PracticeUpdate Diabetes March 2019

TOP STORIES 2018 5

The ASCEND Study By Richard E. Pratley MD

For years, diabetes has been described as a “cardiovascular disease equivalent” based upon evidence from several observational studies and clinical trials demonstrating that the risk for cardiovascular events is comparable among patients with diabetes who do not have prior cardiovascular disease (CVD) and those without diabetes who have had a prior CV event. S ince daily aspirin has been shown to decrease the risk of recurrent events among patients with CVD, it is rea-

prevention of CVD in patients with diabetes. While the ASCEND study providesmore pre- cision around the benefit/risk ratio, it is not likely to change this recommendation. As Dr. Paul Ridker stated in an accompanying editorial “For secondary prevention, in which risk is determined largely by the extent of ath- erosclerotic disease, the benefits of aspirin outweigh the risks of bleeding. In contrast, for primary prevention, in which risk is deter- mined largely by age and the presence or absence of diabetes, the benefit–risk ratio for prophylactic aspirin in current practice is exceptionally small.” 4 References 1. Belch J, MacCuish A, Campbell I, et al. The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: Factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008;337:a1840-a1840. 2. Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patientswith type 2 diabetes: a randomized controlled trial. JAMA 2008;300:2134-2141. 3. ASCEND Study Collaborative Group, Bowman L, MafhamM, Wallendszus K, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018 Oct 18;379(16):1529-1539. 4. Ridker PM. Should aspirin be used for primary prevention in the post-statin era? N Engl J Med 2018 Oct 18;379(16):1572-1574. www.practiceupdate.com/c/77381

sight-threatening bleeding event in the eye, gastrointestinal bleeding, or other seri- ous bleeding) occurred in more patients assigned to aspirin (314 subjects, 4.1%) than placebo (245 subjects, 3.2%) for a rate ratio of 1.29 (95% CI, 1.09 to 1.52; P = .003). Most major bleeding events were gastro- intestinal/extracranial in nature. Intracranial hemorrhage events were relatively infre- quent and not significantly different in patients randomized to aspirin vs. placebo (55 participants, 0.7% vs 45 participants, 0.6%, respectively, RR 1.22, 95% CI 0.82– 1.81). Furthermore, fatal bleeding events were rare and occurred with a similar inci- dence among subjects assigned to aspirin (19 participants, 0.2%) vs. placebo (16 par- ticipants, 0.2%). All-cause mortality was not significantly different between groups (748 [9.7%] vs 792 [10.2%] in subjects assigned to aspirin vs. placebo, respectively; RR 0.94 [95% CI 0.88–1.04]). Finally, no difference in the incidence of gastrointestinal tract can- cer was noted between groups. How do these data change clinical practice? For patients with diabetes but no evidence of CVD, the benefit of aspirin to decrease the risk of vascular events needs to be balanced against the increased risk of major bleed- ing which is similar in magnitude. Currently, aspirin is not recommended for the primary

sonable to ask whether aspirin would also decrease the risk in those with diabetes who have a comparably high CVD risk. To date, the data have been mixed. Two small trials, one in Scotland and one in Japan, did not provide strong evidence for the use of aspirin in the primary prevention of CVD among patients with diabetes. 1,2 To address this important knowledge gap, investigators from the UK undertook the ASCEND study, a large pragmatic trial test- ing the effects of aspirin for the primary prevention of CVD in patients with diabe- tes. 3 A group of 15,480 adults with diabetes (94% of whom had type 2 diabetes), but no evidence of CVD, were randomized to receive aspirin (100 mg daily) or matching placebo. Subjects were followed for a mean of 7.4 years. The primary endpoint (myocar- dial infarction, stroke or transient ischemic attack, or death from any vascular cause) occurred in 658 subjects (8.5%) assigned to aspirin vs. 743 (9.6%) subjects assigned to placebo (rate ratio [RR], 0.88; 95% confi- dence interval, 0.79 to 0.97; P = .01). Counterbalancing this benefit, major bleeding events (intracranial hemorrhage,

VOL. 3 • NO. 1 • 2019