Meta-analysis Questions One-Size-Fits-All Anticoagulant Strategy in STEMI Patients

“The result of the present study questions current practices and provides a thorough hierarchical analysis of the relative efficacy and safety of currently used anticoagulants for physicians to make a rational decision based on patients’ risk of bleeding versus thrombotic events,” Sripal Bangalore, MD, MHA, of the New York University School of Medicine (New York, NY), and colleagues write. “In other words, a ‘one-size-fits-all’ approach may not be wise.”

Heparin Plus GPI Best for Preventing Ischemic Events, Bivalirudin Better for Bleeding

The risks of MACE at 30 days (primary efficacy endpoint; death, MI, urgent TVR or TLR, or stroke) each were higher with unfractionated heparin, bivalirudin, and fondaparinux alone compared with unfractionated heparin plus GPI and LMWH plus GPI individually (table 1).

In a probability analysis, the hierarchy for treatment efficacy for MACE was:

• LMWH plus GPI
• Unfractionated heparin plus GPI
• Bivalirudin
• Unfractionated heparin
• Fondaparinux

However, for short-term major bleeding, bivalirudin carried lower risk than did unfractionated heparin, whether with GPI (RR 0.47; 95% CI 0.30-0.74) or without (RR 0.58; 95% CI 0.37-0.90).

Although there were no increases in death when each of the agents was compared with unfractionated heparin plus GPI, mortality with LMWH plus GPI was lower than with unfractionated heparin alone (RR 0.45; 95% CI 0.21-0.95) or fondaparinux (RR 0.39; 95% CI 0.16-0.97).

Additionally, compared with unfractionated heparin with or without a GPI, bivalirudin was associated with a 39% increase in MI, a 44% increase in urgent revascularization, and a 65% increase in stent thrombosis. However, the test for subgroup interaction was not significant (P for interaction > .05).

Overall, bivalirudin was associated with a 48% decrease in major bleeding compared with unfractionated heparin plus GPI (event rates of 2.40% vs 4.53%), a 32% decrease in major bleeding compared with unfractionated heparin (event rates of 2.36% vs 3.19%), a 47% decrease in minor bleeding compared with unfractionated heparin plus GPI (event rates of 4.08% vs 7.72%), and numerically lower minor bleeding compared with unfractionated heparin alone (event rates of 6.97% vs 8.44%).

Hence, the hierarchy for treatment safety was:

• Bivalirudin
• Unfractionated heparin
• LMWH plus GPI
• Unfractionated heparin plus GPI
• Fondaparinux  

Guidelines and Clinician Choice

The 2013 ACC/AHA guideline for management of STEMI patients recommends unfractionated heparin with or without planned GPI or bivalirudin as Class I indications for patients undergoing primary PCI, with a preference for bivalirudin over unfractionated heparin plus GPI in those at high risk of bleeding.

However, newly released 2014 European Society of Cardiology guidelines downgraded bivalirudin for STEMI from a Class 1 indication to a Class IIa based primarily on the findings of the controversial HEAT-PPCI trial, which compared bivalirudin with unfractionated heparin, both with bailout GPI use. Bivalirudin was associated with an increase in the primary ischemic outcome driven by more recurrent MI, revascularization, and stent thrombosis but offered no reduction in major bleeding. When the European guidelines were released, the task force noted that that the mortality benefit observed in HORIZONS-AMI was not confirmed by EUROMAX, in which the excess of stent thrombosis remained despite prolonged bivalirudin infusion.

“I think we are seeing a trend now toward more discussion, more awareness that the ‘one-size-fits-all-approach’ cannot be used when you have so many players in the equation,” Dr. Bangalore told TCTMD in a telephone interview. “No single trial has tested every available agent against each other, not to mention [PCI] access type and newer antiplatelets.”

The key message for clinicians, he said, “is that you have to individualize the risk of bleeding weighed against the risk of ischemic events when you are choosing these agents. I think our analysis helps to put these various agents into perspective.”

For instance, Dr. Bangalore continued, if a patient has a very high risk of bleeding, bivalirudin would be the obvious choice for femoral PCI.

On the other hand, in a patient with significant thrombus, bivalirudin might be useful, he said. “But this background knowledge would indicate to me to be aware of potential increased risk of stent thrombosis and maybe factor newer-generation stents or longer infusion time into the equation or to change tactics and use a more potent anticoagulant strategy, which would be heparin plus GPI.”

Disclosure:

• Dr. Bangalore reports no relevant conflicts of interest.

Related Stories:

• BRIGHT: Prolonged Bivalirudin Results in Comparable Stent Thrombosis, Reduced Bleeding vs. Heparin
• Meta-analysis: Less Bleeding, More Stent Thrombosis with Bivalirudin vs. Heparin After PCI
• Study Identifies Predictors of Stent Thrombosis, Mortality After Primary PCI