection. Out of the 19 of 60 cardiologists (32%) who responded to our questionnaire; 17 (90%) and 13 (68%) stated that a strict indication is very important when initiating therapy with ASA plus clopidogrel or ASA plus VKA, respectively.

Conclusions: There is room to further develop adherence to guideline-based prescribing of antithrombotic combination therapies and to improve prescription of gastric protection for patients receiving these high-risk combinations.

Keywords: Vitamin K antagonists; acetylsalicylic acid; anti-thrombotic drugs; bleeding risk; clopidogrel; combination therapy; gastric bleeding; guideline adherence.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aspirin / therapeutic use
  • Attitude of Health Personnel
  • Clopidogrel
  • Community Pharmacy Services
  • Comorbidity
  • Drug Interactions
  • Drug Prescriptions
  • Drug Therapy, Combination
  • Drug Utilization Review / trends
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Guideline Adherence / trends*
  • Health Care Surveys
  • Health Knowledge, Attitudes, Practice
  • Hemorrhage / chemically induced
  • Hemorrhage / prevention & control
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Platelet Aggregation Inhibitors / therapeutic use
  • Practice Guidelines as Topic*
  • Practice Patterns, Physicians' / trends*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Surveys and Questionnaires
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Vitamin K / antagonists & inhibitors


  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Vitamin K
  • Clopidogrel
  • Ticlopidine
  • Aspirin