Faculty Bibliography

Limited data are available on the off-label use of drug-eluting stents (DESs) in clinical practice. We used data from the American College of Cardiology National Cardiovascular Data Registry to describe the rates and outcomes of DES use in 4 common off-label situations: ST-elevation myocardial infarction, in-stent restenosis, coronary artery bypass grafts, and chronic total occlusions. The rates of in-hospital adverse events for each off-label situation were determined and compared with the expected rates calculated from a validated model. From approval of DESs to the end of 2004, a total of 408,033 procedures involved placement of a DES. The use of DESs increased from 19.7% at the start of the study to 78.2% by the end of fourth quarter of 2004. Off-label use of DESs occurred in 24.1% of procedures. The rates of in-hospital adverse events with DES use in ST-elevation myocardial infarction, in-stent restenosis, coronary artery bypass grafting, and chronic total occlusions were lower than expected from the validated model. In conclusion, off-label use of DESs is common and is associated with a low rate of short-term adverse events. Randomized clinical trials are needed to confirm the efficacy of DESs in these clinical and angiographic settings. These data also highlight the importance of multicenter registries in tracking new technologies.

For many years, the traditional treatment for hospitalized patients in the United States who have developed anemia, whether associated with medical illness, surgical procedures or trauma, has been red blood cell transfusion, despite the absence of supporting data in many patient populations. Emerging evidence suggests that transfusions may, in fact, be associated with risk beyond commonly held concerns of microbial transmission and acute antigen-antibody reactions. The following overview represents a biological paradigm for understanding the relationship between medical illness, surgical procedures, inflammatory states, anemia, red blood cell transfusion and immunothrombotic phenomena among hospitalized patients.

OBJECTIVES/OBJECTIVE:The goal of this study was to determine the association between Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding and clinical outcomes. BACKGROUND:There are limited data on the relative utility of either scale at predicting clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes (ACS). METHODS:Pooled data from two randomized trials of patients with ACS (n = 15,454) were analyzed to determine the association between TIMI and GUSTO bleeding and 30-day and 6-month death/myocardial infarction (MI) using Cox proportional hazards modeling that included bleeding as a time-dependent covariate. RESULTS:There was a stepwise increase in the adjusted hazard of 30-day death/MI with worsening GUSTO bleeding (hazard ratio [95% confidence interval], GUSTO mild 1.20 [1.05 to 1.37]; moderate 3.28 [2.88 to 3.73]; severe 5.57 [4.33 to 7.17]), and an increased risk with all three levels of TIMI bleeding (TIMI minimal 1.84 [1.63 to 2.08]; TIMI minor 1.64 [1.31 to 2.04]; major 1.45 [1.23 to 1.70]). When both bleeding scales were included in the same model, the risk with GUSTO bleeding persisted; however, the association between TIMI bleeding and outcome was no longer significant. CONCLUSIONS:Both scales identify ACS patients with bleeding complications at risk for adverse outcomes. In a model that included both definitions, the risk with GUSTO bleeding persisted while the risk with TIMI bleeding did not. This suggests that bleeding assessed with clinical criteria is more important than that assessed by laboratory criteria in terms of outcomes. Future clinical trials should consider using a combination of the GUSTO bleeding scale and the need for transfusion to assess bleeding complications.

The increased rate of bleeding during and after cardiac procedures is a concern. The best strategy is prevention of bleeding complications with anticoagulant therapy that provides an adequate anti-thrombotic effect while reducing bleeding. The independent relationship between bleeding and blood transfusion and mortality among patients with coronary artery disease is reviewed. Findings suggest that in the modern era of percutaneous coronary intervention, prevention of bleeding should be a goal of therapy, which can be achieved while preserving the low rate of ischemic complications.

Bleeding is a complication of current therapies for acute coronary syndrome (ACS). No studies have examined the effect of bleeding events on clinical outcomes. We analyzed pooled data from 4 multicenter, randomized clinical trials of patients who had ACS (n = 26,452) to determine an association between bleeding severity as measured by the GUSTO scale and 30-day and 6-month mortality rates using Cox proportional hazards modeling that incorporated bleeding as a time-dependent covariate. The analysis was repeated to examine procedure- and non-procedure-related bleeding and after censoring at the time of coronary artery bypass grafting. Of all the patients included, 27.6% had > or =1 bleeding episode. Patients who bled were older and sicker at presentation than were those who did not bleed. Unadjusted rates of 30-day and 6-month mortality increased as bleeding severity increased. There were stepwise increases in the adjusted hazards of 30-day mortality (mild bleeding, hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3 to 1.9; moderate bleeding, HR 2.7, 95% CI l 2.3 to 3.4; severe bleeding, HR 10.6, 95% CI 8.3 to 13.6) and 6-month mortality (mild bleeding, HR 1.4, 95% CI 1.2 to 1.6; moderate bleeding, HR 2.1, 95% CI 1.8 to 2.4; severe bleeding, HR 7.5, 95% CI 6.1 to 9.3) as bleeding severity increased. Results were consistent after censoring for coronary artery bypass grafting and for procedure- and non-procedure-related bleeds. In conclusion, the GUSTO bleeding classification identifies patients who are at risk for short- and long-term adverse events. Therapies that minimize bleeding risk and maintain an anticoagulant effect may improve outcomes among patients who have ACS.

