BARI 2D: A Reanalysis Focusing on Cardiovascular Events

BARI 2D Study Group; John P. Bantle; Michael Steffes

doi:10.1016/j.mayocp.2019.04.015

BARI 2D: A Reanalysis Focusing on Cardiovascular Events

BARI 2D Study Group, John P. Bantle, Michael Steffes

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Abstract

OBJECTIVE: To reanalyze the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial using a new composite cardiovascular disease (CVD) outcome to determine how best to treat patients with type 2 diabetes mellitus and stable coronary artery disease.

PATIENTS AND METHODS: From January 1, 2001, to November 30, 2008, 2368 patients with type 2 diabetes mellitus and angiographically proven coronary artery disease were randomly assigned to insulin-sensitizing (IS) or insulin-providing (IP) therapy and simultaneously to coronary revascularization (REV) or no or delayed REV (intensive medical therapy [MED]), with all patients receiving intensive medical treatment. The outcome of this analysis was a composite of 8 CVD events.

RESULTS: Four-year Kaplan-Meier rates for the composite CVD outcome were 35.8% (95% CI, 33.1%-38.5%) with IS therapy and 41.6% (95% CI, 38.7%-44.5%) with IP therapy (P=.004). Much of this difference was associated with lower in-trial levels of fibrinogen, C-reactive protein, and hemoglobin A 1c with IS therapy. Four-year composite CVD rates were 32.7% (95% CI, 30.0%-35.4%) with REV and 44.7% (95% CI, 41.8%-47.6%) with MED (P<.001). A beneficial effect of IS vs IP therapy was present with REV (27.7%; 95% CI, 24.0%-31.4% vs 37.5%; 95% CI, 33.6%-41.4%; P<.001), but not with MED (43.6%; 95% CI, 39.5%-47.7% vs 45.7%; 95% CI, 41.6%-49.8%; P=.37) (homogeneity, P=.05). This interaction between IS therapy and REV was limited to participants preselected for coronary artery bypass grafting (CABG). The lowest composite CVD rates occurred in patients preselected for CABG and assigned to IS therapy and REV (17.3%; 95% CI, 11.8%-22.8%).

CONCLUSION: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, the IS treatment strategy and the REV treatment strategy each reduces cardiovascular events. The combination of IS drugs and CABG results in the lowest risk of subsequent CVD events.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006305.

Original language	English (US)
Pages (from-to)	2249-2262
Number of pages	14
Journal	Mayo Clinic Proceedings
Volume	94
Issue number	11
DOIs	https://doi.org/10.1016/j.mayocp.2019.04.015
State	Published - Nov 2019

Bibliographical note

Funding Information:
Grant Support: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study is funded by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (grant nos. U01 HL061744, U01 HL061746, U01 HL061748, and U01 HL063804), with significant supplemental funding from GlaxoSmithKline. A full listing of all sponsors can be found in the Supplementary Appendix available at NEJM.org. (N Engl J Med. 2009;360(24):2503-2515). As a National Institutes of Health (NIH)?funded trial, we are required to abide by the NIH PubMed Central Policy that we retain the right to provide a copy of the final manuscript to the NIH upon acceptance for publication by your journal, for public archiving in PubMed Central as soon as possible, but no later than 12 months after publication. Maria Mori Brooks, PhD, serves as the guarantor of this manuscript.Potential Competing Interests: Dr Green has received a grant, support for travel to meetings for the study or other purposes, and support for medicines and equipment from Duke University via funds received from the National Institute of Diabetes and Digestive and Kidney Diseases. She is a board member of Novo Nordisk (outside the submitted work); serves as a consultant to AstraZeneca, Boehringer Ingelheim, Daiichi, and Merck (outside the submitted work); and has received grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi (outside the submitted work). Dr Sako has received support for travel to meetings for the study or other purposes from the BARI 2D study. He owns stocks in Medtronic (outside the submitted work). Dr Brooks has received grants from the National Institutes of Health (NIH) and pharmaceutical companies. Dr Bantle has received a grant from the NIH. Dr Chaitman has received a grant from Saint Louis University. He serves as a consultant to Novo Nordisk, Eli Lilly, and Merck (outside the submitted work). Dr King serves as a consultant to Capricor, Stentys, Harvard Clinical Research Institute, Merck, Cardiovascular Research Foundation, Mount Sinai School of Medicine, and Baim Institute for Clinical Research (outside the submitted work). Dr Schneider has received a grant and support for travel to meetings for the study or other purposes from the NIH. Dr Frye has received grants from the NIH, Glaxo, SmithKline and other industry. The other authors report no competing interests.

