• No results found

Long-Term Effect of Dual Antiplatelet Treatment after Off-Pump Coronary Artery Bypass Grafting

N/A
N/A
Protected

Academic year: 2021

Share "Long-Term Effect of Dual Antiplatelet Treatment after Off-Pump Coronary Artery Bypass Grafting"

Copied!
7
0
0

Loading.... (view fulltext now)

Full text

(1)

O

RIGINAL

A

RTICLE

_____________________________________________________________

Long-Term Effect of Dual Antiplatelet

Treatment after Off-Pump Coronary

Artery Bypass Grafting

Jos

e L

opez, M.D.,* Carlos Morales, M.D.,* Pablo Avanzas, M.D.,

y

Francisco Callejo, M.D.,* Daniel Hern

andez-Vaquero, M.D.,* and Juan C. Llosa, M.D.*

*

Department of Cardiac Surgery, University Central Hospital of Asturias, Oviedo, Asturias,

Spain; and

y

Department of Cardiology, University Central Hospital of Asturias, Oviedo,

Asturias, Spain

ABSTRACT Objectives: Recent studies have found increased long-term cardiovascular morbidity after

off-pump coronary artery bypass surgery (OPCAB). We evaluated the efficacy and safety of dual antiplatelet therapy (DAT) in the prevention of cardiovascular events at two years after OPCAB surgery. Methods:

Retrospective study that included all patients that underwent OPCAB surgery in our institution between 2009 and 2010. Single or dual antiplatelet therapy was initiated at hospital discharge, and its effect in patients’ prognosis was analyzed. Follow-up was conducted by telephone and using the hospital databases. The primary end-point was the composite of acute coronary syndrome (ACS), revascularization, stroke, or cardiovascular death.Results:The study included 237 patients divided into: (A) 128 patients who received single antiplatelet therapy and (B) 109 patients who received dual antiplatelet therapy. The mean follow-up was 23.85 months (standard deviation 0.5 months). 13.9% of patients had a primary end-point event. Patients in group A had a higher event rate compared with group B (18.8% vs. 8.3%, p = 0.02), with a significant reduction in hospital readmissions for ACS (10.9% vs. 3.7%, p = 0.035). In the multivariate analysis, dual antiplatelet therapy was an independent protective factor in the occurrence of events (hazard ratio = 0.395, 95% CI, 0.176 to 0.885, p = 0.024). There were no significant differences between the two groups with respect to bleeding events.Conclusion:Dual antiplatelet therapy after OPCAB surgery is associated with a decrease in the appearance of new cardiovascular events, due to a reduction in the number of hospital readmissions for ACS.

doi: 10.1111/jocs.12144

(J Card Surg 2013;28:366–372)

Coronary artery bypass surgery has shown its efficacy in the treatment of ischemic heart disease and provides excellent medium and long-term results to reduce mortality and improve symptoms.1 The long-term success of coronary surgery is based on graft patency. Antiplatelet therapy plays an essential role in achieving this goal, since platelets are intimately related to the pathogenesis of thrombosis of the grafts. According to current recommendations, patients un-dergoing coronary artery bypass surgery should receive antiplatelet therapy with acetylsalicylic acid (ASA; class Ia recommendation) for life, or if a patient is intolerant to aspirin, then clopidogrel (class IIa recommendation) should be provided.2 Furthermore, ASA treatment

should be initiated within the first 48 hours postopera-tively. It is the most critical time period to prevent early thrombosis of the grafts.3

Despite adequate treatment with ASA, a significant number of coronary grafts suffer early closure,4which results in cardiovascular events following surgery.5This closure is due to an increased tendency to thrombosis, as well as an increased resistance to the ASA antiplatelet action, which occurs in the first days after surgery.6 ASA resistance appears in about 30% of patients that have undergone off-pump coronary artery bypass surgery.7Another mechanism related to graft closure is the phenomenon of intimal hyperplasia.8 This platelet-mediated pathogenesis may foment post-operative graft closure after one year. It affects 10–15% of saphenous vein grafts. Experimental evi-dence shows that intimal hyperplasia may increase with the use of clopidogrel.9

Multiple studies have been conducted10–14 (with mixed results) to evaluate whether the use of dual antiplatelet therapy (DAT) in the first months after

Conflict of interest: There are no conflict of interest in the submission.

