Abstract
Bivalirudin, as a direct thrombin inhibitor, is considered to be safer compared with other anticoagulants, such as heparin; however, relevant data in China are unclear. The present study aimed to compare the safety of bivalirudin and heparin as anticoagulants in Chinese patients who underwent percutaneous coronary intervention (PCI). In the present study, 2,377 patients with ST-segment elevation myocardial infarction (STEMI), unstable angina, non-STEMI or stable coronary artery disease who underwent primary PCI while receiving bivalirudin or heparin (low molecular weight heparin or unfractionated heparin) were reviewed, and then analyzed as the bivalirudin group (n=944) and heparin group (n=1,433). The net adverse clinical events (NACEs) within 30 days were obtained, which were defined as major adverse cardiac and cerebral events (MACCEs) + Bleeding Academic Research Consortium (BARC) grade 2-5 bleeding events. Compared with the heparin group, the incidence of NACEs was reduced in the bivalirudin group (9.3 vs. 13.4%; P=0.003). However, no discrepancy was found in the incidence of MACCEs between the groups (5.9 vs. 7.6%; P=0.116). Moreover, the incidences of BARC 2-5 (4.8 vs. 8.7%; P<0.001) and BARC 3-5 bleeding events (1.9 vs. 4.4%; P=0.001) were decreased in the bivalirudin group compared with the heparin group. Following adjustment using multivariate logistic regression analysis, bivalirudin treatment (vs. heparin treatment) was independently associated with lower risks of NACEs [odds ratio (OR), 0.587; P<0.001], MACCEs (OR, 0.689; P=0.041) and BARC 2-5 (OR, 0.459; P<0.001) and 3-5 bleeding events (OR, 0.386; P=0.002). Overall, the present study demonstrated that bivalirudin decreased the risks of NACEs and bleeding events compared with heparin in Chinese patients who undergo PCI. However, further validation is required.
Keywords: bivalirudin, percutaneous coronary intervention, net adverse clinical events, major adverse cardiac and cerebral events, bleeding events
Introduction
Percutaneous coronary intervention (PCI) alleviates coronary artery stenosis or occlusion and restores blood flow by implanting stents; this has been one of the key methods used in the treatment of coronary artery diseases (1,2). Notably, patients who undergo PCI exhibit an unstable hypercoagulable state in their blood, resulting in a high risk of thrombosis (3-5). In order to prevent the occurrence of thrombosis, treatment with anticoagulants is also usually applied simultaneously in patients who undergo PCI, (6,7). However, bleeding and even mortality may occur during or after receiving anticoagulants in patients who undergo PCI (8,9). Therefore, it is critical to select appropriate anticoagulants in order to both effectively prevent thrombosis and minimize the risk of bleeding events.
Generally, bivalirudin, unfractionated heparin, enoxaparin and fondaparinux are the most commonly applied anticoagulant drugs used during PCI (10). Bivalirudin, as a direct thrombin inhibitor with a rapid onset and a short half-life, has been reported to be safer for use compared with heparin in several previous studies (11-14). For example, a previous study demonstrated that bivalirudin decreases the incidence of net adverse clinical events (NACEs) and major bleeding within 1 year compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary PCI (13). Moreover, another study indicated that in patients with coronary artery disease complicated with diabetes who undergo PCI, bivalirudin decreases the risk of 30-day major adverse cardiac and cerebral events (MACCEs) compared with heparin (14). In addition, another study demonstrated that compared with heparin alone and heparin plus tirofiban, bivalirudin achieves a reduction in bleeding event rates in patients with acute myocardial infarction who undergo primary PCI (15). However, the aforementioned studies were both conducted in countries other than China. Due to the short time period since bivalirudin has begun to be been marketed in China, the safety of the use of bivalirudin among Chinese patients who undergo PCI remains unclear; thus, this is a key issue which needs to be resolved.
Therefore, the present study aimed to compare the incidences of NACEs, MACCEs and bleeding events between the use of bivalirudin and heparin in Chinese patients who underwent PCI.
Patients and methods
Patients
The present cohort study reviewed 2,377 patients [mean age: 64.8±11.3 years; males: 1,644 (69.2%)] who underwent primary PCI and received bivalirudin or heparin as anticoagulants in HanDan Central hospital (Handan, China) between December, 2017 and February, 2022. The screening criteria were as follows: i) An age >18 years; ii) patients who underwent primary PCI; iii) patients who had the clinical manifestation of STEMI, unstable angina (UA), non-STEMI (NSTEMI) or stable coronary artery disease (SCAD); and iv) patients who received bivalirudin or heparin [low molecular weight heparin (LMWH) or unfractionated heparin (UFH)] as anticoagulants. Patients who had the following conditions were ineligible: i) Had incomplete clinical data for study use; ii) were complicated with cancers or severe hematological diseases; and iii) women who were pregnant or breastfeeding. The present study was approved by the Ethics Committee of HanDan Central Hospital (Handan, China; approval no. 20230816001). Patients or their families provided written informed consent. Clinical characteristics of patients are given in Table I.
Table I.
Clinical characteristics of patients.
