Bivalirudin Shows Advantage Over GPIs—But Not Heparin Alone—in STEMI Patients

Compared with glycoprotein IIb/IIIa inhibitors (GPIs), the antithrombin agent bivalirudin reduces the risk of bleeding complications in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), according to data from a large Canadian registry. However, the study, published online November 13, 2012, ahead of print in Circulation: Cardiovascular Interventions, was not able to detect an advantage with bivalirudin over heparin alone.

Investigators led by Michel R. Le May, MD, of the University of Ottawa Heart Institute (Ottawa, Canada), looked at outcomes of patients in the Ottawa STEMI Registry who were treated between July 2004 and December 2010. Adjuvant antithrombotic therapy included bivalirudin with provisional GPI use (n = 748), GPIs (n = 699), and unfractionated heparin alone (n = 676).

GPI Patients Fare Worst of All

Compared with GPI use, bivalirudin resulted in a 4.6% absolute reduction in the rate of non-CABG-related TIMI major bleeding, the primary outcome. There was no significant reduction in bleeding compared with heparin alone. Bivalirudin also reduced the secondary composite endpoint of in-hospital death, major bleeds, stroke, and reinfarction compared with GPIs, but not heparin (table 1).

Table 1. Primary and Secondary Endpoints

^a  P < 0.001 for comparison of bivalirudin vs. GPI.
^b P = 0.59 for comparison of bivalirudin vs. heparin.
^c P = 0.02 for comparison of bivalirudin vs. GPI.
^d P = 0.83 for comparison of bivalirudin vs. heparin.

Propensity score-adjusted analysis confirmed that in-hospital major bleeds occurred less frequently with bivalirudin compared with GPIs (OR 2.96; 95% CI 1.60-5.45; P < 0.001) but not compared with heparin alone (OR 1.21; 95% CI 0.60-2.43; P = 0.58). Notably, propensity score adjustment demonstrated that the composite outcome occurred less frequently with bivalirudin compared with GPI and heparin combined (OR 1.62; 95% CI 1.07-2.44; P = 0.02). However, as with the primary endpoint, no difference was observed when bivalirudin was compared with heparin alone (OR 1.05; 95% CI 0.68-1.63; P = 0.83).

Bleeding complications were common. However, patients receiving either bivalirudin or heparin experienced approximately half the number of major bleeding complications (3.1% and 3.6%, respectively) as patients receiving GPI (7.4%). There also was a marked reduction in the risk of TIMI minor bleeds in the bivalirudin and heparin groups (4.1% and 9.5%, respectively) compared with the GPI group (13.2%). The risk of transfusion, however, did not differ between treatment arms.

Although the overall mortality rate at 180 days was low for the cohort (6.2%), patients who experienced major bleeds had a fivefold increase in mortality. Interestingly, there was a numerical increase in stent thrombosis in the bivalirudin group (1.9%) compared with the GPI and heparin groups (1.0% and 0.6%, respectively).

Confirmatory, But Not Conclusive

According to the authors, the data “add to the growing evidence that bivalirudin confers equivalent reductions in ischemic endpoints with an improved safety profile.” In addition, they say, the finding of a fivefold increase in the risk of death out to 180 days in patients with major bleeding confirms “the prognostic implication of bleeding seen in data from randomized control trials.”

Importantly, they add, the current results compliment data from the HORIZONS trial and “confirm the efficacy and safety of bivalirudin in a cohort of unselected patients managed by [primary PCI].” The latter is important, Dr. Le May and colleagues note, because it suggests the findings from randomized trials of bivalirudin are applicable to clinical practice in a ‘real-world’ setting.

But unlike those trials, the Ottawa registry allowed for comparison of patients who received heparin only. The authors acknowledge that it is possible that the lack of difference between the bivalirudin and heparin groups may simply reflect the small sample size and resultant lack of statistical power. Regardless, they add, randomized trials are needed to demonstrate whether bivalirudin can be used preferentially over heparin.

Study Details

Baseline characteristics were similar between antithrombotic groups. However, fewer patients receiving bivalirudin presented in Killip class IV (1.5%) compared with GPI (4.9%) or heparin (3.7%; P < 0.001). In addition, more patients in the heparin group underwent radial PCI (26.2%) compared with the GPI (5.7%) or bivalirudin groups (5.6%; P < 0.001).

All patients received aspirin 160 mg to chew, a 600-mg load of clopidogrel followed by 75 mg daily, and an unfractionated heparin bolus of 60 U/kg to a maximum of 4,000 U at time of first medical evaluation by a physician.

 

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Source:
Hibbert B, MacDougall A, Labinaz M, et al. Bivalirudin for primary percutaneous coronary interventions: Outcome Assessment in the Ottawa STEMI registry. Circ Cardiovasc Interv. 2012;Epub ahead of print.

 

 

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• Registry Finds Overall Decrease in Post-PCI Bleeding but Not in STEMI
• Registry Confirms Bivalirudin Better for STEMI in ‘Real World’