Frequency, clinical and angiographic characteristics, and outcomes of high-risk non-ST-segment elevation acute coronary syndromes patients with left circumflex culprit lesions.

BACKGROUND: The relationship between culprit vessel, infarct size, and outcomes in non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unclear. In some reports, the left circumflex artery (LCX) was more often the culprit at angiography than the right coronary artery (RCA) or left anterior descending artery (LAD), and infarcts were larger with LCX culprits. METHODS: We determined culprit vessel frequency and initial patency (TIMI flow grade), median fold elevation of peak troponin above the upper limit of normal, and outcomes (30-day death or myocardial infarction [MI] and 1-year mortality) by culprit vessel in high-risk NSTE ACS patients in the EARLY ACS trial. RESULTS: Of 9406 patients, 2066 (22.0%) had angiographic core laboratory data. We evaluated 1774 patients for whom the culprit artery was not the left main, a bypass graft, or branch vessel. The culprit was the LCX in 560 (31.6%), LAD in 653 (36.8%), and RCA in 561 (31.6%) patients. There were fewer women (24.1%) and more prior MI (25.5%) among patients with a culprit LCX compared with those with a culprit LAD or RCA. Patients with LCX (21.2%) and RCA (27.5%) culprits more often had an occluded artery (TIMI 0/1) than did those with LAD (11.3%). Peak troponin elevation was significantly higher for LCX than RCA or LAD culprits. LCX culprit vessels were not associated with worse 30-day or 1-year outcomes in adjusted models. CONCLUSIONS: Among patients with NSTE ACS, the frequencies of LCX, LAD, and RCA culprits were similar. Although LCX lesions were associated with higher peak troponin levels, there was no difference in short- or intermediate-term outcomes by culprit artery.

Duration of eptifibatide infusion after percutaneous coronary intervention and outcomes among high-risk patients with non-ST-segment elevation acute coronary syndrome: insights from EARLY ACS.

BACKGROUND AND OBJECTIVES: Eptifibatide is indicated during percutaneous coronary intervention (PCI) with continuation for 18-24 hours post procedure but is associated with bleeding. We examined the efficacy and safety of shorter post-PCI eptifibatide infusions in high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients. METHODS: EARLY ACS patients treated with PCI and eptifibatide were grouped by post-procedure infusion duration: <10, 10-13, 13-17, and 17-25 (per protocol) hours. Adjusted estimated event rates for 96-hour death/myocardial infarction (MI)/recurrent ischaemia requiring urgent revascularization (RIUR), 30-day death/MI, post-PCI packed red blood cell (PRBC) transfusion, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate/severe bleeding were obtained using inverse-propensity weighting to account for informative censoring of infusions. RESULTS: Among 3271 eptifibatide-treated PCI patients, there were 66 96-hour death/MI/RIUR events, 94 30-day death/MI events, 127 PRBC transfusions, and 115 GUSTO moderate/severe bleeds. Compared with per protocol, patients receiving post-PCI infusions <10 hours had similar adjusted estimated rates of 96-hour death/MI/RIUR (absolute difference 0.021 higher; 0.040 vs. 0.019, 95% CI -0.023 to 0.064; p=0.35) and 30-day death/MI (0.020 higher; 0.046 vs. 0.026, 95% CI -0.021 to 0.062; p=0.34). There were also no differences in ischaemic outcomes between infusions of 10-17 hours and per-protocol infusions. Adjusted estimated rates of PRBC transfusion were higher for the <10-hour infusion group compared with per protocol (0.048 higher; 0.079 vs. 0.031, 95% CI 0.005 to 0.091, p=0.03) but were similar for other groups. Adjusted GUSTO moderate/severe bleeding rates were similar to per-protocol rates for all groups. CONCLUSIONS: In high-risk NSTE ACS patients, post-PCI eptifibatide infusions <18 hours were not associated with worse ischaemic outcomes. Shorter eptifibatide infusions in this population may be feasible.

Bleeding risk and safety profile related to the use of eptifibatide: a current review.

INTRODUCTION: Eptifibatide is a glycoprotein IIb/IIIa inhibitor that blocks the final common pathway of platelet aggregation. Its major adverse effect is bleeding. Balancing its safety and efficacy is paramount for its appropriate usage. AREAS COVERED: The development of eptifibatide and its mechanism of action are explored. Clinical trials evaluating its efficacy and safety in a variety of clinical settings, as well as newer dosing regimens, are discussed. Readers will be able to understand the bleeding risks of eptifibatide in specific patient populations. EXPERT OPINION: The risk of bleeding with eptifibatide needs to be weighed against the potential benefits. Understanding which patients are at higher risk of bleeding will help the clinician make appropriate decisions.

Prevention of contrast induced nephropathy: recommendations for the high risk patient undergoing cardiovascular procedures.

Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality. Chronic kidney disease is the primary predisposing factor for CIN. As estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk. Modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration. The cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion. In the patient at increased risk for CIN it is often appropriate to withhold potentially nephrotoxic medications, and consider the use of n-acetylcysteine. In patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal.

Provisional glycoprotein IIb/IIIa blockade in a randomized investigation of bivalirudin versus heparin plus planned glycoprotein IIb/IIIa inhibition during percutaneous coronary intervention: predictors and outcome in the Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial.

