Trends in use of anti-thrombotic agents and outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) managed with an invasive strategy.

OBJECTIVE: To analyze trends in utilization of anti-thrombotic agents (ATA) and in-hospital clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients managed with an invasive strategy from 2007 to 2010. METHODS & RESULTS: Using ACTION Registry(®)-GWTG™ data, we analyzed trends in use of ATA and in-hospital clinical outcomes among 64,199 NSTEMI patients managed invasively between 2007 and 2010. ATA included unfractionated heparin (UFH), low molecular weight heparin (LMWH), glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin. Although the proportion of NSTEMI patients treated with PCI within 48h of hospital arrival was similar in 2007 and 2010, percentage use of bivalirudin (13.4-27.3%; p<0.01) and UFH increased (60.0-67.5%, p<0.01), and that of GPI (62.3-41.0%; p<0.01) and LMWH (41.5-36.8%; p<0.01) declined. Excess dosing of UFH (75.9-59.3%, p<0.01), LMWH (9.6-5.2%; p<0.01) and GPI (8.9-5.9%, p<0.01) was also significantly lower in 2010 compared with 2007. Though in-hospital mortality rates were similar in 2007 and 2010 (2.3-1.9%, p=0.08), the rates of in-hospital major bleeding (8.7-6.6%, p<0.01) and non-CABG related RBC transfusion (6.3-4.6%, p<0.01) were significantly lower in 2010 compared with 2007. CONCLUSION: Compared with 2007, patients with NSTEMI, who were managed invasively in 2010 received GPI and LMWH less often and bivalirudin and UFH more frequently. There were sizeable reductions in the rates of excess dosing of UFH (though still occurred in 67% of patients), GPI and LMWH. In-hospital major bleeding complications and post-procedural RBC transfusion were lower in 2010 compared with 2007.

The prognostic value of hemoglobin in patients with anal cancer treated with chemoradiotherapy.

PURPOSE: This study aimed to evaluate the impact of hemoglobin level on clinical outcome (local response, progression-free survival, and overall survival) in patients with carcinoma of the anal canal treated with definitive chemoradiotherapy. METHODS: This is a retrospective study of patients with anal cancer treated between 1992 and 2005 with definitive chemoradiotherapy at Tom Baker Cancer Centre. Patient treatment, laboratory, and outcome data were extracted from the chart. RESULTS: Seventy-two patients treated with definitive chemoradiotherapy were identified. The median age was 56 years, the male-to-female ratio was 1:2, and the median tumor size was 3.5 cm. At 6 weeks after the completion of chemoradiotherapy, 62% of patients (38/61) had complete clinical response, and 34% (21/61) had achieved a partial clinical response. At 3 months after treatment, complete clinical response was observed in 78% (49/63) and a partial response in 16% (10/63). The median pretreatment hemoglobin level was 138.5 g/L, and the median on-treatment hemoglobin level was 129 g/L. Distant relapse was associated with hemoglobin levels in the lowest quartiles, pretreatment and on-treatment (P = .007 and P = .008, respectively). Hemoglobin levels were not associated with response at 6 weeks or 3 months. A pretreatment hemoglobin level of <130 g/L was associated with worse progression-free and overall survival (P < .0001, both). A hemoglobin on-treatment level of <121 g/L was associated with progression-free and overall survival (P < .0001 and P = .019, respectively), when stratified by gender. CONCLUSIONS: Hemoglobin status was correlated with progression-free and overall survival, and distant relapse, but not clinical response, in patients with carcinoma of the anal canal treated with chemoradiotherapy. The clinically relevant cut point, and the value of correcting hemoglobin levels before or during treatment, remains to be elucidated.

Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy.

