Content of this journal is licensed under a Abstract
Background:
No evidence exists on the impact of bivalirudin in patients with the acute coronary syndrome undergoing rotational atherectomy. This study aimed to evaluate the impact of bivalirudin on patients with acute coronary syndrome undergoing rotational atherectomy.
Methods:
This was a retrospective cohort study conducted in our hospital between January 2017 and December 2019. The study included patients with acute coronary syndrome undergoing rotational atherectomy. Furthermore, 2 cohorts were included in this study (bivalirudin cohort and control cohort unfractionated heparin). The primary endpoint was in-hospital net adverse clinical events. The secondary endpoint was all-cause mortality at 23 months.
Results:
The study included 157 patients with 33 (21.0%) in the bivalirudin cohort and 124 (79.0%) in the control cohort. Net adverse clinical events during hospitalization in the bivalirudin cohort were higher than that in the control cohort [9 (27.3%) vs. 14 (11.3%), P = .021]. However, there was no significant difference in all-cause mortality at 23 months between the 2 cohorts [25 (20.2%) vs. 10 (30.3%), P = .214]. After adjusting for potential confounders, the usage of bivalirudin was not associated with net adverse clinical event (odds ratio = 0.90; 95% CI: 0.18-4.45; P = .890), and the hazard ratio for all-cause mortality at 23 months was 1.01 (95% CI: 0.33-3.15; P = .983).
Conclusion:
Bivalirudin appears to exhibit a similar impact as unfractionated heparin on patients with acute coronary syndrome undergoing rotational atherectomy in real-life setting.
Keywords: Heparin, bivalirudin, acute coronary syndrome, rotational atherectomy
HIGHLIGHTS
Twenty-one percent of patients with acute coronary syndrome undergoing rotational atherectomy received bivalirudin.
Bivalirudin cohort had higher bleeding risks.
In-hospital net adverse clinical events in the bivalirudin group were higher than that of heparin.
All-cause mortality at 23 months was comparable between 2 cohorts.
Perioperative anticoagulant did not affect in-hospital net adverse clinical event or all-cause death.
Introduction
Rotational atherectomy (RA) has been well demonstrated as a mainstay of the percutaneous method for coronary calcification,1,2 a serious challenge in patients undergoing percutaneous coronary intervention (PCI) that often leads to procedure failure through device delivery failure, stent under expansion, and restenosis after the procedure.3,4 Since 30.4% of moderate-to-severe coronary calcifications occur in acute coronary syndrome (ACS),3 RA in patients with ACS had been proved to be effective5,6 but was associated with increased risk of ischemic and bleeding events during the perioperative period.7-9 Thus, appropriate selection of the anticoagulant agent during RA is critically important for reducing ischemic and bleeding risk.
The most frequently used anticoagulant therapy is unfractionated heparin (UFH) and bivalirudin, and heparin was perfered as the standard anticoagulation theapy during PCI in previous trials.9,10 Bivalirudin (20-amino-acid synthetic polypeptides) binds directly to blood coagulation, thus decreasing its enzymatic activity. Some published studies demonstrated that bivalirudin has emerged as an intriguing substitute to UFH, with the key benefit being the lower rates of major bleeding without increasing ischemic complications in patients with ACS.11-15 But few data are available regarding the impact of bivalirudin on patients with ACS undergoing RA. Therefore, the present study aimed to determine the impact of bivalirudin on patients with ACS undergoing RA in a real-world setting.
Methods
Study Design and Population
This was a retrospective cohort study. The patients included presented with ACS and were undergoing RA and PCI in our hospital between January 2017 and December 2019.
Inclusion criteria were as follows: (1) age 18-90 years old; (2) patients with clinically diagnosed coronary heart disease who underwent coronary angiography and who were found to have coronary artery stenosis (>70%) with severe calcification and received RA. Exclusion criteria were as follows: (1) patients who are in the menstrual period, pregnant, and lactating; (2) patients with long-term use of anticoagulant drugs (novel oral anticoagulants or oral anticoagulants) and patients who recently underwent thrombolytic therapy; (3) patients with abnormal coagulation function or hemorrhagic disease; (4) patients with severe anemia; (5) clinical diagnosis of stable angina pectoris and ischemic cardiomyopathy; (6) patients with tumor and life expectancy <1 year; (7) patients who were subjected to RA of venous bridge vessels; and (8) patients with incomplete clinical data.
