Clinical Study Data Request Registered Users, Please Login


Proposal 639

Title of the Proposed Research

Low-Dose vs Standard-Dose Unfractionated Heparin for Percutaneous Coronary Intervention in Acute Coronary Syndromes Treated With Fondaparinux in Patients with Peripheral Arterial Disease

Lead Researcher

Saurav Chatterjee, MD

Affiliation

St. Luke’s-Roosevelt Hospital of the Columbia University of Physicians and Surgeons New York, NY, USA

Funding Source

None

Potential Conflicts of Interest

None

Data Sharing Agreement Date

16 September 2013

Lay Summary

Background:
Heparin (a blood thinner) has long-been the anticoagulant of choice in patients with peripheral arterial disease (PAD) undergoing heart balloon and stent procedures. However, it has been debated if the newer generation blood thinners may provide better clinical outcomes in such patients, either by itself or as an adjunct (Mukherjee D, Eagle KA, Smith DE, Kline-Rogers EM, Chetcuti S, Grossman PM, Nallamothu BK, O'Donnell M, DeFranco A, Maxwell-Eward A, McGinnity J,. Meengs WM, Patel K, and Moscucci M. Impact of Extra-Cardiac Vascular Disease on Acute Prognosis in Patients Undergoing Percutaneous Coronary Interventions: Data From the Blue Cross & Blue Shield of Michigan Consortium [BMC2] Am J Cardiol 92 (8), 972-974; Nallamothu BK, Chetcuti S, Mukherjee D, Eagle, KA, Grossman P M, Giri K, McKechnie RS, Kline-Rogers E and Moscucci M. Long-term prognostic implication of extracardiac vascular disease in patients undergoing percutaneous coronary intervention Am J Cardiol 92 (8), 964-966).

How the research will add to medical science or improve patient care: There is paucity of data comparing effectiveness and safety of the combined use of newer anticoagulants like fondaparinux, and heparin-and as such presents an important lacuna in the knowledge of peri-procedural anticoagulation management in patients with PAD undergoing percutaneous coronary interventions (PCI).Also it has been noted that the incidence of PAD has been increasing world-wide (Fowkes FGR, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis. Lancet 2013; http://dx.doi.org/10.1016/S0140-6736(13)61249-0 . Available at: http://www.thelancet.com)-and hence identifying an optimal anticoagulation strategy in such patients with PAD undergoing PCI is an area of significant priority for investigation.

The aims and objectives of the research:
To compare the safety of 2 unfractionated heparin (UFH – a blood thinner) regimens during PCI in high-risk patients with PAD with non–ST-segment elevation acute coronary syndromes (heart attacks) initially treated with fondaparinux.

How the research will be conducted:
Design, Setting, and Participants-Patients with pre-existing PAD will be identified from the double-blind randomized parallel-group trial in 179 hospitals in 18 countries involving 2026 patients undergoing PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non–ST-segment elevation acute coronary syndromes (heart attacks) initially treated with fondaparinux enrolled from February 2009 to March 2010-as identified from the FUTURA/OASIS 8 trial dataset.

Interventions- Patients with PAD at baseline would have had received intravenously either low-dose unfractionated heparin, 50 U/kg, regardless of use of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors or standard-dose unfractionated heparin, 85 U/kg (60 U/kg with GpIIb-IIIa inhibitors), adjusted by blinded activated clotting time (ACT)-in addition to fondaparinux, before undergoing PCI. The two strategies of unfractionated heparin administration as an adjunct to fondaparinux in PAD subjects in the trial will be compared in this analysis to assess optimal blood thinner strategy.

How the findings will be interpreted and communicated:
Main outcome measures that will be evaluated-Composite of major bleeding, minor bleeding, or major vascular access-site complications up to 48 hours after PCI. Key secondary outcomes will include composite of major bleeding at 48 hours with death, myocardial infarction, or target vessel revascularization within day 30, as well as the individual clinical outcomes for the two strategies of heparin use in addition to fondaparinux.

Study Data Provided

Study AR1108888: FondaparinUx Trial with Unfractionated Heparin (UFH) during Revascularization in Acute Coronary Syndromes (ACS) (FUTURA). A prospective study evaluating the safety of two regimens of adjunctive intravenous UFH during PCI in high risk patients with Unstable Angina/Non ST segment elevation myocardial infarction (UA/NSTEMI) initially treated with subcutaneous fondaparinux and referred for early coronary angiography (OASIS 8)

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation