Bivalirudin versus Unfractionated Heparin during Percutaneous Coronary Intervention in Patients at High Risk for Bleeding

Abstract

The overall rate of bleeding complications during interventional therapeutic procedures for coronary heart disease by the femoral approach is 1.5 to 9%. 1 Although bleeding is considered a minor complication related to percutaneous coronary intervention (PCI), 2 on rare occasions, it might lead to life-threatening situations that must be treated by intensive medical or surgical approaches. 3 These events are multifactorial, involving patient-, physician-, and nursing staff-related prognosis-worsening factors. Patient-related factors include: female gender, age > 70 years, and comorbidities such as diabetes mellitus, obesity, hypertension, and diseases with poor clot formation, such as uremia and thrombocytopenia. 4 Physician-related factors include: port of access, mode of arterial puncture (single vs. multiple trials) and anticoagulation regimen. 5 Early data using abciximab during high-risk coronary angioplasty (EPIC trial) showed that bleeding complications occur more often in the IIb-/IIIatreated groups, 6 a trend that persisted under low-dose (EPI-LOG trial), weight-adjusted heparin infusion. 7 One of the alternatives to unfractionated heparin (UFH) is bivalirudin (BIV), a direct and reversible thrombin-inhibition oligopeptide with a relatively short half-life. In previous AbstractLow/medium-bleeding-risk populations undergoing percutaneous coronary intervention (PCI) show significantly less bleeding with bivalirudin (BIV) than with unfractionated heparin (UFH), but this has not been established for high-risk patients. We performed a randomized double-blind prospective trial comparing efficacy and safety of BIV versus UFH combined with dual antiplatelet therapy during PCI among 100 high-risk patients with non-ST elevation myocardial infarction (NSTEMI) or angina pectoris. The baseline characteristics were similar in both treatment arms. A radial approach was used in 84% of patients with a higher rate in the BIV group (90 vs. 78%, p < 0.05). Study end points were: major and minor bleeding, port-of-entry complications, major adverse cardiac events (MACE) in-hospital, and at long-term follow-up. There was one case of major gastrointestinal bleeding in the BIV group and 7% minor bleeding complications in both categories. Rate of periprocedural myocardial infarction (PPMI) in the BIV group was twice that in the UFH group (20 vs. 10%, p < 0.16). In-hospital MACE rate was higher in BIV patients as well (12 vs. 2%, p ¼ 0.1). By univariate analysis, the femoral approach was the predictor of PPMI and in-hospital MACE. In a multivariate model, the independent predictor of PPMI was previous MI (odds ratio, 7.7; p < 0.0158). PPMI was 49.7 times more likely with the femoral approach plus BIV than the nonfemoral approach plus UFH (p < 0.0021). At 41.5 AE 14 months' follow-up, end points did not significantly differ between the groups. In patients at high risk for bleeding undergoing PCI, BIV was not superior to UFH for bleeding complications, and early and late clinical outcomes.

Bivalirudin in Primary PCI: Can Its Glory Being Restored?

“…Peri-procedural bleeding events, up to 50% arise from the access site, remain the most common non-cardiac complication following PCI and have been associated with significant morbidity, mortality, and financial burden to the healthcare system. These events are multifactorial and are associated with: (1) patient-related factors (female sex, age >70 years); (2) comorbidities such as diabetes mellitus, obesity, hypertension, and diseases inhibiting clot formation, such as uremia and thrombocytopenia; (3) and procedural factors (eg, port of access, mode of arterial puncture and anticoagulation regimen) [79] . Numerous randomized trials have demonstrated that major bleeding (both access site and non-access site) is less frequent in patients treated with bivalirudin [37,43,80,81] .…”

“…(1) patient-related factors (female sex, age >70 years); (2) comorbidities such as diabetes mellitus, obesity, hypertension, and diseases inhibiting clot formation, such as uremia and thrombocytopenia; (3) and procedural factors (eg, port of access, mode of arterial puncture and anticoagulation regimen). [79] Numerous randomized trials have demonstrated that major bleeding (both access site and non-access site) is less frequent in patients treated with bivalirudin. [37,43,80,81] Thus, bivalirudin is recommended to reduce bleeding events in STEMI patients with a high risk of bleeding, especially those with multiple high-risk factors.…”