NARA, JAPAN — Low-dose aspirin failed to reduce cardiovascular events in a primary-prevention setting in Japan, according to results of a 10-year follow-up study.
"For the primary prevention of CV events in [diabetes] patients, we should be looking for another strategy," Dr Yoshihiko Saito (Nara Medical University, Japan) told heartwire from Medscape.
Saito and colleagues conducted the follow-up analysis of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial. That trial involved 2539 patients with type 2 diabetes and no preexisting CV disease who were randomized to either aspirin (81 or 100 mg) daily or no aspirin.
Median follow-up came to 10.3 years for 1621 (64%) patients followed until a CV event occurred or until July 2015. A total of 2160 (85%) participants retained their original trial allocation after the study ended in 2008.
Mean patient age was 65 years at baseline, and 55% of patients were males. Mean body-mass index was 24 and mean duration of diabetes was 7.1 years.
Researchers accounted for 317 CV events in the overall population, 151 in the aspirin group and 166 in the no-aspirin group. The CV events included 125 coronary artery events, 133 cerebrovascular events, and 45 vascular events.
They found no significant between-group difference for the primary end point of CV events, including sudden death, coronary artery disease, stroke, and peripheral artery disease.
Low-dose aspirin did not reduce the number of CV events in the per-protocol cohort (hazard ratio [HR] 1.14, 95% CI 0.91–1.42), or after adjustment for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia (HR 1.04, 95% CI 0.83–1.30), or after sensitivity analysis (HR 1.01, 95% CI, 0.82–1.25).
Hemorrhagic events occurred in 80 (6%) in the aspirin group and in 67 (5%) in the no-aspirin group (P=0.2). Gastrointestinal bleeding occurred more often in the aspirin group (25 events, 2%) than the no-aspirin group (12 events, 0.9%, P=0.03).
Researchers observed no significant differences in hemorrhagic stroke.
The researchers wrote that one possible reason for the negative aspirin findings was the evidence for aspirin benefit for primary prevention was documented in the 20th century prior to the availability of intense-dose statins.
"Our results are somewhat generalized to other countries, because the effect of aspirin on reducing the hazard ratio of CV events is similar in the JPAD trial and other trials," Saito told heartwire.
Dr Darren K McGuire (University of Texas Southwestern, Dallas) told heartwire that the new analysis "supports an evolving literature on what we thought at one point was one size fits all for patients with type 2 diabetes. We've made a pretty hasty retreat over the past 10 to 12 years in the guidelines based on the evidence that has emerged, largely driven by this original randomized clinical trial, the JPAD trial.
"I think this is important for two reasons," he continued. "One, the original trial suggested a potential interaction or heterogeneity of the effect of aspirin benefiting the elderly. Based on that, I think even in Japan there was continued treatment of the elder patients with type 2 diabetes for primary prevention, but this longer-term follow-up actually completely undoes that heterogeneity. So there's no subset that appears to benefit for primary prevention now.
"The second thing I think is important is the guidelines across the Atlantic have differed a bit. In Europe now the most recent guidelines don't recommend aspirin for primary prevention in any patient with type 2 diabetes, except a consideration for the very highest-risk patients, whereas in the US the guidelines continue to endorse aspirin for primary prevention given that the patients achieve a certain age and have at least one other risk factor," he said.
"This longer-term follow-up from JPAD suggests that the European guidelines may well be the more appropriate interpretation of the data, and perhaps the American guidelines should reconsider whether aspirin is justified in any patients with type 2 diabetes for primary prevention," he added.
"What was remarkable for me from this study was the incredibly low event rate for major GI bleeding. Although relative risk is increased twofold higher on aspirin, the absolute risk is really quite small for a major bleeding event, and there was no intracranial hemorrhage," he said.