PURPOSE: To evaluate the prognostic value of the posttreatment TNM stage as a predictor of outcome in locally advanced rectal cancers treated with preoperative chemotherapy and radiotherapy. METHODS AND MATERIALS: Between 1993 and 2000, 128 patients with tethered (103) or fixed (25) rectal cancers were treated with 50 Gy preoperative pelvic radiotherapy and two cycles of concurrent 5-fluorouracil infusion (20 mg/kg/d) and leucovorin (200 mg/m(2)/d) chemotherapy on Days 1-4 and 22-25 and a single bolus mitomycin C injection (8 mg/m(2)) on Day 1. Of the 128 patients, 111 had Stage T3 and 17 Stage T4 according to the rectal ultrasound or CT findings and clinical evaluation. All 128 patients underwent surgery 8 weeks after chemoradiotherapy. Postoperatively, the disease stage was determined according to the surgical and pathologic findings using the American Joint Committee on Cancer TNM staging system. RESULTS: Of the 128 patients, 32 had postchemoradiotherapy (pCR) Stage 0 (T0N0M0), 37 pCR Stage I, 26 pCR Stage II, 28 pCR Stage III, and 5 pCR Stage IV disease. Of the 128 patients, 79 had pCR Stage T0-T2, 35 pCR Stage T3, and 14 pCR Stage T4. The rate of T stage downstaging was 66% (84 of 128). Of the 128 patients, 25% achieved a pathologic complete response, and 31 (24%) had positive nodal disease. Lymphovascular or perineural invasion was found in 13 patients (10%). The 5-year disease-specific survival rate was 97% for pCR Stage 0, 88% for pCR Stage I, 74% for pCR Stage II, 44% for pCR Stage III, and 0% for pCR Stage IV (p = 0.0000059). The 5-year relapse-free survival rate was 97% for pCR Stage 0, 80% for pCR Stage I, 72% for pCR Stage II, 42% for pCR Stage III, and 0% for pCR Stage IV (p < 0.000001). In univariate analysis, the pretreatment tumor status (fixed vs. tethered tumors), the pCR TNM stage, T stage downstaging, pathologic T4 tumors, node-positive disease after chemoradiotherapy, and lymphovascular or perineural invasion were statistically significant prognosticators of disease-specific survival and relapse-free survival. pCR Stage T4 disease was a strong predictor of local recurrence. The 5-year local control rate was 98% for pCR T0-T2, 89% for pCR T3, and 65% for pCR T4 disease (p = 0.00044). In multivariate analysis, the pCR TNM stage was the most statistically significant independent predictor of survival (p = 0.003) and relapse-free survival (p < 0.001). CONCLUSION: For patients who underwent preoperative chemoradiotherapy for locally advanced rectal cancer, the pCR TNM stage was a strong prognosticator of recurrence and survival. It can be used to identify high-risk patients for additional postoperative therapy.

Cardiac rehabilitation in the elderly.

BACKGROUND: Although patients >/=65 years old account for the majority of cardiac admissions and procedures in the United States, studies of cardiac rehabilitation have traditionally focused on younger patients. Only recently has the effectiveness of cardiac rehabilitation in the elderly population begun to receive more attention. METHODS: We present a comprehensive literature review of studies that have looked specifically at the effectiveness of cardiac rehabilitation in the elderly. We discuss the methodologic limitations of studies to date, compare outcomes among elderly rehabilitation patients with those of younger patients, and examine barriers to participation among the elderly. RESULTS: The majority of studies published to date have been small observational case series. Despite these limitations, these studies generally show consistent improvements in exercise capacity, cardiac risk factors, and quality-of-life parameters in elderly cardiac rehabilitation patients. These benefits appear to be similar to those seen in younger patients. In spite of this, participation rates among the elderly are low, primarily because of less aggressive referral. CONCLUSIONS: Although further studies are necessary, the current literature shows that cardiac rehabilitation is associated with improved outcomes after a cardiac event, regardless of age. However, innovative recommendation and referral strategies are needed because few elderly patients actually enroll.

Medical and surgical management of coronary artery disease in women.

Women and men with coronary artery disease (CAD) differ in their presenting symptoms, baseline risk factors, age, and body size. These differences account for most of the previously reported differences in the management of women with CAD. When using larger databases and adjusting for confounding factors, women increasingly resemble men in terms of the care they receive and their outcomes. We reviewed recent articles on the pharmacologic and surgical management of women with CAD. Although women and men with CAD should be treated similarly, physicians still must recognize the sometimes atypical presentation of CAD in women and be mindful of the smaller body size of women regarding drug dosing and revascularization.

Representation of elderly persons and women in published randomized trials of acute coronary syndromes.

