Methylphenidate and Dextroamphetamine Abuse Methylphenidate and Dextroamphetamine Abuse in Substance-Abusing Robert J. Williams, PhD1; Leslie A. Goodale, RN2; Michele A. Shay-Fiddler, MSW2; Susan P. Gloster, BN3; Samuel Y. Chang, MD2 1. Addiction Counselling Program; School of Health Sciences; University of Lethbridge 2. Addiction Centre; Foothills Medical Centre; Calgary, Alberta 3. Lethbridge Regional Hospital; Lethbridge, Alberta
Braz J Cardiovasc Surg 2016;31(2):106-14 Clopidogrel use After Myocardial Revascularization:
Prevalence, Predictors, and One-Year Survival Rate
Paulo Roberto L. Prates1,2, MD; Judson B. Williams3,4, MD; Rajendra H. Mehta4,5, MD, MSc; Susanna R. Stevens5, MSc; Laine Thomas5, PhD; Peter K. Smith3, MD; L. Kristin Newby4,5, MD; Renato A. K. Kalil1,2, MD, PhD; John H. Alexander4,5, MD, MHS; Renato D. Lopes4,5, MD, PhD Abstract
Introduction: Antiplatelet therapy after coronary artery
arterial disease and cerebrovascular disease. Patients who
bypass graft (CABG) has been used. Little is known about the
received aspirin during hospitalization were less likely to receive
predictors and efficacy of clopidogrel in this scenario.
clopidogrel at discharge (P≤0.0001). Clopidogrel was associated
Objective: Identify predictors of clopidogrel following CABG.
with similar 1-year mortality compared with those who did not
Methods: We evaluated 5404 patients who underwent
use clopidogrel (4.4% vs. 4.5%, P=0.72). There was, however,
CABG between 2000 and 2009 at Duke University Medical
an interaction between the use of cardiopulmonary bypass and
Center. We excluded patients undergoing concomitant valve
clopidogrel, with lower 1-year mortality in patients undergoing
surgery, those who had postoperative bleeding or death before
off-pump CABG who received clopidogrel, but not those
discharge. Postoperative clopidogrel was left to the discretion
undergoing conventional CABG (2.6% vs 5.6%, P Interaction = 0.032).
of the attending physician. Adjusted risk for 1-year mortality
Conclusion: Clopidogrel was used in nearly one-fifth of
was compared between patients receiving and not receiving
patients after CABG. Its use was not associated with lower
clopidogrel during hospitalization after undergoing CABG.
mortality after 1 year in general, but lower mortality rate in those
Results: At hospital discharge, 931 (17.2%) patients were
undergoing off-pump CABG. Randomized clinical trials are needed
receiving clopidogrel. Comparing patients not receiving
to determine the benefit of routine use of clopidogrel in CABG.
clopidogrel at discharge, users had more comorbidities,
Keywords: Myocardial Revascularization. Coronary Artery
including hyperlipidemia, hypertension, heart failure, peripheral
Bypass. Blood Platelets.
Abbreviations, acronyms & symbols
Antiplatelet therapy is beneficial in secondary prevention = Coronary artery bypass graft
following coronary artery bypass graft (CABG) surgery; however, = Confidence interval
there is no consensus about when to initiate therapy, how to = Clopidogrel in unstable angina to prevent
dose, or the optimal combination of agents[1-4]. Clopidogrel also recurrent ischemic Events
reduces ischemic events and mortality in patients with coronary and peripheral arterial disease[5-8]. While the use of aspirin = Hazard risk
after CABG surgery is widespread[2,4,9,10], clopidogrel, the most = Percutaneous coronary intervention
commonly used P2Y inhibitor, in addition to aspirin, has been PREVENT IV
= Project of Ex-vivo Vein graft ENgineering via
used less often than aspirin alone.
Although it has been shown that antiplatelet therapy improves the patency of venous grafts[2,4,12], little is known about 1Department of Cardiovascular Surgery, Instituto de Cardiologia–Fundação Uni- acquisition, analysis, and interpretation of data; preparation, review, or approval versitária de Cardiologia, Porto Alegre, RS, Brazil.
of the manuscript.
2Clinical Research Center- Instituto de Cardiologia–Fundação Universitária de Car-diologia, Porto Alegre, RS, Brazil.
