Catheterization and Cardiovascular Interventions 89:414–415 (2017)
Editorial Comment Bivalirudin Versus Heparin for Peripheral Vascular Intervention: You Get What You Pay for. . . Carey Kimmelstiel,1* MD, FACC, FACP, FSCAI , and Efthymios N. Deliargyris,2 MD, FACC, FESC, FSCAI 1 Division of Cardiology, The Cardiac Catheterization Laboratory, Tufts Medical Center, Boston, Massachusetts 2 Science and Strategy Consulting Group, Basking Ridge, New Jersey
Key Points
There are no randomized trials comparing bivalirudin with heparin in patients undergoing peripheral vascular intervention. Retrospective analyses suggest that bivalirudin treatment during peripheral vascular intervention is associated with less bleeding and a reduction in major adverse clinical events. Despite a higher acquisition cost compared with heparin, bivalirudin may actually provide more value and possibly reduce the total cost of care associated with peripheral interventions.
Striking the optimal balance between preventing thrombosis and minimizing bleeding risk is a foundational principle for optimizing outcomes in patients with underlying atherothrombotic disease. There is no more challenging clinical scenario to maintain this balance than during interventional procedures where operators have to account for the additional prothrombotic impact of intravascular devices and iatrogenic plaque disruption while having to manage an arterial access site. Accordingly, adequate anticoagulation is crucial in order to limit ischemic complications and increase the likelihood of a successful procedure, but does add bleeding risk. Analysis of data derived from studies in populations undergoing percutaneous coronary intervention (PCI) have documented that patients experiencing a bleeding complication are at elevated risk of death and recurrent ischemic events [1]. C 2017 Wiley Periodicals, Inc. V
The similarities between PCI and peripheral vascular interventions (PVI) are obvious, ranging from overlapping patient populations with shared risk factors and comorbidities, treating physicians, procedural techniques, and adjunct pharmacology. It is therefore to be expected that PCI practices, including anticoagulant use, are increasingly extrapolated to the blooming field of PVI. Multiple trials have examined the direct thrombin inhibitor bivalirudin in patients undergoing PCI with the preponderance of evidence showing less bleeding and thrombocytopenia, comparable ischemic events and improved net clinical outcomes compared with heparin based regimens [2]. Can we expect that bivalirudin would perform as well in the PVI arena? In this issue of Catheterization and Cardiovascular Interventions, Ortiz et al. report a retrospective comparative analysis of heparin versus bivalirudin in patients undergoing infrainguinal PVI from the Vascular Quality Initiative Registry [3]. Propensity score matching (PSM) was employed to counter the potential for selection bias that may underlie nonrandomized data. The results from the comparison of 1,524 PSM pairs showed that bivalirudin treatment during PVI was associated with a lower rate of access site hematomas, shorter hospital length of stay (LOS), and lower rates of discharge to a nursing home or rehabilitation center. These findings are consistent and build on prior published data, not cited in the present study, where our group performed a similar analysis of bivalirudin versus heparin in a larger consecutive population of patients undergoing PVI from the Premier database. We showed that bivalirudin-treated patients experienced lower in-hospital mortality, need for blood product transfusion, major adverse cardiac events, and net adverse clinical events. These associations were consistent both in the overall unadjusted study population
Conflict of interest: C. Kimmelstiel has no conflicts to report. E. N. Deliargyris is a shareholder of The Medicines Company. *Correspondence to: Carey Kimmelstiel, Division of Cardiology, Tufts Medical Center, 750 Washington Street, Boston, MA 02111. E-mail:
[email protected] Received 29 December 2016; Revision accepted 30 December 2016 DOI: 10.1002/ccd.26938 Published online 17 February 2017 in Wiley Online Library (wileyonlinelibrary.com)
Bivalirudin Versus Heparin
and the 3,649 PSM pairs, and remained consistent in all clinically relevant subgroups [4]. Currently, both bivalirudin and heparin are used in PVI, however, there are no randomized studies comparing their relative efficacy and safety in this setting. In this situation, clinicians frequently rely on registries to provide insight into real-world clinical outcomes. Although the level of evidence generated from nonrandomized registry data is inferior when compared with randomized trials, and as such should always be interpreted with caution, the results presented here and in previous studies do provide valuable and reassuring information for clinicians as to the performance of bivalirudin in this population. In addition, Ortiz et al. are to be congratulated for performing an analysis that suggests a strong link between reductions in a relevant clinical outcome (i.e. access site bleeding) in patients undergoing PVI and improved efficiency and throughput of the care pathway. In an era of increasing sensitivity to the cost of care, the observations from both of these real world datasets suggest that the use of a treatment with higher acquisition cost may actually eventuate in cost savings via a reduction in hospital LOS and need for skilled nursing care following discharge. Making assessments based solely on the consideration of acquisition cost obscures true understanding of value in health care and leads to short-term cost containment efforts that are incremental, ineffective and sometimes even counterproductive. As defined by Porter, “value is
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defined as health outcomes achieved per dollar/pound/ euro spent” [5]. Many products that have higher initial acquisition costs produce better patient outcomes or reduce total costs of care compared to “cheaper” products, and are therefore considered to provide value for money. It is currently very popular to lobby for cheaper drugs, but maybe at the end of the day you end up getting exactly what you paid for.
REFERENCES 1. Eikelboom JW, Mehta SR, Anand SS, Xie C, Fox KA, Yusuf S. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006;114:774–782. 2. Bertrand OF, Jolly SS, Rao SV, Patel T, Belle L, Bernat I, Parodi G, Costerousse O, Mann T. Meta-analysis comparing bivalirudin versus heparin monotherapy on ischemic and bleeding outcomes after percutaneous coronary intervention. Am J Cardiol 2012;110:599–606. 3. Ortiz D, Singh M, Jahangir A, Allaqaband S, Khitha J, Bajwa TK, Mewissen MW. Bivalirudin versus unfractionated heparin during peripheral vascular interventions: A propensity-matched study. Catheter Cardiovasc Interv 2017;89:408–413. 4. Kimmelstiel C, Pinto D, Aronow HD, Weintraub AR, Dangas G, Fan W, Prats J, Deliargyris EN, Katzen BT. Bivalirudin is associated with improved in-hospital outcomes compared with heparin in percutaneous vascular interventions: Observational, propensity-matched analysis from the premier hospital database. Circ Cardiovasc Interv 2016;9: e002823. doi: 10.1161/CIRCINTERVENTIONS.115.002823. PMID: 26747849. 5. Porter ME. What is value in health care? N Engl J Med 2010; 363:2477–2481.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