| Items | Heparin group (n=1433) | Bivalirudin group (n=944) | P-value |
|---|---|---|---|
| Demographics | |||
| Age (years), mean ± SD | 65.1±11.3 | 64.4±11.3 | 0.122 |
| Sex, n (%) | 0.144 | ||
| Female | 458 (32.0) | 275 (29.1) | |
| Male | 975 (68.0) | 669 (70.9) | |
| BMI (kg/m2), mean ± SD | 24.0±3.1 | 24.1±3.1 | 0.435 |
| Comorbidities | |||
| History of hypertension, n (%) | 0.277 | ||
| No | 488 (34.1) | 342 (36.2) | |
| Yes | 945 (65.9) | 602 (63.8) | |
| History of diabetes mellitus, n (%) | 0.721 | ||
| No | 1070 (74.7) | 711 (75.3) | |
| Yes | 363 (25.3) | 233 (24.7) | |
| History of cardiac surgery, n (%) | 0.292 | ||
| No | 1310 (91.4) | 851 (90.1) | |
| Yes | 123 (8.6) | 93 (9.9) | |
| Disease features | |||
| Clinical manifestation, n (%) | 0.577 | ||
| STEMI | 608 (42.4) | 402 (42.6) | |
| UA | 467 (32.6) | 309 (32.7) | |
| NSTEMI | 188 (13.1) | 136 (14.4) | |
| SCAD | 170 (11.9) | 97 (10.3) | |
| CRUSADE score, median (IQR) | 28.0 (21.0-38.0) | 27.0 (20.0-36.0) | 0.019 |
| Bleeding risk, n (%) | 0.013 | ||
| Very low risk (CRUSADE score ≤20) | 313 (21.8) | 248 (26.3) | |
| Low risk (CRUSADE score 21-30) | 488 (34.1) | 312 (33.1) | |
| Moderate risk (CRUSADE score 31-40) | 336 (23.4) | 219 (23.2) | |
| High risk (CRUSADE score 41-50) | 175 (12.2) | 98 (10.4) | |
| Very high risk (CRUSADE score ≥51) | 105 (7.3) | 58 (6.1) | |
| Unknown | 16 (1.1) | 9 (1.0) | |
| Operative timing, n (%) | 0.464 | ||
| Elective operation | 787 (54.9) | 504 (53.4) | |
| Emergency operation | 646 (45.1) | 440 (46.6) | |
| Lesional vessel, No. (%) | 0.605 | ||
| Single | 1136 (79.3) | 740 (78.4) | |
| Multiple | 297 (20.7) | 204 (21.6) | |
| Treatment-related information | |||
| PCI type, n (%) | 0.408 | ||
| Balloon | 61 (4.3) | 47 (5.0) | |
| Stent | 1372 (95.7) | 897 (95.0) | |
| Stent diameter (mm), median (IQR) | 3.0 (3.0-3.5) | 3.0 (2.8-3.5) | 0.239 |
| Total stent length (mm), median (IQR) | 33.0 (23.0-38.0) | 33.0 (23.0-38.0) | 0.819 |
SD, standard deviation; BMI, body mass index; STEMI, ST-segment elevation myocardial infarction; UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial infarction; SCAD, stable coronary artery disease; CRUSADE, Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines; IQR, interquartile range; PCI, percutaneous coronary intervention.
Treatment
Bivalirudin or heparin (LMWH or UFH) were administered to the eligible patients for anticoagulant treatment. The treatment was not intervened with in the present study; the appropriate medication was selected was based on the actual clinical status of the patient. Furthermore, there were no restrictions on the addition of GPIs. As a result, patients who received bivalirudin were considered as the bivalirudin group (n=944) and patients who received LMWH or UFH were considered as the heparin group (n=1,433). The detailed regimens of bivalirudin and heparin were the same as those described in a previous study (16).
Data collection and assessment
Demographics, comorbidities, disease features and treatment-related information were obtained for analysis. The Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA guidelines (CRUSADE) score was evaluated based on 8 predictors and ranged from 1-100 points (17). Patients were classified into 5 categories of bleeding risk based on CRUSADE score: Very low, ≤20 points; low, 21-30 points; moderate, 31-40 points; high, 41-50 points; and very high risk, ≤51 points (17). Additionally, within 30 days after PCI, NACEs, MACCEs, Bleeding Academic Research Consortium grades 2-5 (BARC 2-5) bleeding events and BARC 3-5 bleeding events were assessed. NACEs was defined as the composite of MACCEs and BARC 2-5 bleeding events (18). MACCEs was defined as the composite of all-cause death, cardiac mortality, recurrent myocardial infarction, ischemia-driven target vessel revascularization and stroke (18). BARC 2-5 bleeding events and BARC 3-5 bleeding events were assessed according to BARC criteria (19).
Statistical analysis
Statistical analysis was carried out using SPSS V22.0 software (IBM Corp.). Graph plotting was performed using GraphPad Prism V6.1 software (GraphPad Software Inc.). Comparisons between the two groups were performed using the unpaired Student's t-test, χ2 test or Wilcoxon rank sum test. Factors associated with NACEs, MACCEs, BARC 2-5 bleeding events or BARC 3-5 bleeding events were assessed using logistic regression analysis, and all factors analyzed in the univariate logistic regression analysis were included in the multivariate logistic regression analysis with the forward stepwise mode. A value of P<0.05 was considered to indicate a statistically significant difference.
Results
Clinical features
The heparin group included 458 (32.0%) females and 975 (68.0%) males with a mean age of 65.1±11.3 years. Moreover, the bivalirudin group included 275 (29.1%) females and 669 (70.9%) males with a mean age of 64.4±11.3 years. The median value [interquartile range (IQR)] of the CRUSADE score in the bivalirudin group was lower compared with that in the heparin group [27.0 (20.0-36.0) vs. 28.0 (21.0-38.0); P=0.019]. Moreover, the bleeding risk stratified by the CRUSADE score revealed a significant difference between the bivalirudin and heparin groups (P=0.013). In terms of demographics, comorbidities, other disease features and treatment-related information, there were no significant differences between the groups (all P>0.05). The detailed clinical features of the patients are presented in Table I.
Incidences of NACEs, MACCEs, BARC 2-5 bleeding events and BARC 3-5 bleeding events
The incidence of NACEs in the bivalirudin group was significantly lower compared with that in the heparin group (9.3 vs. 13.4%; P=0.003). Moreover, no significant difference was found in the incidence of MACCEs between the bivalirudin and heparin groups (5.9 vs. 7.6%; P=0.116). Furthermore, among the MACCEs, the incidences of all-cause mortality (3.7 vs. 4.5%; P=0.325), cardiac mortality (3.0 vs. 3.4%; P=0.541), recurrent myocardial infarction (1.6 vs. 2.0%; P=0.442), ischemia-driven revascularization (1.9 vs. 1.3%; P=0.263) and stroke (1.6 vs. 1.5%; P=0.809) did not vary significantly between the groups. Of note, the incidences of BARC 2-5 bleeding events (4.8 vs. 8.7%; P<0.001) and BARC 3-5 bleeding events (1.9 vs. 4.4%; P=0.001) in the bivalirudin group were lower compared with those in the heparin group (Table II).
