Antiplatelet Drugs: Weighing Risks and Benefits

Lilian White, MD
Posted on July 7, 2025

Beginning with aspirin, antiplatelet drugs have been in use since the late 1800s. Even before this, willow bark (the plant component aspirin is derived from) is estimated to have been used to treat pain and fevers starting more than 3,500 years ago. A recent AFP article reviewed the Inappropriate Use of Oral Antiplatelet Drugs.

The article notes that over the last 20 years, use of oral antiplatelet medications has risen considerably. This is thought to be due in part from updates in guideline recommendations on the management of ischemic stroke. Other indications for antiplatelet drugs include primary prevention of atherosclerotic cardiovascular disease and colorectal cancer, symptomatic carotid artery and peripheral vascular disease, and coronary artery disease.

Of course, these applications and benefits of antiplatelet medications must be weighed and personalized against the risk of harm to the patient. Common contraindications to use of antiplatelet medications include a thrombocytopenia, a history of intracranial hemorrhage, esophageal varices, and peptic ulcer disease. Treatment with aspirin alone increases the risk of peptic ulcer disease. This risk is increased in patients taking dual antiplatelet therapy (DAPT), and screening for H. pylori is recommended in symptomatic patients.

It is recommended to regularly reassess the appropriateness of antiplatelet medication prescriptions for a patient. Both the risk of major bleeding and the risk of recurrent stroke increase over time, so it is essential to consider patient-specific factors, such as comorbid conditions, in addition to the risk of major bleeding alone when assessing appropriateness. Other factors that increase a patient’s risk of bleeding not included in this calculator include chronic kidney disease; chronic anemia; history of bleeding; history of peptic ulcer disease; H. pylori infection; use of steroids, anticoagulants, or nonsteroidal anti-inflammatory medications; and recent falls. The risk of major bleeding with aspirin alone is approximately 0.6%. The risk of gastrointestinal bleeding appears to be similar between aspirin and clopidogrel (an oral P2Y12 inhibitor) monotherapy. In patients with risk factors for gastrointestinal bleeding, co-therapy with a proton-pump inhibitor is recommended.

Several calculators are available to help assess risk of major bleeding in patients taking antiplatelet medications. The S2TOP-BLEED score may be used to estimate bleeding risk and has been validated for use in patients with noncardioembolic stroke or cardiovascular disease. The S2TOP-BLEED score considers a patient’s age, sex, smoking status, type of antiplatelet regimen (e.g., aspirin alone, aspirin and clopidogrel), prior stroke history, body mass index, blood pressure, history of diabetes, modified Rankin score (i.e., degree of disability), and race [of note, race-based medical decisions are not recommended, as outlined in this AFP article]. A patient’s S2TOP-BLEED score is compared with their age on a table to estimate the patient’s 3-year risk of major bleeding.

DAPT combines aspirin and an oral P2Y12 inhibitor. Current indications for short-term DAPT include following acute coronary syndrome (or related intervention), transient ischemic attack, or stroke. Long-term DAPT is typically not recommended. The DAPT score is validated for estimating bleeding risk in patients following coronary stent placement and consideration of DAPT. In general, a 40% to 50% increased relative risk of major and minor bleeding is found for patients on DAPT compared with those on single antiplatelet therapy. This translates to a 0.6% to 2.0% increased absolute risk of gastrointestinal bleeding.