Mary Helen Hackney

BACKGROUND: Statins taken for cardiovascular indications by patients with breast cancer and lymphoma during doxorubicin treatment may attenuate left ventricular ejection fraction (LVEF) decline, but the effect of statins on LVEF among patients with no cardiovascular indications is unknown. METHODS: A double-blind, placebo-controlled, 24-month randomized trial of 40 mg of atorvastatin per day administered to patients with breast cancer and lymphoma receiving doxorubicin was conducted within the National Cancer Institute Community Oncology Research Program across 31 sites in the United States. At pretreatment and then 6 and 24 months after initiating doxorubicin, we assessed left ventricular (LV) volumes, strain, mass, and LVEF through cardiac magnetic resonance imaging, along with cognitive function and serum markers of inflammation. The primary outcome was the difference in 24-month LVEF between placebo and treatment groups, adjusted for pretreatment LVEF. RESULTS: A total of 279 participants were enrolled in the trial. Participants had a mean (±SD) age of 49±12 years; 92% were women; and 83% were White. The mean (±SD) LVEF values were 61.7±5.5% before treatment and 57.4±6.8% at 24 months in the placebo group and 62.6±6.4% before treatment and 57.7±5.6% at 24 months in the atorvastatin group. On the basis of a multiple imputed data set for missing data and adjusted for each individual's pretreatment LVEF, 24-month declines in LVEF averaged 3.3±0.6 percentage points and 3.2±0.7 percentage points, for those randomly assigned to placebo versus statins, respectively (P=0.93). Across both treatment arms, similar percentages of individuals experienced changes of more than 10 percentage points in LVEF, LV strain, LV mass, cognition, and inflammation biomarkers, including among those with greater than 90% drug compliance. CONCLUSIONS: In patients with breast cancer and lymphoma with no existing indication for statin therapy, prospective statin administration did not affect LVEF declines 2 years after doxorubicin. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01988571.).

Thromboangiitis obliterans (TAO) is a nonatherosclerotic, nonnecrotizing, nonspecific, segmental inflammatory obliterative vasculitis, characterized by decreased flow to the distal extremities and increased risk of amputation. While smoking cessation is viewed as critical to successful treatment, various therapeutic options have been employed. While many treatment regimens seek to diminish platelet function, there are relatively few studies of platelet function in this disease entity and even fewer that have offered evidence of increased platelet activity. The authors report here 2 cases of TAO in which evaluations for hypercoagulable states and of platelet function were performed. Platelet contractile force (PCF) was found to be 82% higher than a normal control in 1 TAO patient and 340% higher than normal in the second patient. This was true despite the fact that platelet aggregations confirmed suppression of aggregation by antiplatelet medications. Elevated PCF has been seen in a variety of conditions, such as coronary artery disease and diabetes mellitus, in which endothelial function is abnormal. Whether high PCF values play a role in the pathogenesis of these diseases or simply serve as markers of enhanced platelet function and/or endothelial dysfunction awaits additional evaluations.