BACKGROUND: Diabetes mellitus is associated with an increased risk of cardiovascular events. Aspirin use reduces the risk of occlusive vascular events but increases the risk of bleeding; the balance of benefits and hazards for the prevention of first cardiovascular events in patients with diabetes is unclear.
METHODS: We randomly assigned adults who had diabetes but no evident cardiovascular disease to receive aspirin at a dose of 100 mg daily or matching placebo. The primary efficacy outcome was the first serious vascular event (i.e., myocardial infarction, stroke or transient ischemic attack, or death from any vascular cause, excluding any confirmed intracranial hemorrhage). The primary safety outcome was the first major bleeding event (i.e., intracranial hemorrhage, sight-threatening bleeding event in the eye, gastrointestinal bleeding, or other serious bleeding). Secondary outcomes included gastrointestinal tract cancer.
RESULTS: A total of 15,480 participants underwent randomization. During a mean follow-up of 7.4 years, serious vascular events occurred in a significantly lower percentage of participants in the aspirin group than in the placebo group (658 participants [8.5%] vs. 743 [9.6%]; rate ratio, 0.88; 95% confidence interval [CI], 0.79 to 0.97; P=0.01). In contrast, major bleeding events occurred in 314 participants (4.1%) in the aspirin group, as compared with 245 (3.2%) in the placebo group (rate ratio, 1.29; 95% CI, 1.09 to 1.52; P=0.003), with most of the excess being gastrointestinal bleeding and other extracranial bleeding. There was no significant difference between the aspirin group and the placebo group in the incidence of gastrointestinal tract cancer (157 participants [2.0%] and 158 [2.0%], respectively) or all cancers (897 [11.6%] and 887 [11.5%]); long-term follow-up for these outcomes is planned.
CONCLUSIONS: Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease at trial entry, but it also caused major bleeding events. The absolute benefits were largely counterbalanced by the bleeding hazard. (Funded by the British Heart Foundation and others; ASCEND Current Controlled Trials number, ISRCTN60635500 ; ClinicalTrials.gov number, NCT00135226 .).
|Family Medicine (FM)/General Practice (GP)|
|General Internal Medicine-Primary Care(US)|
Aspirin for primary prevention has not been consistently shown to be of benefit. Although aspirin is recommended for primary prevention by the ADA, many have questioned this. This study shows that it is beneficial for patients with diabetes without other risk factors, but as with all other aspirin studies, there is also an increase in major bleeding. This study provides solid data to use in discussing this issue with our patients.
This study answers a question that faces most outpatient American primary care providers on nearly a daily basis. The study was a factorial design with 1 gram n-3 fatty acid daily or placebo, but those results are reported separately. Looking at the actual event rates across the 15,480 randomized patients, those taking 100 mg aspirin had 85 fewer serious vascular events at the cost of 69 more major bleeding events. Figure 3 in the article suggests that the overall decrease in cardiovascular mortality is negligible along with a very small increase in fatal bleeding among those patients who were randomized to aspirin even in the subgroup with a >=10% five-year risk of a serious vascular event at baseline. The information is clinically useful and should help providers and patients with diabetes make more informed decisions about taking aspirin for cardiovascular primary prevention.
Great article to feature. Gives good, practical information to patients. "You are 1% less likely to have an event and 1% more likely to have a major bleed. What would you like to do?". Makes shared decisions possible. What I don't like is the use of terms like "low-, moderate-, and high-risk". Just tell us what the actual risk is (which they do in the footnotes).
This is a very important trial that is well done and addresses clinically important questions. The results show that the balance of benefit and risk for ASA for primary prevention are close. In those at highest risk of cardiovascular events, the benefit seems to be worth the risk. For those at the lower end of the risk spectrum, ASA doesn't seem to be worthwhile.