JACC: Bivalirudin safe alternative to heparin in diabetic STEMI patients
Bivalirudin (Angiomax, The Medicines Company) may be a viable alternative to heparin plus glycoprotein IIb/IIIa inhibitors (GPIs) in diabetic STEMI patients undergoing primary PCI, according to a substudy of HORIZONS-AMI trial results published in the July issue of JACC: Cardiovascular Interventions. In fact, patients who were administered bivalirudin saw reduced cardiac mortality at both 30 days and one year.
“Prior studies have demonstrated that GPIs are especially beneficial in patients with diabetes with acute coronary syndromes and/or those undergoing PCI,” wrote Bernhard Witzenbichler, MD, of the Charité Campus Benjamin Franklin in Berlin, and colleagues. “Bivalirudin is a direct thrombin inhibitor with anti-ischemic properties and favorable bleeding event rates when used in elective PCI, in acute coronary syndromes patients and STEMI patients treated with primary PCI.”
To evaluate whether bivalirudin could be useful in high-risk patients with diabetes and STEMI undergoing PCI, Witzenbichler and colleagues used the previously reported HORIZONS-AMI study design to assess the safety and efficacy of bivalirudin compared with GPI in this patient population undergoing primary PCI.
The prospective, randomized, multicenter HORIZONS-AMI trial enrolled 3,602 patients with STEMI who were randomized to receive bivalirudin alone or unfractionated heparin plus a GPI at a 1:1 ratio. The patients were randomized at a 3:1 ratio to receive either the Taxus Express paclitaxel-eluting stent (Boston Scientific) or an uncoated Express bare-metal stent (Boston Scientific).
Diabetes was present in 593 patients; 26.8 percent were treated with insulin, 54.3 percent were treated with oral medications without insulin and 18 percent were treated with diet alone. Of the 593 diabetic patients, 281 patients were randomized to receive treatment with bivalirudin and 312 patients were randomized to receive heparin treatment plus a GPI.
Witzenbichler et al reported that rates of cardiac death were lower in diabetic patients treated with bivalirudin versus those treated with heparin plus GPI at both 30 days and one year (30 days: 2.1 percent vs. 5.5 percent; one year: 2.5 percent vs. 7.1 percent).
Diabetic patients treated with bivalirudin also had lower rates of 30-day stroke events compared to those treated with heparin (0 percent vs. 2 percent). However, the authors reported that there was no significant differences between diabetic patients administered bivalirudin and those administered heparin plus GPI in terms of the one-year event rates of major adverse cardiac event (MACE) rates (14.2 percent vs. 16.2 percent). The rates of major bleeding and stent thrombosis were also similar, (8.7 percent vs. 10.7 percent and 4.2 percent vs. 3.8 percent), respectively.
After interaction testing, the authors reported that the effects of bivalirudin were similar in patients with and without diabetes. “However, diabetic patients with STEMI compared with nondiabetic patients are less likely to achieve normal myocardial perfusion (as measured by reduced restoration of normal angiographic myocardial blush and ST-segment resolution, and a greater incidence of distal embolization), which has been associated with higher mortality,” the authors noted.
While both cardiac mortality and stroke were reduced in the diabetic patient population who were treated with bivalirudin compared to heparin plus GPI, total mortality, major bleeding and net adverse clinical events were not significantly reduced in the diabetic cohort who received bivalirudin.
“Given that subgroups are inherently underpowered,” wrote Witzenbichler and colleagues, “the most appropriate interpretation of these data is that the overall benefits with bivalirudin seen in the main trial seem to apply to patients both with and without diabetes.
“The HORIZONS-AMI diabetes substudy demonstrates that, in both high-risk patients with diabetes and nondiabetic patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin monotherapy (with bail-out GPI in 7.6 percent of patients for refractory thrombotic complications) compared with heparin plus the routine use of a GPI seems to significantly improve 30-day and one-year net clinical outcomes and survival,” the authors concluded.
