Aspirin: Heartbeat versus Bleeding

Whether aspirin should be used to prevent a cardiovascular event remains uncertain. According to the latest studies, the advantages of avoiding severe vascular events are largely offset by the increased risk of bleeding.

Recommendation for primary prevention of cardiovascular events is unclear

Whether aspirin should be used to prevent a cardiovascular event remains uncertain. According to the latest studies, the advantages of avoiding severe vascular events are largely offset by the increased risk of bleeding.

Aspirin has become well established in the acute treatment and secondary prevention of coronary and cerebrovascular diseases. More than 200 studies with 200,000+ patients support the use of low-dose aspirin. However, the use of aspirin in the primary prevention of these coronary and cerebrovascular events remains controversial, and the main guidelines for the use of low-dose aspirin are contradictory in this environment. It is also unclear whether aspirin should routinely be prescribed as primary prevention in diabetic patients, who generally have an increased risk of heart attacks and strokes, in order to prevent a first cardiovascular event. Post-hoc analyses of selected randomized aspirin studies also indicate a reduction in cancer risk, particularly in gastrointestinal cancer. However, this could not be confirmed by the ARRIVE and ASCEND studies presented for the first time at the ESC 2018.

ASCEND and diabetes: 12% risk reduction versus 29% risk increase in severe bleeding

Diabetes is common and several of its patients have no cardiovascular disease. Whether they should nevertheless be treated with aspirin to prevent the first event is uncertain. The randomized placebo-controlled ASCEND study with 15,480 patients with diabetes and without basic cardiovascular disease aged ≥ 40, who received 100 mg aspirin daily over a period of 7.4 years, was intended to clarify this issue.

The results of the study are precarious. Although aspirin significantly reduces the risk of severe vascular events by 12%, it increases the risk of severe bleeding by 29%. The absolute advantages of avoiding severe vascular events were thus largely offset by the increased risk of bleeding. There was no group where the benefits clearly outweighed the risks. "This is an important finding with implications for many millions of people who have diabetes but have not had cardiovascular events," said Professor Jane Armitage, Principal Investigator at the Nuffield Department of Population Health of the University of Oxford, UK, and co-author of the study.

Most ASCEND participants were treated with statins and blood pressure treatments with good blood sugar control. For diabetics treated with statins, there was no additional benefit from aspirin. Freek W. A. Verheugt, Professor of Cardiology at the Heart-Lung Centre of the University Medical Centre of Nijmegen, explains that statins may destroy the effect of aspirin. In addition, aspirin did not reduce the risk of gastrointestinal or other cancers, and no obvious effect was observed even after prolonged follow-up.

ARRIVE and the 10-year CV disease risk: reduction not significant, bleeding risk high

The ARRIVE study attempted to investigate the role of low-dose aspirin in the primary prevention of cardiovascular events in patients with moderate cardiovascular risk (10-20%, 10-year coronary heart disease risk based on European and US risk measurements) with the aim of assessing safety versus efficacy.

The randomized, double-blind, placebo-controlled, multicenter study with primary care was conducted in 7 countries (Germany, Italy, Ireland, Poland, Spain, Great Britain, and the USA). A total of 12,546 (mean age 64 years; almost 30% women) patients were randomly treated with aspirin (N = 6,270) or placebo (N = 6,276). The median follow-up time was 60 months. Follow-up was carried out by family doctors during personal visits, by telephone calls and by obtaining medical records, which were submitted for assessment.

The results showed that treatment with aspirin did not significantly reduce the incidence of cardiovascular events in the study population (HR 0.96; 95% CI 0.81-1.13; P = 0.60). Gastrointestinal bleeding (mostly mild) occurred in 61 (97%) patients in the aspirin group versus 29 (0.46%) in the placebo group. There was no difference in lethal bleeding rates between aspirin and placebo. The safety results were also consistent with previous primary prevention studies which showed an increased risk (HR 2.11, 95% CI 1.36-3.28; P = 0.0007) at a very low rate of predominantly mild gastrointestinal bleeding with low doses of aspirin. No effects on short-term cancer rates were observed, but the duration of follow-up was not sufficient to evaluate longer-term outcomes. In the ARRIVE study, it can also be summarized that the use of aspirin in the primary prevention of cardiovascular events is not clearly recommended.

Key Issues

The use of aspirin remains a decision that should be made in close consultation between physician and patient, as cardiovascular events must be weighed against bleeding risks, patient preferences, costs, and other factors.

Diabetics can also be expected to benefit from proven safe treatments such as statins and antihypertensive drugs that adequately protect against heart attacks and strokes without causing severe side effects such as bleeding. Both studies also clearly showed that cancer risk is not reduced in patients with diabetes or in patients with moderate risk of cardiovascular disease.

The current clinical guidelines vary in their recommendations on the use of aspirin for primary prevention, as there was a previous lack of clear evidence. The results of the ASCEND and ARRIVE studies now provide more clarity.