Efficacy and Safety of Bivalirudin Without Post-Procedure Infusion in Patients with Coronary Heart Disease During Elective Percutaneous Coronary Intervention: A Real-World Study
Antithrombotic therapy remains a cornerstone in preventing ischemic complications during and after percutaneous coronary intervention (PCI). Bivalirudin, a direct thrombin inhibitor, has emerged as an alternative to heparin due to its unique pharmacokinetic profile, including a short half-life (25 minutes), linear clearance, and lack of interaction with plasma proteins or platelet activation. However, prior studies in acute myocardial infarction (AMI) settings raised concerns about acute stent thrombosis (ST) with bivalirudin, attributed to its rapid clearance and delayed onset of oral P2Y12 inhibitors. The BRIGHT trial addressed this by demonstrating reduced net adverse clinical events (NACE) with prolonged bivalirudin infusion post-PCI in AMI patients. Nevertheless, evidence supporting the need for post-procedure bivalirudin infusion in elective PCI populations remains unclear. This real-world study evaluates the efficacy and safety of bivalirudin without post-PCI infusion compared to heparin in patients undergoing elective PCI.
Study Design and Patient Population
This single-center, observational study included 2,465 consecutive coronary heart disease (CHD) patients undergoing elective PCI between January 2015 and June 2017. After applying exclusion criteria—long-term anticoagulant use, post-PCI bivalirudin infusion, severe renal insufficiency, recent stroke or bleeding, and missing data—2,313 patients were analyzed: 613 received bivalirudin, and 1,700 received heparin. Propensity score matching (PSM) balanced baseline characteristics, resulting in 1,198 matched patients (599 per group).
Anticoagulation Protocols
Bivalirudin was administered as a 0.75 mg/kg bolus followed by 1.75 mg/kg/h infusion until PCI completion. Heparin was dosed as a 70–100 U/kg bolus, with 2,000 U hourly supplements. Both groups permitted provisional intracoronary tirofiban (5–10 mL per dose, ≤50 mL total) for slow/no-reflow or thrombotic complications, followed by 0.15 mg/kg/min infusion for 18–36 hours if needed.
Endpoints and Statistical Analysis
The primary endpoint was 30-day NACE, a composite of major adverse cardiac or cerebral events (MACCE: all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] types 1–5). Secondary endpoints included MACCE, bleeding events, and ST at 30 days and 6 months, along with thrombocytopenia. Statistical analyses employed χ², Fisher’s exact, t-tests, Kaplan-Meier estimates, and multivariate logistic regression for subgroup analyses.
Key Findings
30-Day Outcomes
Before PSM, the bivalirudin group exhibited lower 30-day NACE rates (4.4% vs. 6.6%, P = 0.046), driven by a trend toward reduced bleeding (3.8% vs. 5.7%, P = 0.061). MACCE (1.0% vs. 1.0%) and ST (0.2% vs. 0.1%) did not differ significantly. After PSM, NACE remained comparable (4.3% vs. 6.5%, P = 0.097), with no differences in MACCE, bleeding, or ST.
6-Month Outcomes
At 6 months, no significant differences emerged between groups in NACE, MACCE, or bleeding events, regardless of PSM adjustment.
Subgroup Analyses
Bivalirudin demonstrated pronounced benefits in high-risk subgroups:
- Diabetic patients: Reduced 30-day NACE (adjusted odds ratio [aOR]: 0.39, 95% CI: 0.17–0.87) and bleeding (aOR: 0.38, 95% CI: 0.15–0.95).
- High bleeding risk (CRUSADE score >30): Lower bleeding events (aOR: 0.39, 95% CI: 0.17–0.90).
Safety Profile
Bivalirudin did not increase acute ST (0.2% vs. 0.1%, P > 0.05), even without post-procedure infusion. Thrombocytopenia incidence was similar between groups (0.5% vs. 0.1%, P = 0.103).
Discussion
Comparison with Prior Evidence
The BRIGHT trial, which utilized a 3–4-hour post-PCI bivalirudin infusion in AMI patients, reported a 4.1% 30-day bleeding rate. In this elective PCI cohort, omitting post-procedure infusion yielded comparable bleeding rates (3.7%) despite higher baseline bleeding risk (mean CRUSADE score 23.6 vs. 19.6 in BRIGHT). This suggests that prolonged infusion may be unnecessary in elective settings, where oral antiplatelet therapy is initiated earlier, avoiding the “therapeutic gap” seen in AMI.
The Naples III trial, which compared bivalirudin and heparin in elective PCI, reported similar ST rates (0.5% vs. 0.5%), aligning with this study’s findings (0.2% vs. 0.1%). Notably, provisional glycoprotein IIb/IIIa inhibitor (GPI) use was higher in the heparin group pre-PSM (25.8% vs. 10.6%), potentially inflating bleeding rates. After PSM, GPI use balanced (13.0% vs. 10.9%), neutralizing this confounder.
Clinical Implications
Bivalirudin’s safety in elective PCI without post-infusion simplifies regimens, reduces costs, and avoids extended hospital stays. Its benefits in high-risk subgroups—diabetics and those with elevated CRUSADE scores—highlight its role in personalized anticoagulation strategies.
Limitations
As an observational study, unmeasured confounders may persist despite PSM. The single-center design and predominantly Asian population limit generalizability. Additionally, the low ST rates (0.2–0.1%) may underpower comparisons.
Conclusion
In real-world practice, bivalirudin without post-PCI infusion did not increase ST, MACCE, or NACE compared to heparin in elective PCI patients. Its favorable bleeding profile in high-risk subgroups supports selective use, particularly in diabetics and those with elevated bleeding risk. These findings challenge the necessity of prolonged bivalirudin infusion in stable cohorts, advocating for streamlined protocols that maintain efficacy while reducing healthcare burdens.
doi.org/10.1097/CM9.0000000000001757
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