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Low-dose aspirin for primary prevention of vascular events in type 2 diabetes

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Low-dose aspirin for primary prevention of vascular events in type 2 diabetes

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27.09.2018 • Sonuncu dəyişiklik 27.09.2018
Editors

Primary prevention with low-dose aspirin appears to be less (and only marginally) effective in patients with type 2 diabetes than secondary prevention in patients with cardiovascular disease compared with placebo. The effect may be confined to elderly individuals. However, treatment benefits appear to be counterbalanced by increased the risk of bleeding.

The quality of evidence is downgraded by inconsistency (unexplained variability in results).

Low-dose aspirin is suggested for the primary prevention of cardiovascular events in elderly diabetic patients with cardiovascular risk factors.The recommendation is weak because of uncertain trade-off between benefits and harms. A Japanese multicenter, prospective, randomized, open-label trial (JPAD) on low-dose aspirin (81 or 100 mg) for the primary prevention of cardiovascular events in diabetes included 2 539 subjects with type 2 diabetes (median follow-up 4.37 years). There were 68 atherosclerotic events in the aspirin group and 86 in the nonaspirin group (13.6 per 1000 person-years vs. 17.0 per 1000 person-years; HR 0.80, 95% CI 0.58 to 1.10). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in 1 patient (stroke) in the aspirin group and 10 patients (5 fatal myocardial infarctions and 5 fatal strokes) in the nonaspirin group (HR 0.10, 95% CI 0.01 to 0.79). No difference in total mortality was observed (aspirin vs. nonaspirin HR 0.90, 95% CI 0.57 to 1.14). In a subgroup analysis restricted to individuals aged 65 years or older, a significant reduction in the incidence of the primary end point was observed in the aspirin group compared with controls (HR 0.68, 95% CI 0.46 to 0.99). There were 12 gastrointestinal bleeding events and 8 retinal haemorrhage events in the aspirin group and the corresponding numbers were 4 and 4 in the nonaspirin group. 4 patients in the aspirin group and none in the control group required blood transfusion. There was no significant difference in the composite of hemorrhagic stroke and significant gastrointestinal bleeding between the aspirin and nonaspirin groups.

The ASCEND study included 15 480 patients with diabetes (94% type 2 diabetes) but no evident cardiovascular disease. Majority of participants had statins and blood pressure–lowering therapy. They were randomized 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). During a mean follow-up of 7.4 years, there were less serious vascular events in the aspirin group than in the placebo group (658 participants [8.5%] vs. 743 [9.6%]; rate ratio, 0.88, 95% 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 (RR 1.29, 95% CI 1.09 to 1.52; P=0.003), with most of the excess being gastrointestinal bleeding and other extracranial bleeding. The absolute benefits were largely counterbalanced by the bleeding hazard (91 patients would need to be treated to avoid a serious vascular event over a period of 7.4 years, and 112 to cause a major bleeding event). There was no significant difference between the aspirin group and the placebo group in the incidence of gastrointestinal tract cancer (secondary outcome) (157 participants [2.0%] and 158 [2.0%], respectively) or all cancers (897 [11.6%] and 887 [11.5%]).

The PPP (Primary Prevention Project) trial included a subgroup of 1031 people with diabetes aged >/=50 years and without a previous cardiovascular event. In diabetic patients, aspirin treatment was associated with a nonsignificant reduction in the main end point of cardiovascular death, stroke, or myocardial infarction (RR 0.90, 95% CI 0.50 to 1.62) and in total cardiovascular events (RR 0.89, 95% CI 0.62-1.26) and with a nonsignificant increase in cardiovascular deaths (RR 1.23, 95% CI 0.69 to 2.19). In nondiabetic subjects, RRs for the main end point, total cardiovascular events, and cardiovascular deaths were 0.59 (0.37-0.94), 0.69 (0.53-0.90), and 0.32 (0.14-0.72), respectively.

The meta-analysis of the Antithrombotic Trialists' Collaboration on the efficacy of antiplatelet therapy in the prevention of major cardiovascular events in high risk patients (with acute or previous vascular disease or some other predisposing condition) showed a clear benefit for the entire population of more than 140 000 patients (reduction of the combined outcome of any serious vascular event by about one quarter), but no statistically significant benefit was documented in the subgroup of about 5000 diabetic patients (7% risk reduction).

Comment: The quality of evidence is downgraded by imprecise results (wide confidence intervals).

The following decision support rules contain links to this evidence summary:

  • Aspirin for patients with type 2 diabetes

Ədəbiyyat

  1. Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A, PPP Collaborative Group. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care 2003 Dec;26(12):3264-72.
  2. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002 Jan 12;324(7329):71-86.
  3. ASCEND Study Collaborative Group.. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med 2018;():.