Brief oral steroid bursts raise risk of GI bleeding, sepsis, heart failure

Last Updated: 2020-07-06

By Megan Brooks

NEW YORK (Reuters Health) - A short course of corticosteroids is associated with a 1.8- to 2.4-fold increased risk for gastrointestinal bleeding, sepsis, and heart failure (HF) within the first month after initiation, according to results of a large study from Taiwan.

"Oral steroid bursts are not as risk-free as many clinicians thought previously," Dr. Tsung-Chieh Yao from Chang Gung Memorial Hospital in Taoyuan, told Reuters Health by email.

"Physicians who consider prescribing steroid bursts to their patients should weigh the benefits against the potential risks of these severe adverse events. After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after steroid initiation," Dr. Yao suggested.

In a retrospective analysis of 15.9 million adults in Taiwan's National Health Insurance Program, Dr. Yao and colleagues evaluated the relationship between 14 or fewer days of oral corticosteroid exposure and GI bleeding, sepsis and HF.

One quarter of the population received a short course of corticosteroids during the three-year study period (2013-2015). Their mean age was 38 years, and 85% had no baseline comorbid conditions. The median corticosteroid dose was 10 mg/day.

More than half of corticosteroids were prescribed for acute contact dermatitis, rhinosinusitis, laryngitis, pharyngitis, bronchitis, or tonsillitis, the investigators report in Annals of Internal Medicine.

Within 30 days of steroid start, there was a 1.8-fold increased risk for GI bleeding, a 2.0-fold increased risk for sepsis, and a 2.4-fold increased risk for HF, despite a median steroid exposure of just three days.

The incidence rates per 1000 person-years among adults prescribed steroid bursts were 27.1 for GI bleeding, 1.5 for sepsis, and 1.3 for HF, which were significantly higher than the incidence rates among non-steroid users (16.8, 1.4 and 0.4, per 1000 person-years, respectively). The rate increases were highest five to 30 days after exposure but remained elevated after three months.

Dr. Chan said there are several potential explanations for the findings. "First, corticosteroids have been shown in animal studies to increase gastric acid secretion, to reduce gastric mucus, to cause gastrin and parietal cell hyperplasia, and to delay the healing of ulcers, which are potentially responsible for the raised risk of GI bleeding after initiating steroid therapy."

"Second, corticosteroids have many adverse effects on innate and acquired immunity that can predispose to infection, including sepsis (defined as life-threatening organ dysfunction caused by a dysregulated host response to infection)."

"Third, some well-known cardiovascular risk factors, such as hypertension, dyslipidemia, hyperglycemia and fluid retention, have been identified as the main adverse effects of corticosteroids, which may predispose to heart failure."

"In addition, genetic profiles of glucocorticoid receptor across populations might also play a role in raising risk of GI bleeding, sepsis, and heart failure. It will be of importance to further investigate and dissect functional mechanisms of steroid bursts on GI bleeding, sepsis, and heart failure," Dr. Chan said.

Based on the findings, "We recommend using steroid bursts cautiously only when clinically indicated, prescribing the least amount of corticosteroids to control symptoms, and monitoring the potential risks for GI bleeding, sepsis, and heart failure after steroid initiation," Dr. Chan told Reuters Health.

In an editorial, Dr. Beth Wallace and Dr. Akbar K. Waljee from the Center for Clinical Management Research at VA Ann Arbor Healthcare System and Institute for Healthcare Policy and Innovation at Michigan Medicine note that the rate increases with steroid bursts were similar in patients with and without comorbid conditions, "meaning that the potential for harm was not limited to persons at high risk for these adverse events."

Based on the risk differences reported, 41,200 GI bleeding events, 400 cases of sepsis, and 4,000 cases of new HF per year that were directly attributed to brief exposure to oral corticosteroids, they calculate.

"We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people. As providers, we must reflect on how and why we prescribe corticosteroids to develop strategies that prevent avoidable harms," they write.

"Future studies will also be needed to assess the validity of these findings in other populations, evaluate associations between bursts and other corticosteroid-associated AEs (such as major cardiovascular events, venous thromboembolism, and fractures), evaluate how burst dose affects AE frequency, and further examine how age and comorbid conditions modify the risks of burst use," Dr. Wallace and Dr. Waljee add.

Funding for the study was provided by the National Health Research Institutes, Ministry of Science and Technology of Taiwan, Chang Gung Medical Foundation, and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: https://bit.ly/3f6bZHw and https://bit.ly/38IeSfD Annals of Internal Medicine, online July 6, 2020.