Study Compares Cardiovascular Outcomes for Two Classes of Type 2 Diabetes Drugs

Two new, commonly prescribed medication classes provide similar cardiovascular benefits to type 2 diabetes (T2D) patients, although one may reduce rates of heart failure hospitalization more than the other, suggests a recent study conducted by researchers at the Brigham. The two types of drugs researched — glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors — prevent serious complications from cardiovascular disease (CVD) such as strokes, myocardial infarctions, and hospitalization for heart failure (HHF). CVD is the leading cause of death among T2D patients. The research team compared the two drug classes by collecting and analyzing data from two U.S. commercial insurance companies and Medicare on more than 370,000 patients.

“Our findings support the hypothesis that SGLT2 inhibitors and GLP-1 RAs do not largely differ with respect to the risk for hospitalization for MI or stroke, regardless of whether patients have or do not have established CVD at the time of drug initiation,” said Elisabetta Patorno, MD, DrPH, of the Division of Pharmacoepidemiology and Pharmacoeconomics. “However, SGLT2 inhibitors seem to be associated with a consistent decrease in the risk for hospitalization due to heart failure.”

Read more in Annals of Internal Medicine.

Study Examines Risk Factors, Clinical Features, and Management of Acute Kidney Injury from Immunotherapy in Cancer Patients

Immune checkpoint inhibitors (ICPis) have transformed the care of patients with cancer over the last decade. However, ICPis can cause autoimmune toxicities, referred to as immune-related adverse events, that can affect virtually any organ in the body, including the kidneys. ICPi-associated acute kidney injury (ICPi-AKI) occurs in about 3 to 5 percent of patients treated with these agents, and can lead to irreversible loss of kidney function and discontinuation of ICPi therapy. Until now, data on ICPi-AKI has been largely limited to case reports and small case series. Moreover, the safety of ICPi rechallenge after an episode of ICPi-AKI is unclear. In a new study led by Shruti Gupta, MD, and David Leaf, MD, MMSc, of the Division of Renal Medicine, collaborators from 30 sites across 10 countries collected detailed data on 429 patients who developed ICPi-AKI between 2012 and 2020. To study risk factors for ICPi-AKI development, the researchers also collected data on patients who received ICPis contemporaneously but did not develop ICPi-AKI. The researchers found that:

1) Lower baseline kidney function, proton pump inhibitor use, and extrarenal immune-related adverse events were each independent risk factors for development of ICPi-AKI.

2) Early treatment with corticosteroids (within 3 days of ICPi-AKI) is independently associated with a higher likelihood of renal recovery.

3)Among patients rechallenged with an ICPi after an episode of ICPi-AKI, only 16.5 percent developed recurrent ICPi-AKI.

“Currently, many oncologists are reluctant to rechallenge patients with an ICPi after an episode of ICPi-AKI for fear of its recurrence,” said Gupta. “These data have key implications for oncologists and their patients, since we found that the vast majority of patients can be rechallenged safely.”

Read more in the Journal for ImmunoTherapy of Cancer.

Data on Long-Term Outcomes After Firearm Injuries Are Scant

Each year, approximately 115,000 people survive firearm injuries. But the impact of firearm trauma on long-term outcomes has been understudied. As part of the National Trauma Research Action Plan, investigators from the Center for Surgery and Public Health (CSPH) at the Brigham conducted a systemic search of the research literature for studies published on survivors of physical traumatic injury. Out of 747 articles identified, seven reported on outcomes for survivors of firearm injuries. Many of the patients studied screened positive for posttraumatic stress disorder (49 to 60 percent) or were readmitted (13 to 26 percent) within 6 months postinjury.

“Research on the long-term health impact of firearm injury is scant,” said Juan P. Herrera-Escobar, MD, MPH, of CSPH. “A better understanding of the long-term health impact of firearm injury would support systematic change in policy and patient care to improve outcomes.”

Read more in Annals of Surgery.

Credit: Susanna Hamilton, Broad Communications

Large-Scale Genetic Repeat Variations Contribute to Height and Other Human Traits

A new study has found that a type of genetic modification involving long, repeated sequences within the human genome can affect a variety of health-related traits. The study, from researchers at the Broad Institute of MIT and Harvard, Brigham and Women’s Hospital, and Harvard Medical School, found that genetic changes called variable number tandem repeats (VNTRs) are strongly associated with nearly two dozen traits, including height, hair curl, and risk for heart and kidney disease. VNTRs are sections of the genome that stretch from seven up to thousands of base pairs in length, and are repeated a varying number of times in different individuals.

The team expected to see some associations between VNTRs and traits, but were surprised by how strong those links were. “The VNTRs we studied wound up being the top or second biggest genomic contributor to a trait,” said Po-Ru Loh, PhD, of the Brigham’s Division of Genetics and co-senior author of the study. “That really was a surprise.”

Read more in Science and in a Broad Institute news release.

Study Finds High Risks for Mitral Valve Surgery After Transcatheter Edge-to-Edge Repair

Transcatheter edge-to-edge repair (TEER) is performed worldwide to treat patients with severe mitral regurgitation (MR) who is a high risk for traditional open surgery. More than 100,000 procedures have been performed and that number continues to increase. However, mitral valve (MV) surgery after TEER may be necessary in some cases, and the long-term data are lacking. Investigators from Brigham and Women’s Hospital in conjunction with the CUTTING-EDGE registry analyzed the data from the multicenter, international registry, finding that MV surgery after TEER was high risk and less than 10 percent of patients underwent MV repair.

“Our multicenter international study showed that the surgery after TEER is a high risk and does not allow repair as a second surgery,” said co-corresponding author Tsuyoshi Kaneko, MD, of the Division of Cardiac Surgery at the Brigham. “Multiple factors lead to MV surgery after TEER, with a majority of patients requiring valve replacement. The mortality and morbidity risks in MV surgery after TEER are not negligible. Our findings should have a significant impact on choosing surgery versus transcatheter therapy for eligible patients.”

Read more in JACC: Cardiovascular Interventions.