Acute coronary syndrome was diagnosed according to the Fourth Universal Definition of Myocardial Infarction.16 Rotational atherectomy was selected when there was severe calcification or as a bailout measure when device delivery failed. Given its retrospective observational study design, this study is exempt from ethics review. This study protocol was reviewed and approved by our hospital. Informed consent was waived due to the retrospective design.
Data Collection
We divided patients into 2 cohorts based on the anticoagulant therapy used: the UFH cohort and the bivalirudin cohort. Patients’ demographic [age, gender, and body mass index (BMI)] and clinical characteristics [systolic blood pressure on admission, diastolic blood pressure on admission, heart rate on admission, prior PCI, hypertension, diabetes mellitus, clinical diagnosis, left ventricle ejection fraction, white blood cell count, hemoglobin (HGB) count, platelet count, glucose, creatine kinase-MB, cardiac troponin I, N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine, cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, CYP2C19 genotype, medication during hospitalization, P2Y12 inhibitor, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blocker, diuretic, and nitrates] and procedural data were collected from the medical records. Periprocedural complications, in-hospital outcomes including ischemic events [all-cause death, perioperative myocardial infarction (MI), acute stent thrombus, target vessel revascularization (TVR), and heart failure], and bleeding events [Bleeding Academic Research Consortium (BARC) < 3, BARC ≥ 3] were also collected. All patients were followed up for an average of 23 months, and all-cause deaths within 23 months outside the hospital were recorded.
Outcomes
The primary outcome of this study was in-hospital rates of net adverse clinical events (NACEs), which included all-cause death, perioperative MI, TVR, heart failure, and major bleeding defined as BARC ≥ 3 bleeding.17 Increases in cTnI (cardiac troponin I) values (>99th percentile URL) in patients with normal baseline values or an increase in cTn values (>20% of the baseline value) when it is above the 99th percentile URL are utilized to diagnose cardiac procedural MI.16 Target vessel revascularization was defined as repeat revascularization of the target vessel.16 Stent thrombosis was defined based on the Academic Research Consortium definition.6 Procedural success was defined as angiographic success without periprocedural complications, residual stenosis <30% after stent implantation, and thrombolysis for myocardial infarction flow class III.6 The secondary outcome was all-cause mortality at 23 months.
Statistical Analysis
Continuous variables are presented as means ± standard deviations (SDs) or median with interquartile ranges, as appropriate. Categorical variables are presented as numbers and percentages. Inter-cohort differences were compared using Student’s t-test or the Mann–Whitney U-test where appropriate. Categorical variables were tested using the chi-square test or Fisher’s exact test. A univariate and multivariable logistic regression model was used to identify the risk predictors of NACE, and both odds ratio (OR) and 95% CI were calculated. Net adverse clinical event was used as a dependent variable. Anticoagulant, age, gender, BMI, diagnosis, diuretic, target lesion location, target vessel, intra-aortic balloon pump (IABP), Global Registry of Acute Coronary Events (GRACE) ischemic score, Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines (CRUSADE) bleeding score, and procedural complications at baseline were added as independent variables in the multivariate analysis. Univariate and multivariable Cox-proportional hazards regression model was used to identify the risk predictors of all-cause mortality at 23 months, with risk estimates reported as hazard ratios (HRs) with a 95% CI. All variables with P < .10 in the univariate model and clinical factors that may influence outcome (such as age, gender, and BMI) were included in the multivariable model. Proportional-hazards assumption was checked by the Schoenfeld residuals, and no violation was detected. Kaplan–Meier curves were plotted for the 2 cohorts, with the differences compared by the log-rank tests. A P-value <.05 was considered statistically significant. All data analyses were conducted using Statistical Package for Social Sciences software 24.0 (IBM, Armonk, NY, USA).
