Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease

Marc S Sabatine, Gaetano M De Ferrari, Robert P Giugliano, Kurt Huber, Basil S Lewis, Jorge Ferreira, Julia F Kuder, Sabina A Murphy, Stephen D Wiviott, Christopher E Kurtz, Narimon Honarpour, Anthony C Keech, Peter S Sever, Terje R Pedersen

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) recently showed that the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab significantly reduced major vascular events in patients with stable atherosclerotic cardiovascular disease, including patients with prior myocardial infarction (MI). Within the broad group of patients with prior MI, we hypothesized that readily ascertainable features would identify subsets who derive greater clinical risk reduction with evolocumab.

METHODS: The 22 351 patients with a prior MI were characterized on the basis of time from most recent MI, number of prior MIs, and presence of residual multivessel coronary artery disease (≥40% stenosis in ≥2 large vessels). The relative and absolute risk reductions in major vascular events, including the primary end point (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) and the key secondary end point (cardiovascular death, MI, or stroke), with evolocumab in these subgroups were compared.

RESULTS: A total of 8402 patients (38%) were within 2 years of their most recent MI; 5285 patients (24%) had ≥2 prior MIs; and 5618 patients (25%) had residual multivessel coronary artery disease. In a multivariable-adjusted model that simultaneously included all 3 high-risk features and other baseline covariates, more recent MI, multiple prior MIs, and residual multivessel coronary disease remained independent predictors of cardiovascular outcomes, with adjusted hazard ratios (HRs) for the primary end point of 1.37 (95% confidence interval [CI],1.22-1.53), 1.78 (95% CI, 1.59-1.99), and 1.39 (95% CI, 1.24-1.56; all P<0.001). The relative risk reductions with evolocumab for the primary end point tended to be greater in the high-risk subgroups and were 20% (HR, 0.80; 95% CI, 0.71-0.91), 18% (HR, 0.82; 95% CI, 0.72-0.93), and 21% (HR, 0.79; 95% CI, 0.69-0.91) for those with more recent MI, multiple prior MIs, and residual multivessel coronary artery disease, whereas they were 5% (HR, 0.95; 95% CI, 0.85-1.05), 8% (HR, 0.92; 95% CI, 0.84-1.02), and 7% (HR, 0.93; 95% CI, 0.85-1.02) in those without, respectively. Given the higher baseline risk, the respective absolute risk reductions at 3 years exceeded 3% in the high-risk groups (3.4%, 3.7%, and 3.6%) versus ≈1% in the low-risk groups (0.8%, 1.3%, and 1.2%).

CONCLUSIONS: Patients closer to their most recent MI, with multiple prior MIs, or with residual multivessel coronary artery disease are at high risk for major vascular events and experience substantial risk reductions with low-density lipoprotein cholesterol lowering with evolocumab.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.

Original languageEnglish
Pages (from-to)756-766
Number of pages11
JournalCirculation
Volume138
Issue number8
DOIs
Publication statusPublished - Aug 21 2018

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Coronary Artery Disease
Myocardial Infarction
Confidence Intervals
Risk Reduction Behavior
Blood Vessels
Numbers Needed To Treat
Stroke
AMG 145
Unstable Angina
LDL Cholesterol
Coronary Disease
Pathologic Constriction
Hospitalization
Cardiovascular Diseases
Outcome Assessment (Health Care)
Clinical Trials

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Sabatine, M. S., De Ferrari, G. M., Giugliano, R. P., Huber, K., Lewis, B. S., Ferreira, J., ... Pedersen, T. R. (2018). Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease. Circulation, 138(8), 756-766. https://doi.org/10.1161/CIRCULATIONAHA.118.034309

Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease. / Sabatine, Marc S; De Ferrari, Gaetano M; Giugliano, Robert P; Huber, Kurt; Lewis, Basil S; Ferreira, Jorge; Kuder, Julia F; Murphy, Sabina A; Wiviott, Stephen D; Kurtz, Christopher E; Honarpour, Narimon; Keech, Anthony C; Sever, Peter S; Pedersen, Terje R.

In: Circulation, Vol. 138, No. 8, 21.08.2018, p. 756-766.