Address for correspondence: Dr. Jose Lopez Men endez, M.D.,

Department of Cardiac Surgery, University Central Hospital of

Asturias, C/Celestino Villamil s/n, Oviedo, Asturias, Spain. Fax: (þ34)

(2)

revascularization may be beneficial to maintain coronary graft patency.

The objective of this study is to evaluate the efficacy and safety of DAT during the first postoperative year in preventing the occurrence of new cardiovascular events after OPCAB surgery.

MATERIALS AND METHODS Study design

This was a retrospective cohort study, with a two-year follow-up after surgery.

Study population

All patients discharged from hospital after having undergone isolated off-pump coronary artery bypass surgery in our Institution during 2009 and 2010 were included in the study. Patients who required post-operative anticoagulation treatment for any reason (ten patients) and those with proven intolerance to antiplatelet agents (two patients) were excluded.

Patients were classified into two groups, depending on the administered antiplatelet therapy after surgery: 1. Group A: Single antiplatelet therapy (SAT) with ASA or clopidogrel. ASA was administered 100 mg daily; clopidogrel was administered 75 mg daily without a loading dose.

2. Group B: DAT with ASA 100 mg daily and clopidog-rel 75 mg daily during the first postoperative year, and then continue with single antiplatelet therapy with ASA 100 mg daily for life, according to clinical practice guidelines.2

The decision to start single or dual antiplatelet therapy upon discharge was made by the operating surgeon based on practitioner preferences. During 2009 most of the surgeons in our institution adminis-tered SAT, with a slow trend of changing protocols to DAT, so all surgical teams were included in both groups. We did not make any other change in surgical or medical protocols during that time interval. Follow-up was limited to two years after surgery, not taking into account events that occurred beyond that time.

All patients who were taking ASA before surgery continued on that same regimen until discontinuing the day before the operation. The ASA antiplatelet therapy was resumed the day after the operation as long as there was no evidence of significant bleeding. If any patient was receiving clopidogrel prior to surgery, this was discontinued, whenever possible, at least five days prior to the operation. The DAT adding 75 mg of clopidogrel (without loading dose) to ASA was initiated prior to discharge, after removal of the chest drains, between the fourth and seventh postoperative day in most of the cases.

Patients with a known intolerance to ASA received single antiplatelet therapy with clopidogrel, according to the current clinical practice guideline recommenda-tions. Any additional secondary prevention drugs such

as beta blockers, calcium antagonists, statins, angio-tensin-converting-enzyme inhibitors and angiotensin receptor blockers (ACE Inhibitors/ARBs) were initiated according to current cardiological recommendations.2

Study variables

The study variables were recorded prospectively at the time of surgery, and they were collected from the hospital databases. Demographic, clinical and surgical characteristic data were obtained from each patient. The following variables were included: demographic (sex, age, weight, and height), surgical risk (logistic Euro-SCORE I), cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia and smoking), a history of prior coronary intervention, drug treatment upon discharge (antiplatelet therapy, beta blockers, calcium channel blockers, angiotensin-converting-enzyme inhib-itors, and statins), laboratory variables (platelet count, urea, and creatinine), and surgical variables (left internal mammary artery use, right internal mammary artery use, radial artery use, complete revascularization, total arterial revascularization, number of grafts, affected vessels, the urgency of the operation).

Clinical follow-up

A postoperative clinical follow-up was conducted for two years, by telephone consultation and by a review of hospital databases in cases of readmission. 89.5% of the study patients were contacted by phone, with no significant differences between the two groups (SAT 90.6%; DAT 88.1%; p¼0.524). The mean follow-up time was 23.85 months (SD 0.5 months).

