Transradial PCI May Attenuate Bivalirudin Benefits

Bivalirudin reduces bleeding during transfemoral PCI compared with heparin, whether the latter drug is given alone or with glycoprotein IIb/IIIa inhibitors (GPIs), but the effect is minimal or nonexistent during transradial interventions, according to an observational study published online September 16, 2015, ahead of print in the European Heart Journal.

“Our data suggest that heparin as opposed to bivalirudin should be the preferred anticoagulant during transradial intervention due to its lower cost and comparable bleeding outcomes,” Hitinder S. Gurm, MD, of the University of Michigan Health System (Ann Arbor, MI), and colleagues say.

The researchers looked at data on 132,113 patients undergoing PCI between January 2010 and March 2014 at the 47 nonfederal hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium. Most of the procedures (84.3%) were performed using transfemoral access, and the rest were done through the radial artery.

Access Site Influences Relative Drug Benefit

After propensity matching, there were 20,245 patient pairs for the comparison of bivalirudin vs heparin plus GPIs and 25,852 pairs for the comparison of bivalirudin vs heparin monotherapy in the patients treated transfemorally. In the transradial cohort, there were 3,539 and 5,221 pairs for the comparisons of bivalirudin with heparin plus GPIs and with heparin monotherapy, respectively.

Bivalirudin was associated with clear reductions in presumed major bleeding and National Cardiovascular Data Registry (NCDR)-defined bleeding within 72 hours relative to both heparin groups in the transfemoral cohort (table 1).

 

In the transradial cohort, bleeding reductions with bivalirudin were attenuated vs heparin plus GPIs and were no longer significant vs heparin monotherapy (table 2).

Bivalirudin was not associated with less in-hospital mortality compared with heparin, whether with or without GPIs, in either the transfemoral or the transradial group.

In a post hoc analysis, bleeding rates were equivalent between bivalirudin and heparin monotherapy in the transradial group irrespective of patients’ baseline bleeding risk or presentation (ACS vs non-ACS). Bivalirudin reduced NCDR-defined bleeding in all subgroups within the transfemoral cohort, except for those in the lowest tercile of baseline bleeding risk.

Stent thrombosis rates were low, and there were no differences between bivalirudin and heparin monotherapy regardless of access site. In the transfemoral cohort only, however, bivalirudin was tied to a greater risk of stent thrombosis compared with heparin plus GPIs (0.40% vs 0.19%; OR 2.15; 95% CI 1.44-3.27).

Heparin Monotherapy Preferred for Transradial PCI?

Prior studies have shown that transradial access and bivalirudin individually reduce bleeding risk in patients undergoing PCI, but whether bivalirudin adds benefit on top of radial access has remained unclear, according to the authors.

The current findings are consistent with those of other observational analyses, including a retrospective study showing that bivalirudin had a clinical benefit vs heparin during transfemoral but not transradial procedures.

In the randomized EUROMAX trial, bivalirudin reduced bleeding vs heparin with routine or bailout use of GPIs in STEMI patients. However, the trial included both transfemoral and transradial procedures, making it difficult to tease out the effects of access type, according to Dr. Gurm and colleagues.

More recently, the MATRIX trial showed no reduction in MACE or net adverse clinical events with bivalirudin vs heparin during transradial interventions, although there were reductions in bleeding with bivalirudin. However, GPIs were used 5 times more frequently in heparin patients as in bivalirudin patients (26% vs 4.6%).

“This suggests that the use of heparin monotherapy with radial access is as effective at minimizing bleeding complications as bivalirudin,” the authors say.

Dr. Gurm told TCTMD in an email that the current data are strong enough to support preferential use of heparin over bivalirudin for transradial procedures. “The near equivalence of the 2 drugs in this large cohort and the marked cost difference makes it an easy decision,” he said. “I and most of my colleagues have switched to using heparin only as the preferred agent for radial PCI at our center. I know of other major centers that had moved away from bivalirudin even earlier, and I guess they were right.”

Although the cost-effectiveness of bivalirudin vs heparin with a GPI has been established in transfemoral patients, cost-effectiveness is less clear vs heparin monotherapy, he and his colleagues note.

The finding of “nearly identical” outcomes in the heparin monotherapy and bivalirudin groups within the transradial cohort “suggests that use of bivalirudin cannot be cost-effective when compared with heparin during radial PCI,” they write. “Furthermore, among patients undergoing [transradial intervention], the absolute difference in bleeding events among patients treated with bivalirudin with provisional GPI compared with heparin with GPI was small and invokes the need to reassess the cost effectiveness of this approach in this cohort.”

Dr. Gurm and colleagues note that centers in the registry may not represent PCI centers across the United States and that the study may be subject to unmeasured residual confounding. There also was no information on dosing of antithrombotics or activated clotting time values and no way to differentiate between planned and bailout GPI use in the heparin-plus-GPI arm.

However, despite those caveats, the authors say the findings “for femoral-access patients align well with prior studies, suggesting that the results of our study are reliable and relevant to real-world practice.”

Source: 
Perdoncin E, Seth M, Dixon S, et al. The comparative efficacy of bivalirudin is markedly attenuated by use of radial access: insights from Blue Cross Blue Shield of Michigan Cardiovascular Consortium. Eur Heart J. 2015;Epub ahead of print.

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• MATRIX Provides Support for Radial Access, Mixed Results for Bivalirudin