Low-dose acetylsalicylic acid for primary prevention of cardiovascular disease

Should we routinely offer ASA for primary prevention?

There is not enough robust evidence that the benefits of ASA outweigh the risks. The expected benefit of ASA for primary prevention of CVD is a reduction in fatal and nonfatal MI and stroke.¹ Studies have demonstrated mixed outcomes, including statistically significant reduction of MI and stroke, the occurrence of one without the other, or no benefit in prevention of either.^4–6 Meta-analyses have suggested ASA has little or no benefit for primary prevention.^4–6

The primary risk with ASA therapy is bleeding. Studies have consistently found significant increases in hemorrhaging with daily ASA use, mainly GI bleeding (relative risk = 1.40; 95% CI 1.07 to 1.83).^4–6 The absolute rate of GI bleeding with ASA is 3 per 10 000 in the overall population and the absolute rate of intracranial bleeding is 1 per 10 000.¹

When should we offer ASA for primary prevention?

Acetylsalicylic acid should be offered when the benefits outweigh the risks (ie, it should be offered to patients who are at high risk of cardiovascular events and not at increased risk of bleeding). Patients at high risk of cardiovascular events include men older than 50 years or women older than 60 years with 1 or more of the following important risk factors: smoking, hypertension, dyslipidemia, family history of premature CVD, albuminuria, or atrial fibrillation with a CHADS₂ (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and stroke or transient ischemic attack) score of 0 to 1.^1,7,8 Patients at increased risk of bleeding include those with previous GI bleeding, those with peptic ulcer disease, or those taking concurrent medications that can increase bleeding (eg, anticoagulants, nonsteroidal anti-inflammatory drugs).^1,7,8

Because ASA can reduce the risk of first MI by up to 20%,¹ we can offer ASA for primary prevention for those at high risk of CVD events and low risk of bleeding.

Should we stop ASA in patients who have been using it for primary prevention for many years?

We cannot discontinue ASA without careful consideration. This is not an easy question to answer, as there is not a lot of robust evidence to support one option over another. The guidelines do not advise starting ASA for primary prevention but this might not translate into stopping ASA for primary prevention.

When you discontinue daily ASA, there is a risk of hypercoaguability owing to a rebound increase in platelet aggregability.^9–11 Studies have shown a 3-fold increase in thrombotic events upon discontinuation (highest within 11 days after discontinuation but it can last up to 1 year).^9–11 Patients who have been advised to stop ASA based on the recommendation that ASA should not be started for primary prevention have experienced substantial ASA withdrawal effects, as demonstrated in meta-analyses of data from these patients. Case-control studies have demonstrated that people who had recently stopped ASA had a significantly increased risk of nonfatal MI or death (rate ratio = 1.43; 95% CI 1.12 to 1.84); over 1 year, for every 1000 patients there were 4 more cases of nonfatal MI in patients who discontinued low-dose ASA compared with patients who continued taking ASA.¹⁰

Therefore, we might be introducing harm when we stop ASA. A thorough assessment of risk versus benefit should be conducted.