SCAAR: Stent Thrombosis Risk After Primary PCI No Higher With Bivalirudin Than Other Antithrombotics

In a large, real-world population of STEMI patients, early stent thrombosis is equally rare regardless of whether bivalirudin, heparin, or a glycoprotein IIb/IIIa inhibitor (GPI) is used during primary PCI, according to a Swedish registry study presented February 14, 2015, at the Joint Interventional Meeting (JIM) in Rome, Italy.

Take Home: SCAAR: Stent Thrombosis Risk After Primary PCI No Higher With Bivalirudin Than Other Antithrombotics

Presenter David Erlinge, MD, PhD, of Skåne University Hospital (Lund, Sweden), and colleagues looked at data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), part of the national SWEDEHEART registry, on all patients who received a stent during primary PCI from January 2007 through July 2014.

Overall, 16,860 patients were given bivalirudin (Angiomax; The Medicines Company), 11,392 patients a GPI, and 3,246 patients heparin alone. Dr. Erlinge told TCTMD in an email that 4% of bivalirudin-treated patients received bailout GPIs and that nearly all GPI-treated patients also received heparin.

Those given GPIs were younger on average and less likely to be implanted with DES than those treated with bivalirudin or heparin. Use of P2Y12 inhibitors and radial access also tended to be less common in the GPI group.

The rate of Academic Research Consortium–defined definite stent thrombosis within 30 days of PCI (primary outcome) was low and similar across treatment groups:

  • Heparin alone: 0.92%
  • GPI: 0.90%
  • Bivalirudin: 0.84%

Rates for the first 24 hours after PCI and between 2 and 30 days also were similar across groups.

Among the bivalirudin-treated patients, those who developed stent thrombosis had a longer stent length, received more stents, were more likely to have diabetes, and were less likely to have undergone thrombus aspiration, received DES, or been treated with heparin.

What Happened in HEAT-PPCI?

Dr. Erlinge pointed out that the stent thrombosis rates observed in the SCAAR registry are consistent with those seen in most prior clinical trials—except for HEAT-PPCI, in which the rate of definite/probable stent thrombosis was 3.4% with bivalirudin vs 0.9% with heparin (P = .001).

He offered several reasons for the discrepancy, including the lack of early prehospital P2Y12 inhibition and the failure to give a prolonged infusion of bivalirudin after PCI in HEAT-PPCI. “We all know that it takes around 2 hours for ticagrelor [Brilinta; AstraZeneca] or prasugrel [Effient; Eli Lilly/Daiichi Sankyo] to get full effect,” he said in his email to TCTMD. “[The trial researchers] gave them late, just before the procedure, and stopped [bivalirudin] infusion immediately after the procedure.”

Dr. Erlinge also said that the HEAT-PPCI researchers did not systemically use prerandomization low-dose heparin—as is commonly done in Sweden—and that there is a “question about [activated clotting time (ACT)] values that were markedly lower in the bivalirudin group than in previous studies.”

The SCAAR analysis “demonstrates that the single-center HEAT-PPCI results were an outlier,” Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), one of the JIM course directors, told TCTMD in an email.

“This well-done study shows that in a very large patient population (much larger than any randomized trial), in an entire country, and across a broad spectrum of patient and lesion complexity, bivalirudin is associated with similar rates of acute and 30-day stent thrombosis compared with heparin alone or even heparin plus [GPIs],” commented Dr. Stone, who was the principal investigator for the ACUITY and HORIZONS-AMI trials..

To achieve these low rates, either early use of ticagrelor or prasugrel is recommended (or perhaps a single bolus of heparin or perhaps cangrelor when available) or a 3- to 4-hour postprocedure bivalirudin infusion at the PCI dose,” he added. “These measures will allow the benefits of bivalirudin in preventing bleeding, thrombocytopenia, and recurrent ischemia (and possibly lower cardiac mortality) to emerge compared with other regimens.”

At the Right Dose, Heparin “Hard to Beat”

HEAT-PPCI lead investigator Rod H. Stables, MD, of the Liverpool Heart and Chest Hospital (Liverpool, England), suggested to TCTMD that the reason why acute stent thrombosis was “so high” with bivalirudin in that trial is because patients “were treated with bivalirudin in accordance with the labelled dosing at the time. They did not receive any additional heparin or continued infusion of bivalirudin.” Both approaches, he said, would reduce stent thrombosis.

Moreover, “[t]here is no issue in HEAT with bivalirudin dosing or observed ACT values,” he stressed in an email, adding that relevant details were published in the Lancet paper’s supplementary appendix. “The Medicines Company oversaw the training of HEAT staff and use of bivalirudin in HEAT. The study used the correct dose regimes, producing the expected antithrombotic effect. It is time for the ‘ACT disinformation issue’ to be buried once and for all.”

Dr. Stables said he suspected that “antiplatelet therapy is not central to the avoidance of very early stent thrombosis…. The key is [an] adequate antithrombotic effect that is sustained for some hours after the index procedure.”

Overall, heparin at a dose of 60-70 U/kg “will be hard to beat,” he concluded. “Use of bivalirudin infusions pre- and post-PPCI will increase drug and nursing costs…. There are signals that the use of infusions may abolish the stent thrombosis hazard, but the overall safety and efficacy of the approach remain in doubt.”

Dr. Erlinge noted that it is difficult to directly compare drugs in a registry study because of the possibility of hidden confounders. Bivalirudin, for example, has been used “especially for frail patients with high bleeding risk,” he said, pointing out that bleeding complications could not be evaluated using the SCAAR data.

Bivalirudin will be further evaluated in the VALIDATE-SWEDEHEART registry–based randomized trial, which will compare bivalirudin and heparin in about 3,000 patients with STEMI and 3,000 with NSTEMI. It is expected to be completed by June 2016.

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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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Sources
  • Erlinge D. Predictors of stent thrombosis after primary PCI in the real-world: new insights from the SCAAR registry. Presented at: Joint Interventional Meeting; February 14, 2015; Rome, Italy.

Disclosures
  • Dr. Erlinge reports receiving speaker fees from AstraZeneca, Eli Lilly, and The Medicines Company.
  • Dr. Stone reports no relevant conflicts of interest.
  • Dr. Stables reports receiving grants from AstraZeneca and The Medicines Company.

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