GLP-1 receptor agonists and SGLT2 inhibitors, two classes of drugs most commonly prescribed to treat type 2 diabetes or weight loss, may reduce the risk of heart attack, second stroke and death in adults who have had an initial stroke episode, according to a preliminary study. to be presented at the 2024 American Heart Association Scientific Sessions. The meeting, November 16-18, 2024, in Chicago, is a leading global exchange of the latest scientific advances, research and evidence-based clinical practice updates in cardiovascular science.
Unfortunately, a quarter of people who survive a stroke will have another stroke and are also at risk for other cardiovascular events, such as a heart attack, as many of the risk factors for a stroke are also associated with other forms of heart disease. Managing these risks, as well as considering innovative approaches to reduce the chances of another stroke, heart attack, or death in this population are all critical steps in increasing stroke survival and improving the quality of life for people who have suffered a stroke”.
M. Ali Sheffeh, MD, lead study author, an internal medicine physician and researcher at the Mayo Clinic in Rochester, Minnesota
In this study, Sheffeh and colleagues evaluated whether two classes of drugs to treat Type 2 diabetes are associated with a reduced risk of heart attack, second stroke, or death in stroke survivors.
One class of drugs – glucagon-like peptide-1 (GLP-1) receptor agonists – treats type 2 diabetes by stimulating the release of insulin from the pancreas, delaying stomach emptying and reducing the release of glucagon, a hormone in the body that increases the blood sugar.
The GLP-1 drugs liraglutide and semaglutide, as well as the dual GLP-1 and glucose-independent insulinotropic polypeptide (GIP) tirzepatide, have been approved by the US Food and Drug Administration for weight loss and cardiovascular disease risk reduction in humans with obesity or overweight.
The other class of drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors, lowers blood sugar levels by prompting the kidneys to remove excess glucose from the body through the urine. The SGLT2 drugs canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin are FDA-approved for the treatment of type 2 diabetes.
To analyze the impact of these two classes of drugs, this study reviewed the medical records of more than 7,000 adults who had strokes caused by blood clots or ischemic strokes between January 2000 and June 2022. All participants had received stroke care at hospitals in multiple systems. of health in Minnesota or Wisconsin. The researchers evaluated the results for people who were prescribed either a GLP-1 drug or an SGLT2 drug after their initial stroke to determine if there was a potential impact on their risk of having a second stroke, heart attack, or death.
After an average follow-up of three years, the analysis found:
- Adults taking either GLP-1 or SGLT2 had a 74% lower risk of death and an 84% lower risk of heart attack.
- Adults taking SGLT2 also had a 67% lower risk of having another stroke.
- All of the reduced risks noted were present even when the researchers accounted for other factors that may have influenced or increased some patients’ risk. These included age, gender, smoking status, hypertension status, type 2 diabetes status, peripheral arterial disease, hyperlipidemia, chronic kidney disease, and history of heart attack or history of heart failure.
- Over the entire study period, the death rate among stroke survivors who received either GLP-1 or SGLT2 was 11.8%, compared with 54% among patients who received neither class of drugs. The rate of heart attacks among patients who received any drug was also 1.5%, compared with 6.1% among patients who did not receive any class of drug.
- The rate of another stroke was similar between patients who received and received no drug, at about 6%.
“When we compared multiple variables, we could still conclude that treatment with any drug was associated with a lower risk of recurrent stroke, even though the rate was similar between patients who received and did not receive any drug,” Sheffeh said. He noted that the drugs significantly reduced the risk of recurrent stroke in an analysis that compared multiple variables, including patients’ risk factors for recurrent stroke—age, gender, hypertension status, type 2 diabetes status, peripheral artery disease, and a history of heart attack or heart failure . However, the risk of recurrent stroke was not significantly lower in an analysis comparing drug use with recurrent stroke and no additional variables.
“Potential protective effects of the drugs were hidden because those in the treatment group may have more high-risk characteristics than patients taking no drug, obscuring any protective effect. What multivariate adjustment does is take these differences into account and to tease out any independent effect,” Shefeh said. “The study results are consistent with other research on the preventive role of these drugs against cardiovascular disease in people with obesity or heart failure’.
The researchers also conducted a subanalysis of patients who took the drugs for at least six months to confirm whether the drugs’ association with a lower risk of heart attack, recurrent stroke, and death could be attributed to the drugs. The results were similar to those of the original study: the drugs were associated with a lower risk of heart attack, recurrent stroke and death, Sheffeh noted.
Background and study details:
- The study included health data on 7,044 adults hospitalized for acute ischemic stroke between January 2000 and June 2022 in the Rochester Epidemiology Project. The database collects data from a partnership of clinics, hospitals and other medical facilities, including those of the Mayo Clinic, Olmstead Medical Center, Olmsted County Public Health Services or Zumbro Valley Health Center in Minnesota, as well as the Mayo Clinic Sealth System in Wisconsin.
- The participants were on average 72 years old. 52% identify as male and 48% identify as female. 94% identify as white adults, 1.5% as black adults, 1.5% as Asian adults, and 3% as “other” race adults.
Limitations of the study include that the analysis was conducted on health data for people treated in one US health system and that most patients in the analysis were white and from one geographic region, meaning the results may not apply to people living in other places or people of other races or ethnicities. In addition, the database did not show why patients were prescribed either drug, although 93 percent of patients who received either drug had type 2 diabetes, Sheffeh noted. The researchers were also unable to assess the burden that stroke had on each patient because this information was not available in the database.
Stroke is the leading cause of disability and the fifth leading cause of death in the US Ischemic strokes, which account for about 85% of all strokes, are caused by a lack of blood flow to the brain due to a clot. This occurs when a vessel that supplies blood to the brain becomes blocked by plaque or fatty deposits within the vessel wall. Plaque can either cause blood vessels to narrow, which blocks blood flow, or cause a clot to break off in another part of the body and travel to smaller vessels near the brain, where it causes a blockage.
“For several years, we have seen from randomized controlled trials that SGLT2 inhibitors and GLP-1 receptor agonists have the ability to reduce the risk of cardiovascular disease, including stroke, heart attack, and death. These new findings are consistent with what we would expect and we have seen that these effects are evident in patients with type 2 diabetes and obesity and in obese patients without type 2 diabetes,” he said. Cheryl Bushnell, MD, MHS, FAHA, professor and vice chair for research in the department of neurology at Wake Forest University School of Medicine in Winston-Salem, North Carolina.
Bushnell is chair of the writing group for the Society’s 2024 Guideline for Primary Stroke Prevention, which details a variety of prevention strategies for people without a prior history of stroke. The new guideline provides evidence-based recommendations for strategies to support brain health and prevent stroke throughout a person’s lifetime by improving healthy lifestyle behaviors and preventive care.
Bushnell also noted the ability of GLP-1 receptor agonists to lower blood pressure and reduce plaque formation associated with atherosclerosis, a risk factor for heart attack and stroke. “Another mechanism that could be very important to this current study is that GLP-1 receptor agonists can actually reduce platelet aggregation, and that in itself could reduce the risk of thrombosis and lead to lower stroke risk,” he said. he said. “We need a clinical trial to know if these SGLT2 inhibitors and GLP-1 receptor agonists could actually change practice, how we can help patients prevent a second or recurrent stroke. These drugs may be very important, however, we don’t have that data yet.”
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