Does Low-Dose Aspirin Reduce Risk of Atherosclerotic Events?
Does Low-Dose Aspirin Reduce Risk of Atherosclerotic Events?
Okada S, Morimoto T, Ogawa H, et al, for the Japanese Primary Prevention of Artherosclerosis with Aspirin for Diabetes (JPAD) Trial Investigators
Diabetes Care. 2011;34:1277-1283
The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial was a randomized, controlled, open-label trial in which 2539 patients with type 2 diabetes and no previous cardiovascular disease (CVD) were randomly assigned to either the low-dose aspirin group (81 or 100 mg daily) or to the no-aspirin group. In this subanalysis, all participants were classified into 1 of 3 subgroups according to the diabetes management at baseline: insulin, oral antihyperglycemic agents (OHA), or diet alone. Patients with insulin and OHA combination therapy were included in the insulin group. The diet-alone group consisted of patients who used neither insulin nor OHAs. The primary endpoint was the occurrence during the follow-up period of any atherosclerotic event, which was a composite of death from coronary, cerebrovascular, or aortic causes; nonfatal acute myocardial infarction; unstable angina; newly developed exertional angina; nonfatal ischemic and hemorrhagic stroke; transient ischemic attack; and nonfatal aortic and peripheral vascular disease. The median follow-up period was 4.4 years.
Three hundred twenty-six patients were treated with insulin, while 1750 were with OHAs, and 463 with diet alone. The incidence of atherosclerotic events was 26.6 cases per 1000 person-years in the insulin, 14.6 in the OHA, and 10.4 in the diet-alone groups. Low-dose aspirin did not affect the incidence of atherosclerotic events in the insulin group (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.60-2.40) or in the OHA group (HR, 0.84; 95% CI, 0.57-1.24). However, in the diet-alone group, low-dose aspirin significantly reduced atherosclerotic events (HR, 0.21; 95% CI,0.05-0.64) despite the low atherosclerotic event rate. The number of patients who suffered gastrointestinal bleeding was 1 in the insulin group (assigned to aspirin) and 7 in the OHA group (4 assigned to aspirin). No patients experienced gastrointestinal bleeding in the diet-alone group. Hemorrhagic stroke events were also rare and did not differ by aspirin assignment in any diabetes treatment group.
Based on the results of JPAD and another randomized trial of aspirin for primary CVD prevention in patients with diabetes, the American Diabetes Association, American Heart Association, and the American College of Cardiology currently recommend low-dose aspirin only for patients with diabetes who have a 10-year CVD risk of more than 10%. Furthermore, aspirin is specifically not recommended for those with 10-year CVD risk under 5%, because the low benefit is likely to be outweighed by the risks for significant bleeding. The current subanalysis of JPAD, however, found that only those patients in the diet-alone group benefitted from low-dose aspirin therapy. Despite being at the lowest CVD risk, aspirin reduced CVD events by 79% in these patients and generated no bleeding events. So what do we make of this? The authors speculate that low-dose aspirin might be most beneficial in early clinical stages of diabetes (ie, prior to the need for pharmaceutical management of hyperglycemia). That is a testable hypothesis. It should also be noted that the diet-alone group was not necessarily at low risk for CVD; the mean age of patients was 65 years and 72% were hypertensive. Thus, these findings may not be contrary to current guidelines. So, while this subanalysis of JPAD is intriguing, the answer to whether aspirin should be used for primary CVD prevention in patients with diabetes remains a definite maybe.
Abstract
Differential Effect of Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Diabetes Management: A Subanalysis of the JPAD Trial
Okada S, Morimoto T, Ogawa H, et al, for the Japanese Primary Prevention of Artherosclerosis with Aspirin for Diabetes (JPAD) Trial Investigators
Diabetes Care. 2011;34:1277-1283
Study Summary
The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial was a randomized, controlled, open-label trial in which 2539 patients with type 2 diabetes and no previous cardiovascular disease (CVD) were randomly assigned to either the low-dose aspirin group (81 or 100 mg daily) or to the no-aspirin group. In this subanalysis, all participants were classified into 1 of 3 subgroups according to the diabetes management at baseline: insulin, oral antihyperglycemic agents (OHA), or diet alone. Patients with insulin and OHA combination therapy were included in the insulin group. The diet-alone group consisted of patients who used neither insulin nor OHAs. The primary endpoint was the occurrence during the follow-up period of any atherosclerotic event, which was a composite of death from coronary, cerebrovascular, or aortic causes; nonfatal acute myocardial infarction; unstable angina; newly developed exertional angina; nonfatal ischemic and hemorrhagic stroke; transient ischemic attack; and nonfatal aortic and peripheral vascular disease. The median follow-up period was 4.4 years.
Three hundred twenty-six patients were treated with insulin, while 1750 were with OHAs, and 463 with diet alone. The incidence of atherosclerotic events was 26.6 cases per 1000 person-years in the insulin, 14.6 in the OHA, and 10.4 in the diet-alone groups. Low-dose aspirin did not affect the incidence of atherosclerotic events in the insulin group (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.60-2.40) or in the OHA group (HR, 0.84; 95% CI, 0.57-1.24). However, in the diet-alone group, low-dose aspirin significantly reduced atherosclerotic events (HR, 0.21; 95% CI,0.05-0.64) despite the low atherosclerotic event rate. The number of patients who suffered gastrointestinal bleeding was 1 in the insulin group (assigned to aspirin) and 7 in the OHA group (4 assigned to aspirin). No patients experienced gastrointestinal bleeding in the diet-alone group. Hemorrhagic stroke events were also rare and did not differ by aspirin assignment in any diabetes treatment group.
Viewpoint
Based on the results of JPAD and another randomized trial of aspirin for primary CVD prevention in patients with diabetes, the American Diabetes Association, American Heart Association, and the American College of Cardiology currently recommend low-dose aspirin only for patients with diabetes who have a 10-year CVD risk of more than 10%. Furthermore, aspirin is specifically not recommended for those with 10-year CVD risk under 5%, because the low benefit is likely to be outweighed by the risks for significant bleeding. The current subanalysis of JPAD, however, found that only those patients in the diet-alone group benefitted from low-dose aspirin therapy. Despite being at the lowest CVD risk, aspirin reduced CVD events by 79% in these patients and generated no bleeding events. So what do we make of this? The authors speculate that low-dose aspirin might be most beneficial in early clinical stages of diabetes (ie, prior to the need for pharmaceutical management of hyperglycemia). That is a testable hypothesis. It should also be noted that the diet-alone group was not necessarily at low risk for CVD; the mean age of patients was 65 years and 72% were hypertensive. Thus, these findings may not be contrary to current guidelines. So, while this subanalysis of JPAD is intriguing, the answer to whether aspirin should be used for primary CVD prevention in patients with diabetes remains a definite maybe.
Abstract