Citations

Purpose To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy. Patients and Methods This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly. Results The study accrued 344 patients; 330 were assessable for efficacy and 305 were assessable for QOL. Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, −3.8 to +5.3) compared with 2.8 g/dL (range, −2.2 to +7.5) for epoetin-treated patients (P < .0001). During the study, 31.7% of placebo-treated patients achieved a ≥ 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P < .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6% and 25.3% (P = .005), respectively. The placebo group received 256 units of RBCs compared with 127 units in the epoetin group (P < .0001). The incidence of toxicity in the groups was similar. Changes in the average QOL scores from baseline to the end of the study were similar in the two groups (P = not significant). The HgB responders (irrespective of treatment arm) had a mean change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a baseline of +5.1 compared with −2.1 for the nonresponders (P = .006). Conclusion Epoetin alfa significantly improved HgB and reduced transfusions in this patient population. These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia.

Background— Coronary bypass surgery (CABG) and angioplasty (PTCA) have been compared in several randomized trials, but data about long-term economic and quality-of-life outcomes are limited. Methods and Results— Cost and quality-of-life data were collected prospectively from 934 patients who were randomized in the Bypass Angioplasty Revascularization Investigation (BARI) and followed up for 10 to12 years. CABG had 53% higher costs initially, but the gap closed to <5% during the first 2 years; after 12 years, the mean cumulative cost of CABG patients was $123 000 versus $120 750 for PTCA, yielding a cost-effectiveness ratio of $14 300/life-year added. CABG patients experienced significantly greater improvement in their physical functioning for the first 3 years but not in later follow-up. Recurrent angina substantially reduced all quality-of-life measures throughout follow-up. Cumulative costs were significantly higher among patients with diabetes, heart failure, and comorbid conditions and among women; costs also were increased by angina, by the number of revascularization procedures, and among patients who died. Conclusion— Early differences between CABG and PTCA in costs and quality of life were no longer significant at 10 to 12 years of follow-up. CABG was cost-effective as compared with PTCA for multivessel disease.

Purpose Primary systemic amyloidosis (AL) is a multisystemic disorder resulting from an underlying plasma cell dyscrasia. There is no formal staging system for AL, making comparisons between studies and treatment centers difficult. Our group previously identified elevated serum cardiac troponin T (cTnT) as the most powerful predictor of overall survival. Others have reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. We sought to develop a staging system for patients with AL. Patients and Methods Two hundred forty-two patients with newly diagnosed AL who were seen at the Mayo Clinic between April 1979 and November 2000, and who had echocardiograms and stored serum samples at presentation were eligible for this retrospective review. NT-proBNP measurements were performed on 242 patients in whom cTnT and cardiac troponin I (cTnI) had been previously run. Two prognostic models were designed using threshold values of NT-proBNP and either cTnT or cTnI (NT-proBNP < 332 ng/L, cTnT < 0.035 μg/L, and cTnI < 0.1 μg/L). Depending on whether NT-proBNP and troponin levels were both low, were high for only one level, or were both high, patients were classified as stage I, II, or III, respectively. Results Using the cTnT+NT-proBNP model 33%, 30%, and 37% of patients were stages I, II, and III, respectively, with median survivals of 26.4, 10.5, and 3.5 months, respectively. The alternate cTnI+NT-proBNP model predicted median survivals of 27.2, 11.1, and 4.1 months, respectively. Conclusion Stratification of AL patients into three stages is possible with two readily available and reproducible tests setting the stage for more consistent and reliable cross comparisons of therapeutic outcomes.

Background and Purpose— Following publication of concerns about the results of the National Institute of Neurological Disorders and Stroke (NINDS) intravenous tissue plasminogen activator (t-PA) in acute stroke treatment trial, NINDS commissioned an independent committee “to address whether there is concern that eligible stroke patients may not benefit from t-PA given according to the protocol used in the trials and, whether the subgroup imbalance (in baseline stroke severity) invalidates the entire trial.” Methods— The original NINDS trial data were reanalyzed to assess the t-PA treatment effect, the effect of the baseline imbalance in stroke severity between the treatment groups on the t-PA treatment effect, and whether subgroups of patients did not benefit from receiving t-PA. Results— A clinically important and statistically significant benefit of t-PA therapy was identified despite subgroup imbalances in baseline stroke severity and an increased incidence of symptomatic intracerebral hemorrhage in t-PA treated patients. The adjusted t-PA to placebo odds ratio (OR) of a favorable outcome was 2.1 (95% CI, 1.5 to 2.9). Although these exploratory analyses found no statistical evidence that the t-PA treatment effect differed among patient subgroups, the study was not powered to detect subgroup treatment differences. Conclusions— These findings support the use of t-PA to treat patients with acute ischemic stroke within 3 hours of onset under the NINDS t-PA trial protocol. Health professionals should work collaboratively to develop guidelines to ensure appropriate use of t-PA in acute ischemic stroke patients.

Background— This study evaluated long-term results of aortic root replacement and valve-preserving aortic root reconstruction for patients with aneurysms involving the aortic root. Methods and Results— Two-hundred three patients aged 53±16 years (mean±SD; 153 male, 50 female) underwent elective or urgent aortic root surgery from 1971 to 2000 for an aortic root aneurysm: 149 patients underwent a composite valve conduit reconstruction, and 54 patients underwent valve-preserving aortic root reconstruction. Fifty patients had Marfan syndrome. In-hospital and 30-day mortality was 4.0% (8/203) overall: for a composite valve conduit procedure, the corresponding value was 4.0% (6/149) and for valve-preserving procedure, 3.7% (2/54) ( P =NS). Morbidity included 3 strokes (1%), 10 perioperative myocardial infarctions (5%), and 8 reoperations for bleeding (4%). Actuarial survival at 5, 10, 15, and 20 years was 93% (95% confidence interval [CI] = 88% to 97%), 79% (95% CI = 71% to 87%), 67% (95% CI = 57% to 79%), and 52% (95% CI = 36% to 69%), respectively. Freedom from reoperation was 72% (95% CI = 54% to 86%) at 20 years. Complications with anticoagulation occurred in 29 patients; with valve thrombosis, in 2; and with hemorrhage, in 27 (4 life threatening and 23 minor). Freedom from thromboembolism was 91% (95% CI = 77% to 98%) at 20 years. Freedom from endocarditis was 99% (95% CI = 92% to 100%) at 20 years. Multivariate analysis revealed preoperative mitral valve regurgitation (+3 to 4) and older age to be significant predictors of late death ( P ≤0.005), and Marfan syndrome, initial valve-preserving aortic root reconstruction, and need for a concomitant procedure at initial operation to be significant predictors of the need for reoperation ( P ≤0.01). Conclusions— Aortic root replacement for aortic root aneurysms can be done with low morbidity and mortality. Composite valve conduit reconstruction resulted in a durable result. There were few serious complications related to the need for long-term anticoagulation or a prosthetic valve. Reoperation was most commonly required because of failure of the aortic valve when a valve-preserving aortic root reconstruction was performed or for other cardiac or aortic disease elsewhere.