Defining the study objectives

The primary objective of the study was monitoring the presence of any of the following conditions: hospitalization for acute coronary syndrome (ACS), revascularization, stroke, or cardiovascular death. 1. ACS: Defined by the European Society of Cardiology

clinical practice guidelines15,16as requiring hospital-ization. This includes patients with ACS with ST-segment elevation16 and without ST-segment elevation.15

2. New revascularization: The performance of at least one new angioplasty with or without stenting after surgery.

3. Cerebrovascular accident17: The onset of a new neurological deficit of vascular origin that lasts more than 24 hours or results in death.

4. Cardiovascular death17: All deaths from a known cardiovascular cause or any death of an unknown etiology.

The safety end-points, considered as the presence of major and minor bleeding, are according to the following definitions18:

1. Major bleeding, potentially life-threatening: Clinically apparent with a drop in hemoglobin of>5 g/dL, or a

(3)

transfusion of at least 4 U PRBC; or fatal; or intracranial; or intrapericardial with cardiac tampo-nade; or resulting in hypovolemic shock or severe hypotension that requires vasopressors or surgery. Other major bleeding: Clinically apparent, with a drop in hemoglobin of 3 to 5 g/dL, or that requires a transfusion of 2 to 3 U PRBC; or significantly disabling.

2. Minor bleeding: Requiring medical intervention to stop or treat bleeding.

Statistical analysis

The statistical analysis was performed using the IBM SPSS Statistics for Mac (Version 20.0, IBM Corp., Armonk, NY, USA). The continuous variables were expressed as meanstandard deviation (SD). The categorical variables were expressed as frequency and proportions. Student’s unpaired t-test was used to compare the continuous variables, and the chi square test was used for the categorical variables. Multivariate analysis was performed using Cox proportional hazards regression, and output as hazard ratios, with 95% confidence intervals, was used to assess the variables associated with subsequent events during the follow-up. All the variables in which association with the combined event was significant or close to significance (p-value<0.1) in the univariate analysis were entered in the multivariate model. The EuroSCORE I was not included in the multivariate model because it is a composite of several of the variables that were studied individually (age, sex, creatinine, emergency of the

operation, and ventricular function are included in the EuroSCORE I). Time to major adverse cardiovascular event was determined for the study groups by the Kaplan–Meier method, and groups were compared with log-rank test.

A p-value of less than 0.05 was considered statisti-cally significant.

Ethical considerations

The identification of the patients is encoded, complying with the requirements of the Organic Law on Data Protection 15/1999. The Clinical Research Ethics Committee of the Hospital authorized the completion of this project.

RESULTS Study patient characteristics

A total of 258 patients were operated with off-pump coronary artery bypass surgery throughout this study. A total of 21 patients from this number were excluded (10 required oral anticoagulation, two did not receive antiplatelet therapy upon discharge due to intolerance, and nine who died before discharge), so the resulting study population included 237 patients. Group A consisted of 128 patients (54%) who received single antiplatelet therapy with ASA (or clopidogrel if intolerant to ASA) upon discharge and group B consisted of 109 patients (46%) who received DAT with ASA and clopidogrel.

Table 1 shows the baseline characteristics of the study population overall and by subgroups. Baseline

TABLE 1

Baseline Parameters of the Study Population

Total (N = 237) SAT (N = 128) DAT (N = 109) P-Value Age, years (SD) 65.80 (9.96) 68.01 (9.87) 63.2 (9.45) <0.001

Male sex, n (%) 181 (76.4) 91 (71.1) 90 (82.6) 0.038

Logistic EuroSCORE I, % (SD) 4.16 (5.08) 4.43 (4.96) 3.83 (5.21) 0.363 Prior coronary intervention, n (%) 32 (13.5) 15 (11.7) 17 (15.6) 0.384 Preserved ventricular function, n (%) 183 (77.2) 99 (77.3) 84 (77.1) 0.350 Cardiovascular risk factors

