Carlson, Mark D.

Background— The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction ≤35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. Methods and Results— SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death. Conclusions— ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.

Purpose Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. Patients and Methods Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. Results A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. Conclusion Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.

Purpose Despite the utility of newer antidepressants for alleviating hot flashes, antidepressants do not work adequately enough in many patients. Gabapentin is a nonhormonal agent that also can reduce hot flashes. No data have been available to address whether the combination of both agents would more effectively alleviate hot flashes, compared with gabapentin alone, in patients with inadequate hot flash control with an antidepressant alone. Patients and Methods This was a randomized trial in which 118 patients with inadequate hot flash control on an antidepressant were randomly assigned to receive both an antidepressant and gabapentin versus being weaned off the antidepressant and receiving gabapentin alone. Patients were observed for 5 weeks (including a baseline week in which patients continued on their current antidepressant without gabapentin) during which time they completed validated daily hot flash diaries. Results Ninety-one patients provided complete data at the 5-week assessment. Regardless of whether or not the antidepressant was continued when gabapentin was started, there was an approximately 50% median reduction in hot flash frequencies (54%; 95% CI, 34% to 70% for combined treatment v 49%; 95% CI, 26% to 58% for gabapentin alone) and scores (56%; 95% CI, 26% to 71% for combined treatment v 60%; 95% CI, 33% to 73% for gabapentin alone). Conclusion Gabapentin seems to decrease hot flashes by approximately 50% in women with inadequate hot flash control who were using an antidepressant. This study saw no significant additional hot flash reduction from continuation of the antidepressant.