Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial)

Jeffrey B. Washam, Anne S. Hellkamp, Yuliya Lokhnygina, Jonathan P. Piccini, Scott D. Berkowitz, Christopher C. Nessel, Richard C. Becker, Günter Breithardt, Keith A. A. Fox, Jonathan L. Halperin, Graeme J. Hankey, Kenneth W. Mahaffey, Daniel E. Singer, Manesh R. Patel, ROCKET AF Investigators

    Research output: Contribution to journalArticle

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    Abstract

    Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF.

    Original languageEnglish
    Pages (from-to)588-594
    Number of pages7
    JournalAmerican Journal of Cardiology
    Volume120
    Issue number4
    DOIs
    Publication statusPublished - 15 Aug 2017

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    Calcium Channel Blockers
    Warfarin
    Atrial Fibrillation
    Safety
    Hemorrhage
    Embolism
    Stroke
    Intracranial Hemorrhages
    Cytochrome P-450 CYP3A
    Factor Xa
    Vitamin K
    P-Glycoprotein
    Random Allocation
    Metabolic Networks and Pathways
    Rivaroxaban
    Chronic Obstructive Pulmonary Disease
    Nervous System
    Cause of Death
    Heart Failure

    Cite this

    Washam, Jeffrey B. ; Hellkamp, Anne S. ; Lokhnygina, Yuliya ; Piccini, Jonathan P. ; Berkowitz, Scott D. ; Nessel, Christopher C. ; Becker, Richard C. ; Breithardt, Günter ; Fox, Keith A. A. ; Halperin, Jonathan L. ; Hankey, Graeme J. ; Mahaffey, Kenneth W. ; Singer, Daniel E. ; Patel, Manesh R. ; ROCKET AF Investigators. / Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial). In: American Journal of Cardiology. 2017 ; Vol. 120, No. 4. pp. 588-594.
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    title = "Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial)",
    abstract = "Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2{\%}) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95{\%} CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95{\%} CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF.",
    author = "Washam, {Jeffrey B.} and Hellkamp, {Anne S.} and Yuliya Lokhnygina and Piccini, {Jonathan P.} and Berkowitz, {Scott D.} and Nessel, {Christopher C.} and Becker, {Richard C.} and G{\"u}nter Breithardt and Fox, {Keith A. A.} and Halperin, {Jonathan L.} and Hankey, {Graeme J.} and Mahaffey, {Kenneth W.} and Singer, {Daniel E.} and Patel, {Manesh R.} and {ROCKET AF Investigators}",
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    Washam, JB, Hellkamp, AS, Lokhnygina, Y, Piccini, JP, Berkowitz, SD, Nessel, CC, Becker, RC, Breithardt, G, Fox, KAA, Halperin, JL, Hankey, GJ, Mahaffey, KW, Singer, DE, Patel, MR & ROCKET AF Investigators 2017, 'Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial)' American Journal of Cardiology, vol. 120, no. 4, pp. 588-594. https://doi.org/10.1016/j.amjcard.2017.05.026

    Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial). / Washam, Jeffrey B.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Piccini, Jonathan P.; Berkowitz, Scott D.; Nessel, Christopher C.; Becker, Richard C.; Breithardt, Günter; Fox, Keith A. A.; Halperin, Jonathan L.; Hankey, Graeme J.; Mahaffey, Kenneth W.; Singer, Daniel E.; Patel, Manesh R.; ROCKET AF Investigators.

    In: American Journal of Cardiology, Vol. 120, No. 4, 15.08.2017, p. 588-594.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial)

    AU - Washam, Jeffrey B.

    AU - Hellkamp, Anne S.

    AU - Lokhnygina, Yuliya

    AU - Piccini, Jonathan P.

    AU - Berkowitz, Scott D.

    AU - Nessel, Christopher C.

    AU - Becker, Richard C.

    AU - Breithardt, Günter

    AU - Fox, Keith A. A.

    AU - Halperin, Jonathan L.

    AU - Hankey, Graeme J.

    AU - Mahaffey, Kenneth W.

    AU - Singer, Daniel E.

    AU - Patel, Manesh R.

    AU - ROCKET AF Investigators

    PY - 2017/8/15

    Y1 - 2017/8/15

    N2 - Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF.

    AB - Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF.

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