Hypertension, n (%) 160 (67.5) 84 (65.6) 76 (69.7) 0.502 Dyslipidemia, n (%) 159 (67.1) 86 (67.2) 73 (67) 0.972 Diabetes mellitus, n (%) 94 (39.7) 50 (39.1) 44 (40.4) 0.838 History of smoking, n (%) 125 (52.7) 58 (61.5) 67 (45.3) 0.013 Preoperative laboratory data

Creatinine, mg/dL (SD) 1.07 (0.72) 1.07 (0.54) 1.06 (0.88) 0.909 Platelet count, 1000/mL (SD) 231.719 (69) 234 (71) 229 (67) 0.586 Surgical procedure data

Number of grafts, n (SD) 2.47 (0.953) 2.33 (0.97) 2.63 (0.91) 0.017 Complete revascularization, n (%) 185 (78.1) 95 (74.2) 90 (82.6) 0.122

ITA graft, n (%) 211 (89.4) 116 (90.6) 95 (88) 0.508

Total arterial revascularization, n (%) 62 (27.2) 37 (30.1) 25 (23.8) 0.289 Medical treatment after hospital discharge

Beta blockers, n (%) 191 (80.6) 104 (81.2) 87 (79.8) 0.781 Calcium antagonist, n (%) 51 (21.5) 21 (16.4) 30 (27.5) 0.038

Statins, n (%) 216 (91.1) 118 (92.2) 98 (89.9) 0.538

ACE inhibitors/ARBS, n (%) 86 (36.3) 51 (39.8) 35 (32.1) 0.217 SAT, single antiplatelet therapy; DAT, dual antiplatelet therapy; SD, standard deviation; ITA, internal thoracic artery; ACE, angiotensin converting enzyme; ARBS, angiotensin receptor blockers.

Bold values in Table 1 are those in which a statistical significant difference was found (P<0.05). These values are also the ones commented in the text as differences found between groups.

(4)

differences included: patients in the DAT group had a significantly lower mean age, a higher proportion of males, and a smaller percentage of smoking history compared to the single antiplatelet group. There were no other significant differences in the preoperative variables. The number of grafts performed was significantly higher in the DAT group (2.630.91 vs. 2.330.97; p¼0.017), but there was no significant difference in the degree of complete revascularization, the use of the left internal mammary artery or total arterial revascularization. Medication regimen at dis-charge was similar in both groups except for a greater use of calcium channel blockers (p¼0.038) in the DAT group.

Event analysis

The mean follow-up time was 23.85 (0.5) months. The overall analysis of events (Table 2) shows that the primary objective occurred in 13.9% of patients, presented as 7.6% readmission for ACS, 5.1% for new coronary revascularization, 1.3% due to a stroke and 3.4% died during the follow-up period.

Regarding the subgroup analysis, the study’s primary objective occurred in 18.8% of patients treated with single antiplatelet therapy, compared with 8.3% of patients with DAT (p¼0.020; Fig. 1). These differences in the occurrence of events were largely based on a higher number of hospital readmissions due to ACS. 10.9% of patients with single antiplatelet therapy required readmission, compared to 3.7% with dual antiplatelet therapy (p¼0.035). There were no differ-ences in the number of new unplanned coronary interventions or new stroke incidents during follow-up. Mortality was slightly lower in the DAT group, although this difference did not reach statistical significance.

In the univariate analysis (Table 3), the logistic EuroSCORE I correlated significantly with the occur-rence of events. The use of a left internal mammary artery (p¼0.046), beta-blockers (p¼0.043), and statins (p¼0.009) was associated with a lower rate of events.

DAT was found to be a protective factor in the occurrence of events, with a HR of 0.427 (95% CI, 0.198 to 0.918; p¼0.029).

