Antiplatelet therapy is recommended after coronary artery bypass grafting, because it improves saphenous vein graft (SVG) patency and clinical outcomes. We investigated the association between prehospital antiplatelet regimens and outcomes after SVG intervention. Patients who underwent SVG intervention from 2003 to 2008 were divided into 3 groups: (1) no antiplatelet therapy, (2) the use of aspirin or clopidogrel, and (3) the use of dual antiplatelet therapy (DAPT) at admission. Clinical follow-up examinations were performed at 30 days and 1 year. The primary outcome was the composite of all-cause mortality, myocardial infarction, the need for revascularization, and stroke at 30 days. The relation between antiplatelet therapy and outcomes was adjusted for factors associated with the outcomes. A total of 225 patients underwent SVG intervention, 87% were men, and the mean age was 70 years. Of the 225 patients, 21 (9.4%) were not receiving antiplatelet therapy, 102 (45.3%) were receiving aspirin/clopidogrel, and 102 (45.3%) were receiving DAPT. The patients without antiplatelet therapy were more frequently women, had presented earlier after coronary artery bypass grafting, and were less frequently taking other cardiac-related medications. The patients taking aspirin or DAPT were more often smokers and had a greater peripheral vascular burden. The incidence of the 30-day and 1-year primary outcomes was greater in patients without preadmission antiplatelet use (38.1% vs 14.9% and 13.9%, overall p = 0.01; 52.4% vs 29.5% and 28.3%, overall p = 0.03). After adjustment, antiplatelet use remained associated with the primary outcome. In conclusion, prehospital use of antiplatelet therapy was associated with a lower occurrence of major adverse cardiac events after SVG intervention. We did not find that DAPT improved outcomes compared to single antiplatelet therapy.
Saphenous vein graft (SVG) disease and progression of native atherosclerosis are the Achilles’ heel of long-term efficacy of coronary artery bypass grafting (CABG). To improve SVG patency and outcomes, the current guidelines recommend indefinite acetylsalicylic acid (aspirin, ASA) use for patients after CABG. Despite its use, SVG failure occurs in up to half of all CABG patients and currently accounts for 5% to 10% of all patients undergoing percutaneous coronary intervention (PCI). Studies have shown that SVG intervention is associated with considerable morbidity and mortality, lower reperfusion rates, and greater restenosis rates compared with native-vessel PCI. Recent efforts to further improve the outcomes in patients with previous CABG, by combining the antiplatelet properties of ASA and clopidogrel, have thus far been conflicting. Currently, it remains unknown to what extent prehospital antiplatelet therapy might affect the outcomes after SVG intervention. Therefore, we investigated the association of prehospital antiplatelet therapy on the clinical outcomes in patients undergoing SVG intervention.
Methods
Data were obtained from patients who underwent PCI of ≥1 SVG lesion at the Academic Medical Center, University of Amsterdam (Amsterdam, The Netherlands) from January 2003 to December 2008. We included consecutive patients who presented with stable angina or acute coronary syndrome and underwent PCI of ≥1 SVG. Patients with arterial graft failure requiring intervention were excluded from the analysis. PCI was performed according to the standard PCI guidelines. The medical history and use of medication, including ASA and clopidogrel use, was obtained from the hospital records, referral letters, and/or at catheterization laboratory in patients with acute presentation. At the start of the procedure, all patients received a loading dose of clopidogrel and unfractionated heparin 5,000 IU according to protocol. In ASA-naive patients, a loading dose of ASA 500 mg was administered as an intravenous bolus. The procedural use of thrombus aspiration and distal protection devices, stent type, and the use of glycoprotein IIb/IIIa inhibitors were at the operator’s discretion. After the procedure, all patients were treated with clopidogrel 75 mg/day (for ≤12 months), in addition to ASA 100 mg indefinitely.
The baseline characteristics and procedural and angiographic data were retrieved from our local electronic database. The patients’ vital status was verified in the electronic hospital records and in the Dutch national population registry. The 1-year clinical follow-up data were obtained from a mailed questionnaire or telephone interview. The patients were monitored for major cardiac and cerebrovascular events and the need for additional revascularization. The clinical follow-up data were completed using in- and outpatient charts from our hospital and referral centers. When source documentation was insufficient for adjudication, the referring cardiologist and/or family physician was contacted to complete follow-up information.
The primary outcome was the composite of all-cause mortality, myocardial infarction, the need for additional revascularization, and stroke at 30 days of follow-up. The secondary end point was the composite of all-cause mortality, myocardial infarction, and the need for additional revascularization at 1 year of follow-up and the individual components. Spontaneous or procedure-related myocardial infarction was defined according to the Academic Research Consortium definitions. The need for additional revascularization was defined as any additional PCI or redo CABG.