Drs. Williams, Smith, and Alexander are supported in part by grant U01-HL088953 3Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke from the National Institutes of Health Cardiothoracic Surgical Trials Network. University Medical Center, Durham, NC. None of the other authors have any conflict of interest to report related to this study.
4Department of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC. Correspondence Address: 5Duke Clinical Research Institute, Durham, NC.
Renato D. Lopes Duke Clinical Research Institute, Box 3850, 2400 Pratt Street, Room 0311 Terrace This study was carried out at the Instituto de Cardiologia do Rio Grande do Sul - Level, Durham, NC 27705. Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil. This work was supported by the Duke Clinical Research Institute (DCRI). The Article received on December 8th, 2015 DCRI provided funding for the design, conception, and conduct of the study; Article accepted on March 8th, 2016 Brazilian Journal of Cardiovascular Surgery Prates PRL, et al. - Clopidogrel use After Myocardial Revascularization Braz J Cardiovasc Surg 2016;31(2):106-14 which patients are receiving clopidogrel after CABG surgery or for categorical variables. Baseline and in-hospital patient about its association with patient outcomes. In this large single- characteristics for those who did and did not receive in-hospital center study we described the clinical and surgical characteristics clopidogrel following CABG surgery were compared using and predictors of patients receiving clopidogrel following CABG the Wilcoxon rank sum test for continuous variables and chi- surgery, determined the rates of clopidogrel use after 1 year, and square or Fisher's exact tests for categorical variables. Because compared the 1-year risk-adjusted mortality in patients receiving of recent findings demonstrating differences between patients and not receiving clopidogrel.
undergoing on- and off-pump CABG surgery, unadjusted Kaplan-Meier rates for 1-year survival are shown for the 4-level stratification of patients who did and did not receive clopidogrel and had on-pump versus off-pump CABG surgery.
Multivariable logistic regression was used to determine the We evaluated 6588 patients undergoing CABG surgery association between baseline and in-hospital demographics and between 2000 and 2007 at Duke University Medical Center clinical factors with in-hospital clopidogrel use following CABG (Durham, NC, USA). A total of 815 patients were excluded for surgery. All variables as well as their interactions with on- and concomitant valve surgery, 177 were excluded for in-hospital off-pump CABG surgery were considered for inclusion using reoperation for bleeding or anticoagulation complications, backward elimination with a requirement of alpha <0.05 for 188 died prior to discharge, and 4 additional patients who had retention (Tables 1 and 2).
undergone CABG surgery within 9 days were excluded, resulting Cox proportional hazards analysis was performed to evaluate in a final sample size of 5404. Patients undergoing urgent or the association between post-CABG clopidogrel use and 1-year elective procedures were included. This study was approved by mortality. We adjusted for covariates identified in the PRoject of the Duke University Health System Institutional Review Board. Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) The requirement for individual consent was waived. All patients trial mortality model, developed in a similar CABG population, undergoing surgical procedures signed an informed consent and included the most closely related variables available in our form according to the data collected during hospitalization dataset. In addition, we also adjusted for aspirin use after CABG which can be used in research.
surgery, warfarin use at discharge, on- and off-pump CABG-surgery, in-hospital cerebrovascular accident and renal failure. Adjusted survival curves are shown for the clopidogrel effect in On- and off-pump CABG procedures were performed during the multivariable Cox mortality model. The model was repeated the study period, including both urgent and elective procedures. with the inclusion of the interaction of clopidogrel with on- All patients were operated by the same group of surgeons that and off-pump CABG surgery; adjusted survival curves for this consists of 19 professionals. After median sternotomy, patients interaction are shown.
underwent conventional CABG surgery with the use of internal For the multivariable logistic and Cox models, continuous mammary arteries whenever possible. When performed on and ordinal variables were tested for linearity over the log hazard pump CABG, standard cardiopulmonary bypass was used, and were transformed as necessary to meet this modeling typically with both anterograde and retrograde cold blood assumption. The proportional hazards assumption was checked for each variable in the mortality model and there were no deviations of concern. Statistical analyses were performed using SAS version 9.1 (SAS Institute, Inc., Cary, NC, USA).
