Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Cardiovascular drugs and therapy - 33(2019), 5 vom: 13. Okt., Seite 615-623 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Harskamp, Ralf E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.05.2020 Date Revised 18.05.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.1007/s10557-019-06907-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM301287090 |
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| 041 | |a eng | ||
| 100 | 1 | |a Harskamp, Ralf E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 18.05.2020 | ||
| 500 | |a Date Revised 18.05.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Systematic Review | |
| 650 | 4 | |a Atrial fibrillation | |
| 650 | 4 | |a DOAC | |
| 650 | 4 | |a Drug-drug interactions | |
| 650 | 4 | |a Polypharmacy | |
| 650 | 4 | |a Warfarin | |
| 650 | 7 | |a ATP Binding Cassette Transporter, Subfamily B, Member 1 |2 NLM | |
| 650 | 7 | |a Anticoagulants |2 NLM | |
| 650 | 7 | |a Cytochrome P-450 CYP3A Inducers |2 NLM | |
| 650 | 7 | |a Cytochrome P-450 CYP3A Inhibitors |2 NLM | |
| 700 | 1 | |a Teichert, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Lucassen, Wim A M |e verfasserin |4 aut | |
| 700 | 1 | |a van Weert, Henk C P M |e verfasserin |4 aut | |
| 700 | 1 | |a Lopes, Renato D |e verfasserin |4 aut | |
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