Low cardiac mortality with bivalirudin beyond the reduction in major bleeding

Original title: Reduction in Cardiac Mortality with Bivalirudin in Patients With and Without Major Bleeding: The HORIZONS-AMI Trial. Reference: Gregg W. Stone et al. J Am Coll Cardiol. Epub ahead of print

The HORIZONS -AMI study included 3602 patients experiencing ST  segment elevation myocardial infarction received primary angioplasty, resulting in lower mortality at 30 days and three years in those receiving  anticoagulation with bivalirudin (a direct inhibitor of thrombin) versus those who received heparin plus glycoprotein inhibitors .

The mechanism to explain this difference in mortality could be attributed to the reduction in the rate of major bleeding , however there may be other mechanisms. Treatment with bivalirudin resulted in lower mortality from all causes ( 5.9 % vesus 7.7 % , HR 0.75 , 95% CI 0.58 to 0.97 , P = 0.03 ) and lower cardiac mortality ( 2.9 % versus 5.1 % , HR = 0.56 , 95% CI 0.40 to 0.80 , P = 0.001 ) with a similar noncardiac mortality beyond the bleeding .Bivalirudin bleeding was also less at 3 years ( 6.9 % vrsus 10.5 % , HR = 0.64 , 95% CI 0.51 to 0.80 , P = 0.0001 ) and less reinfarction, unlike stroke rates , stent thrombosis, and revascularization which were similar between the two branches. Patients with major bleeding , as expected , showed increased mortality at 3 years compared with those who did not bleed . However, it is noteworthy that when evaluating only patients who bled , those who received bivalirudin had lower mortality than those who bled more with heparin plus IIbIIIa. Minor bleeding was not associated with mortality , whatever the treatment branch. Acquired thrombocytopenia was strongly associated with cardiac mortality and was significantly more frequent with heparin plus glycoprotein inhibitors.

Conclusion: 

Bivalirudin reduces cardiac mortality in patients experiencing  ST  segment elevation myocardial infarction received primary angioplasty.

Editorial Comment:

This effect on mortality can be only partially explained by the reduction in bleeding,  so more studies are needed to identify the benefit of bivalirudin non hematologic . Possible explanations are the reduction in inflammation and apoptosis besides improving post- ischemic cardiac function by blocking PAR-1 , and PAR -4 receptors.

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