Discharge clopidogrel use was determined by in-hospital medication records, that was found in the electronic medical record, and was defined as administration at any time the day after surgery through the date of discharge. The files were Study Population and Baseline Characteristics
accessed by the institution's research group. In addition to Total of 5404 patients who underwent CABG surgery from clinical data collected during patient visits, medication use 2000–2007 where evaluated. Among these patients, 931 (17.2%) and survival were determined using self-administered mailed received clopidogrel after CABG surgery. Patients who received questionnaires and telephone follow-up for those who did clopidogrel, 789 were alive with complete medication information not return questionnaires. Deaths reported by Duke hospitals, after 1 year and 314 (39.8%) were still taking clopidogrel. Among the National Death Index, and the Social Security Death Index the patients not taking clopidogrel after surgery, 8.9% (345/3868) were used to confirm or supplement the follow-up surveys for were taking it after 1 year. One-year mortality was related to the mortality information. These actions were also performed by the use of clopidogrel at any time in hospital postoperative evolution. institution's research group. Operative mortality was defined as The above data add information about using this medication death occurring within 30 days of the index procedure or before after discharge.
Patient baseline characteristics are shown in Table 1. When compared with patients who did not receive clopidogrel, those who did were younger and had more comorbidities including Summary statistics were expressed as medians (25th, 75th hyperlipidemia, hypertension, peripheral arterial disease, and percentiles) for continuous variables and numbers (percentage) cerebrovascular disease but less heart failure in the prior 2 Brazilian Journal of Cardiovascular Surgery Prates PRL, et al. - Clopidogrel Use After Myocardial Revascularization Braz J Cardiovasc Surg 2016;31(2):106-14 Table 1. Baseline characteristics according to clopidogrel use after CABG.
Age, median (25th, 75th), yrs* Female sex, no. (%)* White race, no. (%) Weight, median (25th, 75th), kg Medical history, no. (%) Diabetes mellitus* Chronic lung disease* Recent MI (30 days) Prior valve procedure CHF within prior 2 weeks* History of cerebrovascular disease* History of peripheral vascular disease* Patient currently on dialysis Cardiogenic shock during the procedure Presenting features Creatinine (most recent in past 60 days), median (25th, 75th)* GFR (most recent in past 60 days), median (25th, 75th)* EF (most recent in past 60 days), median (25th, 75th)* Number of vessels ≥ 50% stenosed, no. (%) Left main disease ≥ 50%, no. (%) Preoperative antiplatelet agents, no. (%) Aspirin administered prior to CABG Clopidogrel administered prior to CABG *Included in multivariable model for mortality. CABG=coronary artery bypass grafting; CHF=congestive heart failure; EF=ejection fraction; GFR=glomerular filtration rate; MI=myocardial infarction; PCI=percutaneous coronary intervention Brazilian Journal of Cardiovascular Surgery Prates PRL, et al. - Clopidogrel Use After Myocardial Revascularization Braz J Cardiovasc Surg 2016;31(2):106-14 Table 2. Operative and postoperative characteristics according to clopidogrel use after CABG.
Surgery type, no. (%) Left or right IMA, no. (%)* SVG harvested endoscopically, no. (%)* On-pump surgery, no. (%)* Cross-clamp time, median (25th, 75th)* Perfusion time, median (25th, 75th)* Number of grafts, no. (%) Worst target artery quality, no. (%)* Worst graft quality, no. (%)* Type of graft, no. (%) Left saphenous vein Right saphenous vein Both left & right saphenous veins Left internal thoracic artery Right internal thoracic artery Both left & right internal thoracic arteries Left radial artery Right radial artery Both left & right radial arteries Length of stay, median (25th, 75th)* Patient discharged on warfarin, no. (%)* Aspirin after surgery and before discharge, no. (%)* MI occurs after surgery and before discharge, no. (%)* Cerebrovascular accident after surgery and before discharge, no. (%)*Atrial fibrillation before discharge, no. (%)* *Included in multivariable model for mortality. IMA=internal mammary artery; MI=myocardial infarction; SVG=saphenous vein graft Brazilian Journal of Cardiovascular Surgery Prates PRL, et al. - Clopidogrel Use After Myocardial Revascularization Braz J Cardiovasc Surg 2016;31(2):106-14 Table 3. Multivariable associations with clopidogrel use after CABG (N=4887).
