Neuza Lopes

Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial.

CONTEXT Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P = .002). CONCLUSION Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01021631.

Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.

Background— Despite routine use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), no conclusive evidence exists that either modality is superior to medical therapy (MT) alone for treating multivessel coronary artery disease with stable angina and preserved ventricular function. Methods and Results— The primary end points were total mortality, Q-wave myocardial infarction, or refractory angina requiring revascularization. The study comprised 611 patients randomly assigned to undergo CABG (n=203), PCI (n=205), or MT (n=203). At the 5-year follow-up, the primary end points occurred in 21.2% of patients who underwent CABG compared with 32.7% treated with PCI and 36% receiving MT alone (P=0.0026). No statistical differences were observed in overall mortality among the 3 groups. In addition, 9.4% of MT and 11.2% of PCI patients underwent repeat revascularization procedures compared with 3.9% of CABG patients (P=0.021). Moreover, 15.3%, 11.2%, and 8.3% of patients experienced nonfatal myocardial infarction in the MT, PCI, and CABG groups, respectively (P<0.001). The pairwise treatment comparisons of the primary end points showed no difference between PCI and MT (relative risk, 0.93; 95% confidence interval, 0.67 to 1.30) and a significant protective effect of CABG compared with MT (relative risk, 0.53; 95% confidence interval, 0.36 to 0.77). Conclusions— All 3 treatment regimens yielded comparable, relatively low rates of death. MT was associated with an incidence of long-term events and rate of additional revascularization similar to those for PCI. CABG was superior to MT in terms of the primary end points, reaching a significant 44% reduction in primary end points at the 5-year follow-up of patients with stable multivessel coronary artery disease.

Ten-Year Follow-Up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II)

Background— This study compared the 10-year follow-up of percutaneous coronary intervention (PCI), coronary artery surgery (CABG), and medical treatment (MT) in patients with multivessel coronary artery disease, stable angina, and preserved ventricular function. Methods and Results— The primary end points were overall mortality, Q-wave myocardial infarction, or refractory angina that required revascularization. All data were analyzed according to the intention-to-treat principle. At a single institution, 611 patients were randomly assigned to CABG (n=203), PCI (n=205), or MT (n=203). The 10-year survival rates were 74.9% with CABG, 75.1% with PCI, and 69% with MT (P=0.089). The 10-year rates of myocardial infarction were 10.3% with CABG, 13.3% with PCI, and 20.7% with MT (P<0.010). The 10-year rates of additional revascularizations were 7.4% with CABG, 41.9% with PCI, and 39.4% with MT (P<0.001). Relative to the composite end point, Cox regression analysis showed a higher incidence of primary events in MT than in CABG (hazard ratio 2.35, 95% confidence interval 1.78 to 3.11) and in PCI than in CABG (hazard ratio 1.85, 95% confidence interval 1.39 to 2.47). Furthermore, 10-year rates of freedom from angina were 64% with CABG, 59% with PCI, and 43% with MT (P<0.001). Conclusions— Compared with CABG, MT was associated with a significantly higher incidence of subsequent myocardial infarction, a higher rate of additional revascularization, a higher incidence of cardiac death, and consequently a 2.29-fold increased risk of combined events. PCI was associated with an increased need for further revascularization, a higher incidence of myocardial infarction, and a 1.46-fold increased risk of combined events compared with CABG. Additionally, CABG was better than MT at eliminating anginal symptoms. Clinical Trial Registration Information— URL: http://www.controlled-trials.com. Registration number: ISRCTN66068876.

Five-Year Follow-Up of a Randomized Comparison Between Off-Pump and On-Pump Stable Multivessel Coronary Artery Bypass Grafting. The MASS III Trial

Background— Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the bodys response to the nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes. Methods and Results— In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22; P=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240±65 versus 300±87.5 minutes; P<0.001), in the length of ICU stay (19.5±17.8 versus 43±17.0 hours; P<0.001), time to extubation (4.6±6.8 versus 9.3±5.7 hours; P<0.001), hospital stay (6±2 versus 9±2 days; P<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients; P<0.001), and blood requirements (31 versus 61% of patients; P<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient; P<0.001). Conclusions— No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66068876.

