BackgroundArterial graft spasm is a severe complication after coronary artery bypass graft (CABG). Among numerous potential antispasmodic agents, systemic application of diltiazem and nitroglycerin had been investigated most frequently over the past three decades. However, it remains inconclusive if either or both agents could improve patient outcomes by preventing graft spasm when applied perioperatively, and, if so, which one would be a better choice. The current systematic review and network meta-analysis aims to summarize the data from all available randomized clinical trials of perioperative continuous intravenous infusion of diltiazem and/or nitroglycerin in patients undergoing on-pump CABG in order to define and compare their roles in graft spasm prevention and their impacts on perioperative outcomes.MethodsWe searched Ovid Medline, PubMed, CINAHL, Google Scholar and Cochrane Center for randomized controlled trials that reported outcome effects of perioperative continuous intravenous infusion of diltiazem and/or nitroglycerin in patients undergoing elective on-pump CABG. Conventional meta-analyses were conducted to evaluate the pairwise comparisons (diltiazem vs. placebo; nitroglycerin vs. placebo; diltiazem vs. nitroglycerin) on perioperative outcomes. Network meta-analyses were implemented to compare the three regimens through direct and indirect comparison.ResultsTwenty-seven studies involving 1,660 patients were included. Pairwise and network meta-analyses found no significant difference in mortality among the groups. There are four studies that reported blood flow measurements of internal mammary artery grafts intraoperatively after dissecting or immediately after distal anastomosis while patients were on continuous intravenous infusion of diltiazem and nitroglycerin. Although insufficient for data synthesis, the measured results from all four studies suggest that both diltiazem and nitroglycerin significantly increased blood flow of arterial grafts compared to placebo. For other perioperative outcomes, compared to diltiazem, patients that received nitroglycerin had higher odds of postoperative atrial fibrillation (OR = 2.67, 95% CI: 1.15 to 6.24) and higher peak serum cardiac enzymes. Patients that received placebo had higher odds of atrial fibrillation (OR = 3.00, 95% CI: 1.18 to 7.63) and lower odds of requiring inotrope support (OR = 0.19, 95% CI: 0.04 to 0.73) compared to diltiazem. Data from the network meta-analysis indicated that diltiazem had significantly lower odds of postoperative atrial fibrillation compared to nitroglycerin (OR = 0.39, 95% CI: 0.18 to 0.85). In fact, the rank from highest to lowest rates of postoperative atrial fibrillation was placebo>nitroglycerin>diltiazem. The rank from highest to lowest odds of requiring inotropic support is nitroglycerin> diltiazem>placebo. However, placebo had significantly higher odds of postoperative myocardial infarction than diltiazem (OR = 4.51, 95% CI: 1.34 to 15.25). The rank from highest to lowest odds of postoperative myocardial infarctio...

Objective: The direct thrombin inhibitor bivalirudin (BIV) was shown to be superior to unfractionated heparin (UFH) in percutaneous coronary interventions for reducing procedural blood loss. The aim of this study was to compare outcome profiles of BIV and UFH in peripheral endovascular procedures (PEPs) by synthesizing the currently available data. Methods: Following the PRISMA statement, we conducted a comprehensive literature search using Medline, Cochrane CENTRAL, PubMed, EMBASE, CINAHL Google scholar, and clinicaltrials.gov. We recruited randomized, controlled trials and well-conducted observational studies that compared UFH and BIV in PEPs requiring anticoagulation, excluding endovascular cardiac procedures and coronary interventions. Random-effects meta-analyses were conducted to compare the outcome profiles of these two agents. Results: Thirteen articles containing 17 studies involving a total of 21,057 patients were enrolled. Of these, 2 were randomized controlled trials, 2 were prospective cohort studies, and 10 were retrospective studies. There were no significant differences between BIV and UFH in terms of procedural success rates, major and minor perioperative bleeding, transfusion, perioperative transient ischemic attack, or hemorrhagic strokes. However, compared with UFH, BIV had significantly lower odds ratios (OR) of perioperative mortality (OR, 0.58; 95% confidence interval [CI], 0.40-0.86), major adverse cardiovascular events (OR, 0.65; 95% CI, 0.51-0.83), net adverse clinical events (OR, 0.75; 95% CI, 0.63-0.88), perioperative myocardial infarction (OR, 0.73; 95% CI, 0.55-0.98), major vascular complications (OR, 0.59; 95% CI, 0.39-0.91), and minor vascular complications (OR, 0.58; 95% CI, 0.40-0.84). Conclusions: Compared with UFH, PEPs using BIV had comparable procedural success rates and odds of perioperative transient ischemic attack and hemorrhagic stroke. However, procedures with BIV had a lower but nonsignificant odds of perioperative bleeding and transfusion. Depending on the procedures conducted, the patients who received BIV will have reduced or comparable odds of perioperative mortality, myocardial infarction, major adverse cardiovascular events, net adverse clinical events, and major and minor vascular complications. Therefore, BIV may be chosen solely as an alternative procedural anticoagulant to UFH for PEPs. (