Worst target artery quality, OR for 1 category increase 1.70 (1.50, 1.94) Left or right IMA 0.55 (0.42, 0.72) Worst graft quality, OR for 1 category increase 1.36 (1.17, 1.58) Age, OR for 10-year increase 0.86 (0.79, 0.93) Left main disease 1.40 (1.16, 1.69) MI before discharge 10.85 (2.75, 42.82) Surgery type (reference is elective) 1.33 (0.88, 1.99) 1.52 (1.21, 1.92) Ejection fraction, OR for 10% increase Linear spline ≥67, OR for off pump 4.10 (2.48, 6.77) Linear spline ≥67, OR for on pump 1.75 (1.23, 2.49) Linear spline ≤67 0.92 (0.85, 0.99) Number of grafts, OR for off pump 1.08 (0.88, 1.32) Number of grafts, OR for on pump 0.75 (0.66, 0.86) Aspirin at discharge 0.46 (0.27, 0.78) Pre-CABG clopidogrel 1.52 (1.13, 2.04) Perfusion time, OR for 30-minute increase 1.13 (1.04, 1.24) SVG harvested endoscopically, OR for off pump 4.66 (1.33, 16.33) SVG harvested endoscopically, OR for on pump 0.67 (0.36, 1.26) Congestive heart failure 0.71 (0.55, 0.91) 0.77 (0.63, 0.93) History of hypertension 1.32 (1.05, 1.65) 1.31 (1.05, 1.63) Cross-clamp time, OR for 30-minute increase 1.18 (1.03, 1.35) Cerebrovascular accident before discharge, OR for off pump 0.24 (0.05, 1.16) Cerebrovascular accident before discharge, OR for on pump 1.68 (0.96, 2.94) Atrial fibrillation before discharge 0.76 (0.59, 0.96) Discharge warfarin, OR for off pump 1.63 (0.60, 4.43) Discharge warfarin, OR for on pump 0.50 (0.28, 0.90) History of cerebrovascular disease 1.28 (1.01, 1.62) *P value for interaction term of variable with on/off-pump. CI=confidence interval; IMA=internal mammary artery; MI=myocardial infarction; OR=odds ratio; PCI=percutaneous coronary intervention; SVG=saphenous vein graft weeks. They were also more likely to have undergone prior percutaneous coronary intervention (PCI) or CABG surgery. Post- The main surgical procedure characteristics are shown in CABG clopidogrel users were also more likely to have received Table 2. Patients who did not receive clopidogrel more often clopidogrel in the preoperative period. Overall, aspirin was used underwent elective surgery (29.2% vs. 19.4%) while those in 98.1% of patients after CABG surgery (96.7% with and 98.4% receiving clopidogrel more often underwent urgent procedures without clopidogrel after CABG surgery).
(65.3% vs. 74.9%). Clopidogrel users were more likely to have bad Brazilian Journal of Cardiovascular Surgery
Prates PRL, et al. - Clopidogrel Use After Myocardial Revascularization Braz J Cardiovasc Surg 2016;31(2):106-14 Table 4. Kaplan-Meier rates for 1-year mortality according clopidogrel use versus not stratified by off and on pump surgeries.
Off pumpNo clopidogrel, no. (%) Clopidogrel, no. (%) On pump*No clopidogrel, no. (%) Clopidogrel, no. (%) *One on-pump patient without and one on-pump patient with clopidogrel after CABG were censored before the 1-year follow-up period. These patients are not included in the alive counts after 1 year but are reflected in the Kaplan-Meier rate.
quality grafts than patients who did not receive clopidogrel. The hospital length of stay was similar among the 2 groups.
In the overall population, 4716 (87.3%) patients had left saphenous vein grafts harvested, 1161 (21.5%) had right saphenous vein grafts harvested, and 785 (14.5%) had saphenous vein grafts from both left and right legs harvested (Table 2). A total of 4875 (90.2%) patients had a left internal thoracic artery graft, 188 (3.5%) had a right internal thoracic artery graft, and 123 (2.3%) had both internal thoracic artery grafts. Left radial grafts were used in 305 (5.6%) patients, 50 (0.9%) patients had a right radial artery graft, and 17 (0.3%) had both a right and left radial artery graft. While right saphenous vein grafts and left radial artery grafts were more commonly used in patients discharged with clopidogrel, left saphenous vein grafts and left internal thoracic artery grafts were more often used in patients Days after hospital discharge
discharged without clopidogrel (Table 2).