As a sensitivity analysis, patients taking clopidogrel in the SAT group were excluded. The SAT group consisted of 118 patients with ASA, and 10 patients with clopidogrel. Patients with clopidogrel alone had worse outcome than patients with ASA; 19 (17.3%) patients with ASA had an event, while 5 (27.8%) patients with clopidogrel had an event, but this difference did not reach statistical significance (p¼0.290). Excluding patients taking clopidogrel alone in SAT, there were 19 events (17.3%) in SAT versus 9 events (8.3%) in DAT, maintaining statistical significance (p¼0.046) with chi square test.

Furthermore, the multivariate analysis using Cox proportional hazards regression (Table 4) shows an independent association of DAT with the study’s primary objective, with a hazard ratio of 0.395 (95% CI, 0.176 to 0.885, p¼0.024). The presence of

TABLE 2 Follow Up

Total (N = 237) SAT (N = 128) DAT (N = 109) P-Value Follow-up time, months (SD) 23.85 (0.54) 23.91 (0.43) 23.77 (0.65) 0.051 Primary objective Composite end-point, n (%) 33 (13.9) 24 (18.8) 9 (8.3) 0.020 ACS, n (%) 18 (7.6) 14 (10.9) 4 (3.7) 0.035 New revascularization, n (%) 12 (5.1) 7 (5.5) 5 (4.6) 0.758 Stroke, n (%) 3 (1.3) 1 (0.8) 2 (1.8) 0.470 Cardiovascular death, n (%) 8 (3.4) 6 (4.7) 2 (1.8) 0.226 Safety objectives Major bleeding, n (%) 2 (0.8) 1 (0.8) 1 (0.9) 0.909 Minor bleeding, n (%) 7 (3) 3 (2.3) 4 (3.7) 0.548

DAT, dual antiplatelet therapy; SAT, single antiplatelet therapy; ACS, acute coronary syndrome.

Bold values in Table 2 are those in which a statistical significant difference was found (P<0.05). These values are also the ones commented in the text as differences found between groups.

When any patient had more than one event, only the first one was taken into account (for example, ACS followed by new revascularization).

Figure 1. Cumulative event-free survival during follow-up. DAT, dual antiplatelet therapy; SAT, single antiplatelet therapy. Survival groups were compared with log-rank test.

(5)

diabetes mellitus also shows an independent associa-tion to the study’s combined event (HR 2.050; 95% CI, HR 1.017 to 0.885, p¼0.045).

Including/forcing-in all variables in the multivariate analysis where there was a statistically significant imbalance in the baseline characteristic, in addition to those identified for inclusion in the univariate analysis, did not affect inferences.

The analysis of the timing of the occurrence of events during follow-up (Table 5) shows DAT as being primarily associated with the reduction of late events (after six months); while the rate of early events (within six months after surgery) was similar between the two groups.

Safety end-points

During follow-up, two patients suffered a major bleeding episode (0.8%) and seven patients suffered a minor bleeding episode (3%; Table 2). DAT did not lead to a significant increase in major bleeding episodes (p¼0.909) nor in minor bleeding episodes (p¼0.548). Major bleeding episodes were: (a) SAT: one patient suffered acute upper digestive tract hemorrhage 4.5 months after surgery, with hemodynamic instability, requiring urgent surgery. Active arterial bleeding was found in proximal jejunum. Ten centimeters of intestine were resected, with direct tract reconstruction, with a good outcome; (b) DAT: one patient had an intracranial hemorrhage 21 months after surgery (with SAT at that time, as established in protocol), with a fatal outcome. Minor episodes were digestive tract hemorrhages not fulfilling major bleeding criteria.