Table II.
Comparison of NACEs, MACCEs, BARC 2-5 bleeding events and BARC 3-5 bleeding events between groups.
| Items | Heparin group (n=1433) | Bivalirudin group (n=944) | P-value |
|---|---|---|---|
| NACEs, n (%) | 192 (13.4) | 88 (9.3) | 0.003 |
| MACCEs, n (%) | 109 (7.6) | 56 (5.9) | 0.116 |
| All-cause mortality | 65 (4.5) | 35 (3.7) | 0.325 |
| Cardiac mortality | 49 (3.4) | 28 (3.0) | 0.541 |
| Recurrent myocardial infarction | 29 (2.0) | 15 (1.6) | 0.442 |
| Ischemia-driven revascularization | 19 (1.3) | 18 (1.9) | 0.263 |
| Stroke | 21 (1.5) | 15 (1.6) | 0.809 |
| BARC 2-5 bleeding events, n (%) | 125 (8.7) | 45 (4.8) | <0.001 |
| BARC 3-5 bleeding events, n (%) | 63 (4.4) | 18 (1.9) | 0.001 |
NACEs, net adverse clinical events; MACCEs, major adverse cardiac and cerebral events; BARC 2-5 bleeding events, Bleeding Academic Research Consortium grades 2 to 5; BARC 3-5 bleeding events, Bleeding Academic Research Consortium grades 3 to 5.
Independent factors for NACEs
Univariate logistics regression analysis revealed that bivalirudin treatment (vs. heparin treatment; P=0.003) predicted a lower risk of NACEs. Age (≥65 years vs. <65 years; P=0.017), a history of hypertension (yes vs. no; P=0.013), clinical manifestation of SCAD (vs. UA; P<0.001), NSTEMI (vs. UA; P<0.001), STEMI (vs. UA; P<0.001), CRUSADE score (≥41 vs. <40; P=0.001), operative timing (emergency operation vs. elective operation; P<0.001) and total stent length (>33.0 vs. ≤33.0 mm; P=0.020) forecasted higher risks of NACEs (Table III).
Table III.
Logistic regression analysis for NACEs.
| A, Univariate logistic regression analysis | ||||
|---|---|---|---|---|
| 95% CI | ||||
| Items | P-value | OR | Lower | Upper |
| Group (bivalirudin group vs. heparin group) | 0.003 | 0.664 | 0.509 | 0.868 |
| Age (≥65 years vs. <65 years) | 0.017 | 1.363 | 1.057 | 1.756 |
| Sex (male vs. female) | 0.119 | 1.250 | 0.945 | 1.654 |
| BMI (>28 kg/m2 vs. ≤28 kg/m2) | 0.123 | 0.687 | 0.426 | 1.108 |
| History of hypertension (yes vs. no) | 0.013 | 1.420 | 1.078 | 1.869 |
| History of diabetes mellitus (yes vs. no) | 0.151 | 1.226 | 0.928 | 1.618 |
| History of cardiac surgery (yes vs. no) | 0.446 | 0.836 | 0.528 | 1.325 |
| Clinical manifestation | ||||
| UA | Reference | |||
| SCAD | <0.001 | 3.409 | 2.227 | 5.219 |
| NSTEMI | <0.001 | 2.702 | 1.773 | 4.119 |
| STEMI | <0.001 | 2.320 | 1.645 | 3.273 |
| CRUSADE score (≥41 vs. <40) | 0.001 | 1.665 | 1.240 | 2.236 |
| Operative timing (emergency operation vs. elective operation) | <0.001 | 2.246 | 1.736 | 2.906 |
| Lesional vessel (multiple vs. single) | 0.087 | 1.288 | 0.964 | 1.723 |
| PCI type (stent vs. balloon) | 0.193 | 0.702 | 0.412 | 1.197 |
| Stent diameter (≥3.5 mm vs. <3.5 mm) | 0.179 | 1.196 | 0.921 | 1.551 |
| Total stent length (>33.0 mm vs. ≤33.0 mm) | 0.020 | 1.359 | 1.050 | 1.759 |
| B, Forward stepwise multivariate logistic regression analysis | ||||
| 95% CI | ||||
| Items | P-value | OR | Lower | Upper |
| Group (bivalirudin group vs. heparin group) | <0.001 | 0.587 | 0.437 | 0.788 |
| Age (≥65 years vs. <65 years) | 0.008 | 1.455 | 1.101 | 1.923 |
| History of hypertension (yes vs. no) | 0.016 | 1.447 | 1.072 | 1.952 |
| Clinical manifestation | ||||
| UA | Reference | |||
| SCAD | 0.005 | 2.054 | 1.243 | 3.394 |
| NSTEMI | 0.001 | 2.164 | 1.362 | 3.438 |
| STEMI | 0.110 | 1.424 | 0.923 | 2.198 |
| Operative timing (emergency operation vs. elective operation) | <0.001 | 2.352 | 1.664 | 3.324 |
| Lesional vessel (multiple vs. single) | 0.010 | 1.561 | 1.114 | 2.188 |
| Total stent length (>33.0 mm vs. ≤33.0 mm) | 0.015 | 1.405 | 1.070 | 1.846 |
NACEs, net adverse clinical events; OR, odds ratio; CI, confidence interval; BMI, body mass index; UA, unstable angina; SCAD, stable coronary artery disease; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; CRUSADE, Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines; PCI, percutaneous coronary intervention.
According to forward stepwise multivariate logistic regression analysis, bivalirudin treatment [vs. heparin treatment; odds ratio (OR), 0.587; P<0.001] independently estimated a lower risk of NACEs. However, age (≥65 years vs. <65 years; OR, 1.455; P=0.008), a history of hypertension (yes vs. no; OR, 1.447; P=0.016), clinical manifestation of SCAD (vs. UA; OR, 2.054; P=0.005), NSTEMI (vs. UA; OR, 2.164; P=0.001), operative timing (emergency operation vs. elective operation; OR, 2.352; P<0.001), lesional vessel (multiple vs. single; OR, 1.561; P=0.010) and total stent length (>33.0 vs. ≤33.0 mm; OR, 1.405; P=0.015) independently predicted higher risks of NACEs (Table III).