Study patients were divided into 3 groups according to antiplatelet therapy status at hospital admission as follows: (1) no antiplatelet therapy, (2) the use of ASA or clopidogrel, and (3) the use of dual antiplatelet therapy (DAPT). The baseline and procedural characteristics and outcomes were compared. Categorical variables are presented as percentages and were compared using Pearson’s chi-square test. Continuous variables are presented as the mean ± SD and were compared using 1-way analysis of variance. All probability values are 2-sided, using <0.05 as the cutoff for statistical significance. Crude time-to-event data are reported using Kaplan-Meier estimates and were compared with overall and pairwise pooled log-rank testing. Follow-up was censored at the date of last known contact or at 1 year, whichever came first. Unadjusted and adjusted hazard ratios were calculated with Cox regression models for the primary end point and the 1-year composite of all-cause mortality, myocardial infarction, and the need for additional revascularization. Adjustments were made for independent outcome predictors. These were identified as follows. First, univariate predictors were identified from the baseline characteristics ( Table 1 ) using Cox regression analysis. Second, these univariate predictors were entered in a multivariate Cox model. Multivariate predictors with p ≤0.05 using the Wald test were identified by backward selection. SPSS software, version 17.0 (SPSS, Chicago, Illinois) was used to perform the statistical analyses.
| Variable | No Antiplatelet Therapy (n = 21) | ASA or Clopidogrel (n = 102) | DAPT (n = 102) | p Value |
|---|---|---|---|---|
| Age (yrs) | 71.6 ± 8.5 | 70.2 ± 9.3 | 69.1 ± 9.0 | 0.47 |
| Men | 15 (71.4%) | 94 (92.2%) | 87 (85.3%) | 0.03 |
| Body mass index (kg/m 2 ) | 26.6 ± 3.3 | 27.1 ± 4.0 | 26.8 ± 3.2 | 0.84 |
| Diabetes mellitus | 5 (23.8%) | 25 (24.5%) | 27 (26.5%) | 0.66 |
| Current smoker | 1 (4.8%) | 19 (18.8%) | 11 (10.8%) | 0.03 |
| Previous myocardial infarction | 16 (76.2%) | 71 (69.6%) | 72 (70.6%) | 0.88 |
| Previous transient ischemic attack or stroke | 2 (9.5%) | 22 (21.6%) | 10 (9.8%) | 0.08 |
| Peripheral artery disease | 0 (0%) | 22 (21.6%) | 12 (11.8%) | 0.02 |
| Hypertension | 9 (42.9%) | 41 (40.2%) | 48 (47.1%) | 0.61 |
| Hyperlipidemia | 7 (33.3%) | 48 (47.1%) | 59 (57.8%) | 0.08 |
| Ejection fraction <30% | 4 (19.0%) | 13 (12.7%) | 10 (9.8%) | 0.47 |
| Creatinine (μmol/L) | 100.9 ± 46.6 | 86.0 ± 34.8 | 86.0 ± 43.1 | 0.27 |
| Duration since coronary artery bypass grafting (yrs) | 10.9 ± 6.2 | 12.8 ± 5.6 | 14.5 ± 6.1 | 0.02 |
| Previous percutaneous coronary intervention since coronary artery bypass grafting | 6 (28.6%) | 25 (24.5%) | 31 (30.6%) | 0.55 |
| Cardiac-related medications | ||||
| Warfarin | 6 (28.6%) | 5 (4.9%) | 7 (6.9%) | 0.001 |
| β Blockers | 10 (47.6%) | 76 (74.5%) | 84 (82.4%) | 0.003 |
| Calcium antagonist | 6 (28.6%) | 41 (40.2%) | 53 (52.0%) | 0.07 |
| Nitrates | 4 (19.0%) | 48 (47.1%) | 55 (53.9%) | 0.01 |
| Angiotensin-converting enzyme inhibitors | 6 (28.6%) | 38 (37.3%) | 36 (35.3%) | 0.75 |
| Statins | 9 (42.9%) | 78 (76.5%) | 88 (86.3%) | <0.001 |
| Indication for revascularization | ||||
| Stable angina pectoris | 15 (71.4%) | 60 (58.8%) | 67 (65.7%) | 0.42 |
| Unstable angina/non–ST-segment elevated myocardial infarction | 1 (4.8%) | 18 (17.6%) | 23 (22.5%) | 0.15 |
| ST-segment elevated myocardial infarction | 5 (23.8%) | 24 (23.5%) | 12 (11.8%) | 0.07 |
| Procedural characteristics | ||||
| Lesions per patient | 1.3 ± 0.6 | 1.4 ± 0.6 | 1.3 ± 0.6 | 0.83 |
| Type of treated vessel | ||||
| Graft and native | 2 (7.4%) | 17 (11.8%) | 13 (9.8%) | 0.62 |
| Single saphenous vein graft lesion | 23 (85.7%) | 113 (78.9%) | 110 (82.6%) | 0.49 |
| Coronary territory | 0.73 | |||
| Left anterior descending and/or side branch | 5 (23.8%) | 29 (28.4%) | 28 (27.4%) | |
| Circumflex and/or side branch | 10 (47.6%) | 26 (25.5%) | 34 (33.3%) | |