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© 2019 Mayo Foundation for Medical Education and Research

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10.1016/j.mayocp.2019.04.015

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@article{0a58a665c4e14b5f88bb475034ac80c0,

title = "BARI 2D: A Reanalysis Focusing on Cardiovascular Events",

abstract = "OBJECTIVE: To reanalyze the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial using a new composite cardiovascular disease (CVD) outcome to determine how best to treat patients with type 2 diabetes mellitus and stable coronary artery disease.PATIENTS AND METHODS: From January 1, 2001, to November 30, 2008, 2368 patients with type 2 diabetes mellitus and angiographically proven coronary artery disease were randomly assigned to insulin-sensitizing (IS) or insulin-providing (IP) therapy and simultaneously to coronary revascularization (REV) or no or delayed REV (intensive medical therapy [MED]), with all patients receiving intensive medical treatment. The outcome of this analysis was a composite of 8 CVD events.RESULTS: Four-year Kaplan-Meier rates for the composite CVD outcome were 35.8% (95% CI, 33.1%-38.5%) with IS therapy and 41.6% (95% CI, 38.7%-44.5%) with IP therapy (P=.004). Much of this difference was associated with lower in-trial levels of fibrinogen, C-reactive protein, and hemoglobin A 1c with IS therapy. Four-year composite CVD rates were 32.7% (95% CI, 30.0%-35.4%) with REV and 44.7% (95% CI, 41.8%-47.6%) with MED (P<.001). A beneficial effect of IS vs IP therapy was present with REV (27.7%; 95% CI, 24.0%-31.4% vs 37.5%; 95% CI, 33.6%-41.4%; P<.001), but not with MED (43.6%; 95% CI, 39.5%-47.7% vs 45.7%; 95% CI, 41.6%-49.8%; P=.37) (homogeneity, P=.05). This interaction between IS therapy and REV was limited to participants preselected for coronary artery bypass grafting (CABG). The lowest composite CVD rates occurred in patients preselected for CABG and assigned to IS therapy and REV (17.3%; 95% CI, 11.8%-22.8%). CONCLUSION: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, the IS treatment strategy and the REV treatment strategy each reduces cardiovascular events. The combination of IS drugs and CABG results in the lowest risk of subsequent CVD events.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006305.",

author = "{BARI 2D Study Group} and Genuth, {Saul M.} and Helen Vlachos and Brooks, {Maria Mori} and Bantle, {John P.} and Chaitman, {Bernard R.} and Jennifer Green and Kelsey, {Sheryl F.} and King, {Spencer B.} and Robert McBane and Sako, {Edward Y.} and Schneider, {David J.} and Michael Steffes and Frye, {Robert L.}",