Independent factors for MACCEs
Based on univariate logistic regression analysis, bivalirudin treatment (vs. heparin treatment; P=0.117) was not associated with risk of MACCEs. Age (≥65 years vs. <65 years; P=0.028), a history of hypertension (yes vs. no; P=0.034), clinical manifestation of SCAD (vs. UA; P<0.001), NSTEMI (vs. UA; P=0.007), STEMI (vs. UA; P=0.001), CRUSADE score (≥41 vs. <40; P=0.024), operative timing (emergency operation vs. elective operation; P<0.001) and lesional vessel (multiple vs. single; P=0.044) estimated higher risks of MACCEs (Table IV).
Table IV.
Logistic regression analysis for MACCEs.
| A, Univariate logistic regression analysis | ||||
|---|---|---|---|---|
| 95% CI | ||||
| Items | P-value | OR | Lower | Upper |
| Group (bivalirudin group vs. heparin group) | 0.117 | 0.766 | 0.549 | 1.069 |
| Age (≥65 years vs. <65 years) | 0.028 | 1.439 | 1.041 | 1.990 |
| Sex (male vs. female) | 0.394 | 1.165 | 0.820 | 1.657 |
| BMI (>28 kg/m2 vs. ≤28 kg/m2) | 0.560 | 0.845 | 0.479 | 1.489 |
| History of hypertension (yes vs. no) | 0.034 | 1.467 | 1.030 | 2.089 |
| History of diabetes mellitus (yes vs. no) | 0.156 | 1.286 | 0.908 | 1.820 |
| History of cardiac surgery (yes vs. no) | 0.999 | 1.000 | 0.577 | 1.734 |
| Clinical manifestation | ||||
| UA | Reference | |||
| SCAD | <0.001 | 2.928 | 1.729 | 4.960 |
| NSTEMI | 0.007 | 2.097 | 1.224 | 3.592 |
| STEMI | 0.001 | 2.039 | 1.331 | 3.124 |
| CRUSADE score (≥41 vs. <40) | 0.024 | 1.540 | 1.059 | 2.239 |
| Operative timing (emergency operation vs. elective operation) | <0.001 | 1.812 | 1.313 | 2.500 |
| Lesional vessel (multiple vs. single) | 0.044 | 1.444 | 1.010 | 2.065 |
| PCI type (stent vs. balloon) | 0.847 | 1.080 | 0.494 | 2.363 |
| Stent diameter (≥3.5 mm vs. <3.5 mm) | 0.771 | 1.050 | 0.755 | 1.461 |
| Total stent length (>33.0 mm vs. ≤33.0 mm) | 0.131 | 1.284 | 0.928 | 1.775 |
| B, Forward stepwise multivariate logistic regression analysis | ||||
| 95% CI | ||||
| Items | P-value | OR | Lower | Upper |
| Group (bivalirudin group vs. heparin group) | 0.041 | 0.689 | 0.482 | 0.985 |
| Age (≥65 years vs. <65 years) | 0.016 | 1.531 | 1.084 | 2.162 |
| History of hypertension (yes vs. no) | 0.047 | 1.460 | 1.005 | 2.122 |
| Operative timing (emergency operation vs. elective operation) | <0.001 | 1.982 | 1.391 | 2.824 |
| Lesional vessel (multiple vs. single) | 0.019 | 1.613 | 1.081 | 2.407 |
MACCEs, major adverse cardiac and cerebral events; OR, odds ratio; CI, confidence interval; BMI, body mass index; UA, unstable angina; SCAD, stable coronary artery disease; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; CRUSADE, Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines; PCI, percutaneous coronary intervention.
According to forward stepwise multivariate logistic regression analysis, bivalirudin treatment (vs. heparin treatment; OR, 0.689; P=0.041) independently predicted a lower risk of MACCEs. Age (≥65 years vs. <65 years; OR, 1.531; P=0.016), a history of hypertension (yes vs. no; OR, 1.460; P=0.047), operative timing (emergency operation vs. elective operation; OR, 1.982; P<0.001) and lesional vessel (multiple vs. single; OR, 1.613; P=0.019) independently forecasted higher risks of MACCEs (Table IV).
Independent factors for BARC 2-5 bleeding events
In accordance with univariate logistic regression analysis, bivalirudin treatment (vs. heparin treatment; P<0.001) estimated a lower risk of BARC 2-5 bleeding events, whereas clinical manifestation of SCAD (vs. UA; P<0.001), NSTEMI (vs. UA; P<0.001), STEMI (vs. UA; P<0.001), CRUSADE score (≥41 vs. <40; P=0.001) and operative timing (emergency operation vs. elective operation; P<0.001) predicted higher risks of BARC 2-5 bleeding events (Table V).
Table V.
Logistic regression analysis for BARC 2-5 bleeding events.
