Transradial Approach May Balance Bleeding Benefits of Bivalirudin in Primary PCI

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The direct thrombin inhibitor bivalirudin is not associated with a reduction in major bleeding or adverse events compared with heparin and provisional glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing transradial primary percutaneous coronary intervention (PCI). The findings from a large registry study, which appeared online January 7, 2014, ahead of print in the European Heart Journal: Acute Cardiovascular Care, may be explained by already low bleeding rates associated with the transradial approach.

Researchers led by Alessandro Sciahbasi, MD, of Sandro Pertini Hospital (Rome, Italy) looked at 1,009 consecutive patients with ST-segment elevation myocardial infarction (STEMI) treated via transradial primary PCI at 3 Italian hospitals from January 2008 to June 2013. At the discretion of the operators, patients also received either bivalirudin (n = 154) or heparin plus provisional GPIs (n = 855). GPI use was 4% in the bivalirudin group and 55% in the heparin group (P < 0.001).

There were no significant differences between the 2 groups in procedural characteristics, including symptom-to-balloon times, number of stents implanted, mean stent length, or use of thrombectomy devices.

No Real Differences

At 30 days, the primary endpoint of major adverse cardiac events (MACE; death, reinfarction, TVF) was similar between the bivalirudin and heparin groups, as were individual and bleeding endpoints (table 1).

Table 1. Primary and Secondary Outcomes at 30 Days   

Net clinical endpoint: combination of primary hemorrhagic and ischemic endpoints.

When the heparin group was split according to GPI use, major bleeding remained similar (1% for heparin alone vs 1.27% for GPIs; P = 0.98). Minor bleeding, however, was increased with GPI use (2.3% vs. 0.5%; P = 0.03).

Independent predictors of bleeding were the use of intraaortic balloon pump therapy (OR 8.23; 95% CI 2.55-26.61; P < 0.001) and GPI use (OR 2.67; 95% CI 1.1-6.46; P = 0.029). After adjustment for propensity score, bivalirudin use was associated with a trend toward fewer major and minor bleeding complications (OR 0.04; 95% CI 0.002-1.03; P = 0.052).

“In this registry of primary PCI performed through the transradial approach, bivalirudin was not associated with a significant reduction in major bleeding or MACE compared to heparin and provisional [GPI use],” Dr. Sciahbasi and colleagues conclude.

They note that in previous randomized trials such as HORIZONS-AMI, bivalirudin was associated with significant bleeding and mortality reductions out to 30 days vs heparin and provisional GPI use in STEMI patients receiving primary PCI.

Nevertheless, they observe, “To date, few data are available for patients treated through transradial access in acute ST-elevation myocardial infarction.”

In the current study, Dr. Sciahbasi and colleagues point out, bivalirudin’s failure to reduce bleeding complications is probably due to a number of factors:

• The very low rate of overall bleeding complications, probably due to the transradial approach as demonstrated with previous studies
• The low number of patients enrolled, especially in the bivalirudin group
• The rate of GPI use, which was lower than in randomized trials “and could have resulted in a lower than expected rate of bleedings in the heparin group.”

Clinically Relevant Question

In an email communication with TCTMD, Sunil V. Rao, MD, of the Duke Clinical Research Institute (Durham, NC), agreed that the study may have been too underpowered to show any real difference in outcomes. “There may be an effect of radial access that decreases bleeding enough to blunt the effect of other bleeding avoidance strategies. Only a randomized trial will resolve this,” he said, adding that the results should probably not affect clinical decision making at this point. “It certainly is provocative and should lead to more discussion,” Dr. Rao said. “But I think we need to wait for the MATRIX trial before making any practice changes.”

Led by Marco Valgimigli, MD PhD, of University Hospital of Ferrara (Ferrara, Italy), MATRIX intends to compare intended transradial vs transfemoral intervention and bivalirudin monotherapy vs unfractionated heparin (UFH) plus GPI use in patients with ACS intended for an invasive management strategy.

As for the current study, the lack of randomization and small numbers is a problem, concurred Robert J. Applegate, MD, of Wake Forest School of Medicine (Winston-Salem, NC), in an email communication with TCTMD. “There are only 154 bivalirudin patients out of the entire 1,000-patient cohort, so there is substantial selection bias in the registry, and we don’t know what would have happened if the therapies were randomly assigned,” he said.

Nevertheless, “The question of whether bivalirudin is beneficial in radial [primary] PCI STEMIs is very relevant clinically,” Dr. Applegate stressed. “Interestingly, more than half of PCI bleeding is non-access site anyway so there is a logical belief that bivalirudin can help reduce the non-access site bleeding.  This will be affected by the bleeding risk of the patients studied, so if there is a low bleeding rate overall as seen in this study, the magnitude of benefit will be less.  Practically speaking, bivalirudin is a logical extension to bleeding reduction even in radial cases because of its effect on non-access site bleeding.”

 

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Source:
Sciahbasi A, Rigattieri S, Cortese B, et al. Bivalirudin or heparin in primary angioplasty performed through the transradial approach: results from a multicenter registry. Eur Heart J: Acute Cardiovasc Care. Epub ahead of print.

Disclosures:

• Dr. Sciahbasi reports receiving speaker honoraria from Bayer Healthcare.
• Dr. Rao reports serving as a consultant to both Terumo Medical and The Medicines   Company.
• Dr. Applegate reports no relevant conflicts of interest.

Related Stories:

• EUROMAX: Prehospital Bivalirudin Reduces Bleeding in STEMI
• Radial PCI Plus Bivalirudin Effective in Lowering Bleeding Risk
• In Transradial PCI, Bivalirudin Fails to Budge Event Rates vs. Heparin