Research output: Contribution to journalArticle

Sabatine, MS, De Ferrari, GM, Giugliano, RP, Huber, K, Lewis, BS, Ferreira, J, Kuder, JF, Murphy, SA, Wiviott, SD, Kurtz, CE, Honarpour, N, Keech, AC, Sever, PS & Pedersen, TR 2018, 'Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease', Circulation, vol. 138, no. 8, pp. 756-766. https://doi.org/10.1161/CIRCULATIONAHA.118.034309
Sabatine, Marc S ; De Ferrari, Gaetano M ; Giugliano, Robert P ; Huber, Kurt ; Lewis, Basil S ; Ferreira, Jorge ; Kuder, Julia F ; Murphy, Sabina A ; Wiviott, Stephen D ; Kurtz, Christopher E ; Honarpour, Narimon ; Keech, Anthony C ; Sever, Peter S ; Pedersen, Terje R. / Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease. In: Circulation. 2018 ; Vol. 138, No. 8. pp. 756-766.
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abstract = "BACKGROUND: The FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) recently showed that the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab significantly reduced major vascular events in patients with stable atherosclerotic cardiovascular disease, including patients with prior myocardial infarction (MI). Within the broad group of patients with prior MI, we hypothesized that readily ascertainable features would identify subsets who derive greater clinical risk reduction with evolocumab.METHODS: The 22 351 patients with a prior MI were characterized on the basis of time from most recent MI, number of prior MIs, and presence of residual multivessel coronary artery disease (≥40{\%} stenosis in ≥2 large vessels). The relative and absolute risk reductions in major vascular events, including the primary end point (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) and the key secondary end point (cardiovascular death, MI, or stroke), with evolocumab in these subgroups were compared.RESULTS: A total of 8402 patients (38{\%}) were within 2 years of their most recent MI; 5285 patients (24{\%}) had ≥2 prior MIs; and 5618 patients (25{\%}) had residual multivessel coronary artery disease. In a multivariable-adjusted model that simultaneously included all 3 high-risk features and other baseline covariates, more recent MI, multiple prior MIs, and residual multivessel coronary disease remained independent predictors of cardiovascular outcomes, with adjusted hazard ratios (HRs) for the primary end point of 1.37 (95{\%} confidence interval [CI],1.22-1.53), 1.78 (95{\%} CI, 1.59-1.99), and 1.39 (95{\%} CI, 1.24-1.56; all P<0.001). The relative risk reductions with evolocumab for the primary end point tended to be greater in the high-risk subgroups and were 20{\%} (HR, 0.80; 95{\%} CI, 0.71-0.91), 18{\%} (HR, 0.82; 95{\%} CI, 0.72-0.93), and 21{\%} (HR, 0.79; 95{\%} CI, 0.69-0.91) for those with more recent MI, multiple prior MIs, and residual multivessel coronary artery disease, whereas they were 5{\%} (HR, 0.95; 95{\%} CI, 0.85-1.05), 8{\%} (HR, 0.92; 95{\%} CI, 0.84-1.02), and 7{\%} (HR, 0.93; 95{\%} CI, 0.85-1.02) in those without, respectively. Given the higher baseline risk, the respective absolute risk reductions at 3 years exceeded 3{\%} in the high-risk groups (3.4{\%}, 3.7{\%}, and 3.6{\%}) versus ≈1{\%} in the low-risk groups (0.8{\%}, 1.3{\%}, and 1.2{\%}).CONCLUSIONS: Patients closer to their most recent MI, with multiple prior MIs, or with residual multivessel coronary artery disease are at high risk for major vascular events and experience substantial risk reductions with low-density lipoprotein cholesterol lowering with evolocumab.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.",
author = "Sabatine, {Marc S} and {De Ferrari}, {Gaetano M} and Giugliano, {Robert P} and Kurt Huber and Lewis, {Basil S} and Jorge Ferreira and Kuder, {Julia F} and Murphy, {Sabina A} and Wiviott, {Stephen D} and Kurtz, {Christopher E} and Narimon Honarpour and Keech, {Anthony C} and Sever, {Peter S} and Pedersen, {Terje R}",
year = "2018",
month = "8",
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doi = "10.1161/CIRCULATIONAHA.118.034309",
language = "English",
volume = "138",
pages = "756--766",
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TY - JOUR

