Bivalirudin infusion is associated with increased risk of acute stent thrombosis compared with heparin post-primary percutaneous coronary intervention (PCI). However, administering the full dose vs the reduced dose may lessen this risk, according to new data published in JACC: Cardiovascular Interventions.
“Bivalirudin and heparin are the 2 most commonly used adjunctive antithrombotic therapies during primary PCI,” study authors noted. “A bivalirudin-based anticoagulation strategy, compared to a heparin-based strategy, decreases the risk of major bleeding at the expense of an increased risk for acute stent thrombosis.”
In previous trials, bivalirudin was administered post-PCI to alleviate this risk, but the results have been inconsistent. Researchers of the present study hypothesized that continuing the full dose of bivalirudin, but not the low dose, may be successful at preventing acute stent thrombosis. They conducted a traditional meta-analysis and network meta-analysis using mixed-treatment comparison models to evaluate the efficacy of various doses.
Researchers examined 5 randomized controlled trials. According to each trial, the primary efficacy end point was definite acute stent thrombosis, defined as occurring within 24 hours of primary PCI. The primary safety end point was the 30-day incidence of major bleeding, defined by each trial, and the secondary safety end point was subacute stent thrombosis, defined as occurring more than 24 hours but less than 30 days after primary PCI.
A total of 16 294 patients were included. In the direct comparison meta-analysis, researchers found that bivalirudin increased acute stent thrombosis risk compared with heparin (risk ratio [RR]: 2.36; 95% confidence interval [CI]: 1.46-3.02; P<.001), but that this risk was alleviated by continuing the full dose (RR: 0.90; 95% CI: 0.32-2.54; P=.852). However, this was not seen with the lower dose (RR: 3.61; 95% CI: 1.17-11.13; P=.025) or in patients for whom bivalirudin infusion was stopped at the end of PCI (RR: 2.79; 95% CI: 1.38-5.67; P=.004).
In addition, bivalirudin was not associated with an increased risk of subacute stent thrombosis (RR: 1.14; 95% CI: 0.53-2.42; P=.731) compared with heparin. There was also no difference in the rate of acute stent thrombosis between patients who received the full dose of bivalirudin and heparin, in the mixed treatment comparison models (odds ratio [OR]: 0.97; 95% CI: 0.36-2.21). However, the rate of acute stent thrombosis was lower in patients who received heparin compared to those who received the lower dose of bivalirudin (OR: 0.25; 95% CI: 0.12-0.57) or for whom bivalirudin infusion was stopped at the end of PCI (OR: 0.33; 95% CI: 0.17-0.56).
The risk of major bleeding at 30 days decreased with bivalirudin compared with heparin (RR: 0.53; 95% CI: 0.39-0.72; P<.001), and this persisted with continued use of the full dose post-PCI (RR: 0.29; 95% CI: 0.16-0.53; P<.001).
Researchers noted that the mixed comparison models produced similar results to the direct comparison models. Patients who received the full dose of bivalirudin maintained a lower rate of major bleeding at 30 days compared to those who received heparin (OR: 0.26; 95% CI: 0.14-0.46).
In the surface under the cumulative ranking curve analysis, the full dose of bivalirudin had an 83% probability of being ranked as the best therapy for acute stent thrombosis prevention, while heparin had an 82% probability. The low dose of bivalirudin had a probability of 8%, while halting bivalirudin use after PCI had a 25% probability ranking.
“Our findings suggest that 3 to 4 hours post procedure, a Biv-Full (bivalirudin full dose; 1.75 mg/kg/h) infusion may mitigate the risk of AST [acute stent thrombosis] without increase the risk of major bleeding,” researchers wrote. “Paradoxically, in our analyses, Biv-No [bivalirudin infusion that was stopped after PCI] was not associated with decreased risk of bleeding compared to heparin.”
This excludes an anomaly from the HEAT-PPCI (How Effective Are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention) trial in which the relative weight for Biv-No was 25%, but since that trial was a single-center study, the findings may reflect “an exaggerated therapeutic effect relative to a multicenter trial.”
It is important to note that in the majority of selected trials, patients were not randomized to receive or not receive a post-PCI bivalirudin infusion, and therefore, researchers cannot unequivocally state whether the post-PCI infusion of bivalirudin at the full dose was responsible for lower rates of acute stent thrombosis risk. Additionally, each trial had its own protocol and definitions that may have confounded these findings.
“Further randomized controlled trials are needed to evaluate the impact of a post-primary PCI bivalirudin infusion on acute stent thrombosis, cardiovascular mortality, and all-cause mortality,” researchers concluded.
Shah R, Rogers KC, Ahmed AJ, King BJ, Rao SV. Effect of post-primary percutaneous coronary intervention bivalirudin infusion on acute stent thrombosis: meta-analysis of randomized controlled trials. JACC Cardiovasc Interv. 2016. doi: 10.1016/j.jcin.2016.03.031.