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Observational Study
. 2017 Sep;40(9):710-718.
doi: 10.1002/clc.22721. Epub 2017 May 18.

Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry

Jérémie Abtan  1 , Deepak L Bhatt  2 , Yedid Elbez  1 , Emmanuel Sorbets  1   3 , Kim Eagle  4 , Christopher M Reid  5 , Iris Baumgartner  6 , David Wu  7 , Mary E Hanson  7 , Hakima Hannachi  7 , Puneet K Singhal  7 , Philippe Gabriel Steg  1   8 , Gregory Ducrocq  1 ; REACH Registry Investigators
Affiliations
Observational Study

Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry

Jérémie Abtan et al. Clin Cardiol. 2017 Sep.

Abstract

Background: Patients with symptomatic peripheral artery disease (PAD) are at high risk of ischemic events. However, data about predictors of this risk are limited.

Hypothesis: We analyzed baseline characteristics and 4-year follow-up of patients enrolled in the international REduction of Atherothrombosis for Continued Health (REACH) Registry with symptomatic PAD and no history of stroke/transient ischemic attack to describe annual rates of recurrent ischemic events globally and geographically.

Methods: The primary outcome was systemic ischemic events (composite of cardiovascular death, myocardial infarction, or stroke) at 4 years. The secondary outcome was limb ischemic events (composite of lower limb amputation, peripheral bypass graft, and percutaneous intervention for PAD) at 2 years. Multivariate analysis identified risk factors associated with recurrent ischemic events.

Results: The primary endpoint rate reached 4.7% during the first year and increased continuously (by 4%-5% each year) to 17.6% by year 4, driven mainly by cardiovascular mortality (11.1% at year 4). Japan experienced lower adjusted ischemic rates (P < 0.01) vs North America. Renal impairment (P < 0.01), congestive heart failure (P < 0.01), history of diabetes (P < 0.01), history of myocardial infarction (P = 0.01), vascular disease (single or poly, P < 0.01), and older age (P < 0.01) were associated with increased risk of systemic ischemic events, whereas statin use was associated with lower risk (P = 0.03). The limb ischemic event rate was 5.7% at 2 years.

Conclusions: Four-year systemic ischemic risk in patients with PAD and no history of stroke or transient ischemic attack remains high, and was mainly driven by cardiovascular mortality.

Keywords: Ischemic Risk; Peripheral Artery Disease; Vorapaxar.

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Conflict of interest statement

Dr. Deepak L. Bhatt discloses the following relationships: Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; Honoraria: 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), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR‐ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Amarin, Amgen, AstraZeneca, Bristol‐Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site coinvestigator: Biotronik, Boston Scientific, St. Jude Medical; Trustee: American College of Cardiology; Unfunded Research: FlowCo, PLx Pharma, Takeda. Dr. Philippe Gabriel Steg discloses the following relationships: research grant from Merck, Sanofi, and Servier; speaking or consulting fees from Amarin, AstraZeneca, Bayer, Boehringer‐Ingelheim, Bristol‐Myers‐Squibb, CSL‐Behring, Daiichi‐Sankyo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Servier, The Medicines Company. Dr. David Wu, Dr. Mary E. Hanson, Dr. Hakima Hannachi, and Dr. Puneet K. Singhal are employees of Merck & Co., Inc., and own stock and/or stock options in the company. Dr. Gregory Ducrocq discloses the following relationships: speaker's and/or consulting fees from Astra Zeneca, Biotronik, BMIS, Daiichi Sankyo and Lilly; Advisory Board: Lilly; CEC: Sanofi and Phillips; DSMB: Abbot and MicroPort; and travel fees from Astra Zeneca.

A full list of the REACH Registry investigators can be found in Bhatt DL, Steg PG, Ohman EM, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006;295:180–189.

Figures

Figure 1
Figure 1
Cumulative incidence rates of primary outcome of CV death, MI, or stroke for post‐MI patients with no history of TIA/stroke. Abbreviations: CV, cardiovascular; MI, myocardial infarction; TIA, transient ischemic attack
Figure 2
Figure 2
Cumulative incidence rates of cardiovascular outcomes in PAD patients with no history of stroke or TIA by year of follow‐up. Abbreviations: MI, myocardial infarction; PAD, peripheral artery disease; TIA, transient ischemic attack
Figure 3
Figure 3
Hazard ratio for the primary outcome of cardiovascular death, MI, or stroke for post‐MI patients with no history of TIA/stroke according to geographic regions after adjustment with the REACH risk score. Abbreviations: CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; NA, not applicable; TIA, transient ischemic attack
Figure 4
Figure 4
Hazard ratios of determinants for the primary outcome of CV death, nonfatal MI, and nonfatal stroke estimated by multivariate Cox models in PAD patients with no history of TIA/stroke. Abbreviations: ACE, angiotensin‐converting enzyme; CI, confidence interval; CV, cardiovascular; EU, Europe; HR, hazard ratio; MI, myocardial infarction; PAD, peripheral artery disease; TIA, transient ischemic attack; US, United States
See this image and copyright information in PMC

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