Weekly EBM Update 9.3.18

Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus (ASCEND Trial NEJM 9/2018)

Aspirin has long been touted as primary preventative therapy for individuals at increased risk of cardiovascular events, historically defined as a man over age 45 and a woman over age 55. However, these recommendations have been tempered in recent years due to the increasingly highlighted adverse bleeding risk associated with aspirin. This paradigm shift can be seen in the most recent United States Preventative Service Task Force update on aspirin for primary prevention- now recommended (level B) for individuals age 50-59 with 10% 10-year ASCVD risk for the prevention both cardiovascular events and colorectal cancer in adults who are able to remain on it for 10 years. Aspirin is also a component of preventative measures in patients with diabetes, however recent studies have brought its benefit into question. The authors of this multicenter, randomized controlled trial (ASCEND) aimed to evaluate the effectiveness of aspirin in primary prevention of cardiovascular events in patients with diabetes but without overt clinical coronary disease. Patients were randomized to 100 mg of aspirin daily or placebo. The primary outcome was the occurrence of a first serious vascular event: a composite of non-fatal MI, non-fatal stroke (excluding intracerebral hemorrhage (ICH)) or TIA, or death due to a vascular cause. The safety outcome was the composite of confirmed ICH, sight threatening bleeding, GI bleeding, or bleeding that resulted in hospitalization, transfusion, or death. After a mean follow up of 7.4 years, the primary composite cardiovascular outcome occurred in 658 patients in the aspirin group vs 743 in the placebo group (rate ratio: 0.88, p-value: 0.01). The primary safety (bleeding) outcome occurred in 314 patients in the aspirin group compared to 245 in the control group (rate ratio: 1.29, p-value: 0.003). The reduction in cardiovascular events due to aspirin was driven largely in part due to a reduction in TIA.

Take home: Aspirin use led to a significant decrease in the rate of adverse cardiovascular events, however this came a significant increase risk of bleeding. The number needed to treat and harm respectively were: 91, and 112. Aspirin led to a risk reduction of cardiovascular events of 12%, but at a 29% increased risk of bleeding. Aspirin use for primary prevention of cardiovascular events may be outweighed, or at the least- counterbalanced, by its risk for serious bleeding.

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A Single, Post-ACTH Cortisol Measurement to Screen for Adrenal Insufficiency in the Hospitalized Patient (Journal of Hospital Medicine 8/2018)

Adrenal insufficiency is a diagnosis frequently considered amongst hospitalized patients. Initial screening for adrenal insufficiency commonly employs stimulation testing using the high dose (250 mcg) cosyntropin stimulation test (CST). The traditional test involves measuring cortisol levels at 0, 30, and 60 minutes after the administration of cosyntropin, with a cortisol level > 18 mcg/dL at any time point confirming adequate adrenal function. However, the inpatient administration of this test can be complex, requiring coordination from nursing staff to ensure that the samples are drawn at the appropriate time points. The authors of this retrospective cohort study sought to identify the accuracy of testing cortisol levels at a single time point- 30 minutes or 60 minutes- compared to the standard CST method of testing both time points amongst patients in the ICU or medical wards, respectively. The authors found that cortisol levels at 60 minutes had higher concordance with traditional CST compared to the 30-minute level (99.7% vs. 88.0%, respectively) in both ICU and ward patients. Testing at 30 minutes alone lead to a significantly higher rate of false positives (42.7% of positive tests (ie. < 18 mcg/dL) at 30 minutes were negative at 60 minutes (ie. > 18 mcg/dL)), compared to testing at 60 minutes, where 1.8% of tests were false positives at 60 minutes and negative at 30 minutes.

Take Home: It appears that an initial screening approach for adrenal insufficiency with the high dose cosyntropin test followed by a single 60-minute cortisol level has high concordance with traditional (baseline, 30- minute, and 60-minute testing), and leads to significantly fewer false positives than single 30-minute cortisol levels. Simplifying this testing algorithm could lead to better utilization of hospital staff and resources while remaining highly sensitive for adrenal insufficiency. Such implications should be validated in prospective studies.

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