| A, Univariate logistic regression analysis | ||||
|---|---|---|---|---|
| 95% CI | ||||
| Items | P-value | OR | Lower | Upper |
| Group (bivalirudin group vs. heparin group) | <0.001 | 0.524 | 0.369 | 0.744 |
| Age (≥65 years vs. <65 years) | 0.056 | 1.364 | 0.992 | 1.874 |
| Sex (male vs. female) | 0.148 | 1.300 | 0.912 | 1.853 |
| BMI (>28 kg/m2 vs. ≤28 kg/m2) | 0.145 | 0.627 | 0.334 | 1.174 |
| History of hypertension (yes vs. no) | 0.220 | 1.235 | 0.881 | 1.732 |
| History of diabetes mellitus (yes vs. no) | 0.058 | 1.388 | 0.989 | 1.948 |
| History of cardiac surgery (yes vs. no) | 0.079 | 0.540 | 0.272 | 1.073 |
| Clinical manifestation | ||||
| UA | Reference | |||
| SCAD | <0.001 | 3.789 | 2.205 | 6.511 |
| NSTEMI | <0.001 | 3.161 | 1.852 | 5.397 |
| STEMI | <0.001 | 2.515 | 1.600 | 3.953 |
| CRUSADE score (≥41 vs. <40) | 0.001 | 1.876 | 1.315 | 2.677 |
| Operative timing (emergency operation vs. elective operation) | <0.001 | 2.377 | 1.715 | 3.296 |
| Lesional vessel (multiple vs. single) | 0.820 | 1.045 | 0.716 | 1.526 |
| PCI type (stent vs. balloon) | 0.106 | 0.599 | 0.322 | 1.115 |
| Stent diameter (≥3.5 mm vs. <3.5 mm) | 0.070 | 1.350 | 0.975 | 1.869 |
| Total stent length (>33.0 mm vs. ≤33.0 mm) | 0.066 | 1.356 | 0.980 | 1.877 |
| B, Forward stepwise multivariate logistic regression analysis | ||||
| 95% CI | ||||
| Items | P-value | OR | Lower | Upper |
| Group (bivalirudin group vs. heparin group) | <0.001 | 0.459 | 0.310 | 0.678 |
| Age (≥65 years vs. <65 years) | 0.024 | 1.498 | 1.055 | 2.126 |
| History of diabetes mellitus (yes vs. no) | 0.019 | 1.568 | 1.075 | 2.287 |
| Clinical manifestation | ||||
| UA | Reference | |||
| SCAD | 0.009 | 2.356 | 1.241 | 4.473 |
| NSTEMI | 0.002 | 2.632 | 1.445 | 4.791 |
| STEMI | 0.179 | 1.484 | 0.835 | 2.636 |
| Operative timing (emergency operation vs. elective operation) | <0.001 | 2.535 | 1.649 | 3.896 |
| Total stent length (>33.0 mm vs. ≤33.0 mm) | 0.040 | 1.431 | 1.016 | 2.017 |
BARC 2-5 bleeding events, Bleeding Academic Research Consortium grades 2 to 5; OR, odds ratio; CI, confidence interval; BMI, body mass index; UA, unstable angina; SCAD, stable coronary artery disease; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; CRUSADE, Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines; PCI, percutaneous coronary intervention.
Based on further forward stepwise multivariate logistic regression analysis, bivalirudin treatment (vs. heparin treatment; OR, 0.459; P<0.001) independently forecasted a lower risk of BARC 2-5 bleeding events. However, age (≥65 years vs. <65 years; OR, 1.498; P=0.024), a history of diabetes mellitus (yes vs. no; OR, 1.568; P=0.019), clinical manifestation of SCAD (vs. UA; OR, 2.356; P=0.009), NSTEMI (vs. UA; OR, 2.632; P=0.002), operative timing (emergency operation vs. elective operation; OR, 2.535; P<0.001) and total stent length (>33.0 vs. ≤33.0 mm; OR, 1.431; P=0.040) independently predicted higher risks of BARC 2-5 bleeding events (Table V).
Independent factors for BARC 3-5 bleeding events
According to the univariate logistic regression analysis, bivalirudin treatment (vs. heparin treatment; OR, 0.423; P=0.001) was related to a lower risk of BARC 3-5 bleeding events. Nevertheless, a history of diabetes mellitus (yes vs. no; OR, 1.798; P=0.013), the clinical manifestation of SCAD (vs. UA; OR, 3.470; P=0.001), NSTEMI (vs. UA; OR, 2.275; P=0.036), STEMI (vs. UA; OR, 2.128; P=0.017), CRUSADE score (≥41 vs. <40; OR, 3.100; P<0.001), operative timing (emergency operation vs. elective operation; OR, 1.859; P=0.007) and stent diameter (≥3.5 vs. <3.5 mm; OR, 1.743; P=0.018) were associated with a higher risk of BARC 3-5 bleeding events (Table VI).
Table VI.
Logistic regression analysis for BARC 3-5 bleeding events.
| A, Univariate logistic regression analysis | ||||
|---|---|---|---|---|
| 95% CI | ||||
| Items | P-value | OR | Lower | Upper |
| Group (bivalirudin group vs. heparin group) | 0.001 | 0.423 | 0.249 | 0.718 |
| Age (≥65 years vs. <65 years) | 0.167 | 1.377 | 0.875 | 2.166 |
| Sex (male vs. female) | 0.811 | 1.061 | 0.653 | 1.723 |
| BMI (>28 kg/m2 vs. ≤28 kg/m2) | 0.298 | 0.614 | 0.246 | 1.538 |
| History of hypertension (yes vs. no) | 0.086 | 1.554 | 0.939 | 2.574 |
| History of diabetes mellitus (yes vs. no) | 0.013 | 1.798 | 1.134 | 2.851 |
| History of cardiac surgery (yes vs. no) | 0.593 | 0.795 | 0.342 | 1.847 |
| Clinical manifestation | ||||
| UA | Reference | |||
| SCAD | 0.001 | 3.470 | 1.670 | 7.209 |
| NSTEMI | 0.036 | 2.275 | 1.057 | 4.896 |
| STEMI | 0.017 | 2.128 | 1.145 | 3.956 |
| CRUSADE score (≥41 vs. <40) | <0.001 | 3.100 | 1.945 | 4.940 |
| Operative timing (emergency operation vs. elective operation) | 0.007 | 1.859 | 1.182 | 2.924 |
| Lesional vessel (multiple vs. single) | 0.984 | 0.994 | 0.577 | 1.713 |
| PCI type (stent vs. balloon) | 0.213 | 0.581 | 0.247 | 1.366 |
| Stent diameter (≥3.5 mm vs. <3.5 mm) | 0.018 | 1.743 | 1.099 | 2.764 |
| Total stent length (>33.0 mm vs. ≤33.0 mm) | 0.241 | 1.319 | 0.831 | 2.094 |
| B, Forward stepwise multivariate logistic regression analysis | ||||
| 95% CI | ||||
| Items | P-value | OR | Lower | Upper |
| Group (bivalirudin group vs. heparin group) | 0.002 | 0.386 | 0.212 | 0.701 |
| History of diabetes mellitus (yes vs. no) | 0.024 | 1.805 | 1.079 | 3.018 |
| CRUSADE score (≥41 vs. <40) | 0.001 | 2.313 | 1.388 | 3.857 |
| Operative timing (emergency operation vs. elective operation) | 0.001 | 2.379 | 1.431 | 3.954 |
| Stent diameter (≥3.5 mm vs. <3.5 mm) | 0.048 | 1.635 | 1.005 | 2.659 |
BARC 3-5 bleeding events, Bleeding Academic Research Consortium grades 3 to 5; OR, odds ratio; CI, confidence interval; BMI, body mass index; UA, unstable angina; SCAD, stable coronary artery disease; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; CRUSADE, Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines; PCI, percutaneous coronary intervention.
