JPAD study: Mixed benefits of low-dose aspirin in healthy Type 2 diabetics
MedWire News: Low-dose aspirin as primary prevention offers a nonsignificant 20% relative reduction in the risk for atherosclerotic events in patients with Type 2 diabetes, the JPAD study indicates.
Although the trial’s primary endpoint was neutral, secondary analyses uncovered significant benefits associated with low-dose aspirin. Benefits included the prevention of atherosclerotic events in the over-65s and a reduced risk for fatal coronary and cerebrovascular events in the entire cohort. Furthermore, these benefits were achieved without an increased risk for hemorrhagic stroke.
The JPAD (Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes) trial was presented by Hisao Ogawa (Kumamoto University, Japan) at the American Heart Association 2008 Scientific Sessions in New Orleans, Louisiana and published simultaneously online in the Journal of the American Medical Association.
JPAD was the largest primary prevention trial of aspirin in diabetic patients, said Ogawa. It was performed against a background of clinical guidelines recommending aspirin for primary prevention of cardiovascular events in patients with Type 2 diabetes, despite limited evidence to support this advice.
The trial enrolled 2539 Japanese patients aged 30–85 years with Type 2 diabetes and without atherosclerotic or cardiac disease. They were randomized to low-dose aspirin (81 or 100 mg/day) or no aspirin and followed-up for a median of 4.37 years.
The primary endpoint was any atherosclerotic event, a composite of sudden death; death from coronary, cerebrovascular, and aortic causes; nonfatal acute myocardial infarction; unstable angina; new-onset exertional angina; nonfatal ischemic and hemorrhagic stroke; transient ischemic attack; or nonfatal aortic and peripheral vascular disease. Endpoint events were assessed in a blinded manner.
During the study there were 68 atherosclerotic events in the aspirin group and 86 in the nonaspirin group. This event rate was much lower than expected, said Ogawa, causing the trial to be severely underpowered.
For the primary endpoint, the hazard ratio (HR) for aspirin was 0.80, a nonsignificant result (p=0.16).
Of the secondary endpoints, one was positive and favored aspirin: the combination of fatal coronary and cerebrovascular events (HR=0.10; p=0.0037). However, the 95% confidence interval was wide (0.01–0.79), indicating the need for further studies to validate this result.
In a subgroup analysis, low-dose aspirin was associated with a significant reduction in atherosclerotic events in patients aged ≥65 years (HR=0.68; p=0.047) but not in younger patients (HR=1.0).
Aspirin was well tolerated, with no significant increase in the composite of hemorrhagic stroke and severe gastrointestinal bleeding. The HR for all-cause mortality was 0.90 (p=0.67).
“Our findings need to be interpreted in the context of the low incidence of atherosclerotic disease in Japan,” said Ogawa. “We conclude that aspirin as primary prevention is beneficial at least for fatal heart attack and fatal stroke in our entire study and for all atherosclerotic heart disease among those aged 65 and over.”
He added that the study supports the safety of using aspirin for primary prevention of cardiovascular events in patients with Type 2 diabetes.
By Joanna Lyford