Therapy shows neutral CV benefit, increases bleeding risk in type 2 diabetes.
According to data presented at the American Heart Association Scientific Sessions, in patients with type 2 diabetes, low-dose aspirin therapy did not affect the risk for CV events, but increased risk for gastrointestinal bleeding compared with patients not assigned aspirin therapy,
A debate between Ph. Gabriel Steg, MD, professor of cardiology at Paris Diderot University and director of the coronary care unit at Hospital Bichat-Claude Bernard, and Robert A. Harrington, MD, the Arthur L. Bloomfield professor of medicine and chairman of the department of medicine at Stanford University, closed with the clinicians sharing the same sentiment: “We don’t know the answer on the benefits or risks for taking low dose aspirin for patients with type 2 diabetes.”
“It sounds like aspirin is a great idea for diabetics because it is cheap, we know it works in preventing CVD in secondary prevention, and there is some reasonable evidence in primary prevention,” Steg said.
Highlighting results of a meta-analysis of randomized controlled trials by De Berardis and colleagues published in BMJ, Steg said, “The bottom line is, in diabetics, there is no evidence that aspirin provides a substantial clinical benefit in preventing CV events.”
He also discussed two large ongoing trials, ASCEND and ACCEPT-D, that continue to explore the value of aspirin in this population. The researchers are looking at 15,000 patients and 5,170 patients, respectively, with type 1 or type 2 diabetes and no evidence of atherothrombosis.
Steg added that, “The mere fact that trials are ongoing exemplifies that we don’t really have an answer on the benefit of aspirin.”
Giving aspirin to patients only once per day could be one reason it doesn’t work, Steg said, because the time of residence in plasma is short and the population has very increased platelet turnover. He added that, “If you take aspirin in the morning, there will be aspirin in your bloodstream for a few hours; all the platelets that meet aspirin will be irreversibly acetylated and inhibited…By noon, you may start producing more platelets if you are a diabetic; therefore, in the afternoon and evening you will have a rebound aggregation of platelets.”
Evidence shows platelet inhibition in patients with diabetes yields better outcomes, Steg said. He pointed to the CURE trial, which looked at MI, stroke or vascular death with clopidogrel added to aspirin in patients with ACS and type 2 diabetes, and the CHARISMA trials, which broke down efficacy by overall population, primary prevention and secondary prevention.
A team of researchers in Japan analyzed data on 1,621 patients with type 2 diabetes and no pre-existing CVD who participated in the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JAPD), a randomized, open-label, standard-care controlled trial examining the benefit of low-dose aspirin. The mean age at baseline was 65 years, 55% were men and the mean duration of diabetes was 7 years. The study was initiated in 2002; 2,160 patients who retained their original allocation were included in the per-protocol analysis.
Patients were assigned to receive aspirin therapy (81 mg or 100 mg daily; n = 992) or no aspirin (n = 1,168). After the trial ended in April 2008, researchers followed patients biennially until July 2015 (mean, 10.3 years) without changing previously assigned therapies. The original JAPD trial and follow-up period constitute the JAPD2 study.
The primary endpoints were time to first occurrence of CV death, fatal or nonfatal CAD, fatal or nonfatal stroke and peripheral vascular disease.
During follow-up, 317 CV events occurred: 151 in the aspirin group and 166 in the non-aspirin group. Researchers observed no between-group differences for the primary endpoints; the HR for aspirin therapy was 1.14 (95% CI, 0.91-1.42). Results persisted after adjustment for age, sex, glycemic control, kidney function, smoking status, hypertension and dyslipidemia (HR = 1.04; 95% CI, 0.83-1.3).
Within the cohort, 25 patients in the aspirin group and 12 patients in the non-aspirin group developed GI bleeding. There were no between-group differences for hemorrhagic stroke.
“The post-trial follow-up of the JPAD trial, comprising a mean observation during and after the trial of over a decade, indicated that long-term therapy with low-dose aspirin is not associated with lower cardiovascular events in Japanese patients with type 2 diabetes in a primary prevention setting,” Yoshihiko Saito, MD, PhD, from the first department of internal medicine at Nara Medical University in Nara, Japan, and colleagues wrote in a study abstract. “Low-dose aspirin therapy was associated with a significantly increased incidence of gastrointestinal bleeding.”
- The benefits of using low-dose aspirin, alone or with a platelet inhibitor, for the treatment of patients with diabetes at high-risk for CVD are still unclear.
- It remains unclear as to whether low-dose aspirin is enough or if low-dose aspirin should even be considered as a primary prevention strategy.
- More studies are needed to make a conclusion whether patients with diabetes should be on low-dose aspirin.
Saito Y, et al. Presentation 318 – Ancel Keys Memorial Lecture: Lifestyle and Medical. Presented at: American Heart Association Scientific Sessions; Nov. 12-16, 2016; New Orleans.