CONTEXT: Elderly persons and women were underrepresented in randomized controlled trials (RCTs) prior to 1990. Since then, efforts have been made to correct these biases, but their effect is unclear. OBJECTIVE: To determine whether the percentage of elderly persons and women in published clinical trials of acute coronary syndromes has increased and how this enrollment compared with disease prevalence. DATA SOURCES: The MEDLINE and Cochrane databases were searched for English-language articles from January 1966 to March 2000 regarding myocardial infarction, unstable angina, or acute coronary syndromes. Additional data sources included meta-analyses, review articles, and cardiology textbooks. Estimates of community-based myocardial infarction rates came from the National Registry of Myocardial Infarction and the Worcester Heart Study. STUDY SELECTION: Published RCTs of acute coronary syndrome patients were included and trials enrolling 50 patients or fewer, those without clinical end points, papers published in a language other than English, and unpublished manuscripts were excluded. Of 7645 studies identified, 593 RCTs were selected for review. DATA EXTRACTION: The RCTs were abstracted by 2 of the authors for year of publication, source of support (ie, funding), pharmacotherapy, study phase, number of study sites, trial location, number of patients, mean age of the study population, and any age exclusion criteria for enrollment. DATA SYNTHESIS: The number of published RCTs with explicit age exclusions has declined from 58% during 1966-1990 to 40% during 1991-2000. Trial enrollment of patients aged 75 years or older increased from 2% for studies published during 1966-1990 to 9% during 1991-2000, but remains well below their representation among all patients with myocardial infarction (37%) in the United States. Enrollment of women has risen from 20% for studies published between 1966-1990 to 25% during 1991-2000, but remains well below their proportion of all patients with myocardial infarction (43%) in the United States. CONCLUSIONS: Attempts at making cardiovascular RCTs more inclusive appear to have had limited success; thus, women and elderly persons remain underrepresented in published trial literature relative to their disease prevalence. Because safety and efficacy can vary as a function of sex and age, these enrollment biases undermine efforts to provide evidence-based care to all cardiac patients.

Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up.

OBJECTIVES: This study explored the association between the initiation of hormone replacement therapy (HRT) and early cardiac events (<1 year) in women with a recent myocardial infarction (MI). BACKGROUND: Observational studies have linked postmenopausal hormone use with a reduced risk of death from heart disease. However, a recent randomized trial of HRT found no long-term benefit, primarily due to an increase in cardiac events in the first year. METHODS: The Coumadin Aspirin Reinfarction Study (CARS) database contains information on HRT use and menopausal status for women with a recent MI. We classified the 1,857 postmenopausal women in CARS as prior/current HRT users if they took HRT before enrollment, new users if they began HRT during the study period or never users. We assessed the incidence of cardiac events (death, MI, unstable angina [UA]) during follow-up. RESULTS: In our cohort, 28% (n = 524) used HRT at some point. Of these, 21% (n = 111) began HRT after their MI. New users had a higher incidence of death/MI/UA (41% vs. 28%, p = 0.001) during follow-up than never users, largely due to a higher incidence of UA (39% vs. 20%, p = 0.001). After adjustment, new users still had a significantly higher risk of death/MI/UA than never users during follow-up (relative risk [RR] = 1.44 [1.05-1.99]). Prior/current users had no excess risk of the composite end point after adjustment. Users of estrogen/progestin had a lower incidence of death/MI/UA during follow-up than users of estrogen only (RR = 0.56 [0.37-0.85]). CONCLUSIONS: Postmenopausal women who initiated HRT after a recent MI had an increased risk of cardiac events largely due to excess UA during follow-up.

Post-myocardial infarction risk stratification in elderly patients.

BACKGROUND: The purpose of this study was to examine the use of post-myocardial infarction (MI) risk stratification in the elderly. Although expert panels have recommended risk stratification after MI, limited data are available on whether patients actually undergo suggested testing. In particular, concern has been raised that the elderly, who are at high risk for recurrent ischemia and short-term death, are not referred as often as younger patients for post-MI testing. METHODS: We studied the records of 192,311 Medicare patients (age > or = 65 years) admitted with MI between January 1992 and November 1992. By combining Medicare part A and part B data, we created a longitudinal record of patient care within 60 days of an MI admission. We describe the pattern of post-MI testing for ischemia and left ventricular function and outcomes as a function of patient age. RESULTS: Patients > or = 75 years of age were significantly less likely than patients 65 to 74 years of age to have either cardiac catheterization (17% vs 43%) or any test for coronary artery disease severity (24% vs 53%). They were also less likely to have a test of left ventricular function (61% vs 76%). Even after adjustment for baseline characteristics, older patients remained less likely than younger patients to have an assessment of coronary artery disease severity (odds ratio, 0.44) or left ventricular function (odds ratio, 0.65). CONCLUSIONS: Post-MI risk stratification declines with age and falls short of recommendations in our nation's elderly. This lack of testing may result in lost opportunities for therapeutic interventions in this high-risk group.

Outcomes of cardiac surgery in patients > or = 80 years: results from the National Cardiovascular Network.

