eripheral artery disease (PAD) was identified by the Institute of Medicine as one of the top 100 priorities for comparative effectiveness research because of the large population of patients affected with significant morbidity and mortality, the multiple potential treatment options, and the high costs of care to the health care system. 1 The goal of medical therapy in patients with PAD is to reduce the risk of future cardiovascular (CV) morbidity and mortality, improve walking distance and functional status in patients with intermittent claudication (IC), and reduce amputation in patients with critical limb ischemia (CLI).Secondary prevention includes the use of antiplatelet agents and the management of other risk factors, such as tobacco use, diabetes mellitus, hyperlipidemia, and hypertension.It is not clear which antiplatelet strategy (aspirin versus clopidogrel or monotherapy versus dual antiplatelet therapy [DAPT]) is of most benefit.Furthermore, the role of these agents in patients with asymptomatic PAD is also unclear.We conducted a systematic review evaluating various treatment modalities for PAD. 2 This article, which is derived from that review, focuses on the comparative effectiveness and safety of (1) aspirin versus placebo or no antiplatelet, (2) clopidogrel versus aspirin, (3) clopidogrel plus aspirin versus aspirin alone, and (4) other antiplatelet comparisons. Methods
Objectives For patients with peripheral artery disease (PAD), the optimal treatment for cardiovascular protection, symptom relief, preservation of walking and functional status, and prevention of amputation is not known. This review assessed the comparative effectiveness of antiplatelet therapy, medical therapy, exercise, and endovascular and surgical revascularization in PAD patients with intermittent claudication (IC) or critical limb ischemia (CLI). Data sources We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for relevant English-language studies published since January 1995. Review methods Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects. A meta-analysis of direct comparisons was supplemented by a mixed-treatment analysis to incorporate data from placebo comparisons, head-to-head comparisons, and multiple treatment arms. Results A total of 83 studies contributed evidence. Eleven studies—10 randomized controlled trials (RCTs), 1 observational study—evaluated the comparative effectiveness of antiplatelet agents. In asymptomatic PAD patients, there was no difference between aspirin and placebo for all-cause mortality, cardiovascular mortality, myocardial infarction (MI), or stroke. In patients with IC, one RCT suggests that aspirin may reduce MI and composite vascular events compared with placebo but was inconclusive for other outcomes of interest. Another RCT involving IC patients suggests that clopidogrel is more effective than aspirin for reducing cardiovascular mortality, nonfatal MI, and composite vascular events. Clopidogrel and aspirin appear to be equivalent for prevention of nonfatal stroke, but the confidence interval was wide, making this conclusion less certain. In symptomatic (92% IC) and asymptomatic (8%) PAD patients, dual antiplatelet therapy (DAPT)—clopidogrel plus aspirin—had no impact on composite or individual outcomes. Similarly, in IC or CLI patients after unilateral bypass graft, one RCT showed no difference between DAPT and aspirin alone on nonfatal stroke and composite vascular events and was inconclusive for other outcomes. In patients with IC or CLI after an endovascular procedure, one RCT showed no difference between DAPT and aspirin alone in cardiovascular events or mortality at 6 months but was underpowered for those outcomes. Four additional studies assessed other antiplatelet comparisons but were too small to make any meaningful conclusions about effectiveness. Seven RCTs reported different types of bleeding events, and the use of antiplatelet agents was associated with higher rates of minor and moderate bleeding compared with placebo. Thirty-five studies (27 RCTs, 8 observational) evaluated the comparative effectiveness of cilostazol, pentoxifylline, exercise therapy, endovascular revascularization, or surgical revascularization in IC patients, with the majority of the studies comparing one intervention with either placebo or one other intervention. In order to place all treatments in a common framework for comparison, we created a network meta-analysis. Although the data were still too sparse to definitively conclude which treatment is most effective, we were able to depict relative effect sizes and identify which treatments are clearly superior to placebo for which outcomes. No specific treatment had a statistically significant effect on all-cause mortality (12 RCTs). Exercise training improved maximal walking distance (16 RCTs), and exercise training and endovascular intervention improved initial claudication distance (12 RCTs) compared with usual care. Quality-of-life scores (10 RCTs) showed a significant improvement from cilostazol, exercise training, endovascular intervention, and surgical intervention compared with usual care. Seventeen RCTs reported safety concerns. Cilostazol was associated with higher rates of headache, dizziness, and diarrhea, while endovascular interventions were associated with more transfusions, arterial dissections/perforations, and hematomas compared with the usual care groups. Twenty-three studies (1 RCT, 22 observational) in CLI patients and 12 studies (2 RCTs, 10 observational) in IC or CLI patients evaluated the comparative effectiveness of endovascular or surgical treatments. Long-term amputation-free survival and all-cause mortality were not different between the two treatments in the CLI population. Primary patency varied, but secondary patency rates appeared to favor endovascular interventions in the CLI population. In four observational studies comparing endovascular interventions with usual care, there was insufficient evidence on the comparative effect for all clinical outcomes. In observational studies of the IC-CLI population, there were fewer periprocedural complications from endovascular interventions, while RCTs showed lower rates in the surgical intervention arm. Conclusions From a limited number of studies, it appears that aspirin has no benefit over placebo in the asymptomatic PAD patient; clopidogrel monotherapy is more beneficial than aspirin in the IC patient; and DAPT is not significantly better than aspirin at reducing cardiovascular events in patients with IC or CLI. For IC patients, exercise therapy, cilostazol, and endovascular intervention all had an effect on improving functional status and quality of life; the impact of these therapies on cardiovascular events and mortality is uncertain. The comparisons of endovascular and surgical revascularization in CLI are primarily from observational studies, and the heterogeneity of the results makes conclusions for all clinical outcomes less certain. Several advances in care in both medical therapy and invasive therapy have not been rigorously tested and thus provide an impetus for further research.
In the United States, approximately 1.4 million persons access emergency shelter or transitional housing each year (1). These settings can pose risks for communicable disease spread. In late March and early April 2020, public health teams responded to clusters (two or more cases in the preceding 2 weeks) of coronavirus disease 2019 (COVID-19) in residents and staff members from five homeless shelters in Boston, Massachusetts (one shelter); San Francisco, California (one); and Seattle, Washington (three). The investigations were performed in coordination with academic partners, health care providers, and homeless service providers. Investigations included reverse transcription-polymerase chain reaction testing at commercial and public health laboratories for SARS-CoV-2, the virus that causes COVID-19, over approximately 1-2 weeks for residents and staff members at the five shelters. During the same period, the team in Seattle, Washington, also tested residents and staff members at 12 shelters where a single case in each had been identified. In Atlanta, Georgia, a team proactively tested residents and staff members at two shelters with no known COVID-19 cases in the preceding 2 weeks. In each city, the objective was to test all shelter residents and staff members at each assessed facility, irrespective of symptoms. Persons who tested positive were transported to hospitals or predesignated community isolation areas.