BACKGROUND: The REPLACE-2 trial demonstrated the noninferiority of bivalirudin with provisional glycoprotein IIb/IIIa (GPIIb/IIIa) blockade as compared with heparin plus planned GPIIb/IIIa blockade among patients undergoing percutaneous coronary revascularization. Provisional drug was used in 374 (6%) of the 6010 patients. We sought to analyze the predictors for provisional drug use and to assess the outcomes in this cohort. METHODS: Outcome among the 5.2% of patients in the heparin plus GPIIb/IIIa blockade group and the 7.2% of patients in the bivalirudin group who received provisional placebo or GPIIb/IIIa inhibitor, respectively, was compared against patients without provisional drug use and between randomized arms. Multivariate models identified predictors of provisional drug use and outcome at 30 days, 6 months, and 1 year. RESULTS: Myocardial infarction, repeat revascularization, and bleeding events occurred more frequently among patients who required provisional drug than those who did not, but there were no differences in 1-year mortality. Ischemic and hemorrhagic end points occurred at similar rates among patients receiving provisional drug in either the heparin plus GPIIb/IIIa group compared with the bivalirudin group. Independent predictors of provisional drug use were randomization to bivalirudin, recent infarction, multilesion intervention, impaired pretreatment coronary flow, and lesion complexity. Provisional drug use, but not randomization to bivalirudin, independently predicted 30-day and 6-month ischemic events. CONCLUSIONS: Provisional administration of a GPIIb/IIIa inhibitor is associated with more frequent ischemic and bleeding events, reflecting the procedural complications that led to the use of provisional drug. The proportion of bivalirudin-treated patients who will require provisional GPIIb/IIIa blockade, however, is not large enough to have a significant deleterious impact on the overall incidence of ischemic end points or to invalidate the strategy of bivalirudin plus provisional GPIIb/IIIa blockade.

Association of the timing of ST-segment resolution with TIMI myocardial perfusion grade in acute myocardial infarction.

BACKGROUND: More complete ST-segment resolution (ST res) in acute myocardial infarction (MI) has been associated with better epicardial and myocardial reperfusion as assessed with the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and the TIMI myocardial perfusion grade (TMPG), respectively. However, no data exist comparing the speed of ST resolution on continuous electrocardiogram (ECG) monitoring with the TMPG on coronary angiography. We hypothesized that delayed ST res is associated with impaired TMPGs. METHODS: Continuous 12-lead ECG recordings and 60-minute angiographic data were analyzed in 120 patients with acute MI who received tenectaplase monotherapy or combination therapy with low-dose tenectaplase and eptifibatide in the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial. RESULTS: More rapid ST res on continuous ECG monitoring was associated with improved TMPGs on coronary angiography performed 60 minutes after study drug administration. For TMPG 3, the median time to ST resolution was 53 minutes. For TMPG 2, 1, and 0, the corresponding times were 64 minutes, 80 minutes, and 106 minutes, respectively (P =.01 for trend). Likewise, more rapid ST res was also associated with faster epicardial flow. For TFG 3, the median time to ST resolution was 46 minutes, compared with 109 minutes for TIMI flow grades 0 to 2 (P =.001). The corresponding times for a corrected TIMI frame count < or =40 versus >40 were 52 minutes and 112 minutes, respectively (P <.001). CONCLUSIONS: Although the static ECG has been associated with epicardial and myocardial blood flow in the past, this study extends these observations to demonstrate that more rapid ST res on continuous ECG monitoring is associated with improved myocardial perfusion after thrombolytic administration.

Open-label, sequential comparison of eptifibatide with abciximab for patients undergoing percutaneous coronary intervention.

BACKGROUND: Platelet glycoprotein IIb/IIIa antagonists reduce complications following percutaneous coronary intervention (PCI). There are limited data comparing different agents. OBJECTIVE: The purpose of this study was to compare in-hospital and 30-day outcomes in 2 sequential cohorts of consecutive patients undergoing PCI at our institution who received abciximab or eptifibatide. METHODS: The first cohort included patients who received abciximab between September 1, 1998, and January 9, 1999, and the second included patients who were treated with eptifibatide between January 11 and April 27, 1999. Per formulary decision, during the latter period, patients with renal insufficiency continued to be treated with abciximab and were ineligible for therapy with eptifibatide. Major adverse cardiac events (MACEs) were evaluated by one or more of the authors and compared. RESULTS: A total of 319 patients were treated with abciximab and 301 with eptifibatide. There were no differences in baseline characteristics between the 2 groups, with the exception of a significantly higher proportion of patients with chronic renal insufficiency in the abciximab-treated group (4% vs 0% with eptifibatide; P = 0.03) The majority of interventions were performed for an acute coronary syndrome. Procedural success was 97% in both groups. Eptifibatide patients were treated for a mean 20.4 (5.2) hours, with 10.1% receiving the drug before the procedure. There were no differences in overall or individual MACEs in hospital or at 30 days. CONCLUSION: Our data suggest similar in-hospital and 30-day outcomes for abciximab- and eptifibatide-treated patients undergoing PCI.