Results
From 2017 to 2019, there were 256 patients treated with RA in our center. After the removal of 99 patients who met the exclusion criteria, 157 remaining patients were eligible for analysis, with 124 (79.0%) in the UFH cohort and 33 (21.0%) in the bivalirudin cohort. Patients in the bivalirudin cohort were older (75.1 ± 7.5 years vs. 71.1 ± 9.2 years, P = .024) and less likely to be males (36.4% vs. 60.5%, P = .013). They had significantly lower HGB [114 (103-126) × 109/L vs. 123 (112-130) × 109/L, P = .014] and a higher level of NT-proBNP [2626 (1280-5958) pg/mL vs. 796 (210-2415) pg/mL, P = .003]. P2Y12 inhibitor had a significantly different distribution between the 2 cohorts (P = .005). More patients in the bivalirudin cohort used diuretics than that in the UFH cohort (66.7% vs. 39.5%, P = .040). The surgical approach was different between the 2 cohorts significantly (P = .043). The GRACE score and CRUSADE score were both higher in the bivalirudin group than in the heparin group (163 ± 24 vs. 146 ± 30, P = .003 and 48 ± 12 vs. 40 ± 14, P = .002) (Table 1).
Table 1.
Patients’ Demographic, Clinical, and Procedure Characteristics, Procedural Success and Complications, and Outcome During Hospitalization and Follow-up
| Patients | UFH (n = 124) | Bivalirudin (n = 33) | P |
|---|---|---|---|
| Age, years | 71.1 ± 9.2 | 75.1 ± 7.5 | .024 |
| Male | 75 (60.5%) | 12 (36.4%) | .013 |
| Body mass index, kg/m2 | 23.8 ± 3.0 | 22.9 ± 3.7 | .169 |
| Systolic blood pressure on admission, mm Hg | 134.9 ± 18.2 | 135.9 ± 23.4 | .788 |
| Diastolic blood pressure on admission, mm Hg | 76.6 ± 11.3 | 74.7 ± 13.2 | .418 |
| Heart rate on admission, bpm | 77.5 ± 13.8 | 76.8 ± 10.6 | .777 |
| Prior PCI | 33 (26.6%) | 8 (24.2%) | .783 |
| Hypertension | 87 (70.2%) | 24 (72.7%) | .773 |
| Diabetes mellitus | 45 (36.3%) | 12 (36.4%) | .994 |
| Clinical diagnosis | .189 | ||
| UA | 94 (75.8%) | 21 (63.6%) | |
| NSTEMI | 27 (21.8%) | 9 (27.3%) | |
| STEMI | 3 (2.4%) | 3 (9.1%) | |
| Left ventricle ejection fraction, % | 61 (46-67) | 52 (42-62) | .087 |
| White blood cell count (109/L) | 6.13 (4.95-7.77) | 6.26 (4.98-7.39) | .900 |
| Hemoglobin count (g/L) | 123 (112-130) | 114 (103-126) | .014 |
| Platelet count (109/L) | 191 (151-232) | 183 (138-223) | .327 |
| Glucose (mmol/L) | 5.12 (4.64-6.14) | 5.73 (4.96-6.65) | .082 |
| CK-MB (IU/L) | 14 (10-21) | 16 (12-22) | .323 |
| Cardiac troponin I (ng/mL) | 0.02 (0.01-0.29) | 0.85 (0.01-1.95) | .121 |
| NT-proBNP (pg/mL) | 796 (210-2415) | 2626 (1280-5958) | .001 |
| Creatinine (umol/L) | 76 (62-94) | 71 (60-123) | .912 |
| Cholesterol (mmol/L) | 3.90 (3.06-4.58) | 3.98 (3.10-4.86) | .610 |
| Triglyceride (mmol/L) | 1.21 (0.98-1.51) | 1.14 (0.90-1.47) | .718 |
| High-density lipoprotein (mmol/L) | 0.92 (0.79-1.06) | 1.03 (0.76-1.36) | .118 |
| Low-density lipoprotein (mmol/L) | 1.94 (1.51-2.59) | 1.97 (1.57-2.67) | .678 |
| CYP2C19 genotype | .890 | ||
| Fast metabolism | 33 (41.3%) | 9 (40.9%) | |