OBJECTIVES: The purpose of this study was to evaluate characteristics and outcomes of patients age > or =80 undergoing cardiac surgery. BACKGROUND: Prior single-institution series have found high mortality rates in octogenarians after cardiac surgery. However, the major preoperative risk factors in this age group have not been identified. In addition, the additive risks in the elderly of valve replacement surgery at the time of bypass are unknown. METHODS: We report in-hospital morbidity and mortality in 67,764 patients (4,743 octogenarians) undergoing cardiac surgery at 22 centers in the National Cardiovascular Network. We examine the predictors of in-hospital mortality in octogenarians compared with those predictors in younger patients. RESULTS: Octogenarians undergoing cardiac surgery had fewer comorbid illnesses but higher disease severity and surgical urgency than younger patients. Octogenarians had significantly higher in-hospital mortality after cardiac surgery than younger patients: coronary artery bypass grafting (CABG) only (8.1% vs. 3.0%), CABG/aortic valve (10.1% vs. 7.9%), CABG/mitral valve (19.6% vs. 12.2%). In addition, they had twice the incidence of postoperative stroke and renal failure. The preoperative clinical factors predicting CABG mortality in the very elderly were quite similar to those for younger patients with age, emergency surgery and prior CABG being the powerful predictors of outcome in both age categories. Of note, elderly patients without significant comorbidity had in-hospital mortality rates of 4.2% after CABG, 7% after CABG with aortic valve replacement (CABG/AVR), and 18.2% after CABG with mitral valve replacement (CABG/MVR). CONCLUSIONS: Risks for octogenarians undergoing cardiac surgery are less than previously reported, especially for CABG only or CABG/AVR. In selected octogenarians without significant comorbidity, mortality approaches that seen in younger patients.

Potential impact of evidence-based medicine in acute coronary syndromes: insights from GUSTO-IIb. Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes trial.

OBJECTIVES: The purpose of this study to determine whether use of cardiac medications reflects evidence-based recommendations for patients with non-ST elevation acute coronary syndromes. BACKGROUND: Agency for Health Care Policy and Research practice guidelines for unstable angina recommend the use of cardiac medications based on evidence from randomized trials. It is unknown whether practitioners in the U.S., Canada and Europe follow these recommendations in patients with non-ST elevation acute coronary syndromes. METHODS: We studied 7,743 patients with non-ST elevation acute coronary syndromes enrolled in the international Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes trial. The use of aspirin, beta-adrenergic blocking agents, angiotensin-converting enzyme inhibitors and calcium channel blocking agents was determined at discharge for all patients and "ideal" patients (those with indications and no contraindications). Using published estimates of relative mortality reductions with these drugs, we calculated the lives that could have been saved at 1 year if discharge medication use had better matched guideline recommendations. RESULTS: Overall, guideline adherence at discharge in "ideal" patients was 85.6% for aspirin, 59.1% for beta-blockers and 51.7% for angiotensin-converting enzyme inhibitors. Calcium channel blockers were given to 26.7% of patients with a contraindication to these drugs. These rates were similar across locations of enrollment. Women and older patients less often received aspirin when "ideal," and younger patients more often received calcium channel blockers when they were contraindicated. If medication use had been more evidence-based, 1-year mortality might have been reduced by a relative 22%. CONCLUSIONS: There is significant room for improvement in the use of recommended drugs in patients with non-ST elevation acute coronary syndromes. Medication use that more closely follows recommendations could reduce mortality in this population.

Value of exercise treadmill testing in women.

OBJECTIVES: We sought to determine the ability of a treadmill score to provide accurate diagnostic and prognostic risk estimates in women. BACKGROUND: Treadmill testing has been reported to have a lower accuracy for diagnosis of chest pain in women. The diagnostic and prognostic value of the Duke Treadmill Score (DTS) in women is unknown. METHODS: We determined the diagnostic and prognostic value of the DTS in 976 women and 2,249 men who underwent both treadmill testing and cardiac catheterization in a single institution from 1984 to 1994. RESULTS: Women and men differed significantly in DTS (1.6 vs. -0.3, p < 0.0001), disease prevalence (32% vs. 72% significant coronary artery disease [CAD], p < 0.001), and 2-year mortality (1.9% vs. 4.9%, p < 0.0001). The DTS provided information beyond clinical predictors of both coronary disease and survival in women and men. Although overall women had better survival, the DTS performed equally well in stratifying both genders into prognostic categories. The DTS actually performed better in women than in men for excluding disease, with fewer low risk women having any significant coronary disease (> or = 1 vessel with > or =75% stenosis) (20% vs. 47%, p < 0.001), or severe disease (3-vessel disease or > or =75% left main stenosis) (3.5% vs. 11.4%, p < 0.001). CONCLUSIONS: By combining several aspects of treadmill testing, the DTS effectively stratifies women into diagnostic and prognostic risk categories.