OBJECTIVES/OBJECTIVE:In a large contemporary population of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), we sought to describe blood transfusion rates (overall and in patients who did not undergo coronary artery bypass grafting [CABG]), patient characteristics and practices associated with transfusion, variation among hospitals, and in-hospital outcomes in patients receiving transfusions. BACKGROUND:The use of antithrombotic agents and invasive procedures reduces ischemic complications but increases risks for bleeding and need for blood transfusion in patients with NSTE ACS. METHODS:We evaluated patient characteristics and transfusion rates in the overall population (n = 85,111) and determined outcomes and factors associated with need for transfusion in a subpopulation of patients who did not undergo CABG (n = 74,271) from 478 U.S. hospitals between January 1, 2001, and March 31, 2004. RESULTS:A total of 14.9% of the overall and 10.3% of the non-CABG population underwent transfusion during their hospitalization. Renal insufficiency and advanced age were strongly associated with the likelihood of transfusion. Interhospital transfusion rates varied significantly. Non-CABG patients who received transfusions had a greater risk of death (11.5% vs. 3.8%) and death or reinfarction (13.4% vs. 5.8%) than patients who did not undergo transfusion. CONCLUSIONS:Transfusion is common in the setting of NSTE ACS, and patients who undergo transfusion are sicker at baseline and experience a higher risk of adverse outcomes than their nontransfused counterparts. Given the wide variation in transfusion practice, further efforts to understand patient and process factors that result in bleeding and need for transfusion in NSTE ACS are needed.

BACKGROUND:Previous studies suggest that patients hospitalized with acute myocardial infarction (MI) in December have poor outcomes, and some studies have hypothesized that the cause may be the infrequent use of evidence-based therapies during the December holiday season. OBJECTIVE:To compare the care and outcomes of patients with acute MI hospitalized in December and patients hospitalized during other months. DESIGN/METHODS:Retrospective analysis of data from the Cooperative Cardiovascular Project. SETTING/METHODS:Nonfederal, acute care hospitals in the United States. PATIENTS/METHODS:127 959 Medicare beneficiaries hospitalized between January 1994 and February 1996 with confirmed acute MI. MEASUREMENTS/METHODS:Use of aspirin, beta-blockers, and reperfusion therapy (thrombolytic therapy or percutaneous coronary intervention), and 30-day mortality. RESULTS:When the authors controlled for patient, hospital, and physician characteristics, the use of evidence-based therapies was not significantly lower but 30-day mortality was higher (21.7% vs. 20.1%; adjusted odds ratio, 1.07 [95% CI, 1.02 to 1.12]) among patients hospitalized in December. LIMITATIONS/CONCLUSIONS:This was a nonrandomized, observational study. Unmeasured characteristics may have contributed to outcome differences. CONCLUSIONS:Thirty-day mortality rates were higher for Medicare patients hospitalized with acute MI in December than in other months, although the use of evidence-based therapies was not significantly lower.

Despite significant advancements in the treatment of heart failure over the past 2 decades, this patient population is still subject to considerably high morbidity and mortality rates. In recent years, the field of device therapy as adjunctive treatment to the medical management of congestive heart failure has grown in the wake of the large number of randomized trials that have demonstrated the safety and efficacy of these devices. The implantable defibrillator currently represents the standard of care in certain segments of the heart failure population, even in those without a prior arrhythmic event. Biventricular pacing systems appear to have a role in heart failure patients with prolongation of their QRS duration in improving ventricular performance and symptoms, if not mortality. Last, the shortage of organs available for orthotopic transplant has heightened interest in using ventricular-assist devices as destination therapy, and although there is evidence for the feasibility for this approach at the current time, there is a next generation of devices that appear even more promising.

CONTEXT/BACKGROUND:It is unclear if blood transfusion in anemic patients with acute coronary syndromes is associated with improved survival. OBJECTIVE:To determine the association between blood transfusion and mortality among patients with acute coronary syndromes who develop bleeding, anemia, or both during their hospital course. DESIGN, SETTING, AND PATIENTS/METHODS:We analyzed 24,112 enrollees in 3 large international trials of patients with acute coronary syndromes (the GUSTO IIb, PURSUIT, and PARAGON B trials). Patients were grouped according to whether they received a blood transfusion during the hospitalization. The association between transfusion and outcome was assessed using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate and the propensity to receive blood, and a landmark analysis. MAIN OUTCOME MEASURE/METHODS:Thirty-day mortality. RESULTS:Of the patients included, 2401 (10.0%) underwent at least 1 blood transfusion during their hospitalization. Patients who underwent transfusion were older and had more comorbid illness at presentation and also had a significantly higher unadjusted rate of 30-day death (8.00% vs 3.08%; P<.001), myocardial infarction (MI) (25.16% vs 8.16%; P<.001), and death/MI (29.24% vs 10.02%; P<.001) compared with patients who did not undergo transfusion. Using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate, transfusion was associated with an increased hazard for 30-day death (adjusted hazard ratio [HR], 3.94; 95% confidence interval [CI], 3.26-4.75) and 30-day death/MI (HR, 2.92; 95% CI, 2.55-3.35). In the landmark analysis that included procedures and bleeding events, transfusion was associated with a trend toward increased mortality. The predicted probability of 30-day death was higher with transfusion at nadir hematocrit values above 25%. CONCLUSIONS:Blood transfusion in the setting of acute coronary syndromes is associated with higher mortality, and this relationship persists after adjustment for other predictive factors and timing of events. Given the limitations of post hoc analysis of clinical trials data, a randomized trial of transfusion strategies is warranted to resolve the disparity in results between our study and other observational studies. We suggest caution regarding the routine use of blood transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease.

The baseline characteristics, complications, and survival of 489 black and 6,890 non-black patients with acute coronary syndromes were studied. Important racial differences were observed in demographic features, atherosclerosis risk factors, and treatment strategies; however, despite these differences, no independent difference was observed in clinical outcomes according to race. The 1-year mortality rate was 2.9% for black patients and 2.5% for non-black patients (p = 0.93).