| Intermediate metabolism | 37 (46.3%) | 11 (50.0%) | |
| Poor metabolism | 10 (12.5%) | 2 (9.1%) | |
| Medication during hospitalization | |||
| Aspirin | 123 (100%) | 32 (97%) | .077 |
| P2Y12 inhibitor | .005 | ||
| Clopidogrel | 32 (25.8%) | 17 (51.5%) | |
| Ticagrelor | 92 (74.2%) | 16 (48.5%) | |
| Statins | 122 (98.4%) | 32 (97.0%) | .617 |
| ACEI/ARB | 71 (57.3%) | 19 (57.6%) | .974 |
| β-Blocker | 73 (58.9%) | 20 (60.6%) | .857 |
| Diuretic | 49 (39.5%) | 22 (66.7%) | .005 |
| Nitrates | 66 (53.2%) | 18 (54.5%) | .893 |
| Target vessel | .746 | ||
| LM | 38 (30.6%) | 8 (24.2%) | |
| LAD | 58 (46.8%) | 15 (45.5%) | |
| LCX | 4 (3.2%) | 2 (6.1%) | |
| RCA | 24 (19.4%) | 8 (24.2%) | |
| Bifurcation | 68 (55.3%) | 16 (48.5%) | .487 |
| Lesion characteristics | .783 | ||
| Tortuosity | 17 (13.7%) | 3 (9.1%) | |
| Chronic total occlusion | 12 (9.7%) | 3 (9.1%) | |
| Ectasia | 1 (0.8%) | 0 | |
| Surgical approach | .043 | ||
| Radial | 100 (81.3%) | 28 (84.8%) | |
| Brachial | 18 (14.6%) | 1 (3.0%) | |
| Femoral | 5 (4.1%) | 4 (12.1%) | |
| Number of burr | .058 | ||
| 1 | 115 (92.7%) | 27 (81.8%) | |
| >1 | 9 (7.3%) | 6 (18.2%) | |
| Size of burr | .463 | ||
| 1.25 mm | 27 (21.8%) | 8 (24.2%) | |
| 1.5 mm | 86 (69.4%) | 24 (72.7%) | |
| 1.75 mm | 11 (8.9%) | 1 (3.0%) | |
| Times of RA | 3 (2-4) | 3 (3-5) | .381 |
| Burr speed (104/min) | 15 (15-16) | 15 (15-16) | .122 |
| Direct RA | 84 (67.7%) | 22 (66.7%) | .907 |
| Number of implanted stents | 3 (2-3) | 3 (2-4) | .956 |
| Stent diameter | 2.94 (2.75-3.17) | 3 (2.75-3.19) | .404 |
| Stent length, mm | 70 (57-103) | 88 (65-102) | .526 |
| IABP | 23 (18.5%) | 5 (15.2%) | .651 |
| Reason of IABP | .062 | ||
| Preoperative treatment | 1 (4.3%) | 2 (40.0%) | |
| Intraoperative protection | 17 (73.9%) | 3 (60.0%) | |
| Bailout therapy | 5 (21.7%) | 0 | |
| Procedural success | 122 (98.4%) | 33 (100%) | .330 |
| Procedural complications | 31 (25.0%) | 11 (33.3%) | .337 |
| Dissection | 15 (12.1%) | 7 (21.2%) | .199 |
| No/slow reflow | 17 (13.7%) | 5 (15.2%) | .833 |
| Perforation | 3 (2.4%) | 0 | .232 |
| Atrioventricular block | 3 (2.4%) | 0 | .232 |
| Emergency CABG | 2 (1.6%) | 0 | .330 |
| Reversible slow heart rate | 6 (4.8%) | 1 (3.0%) | .640 |
| Temporary pacing | 1 (0.8%) | 0 | .491 |
| GRACE score | 146 ± 30 | 163 ± 24 | .003 |
| CRUSADE score | 40 ± 14 | 48 ± 12 | .002 |
| NACE during hospitalization | 14 (11.3%) | 9 (27.3%) | .021 |
| All-cause death | 6 (4.8%) | 1 (3.0%) | .640 |
| MI | 3 (2.5%) | 5 (15.2%) | .010 |
| Acute stent thrombus | 1 (0.8%) | 1 (3.0%) | .373 |
| TVR | 0 | 0 | |
| Heart failure | 8 (6.7%) | 5 (15.6%) | .132 |
| BARC ≥ 3 | 0 | 0 | |
| BARC < 3 | 2 (1.6%) | 1 (3.0%) | .614 |
| Follow-up | |||
| All-cause death | 25 (20.2%) | 10 (30.3%) | .214 |
P-value for comparison of bivalirudin versus heparin. Data are presented as mean ± SD or median with interquartile ranges, as appropriate for continuous variables, and numbers and percentages for categorical variables.
