Leukocyte Count Is a Modulating Factor for the Mortality Benefit of Bivalirudin in ST-Segment -Elevation Acute Myocardial Infarction: The HORIZONS-AMI Trial
Selected in Circulation Cardiovascular Interventions by M. Dobric
Palmerini T, Brener SJ, Mehran R, Dangas G, Genereux P, Riva DD, Mariani A, Xu K, Stone GW.
Circ Cardiovasc Interv. 2013 Oct 1;6(5):518-26.
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What is known
Anticoagulation with bivalirudin, as compared with heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI), in patients with STEMI undergoing primary PCI, has been shown to result in significantly lower rates of adverse clinical events. These beneficial effects are mainly attributed to the marked reduction in major bleeding, while alternative mechanisms have not been thoroughly investigated.
- Study is a subanalysis of the large Harmonizing Outcome with Revascularisation and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial, including 3,433 patients who had white blood cell (WBC) count at admission (95.3% of total trial population).
- At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with UFH plus GPI in patients in the upper WBC tertile (all-cause death: 4.1% versus 9.3%, respectively; P=0.0004; cardiac death: 2.0% versus 6.9%; respectively; P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles.
- The difference in mortality between bivalirudin and UFH plus GPI in patients in the upper WBC tertile occurred during the first year of follow-up, and a significant interaction between WBC tertiles and bivalirudin was apparent for both 1-year all-cause mortality and cardiac mortality.
- The significant interaction between bivalirudin therapy and WBC tertiles for 1-year mortality was independent of major bleeding.
This study shows interesting phenomenon of differential clinical benefit of bivalirudin according to baseline WBC count in STEMI patients treated with primary PCI. Patients with elevated WBC count (i.e. in upper WBC count tertile) were found to have lower rates of all-cause mortality and cardiac mortality when treated with bivalirudin as compared to anticoagulation based on UFH plus GPI. Such a benefit was not apparent in the lower and intermediate WBC count tertiles. Furtermore, study findings suggest that beneficial effects of bivalirudin might be even beyond its favourable bleeding profile, which is usually considered.
Authors proposed few inflammatory biological mechanisms as an explanation for these results, although it is still unknown whether WBCs are directly involved in the pathophysiological process or just represent a marker of still unknown causative process. Nevertheless, results of this study should be considered hypothesis-generating that may warrant further investigation.