Predictors of Clopidogrel Use
The predictors of clopidogrel use are shown in Table 3. Fig. 1 – One-year mortality according to the clopidrogel use after
Patients who had worse target artery or graft quality, left main disease, prolonged perfusion time, clopidogrel before surgery, or prior PCI were more likely to receive clopidogrel after CABG surgery. Advanced age, internal mammary artery graft, elective surgery, and aspirin use before surgery or at discharge were associated with a lower probability of clopidogrel use following Our study has 2 main findings. First, at Duke University CABG surgery.
Medical Center, postoperative clopidogrel is used in almost one-fifth of the patients undergoing CABG surgery. These patients tend to be sicker and have more comorbidities than Clopidogrel use was associated with similar 1-year mortality those who do not receive clopidogrel after surgery. We also (4.7% vs. 4.5%, adjusted hazard ratio [HR] 1.08, 95% confidence identified several key factors associated with clopidogrel use interval [CI] 0.73–1.59; P=0.70) compared with those not using after CABG surgery. Second, clopidogrel use was associated clopidogrel (Table 4, Figure 1). However, there was an interaction with similar 1-year mortality compared with those patients not between use of cardiopulmonary bypass and clopidogrel, with using it. However, there was an interaction between the use lower 1-year mortality with clopidogrel in patients undergoing of cardiopulmonary bypass and clopidogrel, with lower 1-year off-pump CABG surgery (adjusted HR 0.47, 95% CI 0.19–1.13), but mortality with clopidogrel among patients undergoing off- not in those undergoing on-pump CABG surgery (adjusted HR pump CABG surgery and higher 1-year mortality with clopidogrel 1.35, 95% CI 0.89–2.05; P interaction=0.032) (Figure 2).
among those undergoing on-pump CABG surgery.
Brazilian Journal of Cardiovascular Surgery
Prates PRL, et al. - Clopidogrel Use After Myocardial Revascularization Braz J Cardiovasc Surg 2016;31(2):106-14 significantly associated with less use of clopidogrel during the hospital stay. Whether the patients were treated on or off pump, it appears that clopidogrel was generally chosen for younger patients (perhaps balancing bleeding risks) with poor target artery quality, cerebrovascular disease, and previous coronary interventions. Without randomized data on clopidogrel use following CABG surgery, our study provides insights about potential factors associated with its use that might help physicians decide when to use clopidogrel in this clinical setting.
In a subgroup analysis from the PREVENT IV study, in which all patients received aspirin at hospital discharge, clopidogrel use was associated with a trend for higher rates of occluded vein grafts during 12–18 months (49% vs. 39%; adjusted odds ratio 1.26; P=0.08) and with similar composite rates of death, myocardial infarction, or revascularization (27% vs. 24%; adjusted HR 1.10; Days after hospital discharge
P=0.38) in 5 years compared with those without it. This study found a significant interaction between use of cardiopulmonary on-pump /with clopidogrel
bypass and clopidogrel. Similarly, in our study, the administration on-pump /without clopidogrel
of clopidogrel during the hospital stay was not associated with overall 1-year mortality in patients undergoing CABG surgery, Fig. 2 – One-year mortality according to the clopidrogel use after
even in those cases where an emergency or urgent surgery was on-pump and off-pump CABG.
needed. In patients undergoing off-pump surgery, we found that clopidogrel use was associated with higher 1-year survival; however, in patients undergoing on-pump surgery, clopidogrel Previous studies have demonstrated the benefit of use was associated with higher 1-year mortality.
antiplatelet agents, particularly aspirin, after CABG surgery, Studies show different conclusions regarding the results although there is no consensus on when to initiate and what found when the techniques compared with and without dose should be used. Moreover, these studies do not directly cardiopulmonary bypass[21-23]. On the other hand, several show the impact of therapy on mid- and long-term mortality[3,4,7]. investigators have indicated that off-pump CABG surgery may There are published reports of controlled trials showing benefit increase the risk of thrombosis due to augmented thrombotic of different antiplatelet therapies, including aspirin alone[9,14], activity[24,25]. There is a well-known phenomenon of thrombotic aspirin plus dipyridamole[14-16], and aspirin plus sulfinpyrazone. activity following major general surgery and it is expected after More recent studies have demonstrated improved graft patency major procedures. In fact, Mariani et al. demonstrated that with the use of clopidogrel[7,12]. While the success of the surgical thrombotic activity is increased in the first 24 hours after off- procedure is most critical to the patency of a graft, understanding pump surgery. Clopidogrel appeared to have a role in decreasing the relationship between clopidogrel use and mortality and clotting and protecting the patency of anastomoses. In on- other hard clinical outcomes is critical.