note = "Funding Information: Grant Support: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study is funded by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (grant nos. U01 HL061744, U01 HL061746, U01 HL061748, and U01 HL063804), with significant supplemental funding from GlaxoSmithKline. A full listing of all sponsors can be found in the Supplementary Appendix available at NEJM.org. (N Engl J Med. 2009;360(24):2503-2515). As a National Institutes of Health (NIH)?funded trial, we are required to abide by the NIH PubMed Central Policy that we retain the right to provide a copy of the final manuscript to the NIH upon acceptance for publication by your journal, for public archiving in PubMed Central as soon as possible, but no later than 12 months after publication. Maria Mori Brooks, PhD, serves as the guarantor of this manuscript.Potential Competing Interests: Dr Green has received a grant, support for travel to meetings for the study or other purposes, and support for medicines and equipment from Duke University via funds received from the National Institute of Diabetes and Digestive and Kidney Diseases. She is a board member of Novo Nordisk (outside the submitted work); serves as a consultant to AstraZeneca, Boehringer Ingelheim, Daiichi, and Merck (outside the submitted work); and has received grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi (outside the submitted work). Dr Sako has received support for travel to meetings for the study or other purposes from the BARI 2D study. He owns stocks in Medtronic (outside the submitted work). Dr Brooks has received grants from the National Institutes of Health (NIH) and pharmaceutical companies. Dr Bantle has received a grant from the NIH. Dr Chaitman has received a grant from Saint Louis University. He serves as a consultant to Novo Nordisk, Eli Lilly, and Merck (outside the submitted work). Dr King serves as a consultant to Capricor, Stentys, Harvard Clinical Research Institute, Merck, Cardiovascular Research Foundation, Mount Sinai School of Medicine, and Baim Institute for Clinical Research (outside the submitted work). Dr Schneider has received a grant and support for travel to meetings for the study or other purposes from the NIH. Dr Frye has received grants from the NIH, Glaxo, SmithKline and other industry. The other authors report no competing interests. Publisher Copyright: {\textcopyright} 2019 Mayo Foundation for Medical Education and Research",

year = "2019",

month = nov,

doi = "10.1016/j.mayocp.2019.04.015",

language = "English (US)",

volume = "94",

pages = "2249--2262",

journal = "Mayo Clinic Proceedings",

issn = "0025-6196",

publisher = "Elsevier Ltd",

number = "11",

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TY - JOUR

T1 - BARI 2D

T2 - A Reanalysis Focusing on Cardiovascular Events

AU - BARI 2D Study Group

AU - Genuth, Saul M.

AU - Vlachos, Helen

AU - Brooks, Maria Mori

AU - Bantle, John P.

AU - Chaitman, Bernard R.

AU - Green, Jennifer

AU - Kelsey, Sheryl F.

AU - King, Spencer B.

AU - McBane, Robert

AU - Sako, Edward Y.

AU - Schneider, David J.

AU - Steffes, Michael

AU - Frye, Robert L.

N1 - Funding Information: Grant Support: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study is funded by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (grant nos. U01 HL061744, U01 HL061746, U01 HL061748, and U01 HL063804), with significant supplemental funding from GlaxoSmithKline. A full listing of all sponsors can be found in the Supplementary Appendix available at NEJM.org. (N Engl J Med. 2009;360(24):2503-2515). As a National Institutes of Health (NIH)?funded trial, we are required to abide by the NIH PubMed Central Policy that we retain the right to provide a copy of the final manuscript to the NIH upon acceptance for publication by your journal, for public archiving in PubMed Central as soon as possible, but no later than 12 months after publication. Maria Mori Brooks, PhD, serves as the guarantor of this manuscript.Potential Competing Interests: Dr Green has received a grant, support for travel to meetings for the study or other purposes, and support for medicines and equipment from Duke University via funds received from the National Institute of Diabetes and Digestive and Kidney Diseases. She is a board member of Novo Nordisk (outside the submitted work); serves as a consultant to AstraZeneca, Boehringer Ingelheim, Daiichi, and Merck (outside the submitted work); and has received grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi (outside the submitted work). Dr Sako has received support for travel to meetings for the study or other purposes from the BARI 2D study. He owns stocks in Medtronic (outside the submitted work). Dr Brooks has received grants from the National Institutes of Health (NIH) and pharmaceutical companies. Dr Bantle has received a grant from the NIH. Dr Chaitman has received a grant from Saint Louis University. He serves as a consultant to Novo Nordisk, Eli Lilly, and Merck (outside the submitted work). Dr King serves as a consultant to Capricor, Stentys, Harvard Clinical Research Institute, Merck, Cardiovascular Research Foundation, Mount Sinai School of Medicine, and Baim Institute for Clinical Research (outside the submitted work). Dr Schneider has received a grant and support for travel to meetings for the study or other purposes from the NIH. Dr Frye has received grants from the NIH, Glaxo, SmithKline and other industry. The other authors report no competing interests. Publisher Copyright: © 2019 Mayo Foundation for Medical Education and Research

