Skip to main content
Journal cover image

Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation.

Publication ,  Journal Article
Harskamp, RE; Teichert, M; Lucassen, WAM; van Weert, HCPM; Lopes, RD
Published in: Cardiovasc Drugs Ther
October 2019

PURPOSE: To study whether polypharmacy or drug-drug interactions have differential effect on safety and efficacy in patients treated with direct oral anticoagulants (DOACs) versus warfarin. METHODS: We performed a systematic review and meta-analysis of studies that randomized patients with atrial fibrillation to DOACs or warfarin stratified by the number of concomitant drugs. Outcomes included stroke or systemic embolism (SE), all-cause mortality, major bleeding, and intracranial hemorrhage. Risk ratios (RR) were calculated and Mantel-Haenszel random effects were applied. RESULTS: Two high-quality studies were eligible, including 32,465 participants who received apixaban, rivaroxaban, or warfarin, with a median follow-up of 1.9 years. Of participants, 29% used < 5 drugs, 55% used 5-9 drugs, and 16% used ≥ 10 drugs. Drugs interacting with DOACs (P-glycoprotein/CYP3A4) were used by 6460 (20%) of patients. Patients with higher number of drugs (0-4 vs 5-9 vs ≥ 10) had higher rates of mortality (5.8%, 7.9%, 10.0%) and major bleeding (3.4%, 4.8%, 7.7%). Comparative efficacy or safety of DOACs versus warfarin was not affected by polypharmacy status or P-glycoprotein/CYP3A4 inhibitor use. However, the presence of polypharmacy (p = 0.001) or glycoprotein/CYP3A4-modulating drugs (p = 0.03) was correlated with increased risk of major bleeding when compared with warfarin. Overall, DOAC use was associated with a lower risk of stroke/SE (RR, 0.84; 95%CI, 0.74-0.94), all-cause mortality (RR, 0.91; 95%CI, 0.84-0.98), and intracranial hemorrhage (RR, 0.51; 95%CI, 0.38-0.70) compared with warfarin. CONCLUSIONS: DOACs were more effective than warfarin, and at least as safe. Polypharmacy was associated with adverse outcomes and attenuated the advantage in risk of major bleeding among rivaroxaban users, particularly in the presence of P-glycoprotein/CYP3A4-modulating drugs.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cardiovasc Drugs Ther

DOI

EISSN

1573-7241

Publication Date

October 2019

Volume

33

Issue

5

Start / End Page

615 / 623

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Stroke
  • Risk Factors
  • Risk Assessment
  • Polypharmacy
  • Middle Aged
  • Male
  • Humans
  • Hemorrhage
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Harskamp, R. E., Teichert, M., Lucassen, W. A. M., van Weert, H. C. P. M., & Lopes, R. D. (2019). Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation. Cardiovasc Drugs Ther, 33(5), 615–623. https://doi.org/10.1007/s10557-019-06907-8
Harskamp, Ralf E., Martina Teichert, Wim A. M. Lucassen, Henk C. P. M. van Weert, and Renato D. Lopes. “Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation.Cardiovasc Drugs Ther 33, no. 5 (October 2019): 615–23. https://doi.org/10.1007/s10557-019-06907-8.
Harskamp RE, Teichert M, Lucassen WAM, van Weert HCPM, Lopes RD. Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation. Cardiovasc Drugs Ther. 2019 Oct;33(5):615–23.
Harskamp, Ralf E., et al. “Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation.Cardiovasc Drugs Ther, vol. 33, no. 5, Oct. 2019, pp. 615–23. Pubmed, doi:10.1007/s10557-019-06907-8.
Harskamp RE, Teichert M, Lucassen WAM, van Weert HCPM, Lopes RD. Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation. Cardiovasc Drugs Ther. 2019 Oct;33(5):615–623.
Journal cover image

Published In

Cardiovasc Drugs Ther

DOI

EISSN

1573-7241

Publication Date

October 2019

Volume

33

Issue

5

Start / End Page

615 / 623

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Stroke
  • Risk Factors
  • Risk Assessment
  • Polypharmacy
  • Middle Aged
  • Male
  • Humans
  • Hemorrhage
  • Female