pump surgery, there is a well described decrease in platelet Clopidogrel use in patients with acute coronary syndromes function that could bring benefits for graft patency[26,27]. This demonstrates benefit[5,6,18]. Treatment with clopidogrel reduced benefit does not occur in off-pump surgery where platelet the risk of myocardial infarction and recurrent ischemia, with a function tends to be closer to normal, leaving more room for trend toward lower rates of cerebrovascular accident and death benefit of an antiplatelet agent such as clopidogrel. It is known from cardiovascular causes[5,6,19]. Antiplatelet therapy with aspirin that extracorporeal circulation leads to a decrease in blood has led to improvements in vein graft patency when started coagulation activity, mainly due to consumption of factors and early after CABG[4,7,20]. The combination of clopidogrel and aspirin reduction of platelet activity. This could have a protective after off-pump CABG surgery was previously suggested to impact on patients undergoing on-pump CABG surgery. In this reduce cardiac events and mortality as well as improve graft situation, the pharmacological activity of clopidogrel may not patency in a single-center trial of 249 patients (91.6% for aspirin have as much of a role and this may have contributed to our plus clopidogrel vs. 85.7% for aspirin alone; P=0.043) .
While it remains unknown why some patients received In the Clopidogrel in Unstable angina to prevent Recurrent clopidogrel and others did not, our study identified several ischemic Events (CURE) trial, patients randomized to clopidogrel factors associated with clopidogrel use following CABG surgery: in addition to aspirin had a 20% reduction in cardiovascular death, target vessel quality, graft quality, age, congestive heart failure, myocardial infarction, or cerebrovascular accident in the 9th cerebrovascular accident, prior myocardial infarction, prior PCI, month in the follow-up period. Among patients who underwent prior CABG surgery, and aspirin use at hospital discharge. The CABG surgery, the apparent benefit of clopidogrel was tempered strongest predictor of clopidogrel use after CABG surgery was by a higher major bleeding rate among clopidogrel-treated worse target artery quality. Importantly, almost every patient patients (9.6% vs. 7.5%, respectively). Importantly, these patients (98.1%) received aspirin after the CABG surgery and this was were already on clopidogrel when undergoing CABG surgery Brazilian Journal of Cardiovascular Surgery Prates PRL, et al. - Clopidogrel Use After Myocardial Revascularization Braz J Cardiovasc Surg 2016;31(2):106-14 and did not start clopidogrel for the first time after surgery. Based Authors' roles & responsibilities
in large part on the CURE trial data, the current American College of Cardiology/American Heart Association/Society of Thoracic Analysis and/or data interpretation; manuscript redaction Surgeons guidelines recommend withholding therapy for 5 or critical review of its content; final manuscript approval days among acute coronary syndrome patients requiring CABG Analysis and/or data interpretation; manuscript redaction or critical review of its content; final manuscript approval At the present time, there are not adequate randomized Analysis and/or data interpretation; manuscript redaction clinical trial data to determine whether adding clopidogrel to or critical review of its content; final manuscript approval aspirin prevents adverse clinical outcomes (death, myocardial Statistical analysis; manuscript redaction or critical review infarction, cerebrovascular accident, unstable angina, or of its content; final manuscript approval recurrence of angina) after CABG surgery. Despite this, clopidogrel Statistical analysis; manuscript redaction or critical review is widely but inconsistently prescribed in patients after CABG of its content; final manuscript approval surgery with stable coronary disease, a practice supported Analysis and/or data interpretation; manuscript redaction primarily by subgroup analyses and observational data[12,29-31]. or critical review of its content; final manuscript approval In our study, clopidogrel was used more often in patients with Analysis and/or data interpretation; manuscript redaction poor graft quality, which suggests that cardiologists and cardiac or critical review of its content; final manuscript approval surgeons might be using clopidogrel after CABG surgery in RAKK Analysis and/or data interpretation; manuscript redaction or critical review of its content; final manuscript approval patients with worse coronary disease. While also observational, the data we present do not support a beneficial effect of dual Conception and design study; analysis and/or data interpretation; manuscript redaction or critical review of antiplatelet therapy following CABG surgery, although there may its content; final manuscript approval be some benefit in the off-pump setting.