Coronary Revascularization (Surgical or Percutaneous) Decreases Mortality After the First Year in Diabetic Subjects but not in Nondiabetic Subjects With Multivessel Disease An Analysis From the Medicine, Angioplasty, or Surgery Study (MASS II)

Background— It is currently unknown whether revascularization procedures are associated with an improvement in mortality among diabetic subjects, as compared with a more conservative medical treatment. Methods and Results— In MASS II, a total of 611 patients with stable multivessel coronary disease were randomly assigned to medical treatment, surgery, or angioplasty. From these, 190 patients had diabetes (medical, 75 patients; angioplasty, 56 patients; surgery, 59 patients) and comprised the present study population. Mortality rates were analyzed for the entire 5 years of follow-up. Separate analyzes were also performed for mortality at 2 time intervals: during the first year and after the first year of follow-up. We calculated the probability of death conditional on surviving to the start of the interval analyzed. The cumulative 5-year mortality as well as the mortality during the first year of follow-up was not significantly different among treatment groups, both for diabetic and for nondiabetic subjects. Also, during years 2 to 5, the mortality of the 3 treatment groups was not different for nondiabetic subjects. Among diabetic subjects, however, patients randomized to angioplasty or surgery had a significantly lower mortality between years 2 and 5 than those allocated to medical treatment (P=0.039). Conclusion— Surgery, angioplasty, and medical treatment appear to be associated with similar mortality rates for non-diabetic subjects. For diabetic subjects, however, coronary revascularization (percutaneous or surgical) significantly decreased the risk of death after the first year and up to 5 years, compared with medical treatment alone.

Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

Abstract  We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin‐sensitizing vs. insulin‐providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty‐one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15–2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross‐sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross‐sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.

TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

Background TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR  = 2.32 95%CI 1.27–4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets. Clinical Trial Registration Information Medicine, Angioplasty, or Surgery Study (MASS II): Unique identifier: ISRCTN66068876.

Reduced expression of systemic proinflammatory and myocardial biomarkers after off-pump versus on-pump coronary artery bypass surgery: A prospective randomized study

BACKGROUND The effects of off-pump (OffPCABG) and on-pump (OnPCABG) coronary artery bypass grafting (CABG) on myocardium and inflammation are unclear. OBJECTIVE Compare the inflammatory response and myocardial injury from patients (pts) submitted to OffPCABG with those that undergo OnPCABG. METHODS Patients with normal left ventricular function were assigned to OffPCABG (n = 40) and OnPCABG (n = 41). Blood samples were collected before and 24 hours after surgery for determination of creatine kinase (CK)-MB (CK-MB), troponin I (cTnI), interleukin (IL)-6, IL-8, P-selectin, intercellular adhesion molecule (ICAM)-1 and C-reactive protein (CRP). Mortalities were registered at 12 months. RESULTS Preoperative CK-MB and cTnI levels were 3.1 +/- 0.6 IU and 1.2 +/- 0.5 ng/mL for OffPCABG and 3.0 +/- 0.5 IU and 1.0 +/- 0.2 ng/mL for OnPCABG pts. Postoperative CK-MB and cTnI levels were 13.9 +/- 6.5 IU and 19.0 +/- 9.0 ng/mL for OffPCABG vs 29.5 +/- 11.0 IU and 31.5 +/- 10.1 ng/mL for OnPCABG (P < .01). OffPCABG and OnPCABG pts had similar preoperative IL-6 (10 +/- 7 and 9 +/- 13 pg/mL), IL-8 (19 +/- 7 and 17 +/- 7 pg/mL), soluble P-selectin (70 +/- 21 and 76 +/- 23 pg/mL), soluble ICAM-1 (117 +/- 50 and 127 +/- 52 ng/mL), and CRP (0.09 +/- 0.05 and 0.11 +/- 0.07 mg/L). At 24 hours, for OffPCABG and OnPCABG: IL-6 was 37 +/- 38 and 42 +/- 41 g/mL; IL-8, 33 +/- 31 and 60 +/- 15 pg/mL; soluble P-selectin, 99 +/- 26 and 172 +/- 30 pg/mL; soluble ICAM-1, 227 +/- 47 and 236 +/- 87 ng/mL; and CRP, 10 +/- 11 and 14 +/- 13 mg/L (P < .01 vs preoperation; P < .01 vs OffPCABG). Increased 24-hour postoperative CRP levels was the only marker to have significant positive correlations with events and occurred just for the OnPCABG pts. In-hospital and 1-year mortalities for the OnPCABG and OffPCABG pts were 2.0% and 2.2% (P = .1) and 2.7% and 4.7% (P = .06), respectively. CONCLUSIONS Thus, the absence of CPB during CABG preserves better the myocardium and attenuates inflammation-however, without improving survival.