TABLE 3 Univariate Analysis

Hazard Ratio (95% CI) P-value

Age 1.038 (1.00–1.077) 0.051

Logistic EuroSCORE I 1.072 (1.030–1.117) 0.001

Sex (male) 0.500 (0.246–1.017) 0.056

Prior revascularization 1.434 (0.592–3.472) 0.425

Ventricular dysfunction 0.738 (0.305–1.788) 0.502

Cardiovascular risk factors

Arterial hypertension 1.120 (0.533–2.353) 0.765

Dyslipidemia 0.834 (0.410–1.695) 0.616

Diabetes mellitus 1.894 (0.955–3.759) 0.068

History of smoking 0.728 (0.367–1.445) 0.364

Preoperative laboratory data

Creatinine 1.176 (0.858–1.613) 0.314

Platelet count 1.000 (1.000–1.000) 0.799

Surgical procedure data

Complete revascularization 0.561 (0.272–1.157) 0.118

ITA graft 0.427 (0.185–0.985) 0.046

Total arterial revascularization 1.104 (0.509–2.399) 0.802 Medical treatment after hospital discharge

DAT 0.427 (0.198–0.918) 0.029

Beta blockers 0.474 (0.230–0.978) 0.043

Calcium antagonists 0.796 (0.329–1.928) 0.613

Statins 0.328 (0.142–0.755) 0.009

ACE inhibitors/ARBS 0.746 (0.355–1.567) 0.439

Association with the composite end-point. ITA, internal thoracic artery; ACE, angiotensin converter enzyme; ARBS, angiotensin receptor blockers.

Bold values in Table 3 are those in which a statistical significant difference was found (P<0.05). These values are also the ones commented in the text as differences found between groups.

TABLE 4 Multivariate Analysis

Hazard ratio (95% CI) P-Value Age 1.005 (0.964–1.046) 0.828 Male sex 0.624 (0.301–1.294) 0.205 Diabetes mellitus 2.050 (1.017–4.134) 0.045 DAT 0.395 (0.176–0.885) 0.024 Beta blockers 0.567 (0.261–1.231) 0.151 Statins 0.423 (0.169–1.060) 0.066 ITA graft 0.520 (0.222–1.216) 0.131 Adjusted effect of DAT on the combined event. DAT, dual antiplatelet therapy; ITA, internal thoracic artery.

Bold values in Table 4 are those in which a statistical significant difference was found (P<0.05). These values are also the ones commented in the text as differences found between groups.

TABLE 5

Months Until Appearance of First Event

Months SAT (N = 128) DAT (N = 109) N (% events in group) <6 9 (7.0) 7 (6.4) 6–12 7 (5.5) 1 (0.9) 12–18 5 (3.9) 0 (0.0) >18 3 (2.3) 1 (0.9) Total 24 (18.8) 9 (8.3)

(6)

DISCUSSION

The main finding of our study is that DAT during the first postoperative year after off-pump coronary artery bypass surgery (OPCAB) is associated with a decrease in the occurrence of late cardiovascular events, especially by reducing the number of hospital read-missions due to ACS.

OPCAB is a widely used surgical revascularization method, with multiple studies that show a trend towards better perioperative outcomes, in experienced institutions, when compared to conventional on-pump surgery.19 Despite this perioperative improvement, recent publications have questioned the long-term durability of the grafts that have been performed,5,20 including a possible increased tendency for patients to develop new ischemic events.

Due to concerns about reduced graft patency after OPCAB surgery multiple studies have been conducted in which DAT was started after hospital discharge, maintained for a year, in analogy with the current re-commendations after percutaneous revascularization.2 In the CURE-CABG study21there was a reduction in the trend toward major cardiac events in patients who were treated with DAT after coronary revasculari-zation surgery, although it was not statistically signifi-cant. This trend was consistent with the other groups of the CURE study (patients in the medical therapy and percutaneous intervention arm).

Furthermore, experimental studies9have shown that clopidogrel inhibits intimal hyperplasia, while ASA appears not to reduce it. Intimal hyperplasia appears to correlate with graft closure after the first postopera-tive year.8The CASCADE study13evaluated the effect of clopidogrel in reducing saphenous vein graft intimal hyperplasia after CABG, as determined by intravascular ultrasound (IVUS) at one year. It consisted of a randomized, double-blinded trial, in which 113 patients were randomized into two groups, to receive single or dual antiplatelet therapy. No significant differences were found between the groups in terms of intimal hyperplasia as determined by IVUS, although there was a nonsignificant trend of reduction in the vascular wall thickness in the group treated with ASAþclopidogrel, with a 7% decrease in wall thickness. There were no clinical differences found between the groups, although the study was not powered for this.