Conception and design study; analysis and/or data interpretation; manuscript redaction or critical review of its content; final manuscript approval Our study has several limitations to consider. First, this is an observational study and one cannot account for unmeasured confounders. Thus, a cause and effect relationship between clopidogrel use and mortality cannot be assessed. Second, this is a single-center study and caution should be taken when generalizing our results to other institutions or settings. Third, while target artery quality was measured, other intraoperative technical factors were not measured and may play a role in identifying candidates for dual antiplatelet therapy after CABG surgery. Fourth, discharge clopidogrel was determined using in- 1. Motwani JG, Topol EJ. Aortocoronary saphenous vein graft hospital medication records and it was defined as administration disease: pathogenesis, predisposition, and prevention. Circulation. at any time the day after surgery through the date of discharge. Therefore, the term "clopidogrel at discharge" is not consistent 2. Goldman S, Copeland J, Moritz T, Henderson W, Zadina K, Ovitt T, et and does not necessarily means clopidogrel use at the time of al. Long-term graft patency (3 years) after coronary artery surgery. discharge. In addition, we did not have information on 1-year Effects of aspirin: results of a VA Cooperative study. Circulation. medication use for all patients. We demonstrated that only 3. Goldman S, Copeland J, Moritz T, Henderson W, Zadina K, Ovitt T, et around one-third of the patients who were discharged on al. Improvement in early saphenous vein graft patency after coronary clopidogrel were on it for 1 year, and less than 10% of patients artery bypass surgery with antiplatelet therapy: results of a Veterans who did not receive clopidogrel at discharge were on it for 1 year. Administration Cooperative Study. Circulation. 1988;77(6):1324-32.
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6. CAPRIE Steering Committee. A randomised, blinded, trial of At our institution, clopidogrel was used in almost one-fifth clopidogrel versus aspirin in patients at risk of ischaemic events of patients following CABG surgery. Its use was not associated (CAPRIE). Lancet. 1996;348(9038):1329-39.
with improved overall 1-year survival, yet may have some benefit 7. Gao G, Zheng Z, Pi Y, Lu B, Lu J, Hu S. Aspirin plus clopidogrel therapy among those receiving off-pump CABG. Adequately powered increases early venous graft patency after coronary artery bypass randomized clinical trials are needed to determine whether surgery a single-center, randomized, controlled trial. J Am Coll there is a role for routine or selected use of clopidogrel or newer antiplatelet agents after CABG surgery.
8. Fitchett D, Eikelboom J, Fremes S, Mazer D, Singh S, Bittira B, et al. Brazilian Journal of Cardiovascular Surgery Prates PRL, et al. - Clopidogrel Use After Myocardial Revascularization Braz J Cardiovasc Surg 2016;31(2):106-14 Dual antiplatelet therapy in patients requiring urgent coronary 21. Rodrigues AJ, Evora PR, Tubino PV. On-pumb versus off-pump artery bypass grafting surgery: a position statement of the Canadian coronary artery bypass graft surgery: what do the evidence show? Cardiovascular Society. Can J Cardiol. 2009;25(12):683-9.
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Brazilian Journal of Cardiovascular Surgery
DIABETES PEPTIDES Peptides and Diabetes PEPTIDES FOR DIABETES RESEARCH According to data from the International Diabetes Federa-tion, more than 250 million people around the world suf-fer from diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia. Diabetes mellitus can be divided into two main types, type 1 or insulin-dependent diabetes mellitus (IDDM) and type 2, or non insulin-depen-dent diabetes mellitus (NIDDM). The absolute lack of insu-lin, due to destruction of the insulin producing pancreatic β-cells, is the particular disorder in type 1 diabetes. Type 2 diabetes is mainly characterized by the inability of cells to respond to insulin. The condition affects mostly the cells of muscle and fat tissue, and results in a condition known as „insulin resistance".