Additionally, forward stepwise multivariate logistic regression analysis demonstrated that bivalirudin treatment (vs. heparin treatment; OR, 0.386; P=0.002) was independently associated with a lower risk of BARC 3-5 bleeding events. Nevertheless, a history of diabetes mellitus (yes vs. no; OR, 1.805; P=0.024), the CRUSADE score (≥41 vs. <40; OR, 2.313; P=0.001), operative timing (emergency operation vs. elective operation; OR, 2.379; P=0.001) and stent diameter (≥3.5 vs. <3.5 mm; OR, 1.635; P=0.048) were independently associated with a higher risk of BARC 3-5 bleeding events (Table VI).
Discussion
Bivalirudin plays an anticoagulant role by inhibiting thrombin directly, repressing circulating and clot-bound thrombin, but not combining antithrombin III, which is considered to have certain clinical advantages over heparin in patients receiving PCI (20-22). For example, a previous study suggests that among patients with STEMI who undergo primary PCI and receive aspirin and ticagrelor, bivalirudin reduces the incidence of NACEs compared with heparin (23). Moreover, another study indicated that in patients with STEMI who undergo PCI, bivalirudin decreases all-cause mortality compared with heparin (24). These findings are similar to those of the present study, which revealed that among patients who underwent PCI, bivalirudin decreased the incidence of NACEs compared with heparin, and bivalirudin treatment (vs. heparin treatment) was an independent factor for predicting a low risk of NACEs. This may be due to the following: i) Bivalirudin directly inhibited thrombin, while heparin indirectly inhibited thrombin through antithrombin III activation; thus, bivalirudin decreased the incidence of bleeding events compared with heparin in patients who underwent PCI (22,25). ii) Bivalirudin exerted a regulatory effect on inflammation in patients who underwent PCI, thereby inhibiting atherosclerosis and further decreasing the incidence of MACCEs to a certain extent compared with heparin in those patients (14,26,27). For the aforementioned reasons, bivalirudin decreased the incidence of NACEs compared with heparin.
However, the incidence of MACCEs in patients who undergo PCI continues to be a matter of concern. A previous study demonstrated that, compared with heparin, bivalirudin decreases the risk of 30-day MACCEs in patients with coronary artery disease complicated by diabetes who undergo PCI (14). Another study disclosed that the incidence of MACCEs does not vary between bivalirudin and the unfractionated heparin in patients with STEMI undergoing primary PCI (23). Moreover, in female patients with acute myocardial infarction who undergo emergency PCI, no discrepancy is observed in the incidence of MACCEs between bivalirudin and heparin (28). In the present study, bivalirudin numerically reduced the incidence rate of MACCEs compared with heparin, although there was no significant difference. Moreover, bivalirudin treatment (vs. heparin treatment) was not associated with a risk of MACCEs in univariate logistic regression analysis, while it was independently related to a low risk of MACCEs in forward stepwise multivariate logistic regression analysis. This result may be due to the fact that the result of the univariate logistic regression analysis was affected by some confounding factors, resulting in the concealment of the true effect of bivalirudin treatment. Following adjustment by forward stepwise multivariate logistic regression analysis, the influence of these confounding factors was eliminated, and it was found that bivalirudin treatment (vs. heparin treatment) was independently related to a lower risk of MACCEs. The result from forward stepwise multivariate logistic regression analysis was explained as follows: Compared with heparin, bivalirudin inhibited inflammation in patients who underwent PCI, and thus reduced the MACCEs to a certain extent (14,26,27).
In addition, a previous study has demonstrated that in patients with STEMI who undergo primary PCI, bivalirudin reduces the 30-day incidence of BARC 3-5 major bleeding events compared with heparin (24). In another study on elderly patients with STEMI who underwent primary PCI, bivalirudin decreases the incidence of BARC 2-5 bleeding events compared with unfractionated heparin (29). These findings are partly in accordance with the findings of the present study, which revealed that bivalirudin reduced the incidence of BARC 2-5 and 3-5 bleeding events compared with heparin. In addition, bivalirudin treatment (vs. heparin treatment) was independently associated with low risks of BARC 2-5 and 3-5 bleeding events. The possible reasons for this were the following: i) Compared with heparin, bivalirudin had a shorter half-life and it was metabolized more rapidly in the plasma of patients undergoing PCI, which may lead to a lower risk of bleeding in these patients (21); and ii) the reduction in the risk of bleeding with the use of bivalirudin might be related to its direct inhibition of thrombin, its non-union with platelet factor 4 and its linear pharmacokinetics (25).
As aforementioned, the present study showed that bivalirudin reduced the risks of NACEs, MACCEs and bleeding events compared with heparin in patients who underwent PCI. Notably, bivalirudin is 10-50 times more expensive compared with heparin (30), thus for clinical management, the cost-effectiveness of the two drugs is also an issue worth taking into consideration. Currently, the results of the comparison of cost-effectiveness between bivalirudin and heparin are inconsistent in previous studies. For example, one study revealed that bivalirudin is less cost-effective compared with heparin in patients who undergo PCI (31). Another study showed that bivalirudin is more cost-effective for only a minority of patients who undergo PCI with a high bleeding risk compared with heparin (32). Nevertheless, one study illustrated that the use of bivalirudin in patients with STEMI who undergo primary PCI is cost-effective compared with the use of heparin (33). These controversial results may be due to the existence of some confounding factors (34). Taken together, the comparison of cost-effectiveness between bivalirudin and heparin is uncertain and required to be verified in further studies.
