Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.
Current European Society of Cardiology guidelines for clinical practice recommend dual-antiplatelet therapy for patients with acute coronary syndromes (ACS) or those who undergo percutaneous coronary intervention (PCI). Because pharmacologic limitations of clopidogrel prevent its being fully effective, alternatives have been developed, such as prasugrel. The efficacy of prasugrel has been investigated in the 13,608-patient Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38 (TRITON–TIMI 38). In that trial, patients with moderate- to high-risk ACS scheduled to undergo PCI randomly received prasugrel (a 60-mg loading dose and a 10-mg/day maintenance dose) or clopidogrel (a 300-mg loading dose and a 75-mg/day maintenance dose) for 6 to 15 months (median 14.5). Compared with clopidogrel, the use of prasugrel was associated with significantly reduced ischemic event rates, at the cost of an increased risk for non–coronary artery bypass grafting major bleeding. In an exploratory analysis, 3 subgroups were identified that had greater risk for bleeding in the overall trial population, resulting in less net clinical benefit or in clinical harm. These included patients with histories of stroke or transient ischemic attack, patients aged ≥75 years, and patients with body weight <60 kg. Large real-world registry data are important for further understanding of the current use and outcomes of novel therapies. Currently, data regarding the use of prasugrel in real-world clinical practice are limited. The Swedish Coronary Angiography and Angioplasty Registry (SCAAR) provides complete coverage of all hospitals performing coronary angiography and interventions in Sweden. The objective of the present study was to assess treatment patterns and outcomes after prasugrel or clopidogrel use in patients who undergo PCI in Sweden.
Methods
The patient population was derived from SCAAR, part of the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, which includes complete coverage of all hospitals performing coronary angiography and interventions in Sweden. (The registry is funded by Swedish Health Authorities and is independent of industry support.) Since 2001, SCAAR has been internet-based, with recording of data on-line through a Web interface in the catheterization laboratory; data are transferred in an encrypted format to a central server at the Uppsala Clinical Research Center. Monitoring and verification of registry data have been performed at all hospitals since 2001 by comparing 50 entered variables in 20 randomly selected interventions per hospital and year with the patients’ hospital records. The overall correspondence in these data during the study period was 95.2%. PCI and adjunctive pharmacologic treatment were performed according to European Society of Cardiology guidelines.
From May 2010, when prasugrel became publicly available in Sweden, to December 2011, a total of 33,235 PCIs were performed in 29,002 patients. The study population consisted of all ACS and non-ACS patients who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Clopidogrel-pretreated and clopidogrel-naive patients were permitted for inclusion in the present analysis. Aspirin 75 mg was coadministered once daily according to local clinical practice. The choice, timing, and dosing of antithrombotic medication were at the discretion of the treating physician. In case of multiple PCIs per patient during the study period, only the first procedure was included in the study population.
The main outcomes for the present analysis were 30-day all-cause death and bleeding during initial hospitalization. Bleeding was classified as SCAAR-defined major or minor bleeding. SCAAR classifies major bleeding as fatal, intracranial hemorrhage or any bleeding (observed or not observed) leading to a decrease in hemoglobin of >50 g/L. Minor bleeding is defined as any observed bleeding with a decrease in hemoglobin of >30 to 50 g/L or unobserved bleeding with a decrease in hemoglobin of >40 to 50 g/L. Any bleeding is defined as bleeding requiring intervention. In the present SCAAR Web-based case report form, bleeding is collected using a check box. If any bleeding is checked, the physicians are required to further define bleeding as major or minor. Although death secondary to bleeding is captured as major bleeding, fatal bleeding is not specifically collected in the case report form. All-cause death and procedure-related death are recorded. The study was approved by the local ethics committee at Uppsala University and was in compliance with the Declaration of Helsinki.
