Outpatient Treatment of Low-risk Pulmonary Embolism in the Era of Direct Oral Anticoagulants: A Systematic Review.

BACKGROUND: Clinical guidelines have supported outpatient treatment of low-risk pulmonary embolism (PE) since 2014, but adoption of this practice has been slow. Direct oral anticoagulant (DOAC) therapy for venous thromboembolism (VTE) is now as common as vitamin K antagonist treatment, but data are sparse regarding outcomes for patients with low-risk PE treated with DOACs as outpatients. We conducted a systematic review of literature on outcomes of outpatient management for PE, including comparisons to inpatient treatment and differences by anticoagulant class. METHODS: We searched Medline, Embase, PubMed, CENTRAL, clinicaltrials.gov, and ICTRN for studies published from January 1980 through February 2019 using a predefined strategy developed with a medical librarian. We included English-language randomized controlled trials (RCTs) and prospective nonrandomized trials (NRTs) of adult patients diagnosed with acute, symptomatic PE, and discharged from the emergency department or within 48 hours. Our primary outcome included four major adverse outcomes (all-cause mortality, PE-related mortality, recurrent VTE, and major bleeding) within 30 and 90 days. A preplanned subanalysis of high-quality studies assessed outcomes associated with different anticoagulation treatment classes. RESULTS: Our initial search identified 6,818 records, of which 12 studies (four RCT, eight NRT) with a total of 3,191 patients were included in the review. All RCTs and six NRTs were determined to have low to moderate risk of bias and were classified as high quality. Outpatients in these studies (n = 1,814) had rates of 90-day major adverse outcomes below 1%, including all-cause mortality (0.7%, 95% confidence interval [CI] = 0.4% to 1.2%), PE-related mortality (0.06%, 95% CI = 0.01% to 0.3%), recurrent VTE (0.8%, 95% CI = 0.5% to 1.4%), and major bleeding (0.8%, 95% CI = 0.5% to 1.4%). Exploratory analysis revealed no association between anticoagulant treatment class and rates of major adverse outcomes. CONCLUSION: Among patients with low-risk PE treated as outpatients, few patients experienced major adverse outcomes such as mortality, recurrent VTE, or major bleeding within 90 days.

The Role of Statin Therapy in Hemorrhagic Stroke.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely utilized class of cholesterol-lowering agents, carrying multiple indications for both primary and secondary cardiovascular risk reduction. Concern was raised by previously published post hoc analyses and observational studies that noted an increased risk of hemorrhagic stroke in patients receiving a statin. Subsequent studies have demonstrated conflicting results regarding the role of statin therapy on hemorrhagic stroke risk and patient outcomes. New evidence suggests that statins taken prior to or continued during admission for intracerebral hemorrhage (ICH) may be associated with positive outcomes. Evidence also suggests deleterious outcomes resulting from the abrupt discontinuation of statins upon hospital admission for multiple disease states including ICH. Conflicting data also exist for the use of statins following aneurysmal subarachnoid hemorrhage (aSAH). Recent evidence suggests statins started during admission for aSAH confer no additional benefit in reducing delayed ischemic neurologic deficits despite initial positive results. Larger scale evaluation of the role of statin therapy following hemorrhagic stroke is warranted. The available literature is reviewed to provide guidance for therapeutic decision making.

Total daily pill burden in HIV-infected patients in the southern United States.

The need for antiretroviral therapy coupled with treatment of chronic co-morbidities places HIV-infected patients at risk for polypharmacy. However, few studies have described overall pill burden among HIV-infected patients. HIV-infected outpatients of the UNC Infectious Diseases Clinic were enrolled in this cross-sectional study. Subjects were contacted prior to a scheduled appointment and asked to bring all their medications to the visit. Daily total pill burden and medication type were recorded. 151 subjects were recruited: 76% male, 58% African American, 97% receiving antiretrovirals (ARVs). Median age was 48 (IRQ: 42-54) years. The median number of medications per subject was 8 (IQR: 6-11), and the median individual daily pill burden was 8 pills (IQR: 5-15): 3 pills (range: 2-5) for ARVs and 6 (range: 3-12.5) pills for non-ARVs. Duration of ART (per 2 years increase) and more than 3 co-morbidities was significantly associated with high pill burden (over 10 pills per day) with adjusted OR of 2.09 (95% CI, 1.14-3.84) and 8.04 (95% CI, 2.30-28.15), respectively. As patients with HIV age, strategies to reduce pill burden and number of medications will become increasingly critical to maintaining adherence, preventing medication errors, and serious drug-drug interactions.