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Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety

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Harvard

Hiatt, WR, Bonaca, MP, Patel, MR, Nehler, MR, Debus, ES, Anand, SS, Capell, WH, Brackin, T, Jaeger, N, Hess, CN, Pap, AF, Berkowitz, SD, Muehlhofer, E, Haskell, L, Brasil, D, Madaric, J, Sillesen, H, Szalay, D & Bauersachs, R 2020, 'Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety', Circulation, vol. 142, no. 23, pp. 2219-2230. https://doi.org/10.1161/CIRCULATIONAHA.120.050465

APA

Hiatt, W. R., Bonaca, M. P., Patel, M. R., Nehler, M. R., Debus, E. S., Anand, S. S., Capell, W. H., Brackin, T., Jaeger, N., Hess, C. N., Pap, A. F., Berkowitz, S. D., Muehlhofer, E., Haskell, L., Brasil, D., Madaric, J., Sillesen, H., Szalay, D., & Bauersachs, R. (2020). Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety. Circulation, 142(23), 2219-2230. https://doi.org/10.1161/CIRCULATIONAHA.120.050465

CBE

Hiatt WR, Bonaca MP, Patel MR, Nehler MR, Debus ES, Anand SS, Capell WH, Brackin T, Jaeger N, Hess CN, Pap AF, Berkowitz SD, Muehlhofer E, Haskell L, Brasil D, Madaric J, Sillesen H, Szalay D, Bauersachs R. 2020. Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety. Circulation. 142(23):2219-2230. https://doi.org/10.1161/CIRCULATIONAHA.120.050465

MLA

Vancouver

Author

Hiatt, William R ; Bonaca, Marc P ; Patel, Manesh R ; Nehler, Mark R ; Debus, Eike Sebastian ; Anand, Sonia S ; Capell, Warren H ; Brackin, Taylor ; Jaeger, Nicole ; Hess, Connie N ; Pap, Akos F ; Berkowitz, Scott D ; Muehlhofer, Eva ; Haskell, Lloyd ; Brasil, David ; Madaric, Juraj ; Sillesen, Henrik ; Szalay, David ; Bauersachs, Rupert. / Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization : Impact of Concomitant Clopidogrel on Efficacy and Safety. In: Circulation. 2020 ; Vol. 142, No. 23. pp. 2219-2230.

Bibtex

@article{efe99f8504324730a0f5aa93e20211be,
title = "Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety",
abstract = "BACKGROUND: The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described.METHODS: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization.RESULTS: Of the randomized patients, 3313 (50.6%) received clopidogrel for a median duration of 29.0 days. Over 3 years, the hazard ratio for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI, 0.71-1.01) with clopidogrel and 0.86 (95% CI, 0.73-1.01) without clopidogrel without statistical heterogeneity (P for interaction=0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia within 30 days (hazard ratio, 0.45 [95% CI, 0.14-1.46] with clopidogrel; hazard ratio, 0.48 [95% CI, 0.22-1.01] without clopidogrel; P for interaction=0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use (P for interaction=0.71). With clopidogrel use >30 days, rivaroxaban was associated with more International Society on Thrombosis and Haemostasis major bleeding within 365 days (hazard ratio, 3.20 [95% CI, 1.44-7.13]) compared with shorter durations of clopidogrel (P for trend=0.06).CONCLUSIONS: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02504216.",
author = "Hiatt, {William R} and Bonaca, {Marc P} and Patel, {Manesh R} and Nehler, {Mark R} and Debus, {Eike Sebastian} and Anand, {Sonia S} and Capell, {Warren H} and Taylor Brackin and Nicole Jaeger and Hess, {Connie N} and Pap, {Akos F} and Berkowitz, {Scott D} and Eva Muehlhofer and Lloyd Haskell and David Brasil and Juraj Madaric and Henrik Sillesen and David Szalay and Rupert Bauersachs",
year = "2020",
month = dec,
day = "8",
doi = "10.1161/CIRCULATIONAHA.120.050465",
language = "English",
volume = "142",
pages = "2219--2230",
journal = "Circulation (Baltimore)",
issn = "0009-7322",
publisher = "Lippincott Williams & Wilkins",
number = "23",

}

RIS

TY - JOUR

T1 - Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization

T2 - Impact of Concomitant Clopidogrel on Efficacy and Safety

AU - Hiatt, William R

AU - Bonaca, Marc P

AU - Patel, Manesh R

AU - Nehler, Mark R

AU - Debus, Eike Sebastian

AU - Anand, Sonia S

AU - Capell, Warren H

AU - Brackin, Taylor

AU - Jaeger, Nicole

AU - Hess, Connie N

AU - Pap, Akos F

AU - Berkowitz, Scott D

AU - Muehlhofer, Eva

AU - Haskell, Lloyd

AU - Brasil, David

AU - Madaric, Juraj

AU - Sillesen, Henrik

AU - Szalay, David

AU - Bauersachs, Rupert

PY - 2020/12/8

Y1 - 2020/12/8

N2 - BACKGROUND: The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described.METHODS: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization.RESULTS: Of the randomized patients, 3313 (50.6%) received clopidogrel for a median duration of 29.0 days. Over 3 years, the hazard ratio for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI, 0.71-1.01) with clopidogrel and 0.86 (95% CI, 0.73-1.01) without clopidogrel without statistical heterogeneity (P for interaction=0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia within 30 days (hazard ratio, 0.45 [95% CI, 0.14-1.46] with clopidogrel; hazard ratio, 0.48 [95% CI, 0.22-1.01] without clopidogrel; P for interaction=0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use (P for interaction=0.71). With clopidogrel use >30 days, rivaroxaban was associated with more International Society on Thrombosis and Haemostasis major bleeding within 365 days (hazard ratio, 3.20 [95% CI, 1.44-7.13]) compared with shorter durations of clopidogrel (P for trend=0.06).CONCLUSIONS: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02504216.

AB - BACKGROUND: The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described.METHODS: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization.RESULTS: Of the randomized patients, 3313 (50.6%) received clopidogrel for a median duration of 29.0 days. Over 3 years, the hazard ratio for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI, 0.71-1.01) with clopidogrel and 0.86 (95% CI, 0.73-1.01) without clopidogrel without statistical heterogeneity (P for interaction=0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia within 30 days (hazard ratio, 0.45 [95% CI, 0.14-1.46] with clopidogrel; hazard ratio, 0.48 [95% CI, 0.22-1.01] without clopidogrel; P for interaction=0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use (P for interaction=0.71). With clopidogrel use >30 days, rivaroxaban was associated with more International Society on Thrombosis and Haemostasis major bleeding within 365 days (hazard ratio, 3.20 [95% CI, 1.44-7.13]) compared with shorter durations of clopidogrel (P for trend=0.06).CONCLUSIONS: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02504216.

U2 - 10.1161/CIRCULATIONAHA.120.050465

DO - 10.1161/CIRCULATIONAHA.120.050465

M3 - Journal article

C2 - 33138628

VL - 142

SP - 2219

EP - 2230

JO - Circulation (Baltimore)

JF - Circulation (Baltimore)

SN - 0009-7322

IS - 23

ER -

ID: 62413008