In 2006 a study was published22 demonstrating a reduction in long-term cardiovascular morbidity after the addition of clopidogrel for 30 days after surgery, with a significant reduction in the recurrence of ischemic symptoms.

In a randomized study,11 the increased saphenous vein graft patency with the addition of clopidogrel was demonstrated by multidetector computed tomography. Although these differences did not have clinical correlation, three months after surgery the percentage of graft patency rose from 85.7% to 91.6%, with DAT as an independent variant in preventing graft closure in the multivariate analysis. Similar results were found in the study by Ibrahim et al.,12 although a statistically significant difference in patency was not reached.

In the present study, only patients undergoing coronary surgery without cardiopulmonary bypass were included, because recent publications5,20seemed to indicate that these patients have a higher risk of new events occurring in long-term follow-up, and therefore they may benefit more from DAT than patients operated with conventional surgery.12,22

After a two-year follow-up, we found a significant reduction in the number of hospital readmissions caused by new episodes of ACS. Angiographic studies indicate that among patients who present with a new episode of unstable angina, non-ST elevation ACS or ST-elevation ACS, the culprit lesion in 70% to 85% of cases is an atherosclerotic vein graft stenosis, often with superimposed thrombus.4 Thus, this lower number of admissions due to ACS could translate to a greater maintenance of graft patency, although no imaging study has been carried out to corroborate this idea.

The event rate in the first six postoperative months was similar in both groups; DAT was primarily associated with the reduction of late events, as seven of the nine events with DAT occurred within the first six postoperative months, with few events occurring after that. This early closure, similar in both groups, without the influence of administered antiplatelet therapy, could be perioperative graft occlusion due to varying technical problems (suboptimal grafts, small calibre coronaries, etc.). Dual antiplatelet therapy may prolong the durability of optimal grafts.

As regards safety, DAT did not increase the number of bleeding episodes.

Limitations

The main limitation of the hypothesis of this study is the lack of randomization, which leads us to find differences in the baseline characteristics of both groups. For example, among patients treated with single antiplatelet therapy upon discharge, there was a higher proportion of women and older patients. Although after performing the multivariate analysis (with the consequent variable adjustments) the protec-tive effect of the DAT was maintained as an indepen-dent predictor with statistical significance, confounding by indication cannot be ruled out given the observation-al nature of the study.

Although similar in both groups, the loss to follow-up in this study was relatively high for only two years of follow-up. There was a temporal trend to the use of DAT which might have accounted for the improved results seen with the DAT protocol.

REFERENCES

1. Yusuf S, Zucker D, Peduzzi P, et al: Effect of coronary artery bypass graft surgery on survival: Overview of 10-year results from randomized trials by the coronary artery bypass graft surgery trialists collaboration. Lancet 1994;344:563–570.

2. Taggart DP, Boyle R, de Belder MA, et al: The 2010 ESC/ EACTS guidelines on myocardial revascularization. Heart 2011;97:445–446.

(7)

3. Mangano DT: Aspirin and mortality from coronary bypass surgery. N Engl J Med 2002;347:1309–1317.

4. Fitzgibbon GM, Kafka HP, Leach AJ, et al: Coronary bypass graft fate and patient outcome: Angiographic follow-up of 5,065 grafts related to survival and reopera-tion in 1,388 patients during 25 years. J Am Coll Cardiol 1996;28:616–626.

5. Hattler B, Messenger JC, Shroyer AL, et al: Off-pump coronary artery bypass surgery is associated with worse arterial and saphenous vein graft patency and less effective revascularization: Results from the veterans affairs randomized on/off bypass (ROOBY) trial. Circula-tion 2012;125:2827–2835.

6. Zimmermann N, Gams E, Hohlfeld T: Aspirin in coronary artery bypass surgery: New aspects of and alternatives for an old antithrombotic agent. Eur J Cardiothorac Surg 2008;34:93–108.

