SCAAR: Could Cheap Heparin Replace Pricy Bivalirudin in PCI for Non-STE-ACS?

Shelley Wood

May 21, 2013

PARIS, France – A new analysis from Sweden's SCAAR database is calling into question the use of bivalirudin (Angiomax, the Medicines Company) in the setting of PCI for patients with non-ST-elevation ACS.

Presenting the results here at EuroPCR 2013 , Dr Oskar Angeras (Sahlgrenska University Hospital, Gothenburg, Sweden) said that he and his colleagues are pushing forward with a randomized controlled trial to confirm the registry findings. But in the meantime, his hospital has already switched from bivalirudin to heparin.

"The major impact this has is mainly economical," Angeras said. "Heparin is extremely cheap; bivalirudin is expensive."

And bivalirudin was never tested directly against heparin alone, he explained. In ACUITY, HORIZONS , and ISAR-REACT 4 , bivalirudin was tested against GP IIb/IIIa inhibitors plus heparin in different settings. In the smaller BAT and ISAR-REACT 3 trials, bivalirudin reduced major bleeding compared with heparin, but composite primary end points that included bleeding were no different, and these trials were conducted when only femoral-access PCI was used, and most randomized patients were biomarker negative.

"If you look at the ACUITY study or other studies, the effects are mainly on bleeding; you can't see any mortality differences in the large trials that have been conducted. So we wanted to look only mortality, and I think that's more important than bleeding."

Retrospective Analysis

Angeras and colleagues reviewed rates of 30-day mortality among 41 537 consecutive non-STE ACS patients who received PCI in Sweden over a six-year period, none of whom received GP IIb/IIIa inhibitors. They then used two logistical-regression models to best match patients, and one instrumental-variable model (that took into account unknown confounders) to look for any benefits of one approach over the other.

In all, roughly three times as many patients were treated with heparin alone than with bivalirudin. In the two logistical-regression models, rates of 30-day mortality were lower among heparin-treated patients, although the superiority of heparin disappeared in the instrumental-variable analysis (although here, too, the trend was in favor of heparin over bivalirudin).

The findings were no different across a number of subgroup analyses, including analyses by age, gender, diabetes status, and PCI access site, Angeras reported.

Bivalirudin carries a class 1b recommendation in the European guidelines for non-STE ACS PCI and a class 2a recommendation in the AHA/ACC guidelines.

"It is not a guideline recommendation to use heparin in non-STEMI, that's why it's so important to study this question," he told the media in an early-morning press conference. He also noted that GP IIb/IIIa inhibitor use in Sweden for non-STEMI is only 10%.

"Our large observational study questions the superiority of bivalirudin over heparin in the absence of GP IIb/IIIa blockade in patients with NSTE-ACS undergoing PCI," he said.

Cost-Saving Strategy

To heartwire , Angeras said that bivalirudin had been the antithrombotic of choice for non-STE ACS PCI at his hospital, "so for us, these findings were a surprise." Elsewhere in Sweden, however, most hospitals preferentially use heparin in this setting. Angeras said his hospital has now switched to using heparin and is using the cost savings to increase its use of drug-eluting stents (DES). "DES frequency has gone from about 20% to 80% at our hospital, and bivalirudin the opposite."

Asked to comment on the SCAAR data, Dr Alexander Abizaid (Institute Dante Pazzanese de Cardiologia, São Paulo, Brazil) said: "I think that these are not definitive data. It's an important piece of information because of the number of patients, the sample size, but my take is that we still have to do a randomized trial in the modern era of radial approach."

Abizaid also noted that bivalirudin was never tested in the setting of ticagrelor (Brilinta, AstraZeneca), and ticagrelor is the antiplatelet drug of choice in Sweden and much of Europe in this setting. Bivalirudin is not approved in Brazil, Abizaid added, so his hospital uses heparin and GP IIb/IIIa inhibitors.

Another open question is the bleeding complications. During the hotline session, Angeras noted that the bleeding events as recorded in SCAAR were not consistent, particularly early on, with little differentiation between types of bleeds. "So we are little bit cautious about [interpreting] the bleeding complications in the registry."

Also discussing the findings, Dr Andreas Baumbach (University of Bristol, UK) pointed out that the complicated statistical modeling at the heart of the SCAAR study may have ended up obscuring the essential fact that the decision to use heparin over bivalirudin, or vice versa, arises from individual patient characteristics. When patients are closely matched for the purposes of the model, it's not surprising that a mortality difference disappears, he said.

Heat and Light From Ongoing Studies

Angeras acknowledged this limitation and said this underscores the need for a randomized trial such as the one he and his colleagues are now doing. VALIDATE-SWEDEHEART, he said, is enrolling 6000 STEMI and non-STEMI patients, randomized equally to heparin or bivalirudin. The primary end point is death, MI, or major bleeding at 180 days.

Other ongoing studies, described in detail at EuroPCR today, will also shed light on this question. EUROMAX is randomizing 2200 patients to unfractionated heparin (with routine or bailout GP IIb/IIIa inhibition) or bivalirudin during ambulance transfer for PCI. The results should be ready by TCT 2013, lead investigator Dr Gabriel Steg (Centre Hospitalier Bichaut-Claude Bernard, Paris, France) announced.

The second, HEAT-PPCI , is randomizing 1800 STEMI patients to a moderate heparin dose or bivalirudin in the hospital. Of special interest, said Dr Rod Stables (Royal Brompton Hospital, London, UK), HEAT-PPCI has received ethical approval to obtain postrandomization patient consent, to minimize as much as possible the door-to-balloon time in these patients.

Angeras had no disclosures. Abizaid disclosed receiving research grants from Abbott Vasculature, Boston Scientific, Elixir, and Medtronic. Disclosures for other speakers were unavailable.

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