Earlier this month, the National Institute for Health and Clinical Excellence (NICE) in the U.K. recommended bivalirudin (Angiox in the EU) in combination with aspirin and clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis), for STEMI patients undergoing PCI.
“Prior studies have demonstrated that GPIs are especially beneficial in patients with diabetes with acute coronary syndromes and/or those undergoing PCI,” wrote Bernhard Witzenbichler, MD, of the Charité Campus Benjamin Franklin in Berlin, and colleagues. “Bivalirudin is a direct thrombin inhibitor with anti-ischemic properties and favorable bleeding event rates when used in elective PCI, in acute coronary syndromes patients and STEMI patients treated with primary PCI.”
To evaluate whether bivalirudin could be useful in high-risk patients with diabetes and STEMI undergoing PCI, Witzenbichler and colleagues used the previously reported HORIZONS-AMI study design to assess the safety and efficacy of bivalirudin compared with GPI in this patient population undergoing primary PCI.
The prospective, randomized, multicenter HORIZONS-AMI trial enrolled 3,602 patients with STEMI who were randomized to receive bivalirudin alone or unfractionated heparin plus a GPI at a 1:1 ratio. The patients were randomized at a 3:1 ratio to receive either the Taxus Express paclitaxel-eluting stent (Boston Scientific) or an uncoated Express bare-metal stent (Boston Scientific).
Diabetes was present in 593 patients; 26.8 percent were treated with insulin, 54.3 percent were treated with oral medications without insulin and 18 percent were treated with diet alone. Of the 593 diabetic patients, 281 patients were randomized to receive treatment with bivalirudin and 312 patients were randomized to receive heparin treatment plus a GPI.
Witzenbichler et al reported that rates of cardiac death were lower in diabetic patients treated with bivalirudin versus those treated with heparin plus GPI at both 30 days and one year (30 days: 2.1 percent vs. 5.5 percent; one year: 2.5 percent vs. 7.1 percent).
Diabetic patients treated with bivalirudin also had lower rates of 30-day stroke events compared to those treated with heparin (0 percent vs. 2 percent). However, the authors reported that there was no significant differences between diabetic patients administered bivalirudin and those administered heparin plus GPI in terms of the one-year event rates of major adverse cardiac event (MACE) rates (14.2 percent vs. 16.2 percent). The rates of major bleeding and stent thrombosis were also similar, (8.7 percent vs. 10.7 percent and 4.2 percent vs. 3.8 percent), respectively.
After interaction testing, the authors reported that the effects of bivalirudin were similar in patients with and without diabetes. “However, diabetic patients with STEMI compared with nondiabetic patients are less likely to achieve normal myocardial perfusion (as measured by reduced restoration of normal angiographic myocardial blush and ST-segment resolution, and a greater incidence of distal embolization), which has been associated with higher mortality,” the authors noted.
While both cardiac mortality and stroke were reduced in the diabetic patient population who were treated with bivalirudin compared to heparin plus GPI, total mortality, major bleeding and net adverse clinical events were not significantly reduced in the diabetic cohort who received bivalirudin.
“Given that subgroups are inherently underpowered,” wrote Witzenbichler and colleagues, “the most appropriate interpretation of these data is that the overall benefits with bivalirudin seen in the main trial seem to apply to patients both with and without diabetes.
“The HORIZONS-AMI diabetes substudy demonstrates that, in both high-risk patients with diabetes and nondiabetic patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin monotherapy (with bail-out GPI in 7.6 percent of patients for refractory thrombotic complications) compared with heparin plus the routine use of a GPI seems to significantly improve 30-day and one-year net clinical outcomes and survival,” the authors concluded.
Earlier this month, the National Institute for Health and Clinical Excellence (NICE) in the U.K. recommended bivalirudin (Angiox in the EU) in combination with aspirin and clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis), for STEMI patients undergoing PCI.