PY - 2019/11

Y1 - 2019/11

N2 - OBJECTIVE: To reanalyze the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial using a new composite cardiovascular disease (CVD) outcome to determine how best to treat patients with type 2 diabetes mellitus and stable coronary artery disease.PATIENTS AND METHODS: From January 1, 2001, to November 30, 2008, 2368 patients with type 2 diabetes mellitus and angiographically proven coronary artery disease were randomly assigned to insulin-sensitizing (IS) or insulin-providing (IP) therapy and simultaneously to coronary revascularization (REV) or no or delayed REV (intensive medical therapy [MED]), with all patients receiving intensive medical treatment. The outcome of this analysis was a composite of 8 CVD events.RESULTS: Four-year Kaplan-Meier rates for the composite CVD outcome were 35.8% (95% CI, 33.1%-38.5%) with IS therapy and 41.6% (95% CI, 38.7%-44.5%) with IP therapy (P=.004). Much of this difference was associated with lower in-trial levels of fibrinogen, C-reactive protein, and hemoglobin A 1c with IS therapy. Four-year composite CVD rates were 32.7% (95% CI, 30.0%-35.4%) with REV and 44.7% (95% CI, 41.8%-47.6%) with MED (P<.001). A beneficial effect of IS vs IP therapy was present with REV (27.7%; 95% CI, 24.0%-31.4% vs 37.5%; 95% CI, 33.6%-41.4%; P<.001), but not with MED (43.6%; 95% CI, 39.5%-47.7% vs 45.7%; 95% CI, 41.6%-49.8%; P=.37) (homogeneity, P=.05). This interaction between IS therapy and REV was limited to participants preselected for coronary artery bypass grafting (CABG). The lowest composite CVD rates occurred in patients preselected for CABG and assigned to IS therapy and REV (17.3%; 95% CI, 11.8%-22.8%). CONCLUSION: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, the IS treatment strategy and the REV treatment strategy each reduces cardiovascular events. The combination of IS drugs and CABG results in the lowest risk of subsequent CVD events.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006305.

AB - OBJECTIVE: To reanalyze the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial using a new composite cardiovascular disease (CVD) outcome to determine how best to treat patients with type 2 diabetes mellitus and stable coronary artery disease.PATIENTS AND METHODS: From January 1, 2001, to November 30, 2008, 2368 patients with type 2 diabetes mellitus and angiographically proven coronary artery disease were randomly assigned to insulin-sensitizing (IS) or insulin-providing (IP) therapy and simultaneously to coronary revascularization (REV) or no or delayed REV (intensive medical therapy [MED]), with all patients receiving intensive medical treatment. The outcome of this analysis was a composite of 8 CVD events.RESULTS: Four-year Kaplan-Meier rates for the composite CVD outcome were 35.8% (95% CI, 33.1%-38.5%) with IS therapy and 41.6% (95% CI, 38.7%-44.5%) with IP therapy (P=.004). Much of this difference was associated with lower in-trial levels of fibrinogen, C-reactive protein, and hemoglobin A 1c with IS therapy. Four-year composite CVD rates were 32.7% (95% CI, 30.0%-35.4%) with REV and 44.7% (95% CI, 41.8%-47.6%) with MED (P<.001). A beneficial effect of IS vs IP therapy was present with REV (27.7%; 95% CI, 24.0%-31.4% vs 37.5%; 95% CI, 33.6%-41.4%; P<.001), but not with MED (43.6%; 95% CI, 39.5%-47.7% vs 45.7%; 95% CI, 41.6%-49.8%; P=.37) (homogeneity, P=.05). This interaction between IS therapy and REV was limited to participants preselected for coronary artery bypass grafting (CABG). The lowest composite CVD rates occurred in patients preselected for CABG and assigned to IS therapy and REV (17.3%; 95% CI, 11.8%-22.8%). CONCLUSION: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, the IS treatment strategy and the REV treatment strategy each reduces cardiovascular events. The combination of IS drugs and CABG results in the lowest risk of subsequent CVD events.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006305.

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ER -

BARI 2D: A Reanalysis Focusing on Cardiovascular Events

Abstract

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