Sex Differences in Presentation and Outcome Among Patients With Type 2 Diabetes and Coronary Artery Disease Treated With Contemporary Medical Therapy With or Without Prompt Revascularization: A Report From the BARI 2D Trial (Bypass Angioplasty Revascularization Investigation 2 Diabetes)

OBJECTIVES This study evaluated differences in outcome among women and men enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. BACKGROUND Women and men with coronary artery disease have different clinical presentations and outcomes that might be due to differences in management. METHODS We compared baseline variables, study interventions, and outcomes between women and men enrolled in the BARI 2D trial and randomized to aggressive medical therapy alone or aggressive medical therapy with prompt revascularization. RESULTS At enrollment, women were more likely than men to have angina (67% vs. 58%, p < 0.01) despite less disease on angiography (Myocardial Jeopardy Index 41 ± 24 vs. 46 ± 24, p < 0.01; number of significant lesions 2.3 ± 1.7 vs. 2.8 ± 1.8, p < 0.01). Over 5 years, no sex differences were observed in BARI 2D study outcomes after adjustment for difference in baseline variables (death/myocardial infarction/cerebrovascular accident: hazard ratio: 1.11, 99% confidence interval [CI]: 0.85 to 1.44). However, women reported more angina than men (adjusted odds ratio: 1.51, 99% CI: 1.21 to 1.89, p < 0.0001) and had lower scores for the Duke Activity Status Index (adjusted beta coefficient: -1.58, 99% CI: -2.84 to -0.32, p < 0.01). CONCLUSIONS There were no sex differences in death, myocardial infarction, or cerebrovascular accident among patients enrolled in the BARI 2D trial. However, compared with men, women had more symptoms and less anatomic disease at baseline, with persistence of higher angina rates and lower DASI scores after 5 years of medical therapy with or without prompt revascularization. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

Qualidade de vida após revascularização cirúrgica do miocárdio, angioplastia ou tratamento clínico

BACKGROUND: Although the clinical benefits of coronary interventions seem to be confirmed, their effects on quality of life (QoL) are still scarcely studied. OBJECTIVE: To assess the QoL in multivessel coronary disease in patients randomly undergoing surgery, angioplasty or medical treatment. METHODS: The Short-Form Health Survey (SF-36) questionnaire was answered by 483 patients. Of these, 161 underwent surgical revascularization, 166 underwent angioplasty, and 153 were medically treated. RESULTS: At baseline, 86% of the patients referred angina, 34% referred infarction, and 32% were smokers. Medical Treatment: 12 patients (7.7%) had AMI, 24 (15.3%) underwent surgery, and 19 (12.1%) died. In addition, 5 (3.2%) had stroke, and 40 (25.6%) had angina. As regards the mental component, 64.1% and 30.8% had their condition improved and worsened, respectively. As regards the physical component, 70.5% and 27.6% had their condition improved and worsened, respectively. Surgery: 13 patients (8.1%) had AMI, 2 (1.2%) underwent surgery, and 12(7.4%) died. Also, 9 (5.6%) had stroke and 30 (18.6%) had angina. As regards the mental component, 72.7 % and 25.5% had their condition improved and worsened, respectively. As regards the physical component, 82.6% and 16.1% had their condition improved and worsened, respectively. Angioplasty: 18 patients (10.9%) had AMI, 51 (30.7%) underwent interventions, and 18 (19.9%) died. Additionally, six (3.6%) presented stroke and 35 (21%) reported angina. As regards the mental component, 66.9% and 26.5% had their condition improved and worsened, respectively. As regards the physical component, 77.1% and 20.5% had their condition improved and worsened, respectively. CONCLUSION: Improvement was observed in all domains and in the three therapeutic modalities. Comparatively, surgery had provided a better quality of life after a four-year follow-up.