| Right coronary artery and/or side branch | 5 (23.8%) | 29 (28.4%) | 23 (22.5%) | |
| Combination | 1 (4.8%) | 18 (17.7%) | 17 (16.8%) | |
| Ostial lesion | 3 (14.3%) | 18 (17.6%) | 10 (9.9%) | 0.28 |
| Calcified lesion | 2 (9.5%) | 10 (9.8%) | 15 (14.9%) | 0.51 |
| Thrombus | 6 (28.6%) | 33 (32.4%) | 24 (23.8%) | 0.40 |
| Predilation before stenting | 16 (76.5%) | 62 (60.9%) | 65 (64.0%) | 0.47 |
| Stents per patient | 1.0 ± 0.5 | 1.2 ± 0.7 | 1.1 ± 0.6 | 0.33 |
| Stent type | 0.80 | |||
| Bare metal stent | 19 (90.5%) | 109 (88.6%) | 99 (87.6%) | |
| Drug-eluting stent | 2 (9.5%) | 12 (9.8%) | 10 (9.0%) | |
| Bare metal stent and drug-eluting stent | 0 (0%) | 2 (1.6%) | 4 (3.4%) | |
| Stent length (mm) | 17.5 ± 5.0 | 21.0 ± 7.2 | 21.5 ± 7.4 | 0.09 |
| Stent diameter (mm) | 3.7 ± 0.6 | 3.7 ± 0.5 | 3.7 ± 0.7 | 0.88 |
| Stenosis | ||||
| Preprocedural | 92.5 ± 6.9% | 91.8 ± 11.8% | 93.7 ± 6.5 | 0.39 |
| Postprocedural | 8.3 ± 21.6% | 7.1 ± 23.0% | 8.1 ± 25.2 | 0.95 |
| Thrombolysis In Myocardial Infarction <3 flow (start-of-procedure) | 55.0% | 46.0% | 47.8% | 0.77 |
| Thrombolysis In Myocardial Infarction <3 flow (end-of-procedure) | 90.5% | 86.1% | 90.0% | 0.42 |
| Peak creatine kinase-MB fraction (μg/L) | 134.8 ± 391.1 | 54.3 ± 139.3 | 40.7 ± 108.1 | 0.07 |
Results
The baseline and procedural characteristics are presented in Table 1 . A total of 225 patients were identified who had undergone SVG intervention. Of these 225 patients, 21 (9.4%) were not receiving antiplatelet therapy, 102 (45.3%) were taking either ASA or clopidogrel, and 102 (45.3%) were receiving DAPT at hospital admission. The patients without antiplatelet therapy use at admission were more frequently women and had presented earlier for graft intervention (10.9 ± 6.2 years) than those taking ASA (12.8 ± 5.6 years) or DAPT (14.5 ± 6.1 years). In addition, patients not receiving antiplatelet therapy were less commonly smokers and less frequently had peripheral artery disease. Patients who did not use antiplatelet therapy before hospitalization were more frequently taking warfarin but significantly less frequently taking other cardiac-related medications, including β blockers, nitrates, and statins.
A total of 304 lesions were treated, of which 257 were treated with stenting. Bare metal stents were predominantly used (88.4%). Drug-eluting stents were used in 11.6% of patients, either alone (9.4%) or combined with bare metal stents (2.2%). Intervention of ≥2 SVG lesions was performed in 18.4% patients, and additional revascularization of native vessels was required in 9.6%. No differences were seen in the angiographic, procedural, or lesion characteristics among the 3 cohorts. However, a trend was seen toward greater peak cardiac enzyme release (creatine kinase-MB) in patients without antiplatelet therapy.
Follow-up for the clinical outcomes is listed in Table 2 . Complete 30-day follow-up data on death, myocardial infarction, revascularization, and stroke were available for all but 2 patients. The 1-year follow-up data were missing for 10 patients (4.4%). The primary end point of all-cause mortality, myocardial infarction, the need for additional revascularization, and stroke at 30 days of follow-up was 38.1% in patients without antiplatelet therapy before hospitalization, 14.9% in patients taking ASA or clopidogrel at admission, and 13.9% in patients receiving DAPT at admission (overall p = 0.01). The Kaplan-Meier curves are shown in Figure 1 . At 1 year of follow-up, the composite of all-cause mortality, myocardial infarction, or the need for additional revascularization was 52.4% in patients without antiplatelet therapy, 29.5% in patients taking ASA or clopidogrel, and 28.3% in patients taking DAPT before hospital admission (overall p = 0.03). Kaplan-Meier curves of the composite end point at 1 year are presented in Figure 1 . The results from comparing individual end points at 30 days and 1 year of follow-up are also listed in Table 2 .