Baseline patient and procedural characteristics and concomitant (antithrombotic) pharmacotherapy are presented as mean ± SD, median (interquartile range), or frequency (percentage) as appropriate. Descriptive data are stratified by the presence of ACS (including ST-segment elevation myocardial infarction or non–ST-segment elevation ACS). Normally distributed continuous variables were compared using Student’s t tests and those with skewed distributions using Wilcoxon’s rank-sum tests. Categorical variables were compared using chi-square tests. Interactions between prasugrel and clopidogrel use and patient characteristics were assessed by including an interaction term in a logistic regression model. Outcomes were compared using chi-square tests and are presented as proportions. A prespecified analyses included adverse clinical outcomes after prasugrel or clopidogrel according to diabetic status, hemorrhagic risk, age >75 years, and body weight <60 kg in patients with ACS. Bleeding risk was assessed using the (modified) Mehran bleeding risk score. The modified Mehran bleeding risk score was calculated as follows: female gender, 8 points; age 50 to 59 years, 3 points; age 60 to 69 years, 6 points; age 70 to 79 years, 9 points; age ≥80 years, 12 points; serum creatinine 1.0 to 1.19 mg/dl, 2 points; serum creatinine 1.2 to 1.39 mg/dl, 3 points; serum creatinine, 1.4 to 1.59 mg/dl, 5 points; serum creatinine 1.6 to 1.79 mg/dl, 6 points; serum creatinine 1.8 to 1.99 mg/dl, 8 points; serum creatinine ≥2.0 mg/dl, 10 points; presentation with ST-segment elevation myocardial infarction, 6 points; bivalirudin monotherapy, −5 points.
Results
A flowchart for patient selection is presented in Figure 1 . After exclusion of patients with missing data, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. The baseline characteristics of the study patients are listed in Table 1 . Prasugrel was used primarily in patients with ACS and was generally introduced before cardiac angiography. Generally, patients treated with prasugrel had a lower frequency of ischemic and hemorrhagic risk factors. Despite a higher frequency of hemorrhagic risk factors, Mehran bleeding risk scores were lower in clopidogrel-treated patients. Procedural characteristics are listed in Table 2 . Ad hoc PCI was performed in most patients.
| Characteristic | ACS | Elective Catheterization/PCI | ||||
|---|---|---|---|---|---|---|
| Clopidogrel (n = 18,029) | Prasugrel (n = 2,142) | p Value | Clopidogrel (n = 5,965) | Prasugrel (n = 619) | p Value | |
| Age (yrs) | 67 (60–76) | 65 (57–73) | <0.001 | 67 (61–74) | 66 (60–73) | 0.03 |
| Age ≥75 yrs | 5,342 (29.8%) | 454 (21.3%) | <0.001 | 1,391 (23.6%) | 117 (20.0%) | 0.054 |
| Women | 5,048 (28.0%) | 532 (24.8%) | <0.01 | 1,519 (25.5%) | 175 (28.3%) | 0.13 |
| Body weight <60 kg | 944 (5.9%) | 89 (4.7%) | 0.04 | 219 (4.1%) | 33 (5.6%) | 0.10 |
| Body mass index (kg/m 2 ) | 27.4 ± 4.8 | 27.6 ± 4.5 | 0.07 | 27.7 ± 4.5 | 27.8 ± 4.4 | 0.65 |
| Hypertension (history or medication use) | 9,961 (55.2%) | 1,109 (51.8%) | <0.01 | 4,231 (70.9%) | 434 (70.1%) | 0.36 |
| Dyslipidemia (history or medication use) | 7,752 (43.0%) | 838 (39.1%) | <0.01 | 4,488 (75.2%) | 451 (72.9%) | 0.24 |
| Current smokers | 4,151 (23.0%) | 592 (27.6%) | <0.001 | 659 (11.0%) | 68 (11.0%) | 0.17 |
| Diabetes mellitus | 3,506 (19.4%) | 357 (16.7%) | <0.01 | 1,469 (24.6%) | 122 (19.7%) | 0.03 |
| Previous stroke | 976 (6.1%) | 71 (3.8%) | <0.001 | 70 (5.5%) | 2 (2.1%) | 0.34 |
| Myocardial infarction | 4,321 (24.0%) | 396 (18.5%) | <0.001 | 1,867 (31.3%) | 158 (25.5%) | <0.01 |
| PCI | 3,191 (17.7%) | 303 (14.1%) | <0.001 | 1,897 (31.8)% | 162 (26.2%) | 0.01 |
| Coronary artery bypass grafting | 1,524 (8.5%) | 147 (6.9%) | 0.04 | 900 (15.1%) | 86 (13.9%) | 0.66 |
| Final diagnosis: ST-segment elevation MI | 5,880 (32.6%) | 1,265 (59.1%) | <0.001 | — | — | |
| Final diagnosis: NSTE ACS | 12,149 (67.4%) | 877 (40.9%) | <0.001 | — | — | |
| Creatinine clearance (ml/min) ∗ | 82 (61–106) | 87 (68–109) | <0.001 | 83 (65–104) | 86 (68–106) | 0.23 |
| Mehran bleeding risk score † | 9 (6–15) | 11 (6–15) | 0.001 | 9 (6–14) | 9 (6–14) | 0.48 |
∗ Creatinine clearance was calculated using the Cockcroft-Gault equation.