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blockers; BARC, Bleeding Academic Research Association; CABG, coronary artery bypass grafting; CK-MB, creatine phosphokinase-MB; CYP2C19; cytochrome P450 2C19; IABP, intra-aortic balloon pump; LAD, left anterior descending coronary artery; LCX, left circumflex; LM, left main coronary artery; MI, myocardial infarction; NACE, net adverse clinical events; NSTEMI, non-ST-segment elevation myocardial infarction; NT-proBNP, N-terminal pro-brain natriuretic peptide; PCI, percutaneous coronary intervention; RA, rotational atherectomy; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction; TVR, target vessel revascularization; UA, unstable angina; UFH, unfractionated heparin.
In-hospital NACE was significantly higher in the bivalirudin cohort (27.3% vs. 11.3%, P = .021). The rates of perioperative MI were higher in the bivalirudin cohort than the UFH cohort (15.2% vs. 2.5%, P = .010). No statistically significant differences were found for all-cause death during hospitalization, heart failure, and BARC < 3 bleeding (all P < .05). No case of TVR or BARC ≥ 3 bleeding was recorded in either cohort. Stent thrombosis was considered in 1 patient in the bivalirudin group and 1 patient in the heparin group; however, they both died during hospitalization in the cohort. In addition, there was no significant difference in all-cause mortality at 23 months (30.3% vs. 20.2%, P = .214) (Table 1).
In this study, the univariable analysis revealed that anticoagulant, diagnosis, diuretic, IABP, and procedural complications were independent predictors of NACE (all P < .05). Multivariable analysis revealed that procedural complication (OR = 6.14, 95% CI: 1.61-23.38, P = .008) was an independent predictor of NACE. Notably, anticoagulant therapy was not associated with NACE (OR = 0.90, 95% CI: 0.18-4.45, P = .890) (Table 2).
Table 2.
Multivariable Analysis of In-hospital NACE
|
|
Univariable Analysis | Multivariable Analysis | ||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P | OR | 95% CI | P | |
| Anticoagulant | 0.34 | 0.13-0.88 | .025 | 0.90 | 0.18-4.45 | .890 |
| Age | 0.99 | 0.94-1.04 | .729 | 1.05 | 0.95-1.16 | .317 |
| Gender | 0.70 | 0.29-1.70 | .430 | 0.63 | 0.14-2.94 | .558 |
| Body mass index | 1.17 | 0.99-1.39 | .068 | 1.14 | 0.89-1.45 | .294 |
| Diagnosis | .004 | .335 | ||||
| UA | 1 | 1 | ||||
| NSTEMI | 0.22 | 0.08-0.57 | .002 | 0.32 | 0.06-1.54 | .154 |
| STEMI | 0.19 | 0.03-1.17 | .074 | 0.41 | 0.02-10.27 | .584 |
| Diuretic | 5.50 | 1.93-15.72 | .001 | 2.14 | 0.41-11.30 | .370 |
| Target vessel | .087 | .255 | ||||
| LAD | 1 | 1 | ||||
| LCX | 0.53 | 0.05-5.21 | .586 | 0.42 | 0.02-7.58 | .555 |
| RCA | 1.03 | 0.25 -4.25 | .973 | 0.62 | 0.09-4.36 | .631 |
| LM | 0.30 | 0.11-0.83 | .021 | 0.20 | 0.04-0.97 | .046 |
| IABP | 6.31 | 2.41-16.53 | .000 | 3.30 | 0.70-15.61 | .133 |
| GRACE score | 0.98 | 0.97-1.00 | .054 | 1.00 | 0.97-1.04 | .819 |
| CRUSADE score | 0.98 | 0.94-1.01 | .168 | 0.97 | 0.91-1.04 | .409 |
| Procedural complications | 5.89 | 2.31-15.00 | .000 | 6.14 | 1.61-23.38 | .008 |
P-value for comparison of bivalirudin versus heparin. Data are presented as numbers and percentages for categorical variables.
IABP, intra-aortic balloon pump; LAD, left anterior descending coronary artery; LCX, left circumflex; LM, left main coronary artery; NACE, net adverse cardiac events; NSTEMI, non-ST-segment elevation myocardial infarction; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction; UA, unstable angina.
In this study, the univariable COX analysis revealed that age, diagnosis, glucose, creatinine, high-density lipoprotein, P2Y12 inhibitor, diuretic, IABP, GRACE score, and CRUSADE score were independent predictors of all-cause mortality at 23 months. Multivariable analysis revealed that diuretic (HR = 0.28, 95% CI: 0.08-0.99, P = .048) was an independent predictor of all-cause mortality. Notably, anticoagulant therapy was not associated with all-cause mortality at 23 months (HR = 1.01, 95% CI: 0.33-3.15, P = .983) (Table 3).