There were several limitations to the present study, which should be mentioned: i) The present study was a single-center study, which may have led to bias in the selection process. ii) The present study only evaluated NACEs within 30 days after PCI. Thus, the long-term safety of bivalirudin in patients who undergo PCI remains to be further explored. iii) In the present study, the included patients selected medication based on their actual clinical status rather than randomization, which may have led to potential confounders between groups.
In conclusion, the present study demonstrated that bivalirudin reduced the incidence of NACEs (particularly bleeding events) compared with heparin in Chinese patients who underwent PCI, which may serve as a safer anticoagulant in these patients. However, further validation in larger-scale, multi-center and randomized controlled studies is necessary.
Acknowledgements
Not applicable.
Funding Statement
Funding: No funding was received.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Authors' contributions
LC, JL, YW and ZB contributed to the conception and design of the study. LC, MZ, ZW, JL and ZB were involved in data collection. YZ, YW and ZQ contributed to data analysis. LC and JL confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.
Ethics approval and consent to participate
The study was approved by the Ethics Committee of Handan Central Hospital (Handan, China; approval no. 20230816001). The patients or their families provided written informed consent.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
- 1.Hong SJ, Hong MK. Drug-eluting stents for the treatment of coronary artery disease: A review of recent advances. Expert Opin Drug Deliv. 2022;19:269–280. doi: 10.1080/17425247.2022.2044784. [DOI] [PubMed] [Google Scholar]
- 2.Hoole SP, Bambrough P. Recent advances in percutaneous coronary intervention. Heart. 2020;106:1380–1386. doi: 10.1136/heartjnl-2019-315707. [DOI] [PubMed] [Google Scholar]
- 3.Cao D, Chandiramani R, Chiarito M, Claessen BE, Mehran R. Evolution of antithrombotic therapy in patients undergoing percutaneous coronary intervention: A 40-year journey. Eur Heart J. 2021;42:339–351. doi: 10.1093/eurheartj/ehaa824. [DOI] [PubMed] [Google Scholar]
- 4.Nso N, Nassar M, Zirkiyeva M, Mbome Y, Lyonga Ngonge A, Badejoko SO, Akbar S, Azhar A, Lakhdar S, Guzman Perez LM, et al. Factors impacting stent thrombosis in patients with percutaneous coronary intervention and coronary stenting: A systematic review and meta-analysis. Cureus. 2022;14(e23973) doi: 10.7759/cureus.23973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Loeffen R, Godschalk TC, van Oerle R, Spronk HM, Hackeng CM, ten Berg JM, ten Cate H. The hypercoagulable profile of patients with stent thrombosis. Heart. 2015;101:1126–1132. doi: 10.1136/heartjnl-2014-306685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Towashiraporn K, Krittayaphong R. Current perspectives on antithrombotic therapy for the treatment of acute coronary syndrome. Int J Gen Med. 2022;15:2397–2414. doi: 10.2147/IJGM.S289295. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Bocchino PP, Angelini F, Toso E. Atrial fibrillation and coronary artery disease: A review on the optimal use of oral anticoagulants. Rev Cardiovasc Med. 2021;22:635–648. doi: 10.31083/j.rcm2203074. [DOI] [PubMed] [Google Scholar]
- 8.Angiolillo DJ, Bhatt DL, Cannon CP, Eikelboom JW, Gibson CM, Goodman SG, Granger CB, Holmes DR, Lopes RD, Mehran R, et al. Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention: A North American perspective: 2021 Update. Circulation. 2021;143:583–596. doi: 10.1161/CIRCULATIONAHA.120.050438. [DOI] [PubMed] [Google Scholar]
- 9.Karcioglu O, Zengin S, Ozkaya B, Ersan E, Yilmaz S, Afacan G, Abuska D, Hosseinzadeh M, Yeniocak S. Direct (new) oral anticoagulants (DOACs): Drawbacks, bleeding and reversal. Cardiovasc Hematol Agents Med Chem. 2022;20:103–113. doi: 10.2174/1871525719666210914110750. [DOI] [PubMed] [Google Scholar]
- 10.Bainey KR, Marquis-Gravel G, Mehta SR, Tanguay JF. The evolution of anticoagulation for percutaneous coronary intervention: A 40-year journey. Can J Cardiol. 2022;38 (10 Suppl 1):S89–S98. doi: 10.1016/j.cjca.2022.07.007. [DOI] [PubMed] [Google Scholar]
- 11.Erdoes G, Ortmann E, Martinez Lopez De Arroyabe B, Reid C, Koster A. Role of bivalirudin for anticoagulation in adult perioperative cardiothoracic practice. J Cardiothorac Vasc Anesth. 2020;34:2207–2214. doi: 10.1053/j.jvca.2019.08.022. [DOI] [PubMed] [Google Scholar]
- 12.Zhang Y, Zhang Y, Chang C, Yan S, Chen Z, Zhang L, Chen K, Liu G. Efficacy and safety of bivalirudin during percutaneous coronary intervention in chronic total occlusion: A retrospective study. Clin Ther. 2021;43:844–851. doi: 10.1016/j.clinthera.2021.03.004. [DOI] [PubMed] [Google Scholar]
- 13.Mehran R, Lansky AJ, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartmann F, Gersh BJ, et al. Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-Year results of a randomised controlled trial. Lancet. 2009;374:1149–1159. doi: 10.1016/S0140-6736(09)61484-7. [DOI] [PubMed] [Google Scholar]
- 14.Li J, Chen S, Ma S, Yang M, Qi Z, Na K, Qiu M, Li Y, Han Y. Safety and efficacy of bivalirudin versus unfractionated heparin monotherapy in patients with CAD and DM undergoing PCI: A retrospective observational study. Cardiovasc Ther. 2022;2022(5352087) doi: 10.1155/2022/5352087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Han Y, Guo J, Zheng Y, Zang H, Su X, Wang Y, Chen S, Jiang T, Yang P, Chen J, et al. Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: The BRIGHT randomized clinical trial. JAMA. 2015;313:1336–1346. doi: 10.1001/jama.2015.2323. [DOI] [PubMed] [Google Scholar]