† The modified Mehran bleeding risk score could be calculated in 20,592 patients; the median value was 9 (IQR 6 to 14).
| Characteristic | ACS | Elective Catheterization/PCI | ||||
|---|---|---|---|---|---|---|
| Clopidogrel (n = 18,029) | Prasugrel (n = 2,142) | p Value | Clopidogrel (n = 5,965) | Prasugrel (n = 619) | p Value | |
| Procedural characteristics | ||||||
| Radial artery puncture approach | 10,967 (60.8%) | 1,411 (65.9%) | <0.001 | 3,621 (60.7%) | 369 (59.6%) | 0.78 |
| Stent use | <0.001 | <0.001 | ||||
| Bare-metal stent only | 8,451 (46.9%) | 1,301 (60.7%) | 1,694 (28.4%) | 267 (43.1%) | ||
| ≥1 drug-eluting stent | 7,435 (41.3%) | 694 (32.4%) | 2,826 (47.3%) | 283 (45.7%) | ||
| Antithrombotic agents before coronary angiography | ||||||
| Aspirin | 17,089 (94.8%) | 1,997 (93.2%) | <0.01 | 5,643 (94.6%) | 563 (91.0%) | 0.001 |
| Clopidogrel | 16,837 (93.4%) | 1,264 (59.0%) | <0.001 | 4,979 (83.5%) | 88 (14.2%) | <0.001 |
| Prasugrel | — | 619 (28.9%) | — | — | 93 (15.0%) | — |
| Glycoprotein IIb/IIIa inhibitor | 63 (0.3%) | 4 (0.2%) | 0.22 | 2 (0%) | 0 (0%) | 0.65 |
| Bivalirudin | 109 (0.6%) | 8 (0.4%) | 0.30 | 5 (0.1%) | 0 (0%) | 0.70 |
| Fondaparinux | 6,191 (34.3%) | 499 (23.3%) | <0.001 | 185 (3.1%) | 6 (1.0%) | 0.01 |
| Warfarin | 310 (1.7%) | 22 (1.0%) | 0.04 | 190 (3.2%) | 12 (1.9%) | 0.21 |
| Heparin | 2,402 (13.3%) | 358 (16.7%) | <0.001 | 107 (1.8%) | 21 (3.4%) | 0.02 |
| LMWH | 635 (3.5%) | 42 (2.0%) | <0.001 | 63 (1.1%) | 9 (1.5%) | 0.37 |
| Antithrombotic agents during coronary angiography/PCI | ||||||
| Aspirin | 895 (5.0%) | 91 (4.2%) | 0.15 | 221 (3.7%) | 51 (8.2%) | <0.001 |
| Clopidogrel | 1,498 (8.3%) | 38 (1.8%) | <0.001 | 1,030 (17.3%) | 2 (0.3%) | <0.001 |
| Prasugrel | — | 1,551 (72.4%) | — | — | 529 (85.5%) | — |
| Glycoprotein IIb/IIIa inhibitor | 2,138 (11.9%) | 93 (4.3%) | <0.001 | 149 (2.5%) | 8 (1.3%) | 0.06 |
| Bivalirudin | 6,731 (37.3%) | 1,223 (57.1%) | <0.001 | 574 (9.6%) | 37 (6.0%) | <0.01 |
| Fondaparinux | 82 (0.5%) | 7 (0.3%) | 0.40 | 6 (1.0%) | 0 (0%) | 0.43 |
| Warfarin | 5 (0%) | 0 (0%) | 0.44 | 3 (0.1%) | 0 (0%) | 0.58 |
| Heparin | 12,997 (72.1%) | 1,711 (79.9%) | <0.001 | 4,631 (77.6%) | 583 (94.2%) | <0.001 |
| LMWH | 859 (4.8%) | 13 (0.6%) | <0.001 | 865 (14.5%) | 10 (1.6%) | <0.001 |
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