Table 3.
Univariate and Multivariate Cox Regression Analysis of All-Cause Mortality at 23 Months
|
|
Univariable Analysis | Multivariable Analysis | ||||
|---|---|---|---|---|---|---|
| HR | 95% CI | P | HR | 95% CI | P | |
| Anticoagulant | 1.75 | 0.83-3.71 | .141 | 1.01 | 0.33-3.15 | .983 |
| Age | 1.05 | 1.01-1.10 | .031 | 1.00 | 0.92-1.10 | .987 |
| Gender | 1.06 | 0.53-2.09 | .879 | 0.94 | 0.26-3.40 | .927 |
| Body mass index | 0.91 | 0.81-1.02 | .108 | 0.92 | 0.78-1.09 | .340 |
| Diastolic blood pressure on admission | 0.98 | 0.95-1.00 | .094 | 1.00 | 0.95-1.04 | .816 |
| Diagnosis | .009 | .616 | ||||
| UA | 1 | 1 | ||||
| NSTEMI | 2.99 | 1.47-6.08 | .002 | 1.00 | 0.32-3.16 | .996 |
| STEMI | 2.46 | 0.57-10.66 | .230 | 0.27 | 0.02-3.76 | .330 |
| Hemoglobin count | 0.98 | 0.96-1.00 | .091 | 0.99 | 0.96-1.03 | .664 |
| Glucose | 1.10 | 1.01-1.20 | .029 | 1.05 | 0.90-1.23 | .539 |
| Creatinine | 1.00 | 1.00-1.00 | .029 | 1.00 | 1.00-1.00 | .106 |
| High-density lipoprotein | 0.19 | 0.05-0.82 | .025 | 1.07 | 0.14-7.95 | .947 |
| P2Y12 inhibitor | ||||||
| Clopidogrel | 1 | 1 | ||||
| Ticagrelor | 0.45 | 0.23-0.90 | .023 | 1.79 | 0.53-6.00 | .349 |
| Diuretic | 0.23 | 0.10-0.51 | .001 | 0.28 | 0.08-0.99 | .048 |
| IABP | 0.41 | 0.20-0.86 | .019 | 0.50 | 0.19-1.31 | .157 |
| GRACE score | 1.02 | 1.01-1.04 | .000 | 1.02 | 0.99-1.06 | .165 |
| CRUSADE score | 1.04 | 1.02-1.07 | .002 | 1.00 | 0.93-1.07 | .904 |
IABP, intra-aortic balloon pump; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; UA, unstable angina.
There was no difference in all-cause mortality between the cohorts after an average of 23 (15-29) months follow-up (30.3% vs. 20.2%, P = .214) (Table 1); Kaplan–Meier survival curves were presented in Figure 1. The log-rank test demonstrated no significant differences between the 2 cohorts (P = .132).
Figure 1.
Kaplan–Meier curve of all-cause mortality. Log-rank = 0.132.
Discussion
Among the total number of patients with ACS undergoing RA treated with anticoagulant drugs, there were 2 cohorts of patients—bivalirudin cohort and UFH cohort. Moreover, NACE during hospitalization and all-cause mortality at 23 months were not significantly different between the 2 cohorts, and it may mean that bivalirudin may exhibit a similar impact as UFH on patients with ACS undergoing RA.
