Impact of Diabetes on Bivalirudin Safety and Efficacy in Acute Myocardial Infarction Patients

1. Impact Of Diabetes Mellitus On The Safety And Effectiveness Of Bivalirudin In Patients With Acute Myocardial Infarction Undergoing Primary Angioplasty: The HORIZONS AMI Trial Bernhard Witzenbichler, Giulio Guagliumi, Martin Desaga, Janusz Kochman, Dennis W. Nilsen, Ariel Finkelstein, Morris Mosseri, Helen Parise, Roxana Mehran, Gregg W. Stone

2. Background • Outcomes in the HORIZONS AMI trial were analyzed according to the presence of medically treated diabetes mellitus (DM) at the time of admission. • This subgroup analysis was pre-specified in the protocol / statistical analysis plan. • Since subgroups are generally underpowered, these analyses will be considered exploratory and hypothesis generating. Witzenbichler et al ACC 2008

3. Baseline characteristics • 593 of 3.599 study patients (16.5%) in HORIZONS had medically treated diabetes. Baseline characteristics demonstrate that diabetics represent a significantly higher risk group compared to non-diabetics. Witzenbichler et al ACC 2008

4. Baseline characteristics (ii) Witzenbichler et al ACC 2008

5. Endpoints in non-diabetics, by study drug • Non-Diabetics (n=3006) RR=0.60 [0.61, 0.94] P=0.006 RR=0.55 [0.41, 0.74] P=0.001 RR=1.14 [0.83, 1.56] P= n.s. • *MACE = All cause death, reinfarction, ischemic TVR or stroke Witzenbichler et al ACC 2008

6. Endpoints in diabetics, by study drug • Diabetics (n=593) RR=0.60 [0.61, 0.94] P=0.006 RR=0.55 [0.41, 0.74] P=0.001 RR=1.14 [0.83, 1.56] P= n.s. • *MACE = All cause death, reinfarction, ischemic TVR or stroke Witzenbichler et al ACC 2008

7. 30-day MACE components among diabetics Witzenbichler et al ACC 2008

8. 30 day bleeding endpoints among diabetics Witzenbichler et al ACC 2008

9. Conclusions • Compared to patients without diabetes mellitus, those with diabetes had greater rates of major bleeding (8.8% vs. 6.2%, P=0.02), MACE (8.1% vs. 5.0%, P=0.002) and NACE (14.2% vs. 10.0%, P=0.003). • Among the diabetic subgroup: • Bivalirudin significantly reduced cardiac death at 30 days (p=0.037). • Total and hemorrhagic stroke rate occurred more often in the UFH + GPI group, whereas non-cardiac death rate was slightly increased in the Bivalirudin group, although based on small patient numbers. • All other 30 day endpoints including stent thrombosis rate were not significantly different among diabetics between the two treatment arms • In patients with AMI undergoing primary PCI, Bivalirudin monotherapy significantly reduces major bleeding and net adverse clinical events, effects which are independent of diabetic status (interaction P value for major bleeding = 0.22, for MACE = 0.10, and NACE = 0.90). Witzenbichler et al ACC 2008