- 16.Chen S, Li Y, Qiu M, Jiang Z, Han Y, Li J. Comparison of the effects of heparin and bivalirudin on percutaneous coronary intervention in female patients with coronary. Clin J Med Offic. 2021;49:246–250. 253. [Google Scholar]
- 17.Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, Wang TY, Gibler WB, Ohman EM, Roe MT, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: The CRUSADE (can rapid risk stratification of unstable angina patients suppress ADverse outcomes with early implementation of the ACC/AHA guidelines) bleeding score. Circulation. 2009;119:1873–1882. doi: 10.1161/CIRCULATIONAHA.108.828541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Ki YJ, Lee BK, Park KW, Bae JW, Hwang D, Kang J, Han JK, Yang HM, Kang HJ, Koo BK, et al. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with STEMI. Korean Circ J. 2022;52:304–319. doi: 10.4070/kcj.2021.0293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, et al. Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the bleeding academic research consortium. Circulation. 2011;123:2736–2747. doi: 10.1161/CIRCULATIONAHA.110.009449. [DOI] [PubMed] [Google Scholar]
- 20.Hamzah M, Jarden AM, Ezetendu C, Stewart R. Evaluation of bivalirudin as an alternative to heparin for systemic anticoagulation in pediatric extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2020;21:827–834. doi: 10.1097/PCC.0000000000002384. [DOI] [PubMed] [Google Scholar]
- 21.Kimmelstiel C, Zhang P, Kapur NK, Weintraub A, Krishnamurthy B, Castaneda V, Covic L, Kuliopulos A. Bivalirudin is a dual inhibitor of thrombin and collagen-dependent platelet activation in patients undergoing percutaneous coronary intervention. Circ Cardiovasc Interv. 2011;4:171–179. doi: 10.1161/CIRCINTERVENTIONS.110.959098. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Hu YC, Yao WJ, Jin DX, Zhang JX, Wang L, Zhang R, Xu JH, Cong HL. Bivalirudin in patients undergoing percutaneous coronary intervention and independent predictors of postoperative adverse events in these patients: A real world retrospective study. Medicine (Baltimore) 2021;100(e25003) doi: 10.1097/MD.0000000000025003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Yu XF, Chen HW, Xu J, Xu QZ, Zhang XH, Li BB, Xu BL, Ma LK. Bivalirudin vs heparin on a background of ticagrelor and aspirin in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A multicenter prospective cohort study. Front Cardiovasc Med. 2022;9(932054) doi: 10.3389/fcvm.2022.932054. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Li Y, Liang Z, Qin L, Wang M, Wang X, Zhang H, Liu Y, Li Y, Jia Z, Liu L, et al. Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomised trial. Lancet. 2022;400:1847–1857. doi: 10.1016/S0140-6736(22)01999-7. [DOI] [PubMed] [Google Scholar]
- 25.Shah A, Feldman DN. Outcome of the HORIZONS-AMI trial: Bivalirudin enhances long-term survival in patients with ST-elevation myocardial infarction undergoing angioplasty. Vasc Health Risk Manag. 2012;8:115–123. doi: 10.2147/VHRM.S23491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Keating FK, Dauerman HL, Whitaker DA, Sobel BE, Schneider DJ. The effects of bivalirudin compared with those of unfractionated heparin plus eptifibatide on inflammation and thrombin generation and activity during coronary intervention. Coron Artery Dis. 2005;16:401–405. doi: 10.1097/00019501-200509000-00010. [DOI] [PubMed] [Google Scholar]
- 27.Saad M, Nairooz R, Rashed A, Abdelaziz HK, Mentias A, Abbott JD. Bivalirudin versus heparin in women undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized clinical trials. Cardiovasc Revasc Med. 2017;18:418–424. doi: 10.1016/j.carrev.2017.02.019. [DOI] [PubMed] [Google Scholar]
- 28.Liang Z, Li Y, Wang J, Wang D, Wang S, Ma L, Liu H, Yang L, Stone GW, Han Y. The safety and effectiveness of bivalirudin in female patients with acute myocardial infarction undergoing primary angioplasty: A subgroup analysis of the BRIGHT trial. Catheter Cardiovasc Interv. 2016;87 (Suppl 1):S608–S615. doi: 10.1002/ccd.26407. [DOI] [PubMed] [Google Scholar]
- 29.Chen H, Yu X, Kong X, Li L, Wu J, Ma L. Efficacy and safety of bivalirudin application during primary percutaneous coronary intervention in older patients with acute ST-segment elevation myocardial infarction. J Int Med Res. 2020;48(300060520947942) doi: 10.1177/0300060520947942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Widimský P. Is bivalirudin just an expensive heparin? Eur Heart J. 2016;37:1321–1324. doi: 10.1093/eurheartj/ehw031. [DOI] [PubMed] [Google Scholar]
- 31.Sun KX, Cui B, Cao SS, Wang WJ, Yu F, Wang JW, Ding Y. A meta-analysis and cost-minimization analysis of bivalirudin versus heparin in high-risk patients for percutaneous coronary intervention. Pharmacol Res Perspect. 2021;9(e00774) doi: 10.1002/prp2.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Amin AP, Marso SP, Rao SV, Messenger J, Chan PS, House J, Kennedy K, Robertus K, Cohen DJ, Mahoney EM. Cost-effectiveness of targeting patients undergoing percutaneous coronary intervention for therapy with bivalirudin versus heparin monotherapy according to predicted risk of bleeding. Circ Cardiovasc Qual Outcomes. 2010;3:358–365. doi: 10.1161/CIRCOUTCOMES.110.957290. [DOI] [PubMed] [Google Scholar]
- 33.Schwenkglenks M, Toward TJ, Plent S, Szucs TD, Blackman DJ, Baumbach A. Cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor in the treatment of acute ST-segment elevation myocardial infarction. Heart. 2012;98:544–551. doi: 10.1136/heartjnl-2011-301323. [DOI] [PubMed] [Google Scholar]
- 34.Mehrzad M, Tuktamyshov R, Mehrzad R. Safety, efficiency and cost effectiveness of bivalirudin: A systematic review. World J Cardiol. 2017;9:761–772. doi: 10.4330/wjc.v9.i9.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.