Bivalirudin was a superior anticoagulant for high bleeding risk patients, with distinct pharmacologic advantages that bivalirudin acts as a direct thrombin inhibitor and a reversible, short-acting anticoagulant with a half-life of 25 minutes resulting in lower rates of major bleeding without increasing ischemic complications.15 In this study, bivalirudin was used perioperatively in 21% of patients, which is a slightly lower proportion than previously reported (23%-33%).18,19 We found that these patients in the bivalirudin group were older and more of females and had lower HGB, poorer cardiac function, greater use of diuretics, and more use of clopidogrel than ticagrelor and higher CRUSADE score. These findings were concordant with earlier results,18 meaning that for people with high bleeding risks, bivalirudin as a low risk of bleeding anticoagulants was preferred.20-23
This article was the first to report the impact of bivalirudin on patients with RA in ACS. Allali et al5 investigated the impact of RA on patients presenting with ACS and Kübler et al6 assessed in-hospital and 1-year outcomes in patients undergoing RA presenting with ACS in comparison to elective RA procedures, and they found the feasibility of performing RA in patients with ACS, but neither article mentioned the proportion of bivalirudin used intraoperatively. Delhaye et al18 conducted a retrospective cohort study to explain the safety and efficacy of bivalirudin for PCI with RA. They reported that the endpoint and major bleeding were both similar in the bivalirudin and the UFH groups (1.9% vs. 1.7%, P = .99; 2.2% vs. 1.7%, P = .99), and after adjustment, bivalirudin use was not associated with a reduction in death/Q wave MI/urgent Coronary Artery Bypass Grafting (CABG) and major bleeding compared to UFH. However, one-third of the patients included in their study had a diagnosis of stable angina, leading to little understanding of the impact of bivalirudin on patients diagnosed as ACS undergoing RA. Secondly, in our study, the use of a composite endpoint event—NACE—rather than death/Q wave MI/urgent CABG and major bleeding as the primary outcome was more clinically instructive due to the high risk of bleeding and ischemia in patients with ACS undergoing RA. Thirdly, the present study used perioperative MI rather than Q wave MI as one of the clinical outcome endpoints, mainly because we had considered the impact of coronary microembolism and spasm in patients with ACS undergoing RA.
In the present analysis, we found no difference in acute stent thrombosis between the 2 groups (3.0% vs. 1.6%, P = .373). We obtained similar results for all-cause mortality, perioperative MI, TVR, and heart failure. These findings are in agreement with previous clinical trials.18,24,25 The minimizing adverse hemorrhagic events by transradial access site and angioX (MATRIX) clinical trial gets the similar outcomes comparative with the lower rate of acute stent thrombosis in our study.15 Moreover, from the BRIGHT randomized trial, bivalirudin compared with heparin resulted in similar rates of acute stent thrombosis and low bleeding events.12
Regarding bleeding complications, Delhaye et al18 showed no difference for major bleeding between both bivalirudin and heparin groups (2.2% vs. 1.7%, P = .99) and the transfusion rate (5.6% vs. 8.7%, P = .19). Similarly, we reach the same conclusion, and there were no bleeding events with BARC ≥ grade 3 in both cohorts.
We found that NACE events were higher in the bivalirudin cohort than the heparin cohort but were not associated with NACE and all-cause mortality at 23 months after multivariable adjustment. This may be related to the fact that the effects of factors (e.g., age, gender, anemia, cardiac function, diuretic use, and choice of antithrombotic drug) on NACE events were counteracted by the effects of anticoagulant drugs.
Therefore, our findings imply that patients with ACS receiving RA do not maintain the advantages of bivalirudin over heparin on the decrease of bleeding events and ischemic events. With the results of this study, we showed theoretical basis for the perioperative use of bivalirudin as an anticoagulant in patients diagnosed with ACS undergoing RA.
Study Limitations
The limitation of this study was a retrospective observational study using data from patients admitted to our single-center with a relatively small sample. Large-scale, multicenter studies were necessary to further confirm our study results. Secondly, only all-cause mortality was followed up for long-term, and long-term adverse events with bivalirudin use cannot be explored. Thirdly, the use of tirofiban was entirely at the discretion of the operator, and the actual rate of tirofiban usage is not recorded, which might affect the incidence of bleeding events.
Conclusions
In patients with ACS undergoing RA in a real-world scenario, bivalirudin appeared to have a similar effect as UFH. However, randomized controlled trials with large samples are needed to validate the results in the future.
Footnotes
Data Availability: All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.
Ethics Committee Approval: This study protocol was reviewed and approved by The First Affiliated Hospital of USTC.
Informed Consent: Informed consent was waived due to the retrospective design.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept – L.L., L.M.; Data curation – L.L.; Formal analysis – J.P., B.Z.; Funding acquisition – None; Investigation – L.L.; Methodology – J.Z., L.M., X.K.; Project administration – H.H.; Resources – H.C.; Software – L.L.; Supervision – J.W., D.L.; D.Y.; Validation – J.H.; Visualization – L.L.; Writing – original draft – L.L.; Writing – review and editing – L.M.
Acknowledgments: None.
Declaration of Interests: The authors report no competing interests.
Funding: None.
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