Original Investigation
Ticagrelor for Secondary Prevention of Atherothrombotic Events in Patients With Multivessel Coronary Disease

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Abstract

Background

Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events.

Objectives

The authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial.

Methods

Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months.

Results

A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HRadj]: 1.24; p = 0.026) and for coronary events (7.67% vs. 5.34%, HRadj: 1.49; p = 0.0005). In patients with MVD, ticagrelor reduced the risk of MACE (7.94% vs. 9.37%, HR: 0.82; p = 0.004) and coronary events (6.02% vs. 7.67%, HR: 0.76; p < 0.0001), including a 36% reduction in coronary death (HR: 0.64; 95% confidence interval: 0.48 to 0.85; p = 0.002). In this subgroup, ticagrelor increased the risk of TIMI major bleeding (2.52% vs. 1.08%, HR: 2.67; p < 0.0001), but not ICH or fatal bleeds.

Conclusions

Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

Key Words

cardiovascular outcomes
coronary disease
platelet

Abbreviations and Acronyms

CABG
coronary artery bypass graft
CI
confidence interval
CV
cardiovascular
DAPT
dual antiplatelet therapy
HR
hazard ratio
ICH
intracranial hemorrhage
KM
Kaplan-Meier
MACE
major adverse cardiovascular event(s)
MI
myocardial infarction
MVD
multivessel disease
NNT3yr
number needed to treat for 3 years
PAD
peripheral artery disease
PCI
percutaneous coronary intervention
TIMI
Thrombolysis In Myocardial Infarction

Cited by (0)

Dr. Angiolillo is the recipient of funding from the Scott R. MacKenzie Foundation and the National Institute of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Award to the University of Florida UL1 TR000064 and National Institutes of Health/National Human Genome Research Institute U01 HG007269, outside the submitted work. Dr. Bansilal has served on advisory boards of AstraZeneca, Merck, and Janssen; has received speaking or consulting fees from AstraZeneca and Janssen; has received research support from AstraZeneca; and is currently an employee of Bayer LLC, but not at the time of this research. Dr. Bonaca has received grant support to the TIMI Study Group from AstraZeneca and Merck; and has been a consultant to Aralez, AstraZeneca, Bayer, and Merck. Dr. Cornel has received personal fees from Merck, Eli Lilly, and AstraZeneca. Dr. Storey has received research grants and honoraria from AstraZeneca; research grants from PlaqueTec; and consultancy fees from Actelion, AstraZeneca, Avacta, Bayer, Bristol-Myers Squibb/Pfizer, Novartis, PlaqueTec, The Medicines Company, and Thermo Fisher Scientific. Dr. Bhatt has served on the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the board of directors of the Boston VA Research Institute and the Society of Cardiovascular Patient Care; served as chair of the American Heart Association Quality Oversight Committee; has served on data monitoring committees for the Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, and Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org), Belvoir Publications (editor in chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (CME steering committees); has other relationships with Clinical Cardiology (deputy editor), NCDR-ACTION Registry Steering Committee (chair), and VA CART Research and Publications Committee (chair); has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has been a site coinvestigator for Biotronik, Boston Scientific, and St. Jude Medical (now Abbott); has been a trustee for the American College of Cardiology; and has performed unfunded research for FlowCo, Merck, PLx Pharma, and Takeda. Dr. Steg has received research grants from Merck, Sanofi, and Servier; and speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, and Servier. Dr. Im and Ms. Murphy have received research grant support to their institution from AstraZeneca. Dr. Angiolillo has received individual fees or honoraria for consulting from Amgen, AstraZeneca, Bayer, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, PLx Pharma, Pfizer, and Sanofi; and for participating in review activities from CeloNova and St. Jude Medical; and has institutional payments for grants from Amgen, AstraZeneca, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Matsutani Chemical Industry Co., Merck, Novartis, and Renal Guard Solutions. Dr. Kiss has served on speakers bureaus for Bayer AG, Pfizer, Boehringer Ingelheim, and Merck Sharp & Dohme. Dr. Parkhomenko has received grants and personal fees from Pfizer, Bayer, Janssen, AstraZeneca, Sanofi, and Merck Sharp & Dohme outside the submitted work. Dr. Lopez-Sendon has received grants from Portola Pharmaceuticals, Pfizer, GlaxoSmithKline, Bayer; and grants and personal fees from Merck, AstraZeneca, Menarini, Merck Sharp & Dohme, and Sanofi. Dr. Goudev has received speaking honoraria and advisory board fees from AstraZeneca. Dr. Kontny has received honoraria for consultancy/advisory board membership from AstraZeneca and Merck & Co.; and lecture fees from Novartis. Drs. Held and Jansen are employees of AstraZeneca. Dr. Braunwald has received research grant support to his institution from AstraZeneca. Dr. Sabatine has received research grant support through Brigham and Women’s Hospital from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research Development, MedImmune, Merck, Novartis, Pfizer, Poxel, and Takeda (all >$10,000 per year); and has been a consultant for Amgen, CVS Caremark, Esperion, Intarcia, Ionis, MedImmune, and Merck (all ≤$10,000 per year except Amgen, Esperion, and Ionis). Dr. Oude Ophuis has received personal fees from TIMI during the conduct of the study; grant support and personal fees from Boston Scientific and Abbott; personal fees from AstraZeneca and Merck Sharp & Dohme; and nonfinancial support from Biosensor, WCN, and Vascular Research Network outside the submitted work. Dr. Isaza has reported that he has no relationships relevant to the contents of this paper to disclose. Michael S. Lee, MD, served as Guest Editor for this paper.

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