7. Wang Z, Gao F, Men J, et al: Aspirin resistance in off-pump coronary artery bypass grafting. Eur J Cardiothorac Surg 2012;41:108–112.

8. Hassantash SA, Bikdeli B, Kalantarian S, et al: Pathophys-iology of aortocoronary saphenous vein bypass graft disease. Asian Cardiovasc Thorac Ann 2008;16:331–336. 9. Herbert JM, Tissinier A, Defreyn G, et al: Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits. Arterioscler Thromb 1993; 13:1171–1179.

10. Gao C, Ren C, Li D, et al: Clopidogrel and aspirin versus clopidogrel alone on graft patency after coronary artery bypass grafting. Ann Thorac Surg 2009;88:59–62. 11. Gao G, Zheng Z, Pi Y, et al: Aspirin plus clopidogrel therapy

increases early venous graft patency after coronary artery bypass surgery a single-center, randomized, controlled trial. J Am Coll Cardiol 2010;56:1639–1643.

12. Ibrahim K, Tjomsland O, Halvorsen D, et al: Effect of clopidogrel on midterm graft patency following off-pump coronary revascularization surgery. Heart Surg Forum 2006;9:E581–E856.

13. Kulik A, Le May MR, Voisine P, et al: Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: The clopidogrel after surgery for coronary artery disease (cascade) trial. Circulation 2010;122:2680– 2687.

14. Sun JC, Teoh KH, Lamy A, et al: Randomized trial of aspirin and clopidogrel versus aspirin alone for the prevention of coronary artery bypass graft occlusion: The preoperative aspirin and postoperative antiplatelets in coronary artery bypass grafting study. Am Heart J 2010;160:1178–1184. 15. Hamm CW, Bassand JP, Agewall S, et al: ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent st-segment eleva-tion: The task force for the management of acute coronary syndromes (ACS) in patients presenting without persis-tent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011;32:2999–3054. 16. Van de Werf F, Bax J, Betriu A, et al: ESC guidelines on

management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. Rev Esp Cardiol 2009;62(3):e1–e47.

17. Cannon CP, Battler A, Brindis RG, et al: American College of Cardiology key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes. A report of the American College of Cardiology task force on clinical data standards (acute coronary syndromes writing commit-tee). J Am Coll Cardiol 2001;38:2114–2130.

18. Wallentin L, Becker RC, Budaj A, et al: Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–1057.

19. Wijeysundera DN, Beattie WS, Djaiani G, et al: Off-pump coronary artery surgery for reducing mortality and morbidity: Meta-analysis of randomized and observational studies. J Am Coll Cardiol 2005;46:872–882.

20. Shroyer AL, Grover FL, Hattler B, et al: On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med 2009;361:1827–1837.

21. Fox KA, Mehta SR, Peters R, et al: Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: The Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial. Circulation 2004;110:1202–1208.

22. Gurbuz AT, Zia AA, Vuran AC, et al: Postoperative clopidogrel improves mid-term outcome after off-pump coronary artery bypass graft surgery: A prospective study. Eur J Cardiothorac Surg 2006;29:190–195.

References

Related documents

In this manuscript, numerical solutions of both the fractional diffusion and fractional diffusion-wave equations have been obtained by a Petrov-Galerkin finite element method

This paper gives further information about the common microorganisms which cause the primary and secondary infection in the root canal and causes persistent apical

[r]

Therefore, the aim of this study was to examine the effects of feeding live foods (Chironomids, Gammarid and Daphnia) with or without formulated diets on growth

The dependence of magnetization on the applied magnetic field M ( H ) for NTs in PET template at perpendicular (black solid line) and parallel (red dotted line) direction of the

The book’s central claim is that written instruments of bureaucratic decision-making such as petitions, letters, files, and lists are graphic artifacts that bring together a range

The dependent variable was vaccination of category II vac- cines in children under 5 years old, which was assessed on the ground of primary guardians ’ answers to – “ Has your