T1 - Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease

AU - Sabatine, Marc S

AU - De Ferrari, Gaetano M

AU - Giugliano, Robert P

AU - Huber, Kurt

AU - Lewis, Basil S

AU - Ferreira, Jorge

AU - Kuder, Julia F

AU - Murphy, Sabina A

AU - Wiviott, Stephen D

AU - Kurtz, Christopher E

AU - Honarpour, Narimon

AU - Keech, Anthony C

AU - Sever, Peter S

AU - Pedersen, Terje R

PY - 2018/8/21

Y1 - 2018/8/21

N2 - BACKGROUND: The FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) recently showed that the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab significantly reduced major vascular events in patients with stable atherosclerotic cardiovascular disease, including patients with prior myocardial infarction (MI). Within the broad group of patients with prior MI, we hypothesized that readily ascertainable features would identify subsets who derive greater clinical risk reduction with evolocumab.METHODS: The 22 351 patients with a prior MI were characterized on the basis of time from most recent MI, number of prior MIs, and presence of residual multivessel coronary artery disease (≥40% stenosis in ≥2 large vessels). The relative and absolute risk reductions in major vascular events, including the primary end point (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) and the key secondary end point (cardiovascular death, MI, or stroke), with evolocumab in these subgroups were compared.RESULTS: A total of 8402 patients (38%) were within 2 years of their most recent MI; 5285 patients (24%) had ≥2 prior MIs; and 5618 patients (25%) had residual multivessel coronary artery disease. In a multivariable-adjusted model that simultaneously included all 3 high-risk features and other baseline covariates, more recent MI, multiple prior MIs, and residual multivessel coronary disease remained independent predictors of cardiovascular outcomes, with adjusted hazard ratios (HRs) for the primary end point of 1.37 (95% confidence interval [CI],1.22-1.53), 1.78 (95% CI, 1.59-1.99), and 1.39 (95% CI, 1.24-1.56; all P<0.001). The relative risk reductions with evolocumab for the primary end point tended to be greater in the high-risk subgroups and were 20% (HR, 0.80; 95% CI, 0.71-0.91), 18% (HR, 0.82; 95% CI, 0.72-0.93), and 21% (HR, 0.79; 95% CI, 0.69-0.91) for those with more recent MI, multiple prior MIs, and residual multivessel coronary artery disease, whereas they were 5% (HR, 0.95; 95% CI, 0.85-1.05), 8% (HR, 0.92; 95% CI, 0.84-1.02), and 7% (HR, 0.93; 95% CI, 0.85-1.02) in those without, respectively. Given the higher baseline risk, the respective absolute risk reductions at 3 years exceeded 3% in the high-risk groups (3.4%, 3.7%, and 3.6%) versus ≈1% in the low-risk groups (0.8%, 1.3%, and 1.2%).CONCLUSIONS: Patients closer to their most recent MI, with multiple prior MIs, or with residual multivessel coronary artery disease are at high risk for major vascular events and experience substantial risk reductions with low-density lipoprotein cholesterol lowering with evolocumab.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.

AB - BACKGROUND: The FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) recently showed that the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab significantly reduced major vascular events in patients with stable atherosclerotic cardiovascular disease, including patients with prior myocardial infarction (MI). Within the broad group of patients with prior MI, we hypothesized that readily ascertainable features would identify subsets who derive greater clinical risk reduction with evolocumab.METHODS: The 22 351 patients with a prior MI were characterized on the basis of time from most recent MI, number of prior MIs, and presence of residual multivessel coronary artery disease (≥40% stenosis in ≥2 large vessels). The relative and absolute risk reductions in major vascular events, including the primary end point (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) and the key secondary end point (cardiovascular death, MI, or stroke), with evolocumab in these subgroups were compared.RESULTS: A total of 8402 patients (38%) were within 2 years of their most recent MI; 5285 patients (24%) had ≥2 prior MIs; and 5618 patients (25%) had residual multivessel coronary artery disease. In a multivariable-adjusted model that simultaneously included all 3 high-risk features and other baseline covariates, more recent MI, multiple prior MIs, and residual multivessel coronary disease remained independent predictors of cardiovascular outcomes, with adjusted hazard ratios (HRs) for the primary end point of 1.37 (95% confidence interval [CI],1.22-1.53), 1.78 (95% CI, 1.59-1.99), and 1.39 (95% CI, 1.24-1.56; all P<0.001). The relative risk reductions with evolocumab for the primary end point tended to be greater in the high-risk subgroups and were 20% (HR, 0.80; 95% CI, 0.71-0.91), 18% (HR, 0.82; 95% CI, 0.72-0.93), and 21% (HR, 0.79; 95% CI, 0.69-0.91) for those with more recent MI, multiple prior MIs, and residual multivessel coronary artery disease, whereas they were 5% (HR, 0.95; 95% CI, 0.85-1.05), 8% (HR, 0.92; 95% CI, 0.84-1.02), and 7% (HR, 0.93; 95% CI, 0.85-1.02) in those without, respectively. Given the higher baseline risk, the respective absolute risk reductions at 3 years exceeded 3% in the high-risk groups (3.4%, 3.7%, and 3.6%) versus ≈1% in the low-risk groups (0.8%, 1.3%, and 1.2%).CONCLUSIONS: Patients closer to their most recent MI, with multiple prior MIs, or with residual multivessel coronary artery disease are at high risk for major vascular events and experience substantial risk reductions with low-density lipoprotein cholesterol lowering with evolocumab.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.

U2 - 10.1161/CIRCULATIONAHA.118.034309

DO - 10.1161/CIRCULATIONAHA.118.034309

M3 - Article

VL - 138

SP - 756

EP - 766

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 8

ER -