Aspirin in primary prevention of CVD: The rapidly changing evidence
Aspirin (acetyl salicylic acid) used since 1853, is one of the widely used medications globally for different disease conditions with an estimated production between 50-120 billion pills each year.
Aspirin is recommended in the secondary prevention cardiovascular disease after myocardial infarction. However, the role of Aspirin in primary prevention of cardiovascular disease is less certain. During the past decade the evidence has been less convincing for primary prevention of aspirin for CVD.
Early trials evaluating aspirin for primary prevention, done before the turn of the millennium, suggested reductions in myocardial infarction and stroke (although not mortality), and an increased risk of bleeding. In an effort to balance the risks and benefits of aspirin, international guidelines on primary prevention of cardiovascular disease have typically recommended aspirin only when a substantial 10-year risk of cardiovascular events exists. However, in 2018, three large randomised clinical trials of aspirin for the primary prevention of cardiovascular disease showed little or no benefit and have even suggested net harm. [ARRIVE=aspirin to reduce risk of initial vascular events. ASCEND=a study of cardiovascular events in diabetes. ASPREE=aspirin in reducing events in the elderly.]
American College of Cardiology and American Heart Association released its new guideline in 2019 for primary prevention of CVD, including Aspirin LINK. In essence the recommendation is “Low-dose aspirin might be considered for primary prevention of ASCVD in select higher ASCVD adults aged 40-70 years who are not at increased bleeding risk”
The US Food and Drug Administration (FDA) has never approved the labelling of aspirin for primary prevention of CVD and the European Medicines Agency have not addressed this question.
The 2022 U.S. Preventive Services Task Force (USPSTF) guideline for Aspirin in primary prevention of cardiovascular disease is expected to change significantly from its 2016 guideline because of the changing in current evidence. This change of the USPSTF guideline with the 2019 AHA/ACC guideline on the topic will undoubtedly have a significant effect on prescribing aspirin for primary prevention.
Draft recommendation statement from USPSTF for 2022
Adults ages 40 to 59 years with a 10% or greater 10-year cardiovascular disease (CVD) risk
The decision to initiate low-dose aspirin use for the primary prevention of CVD in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk should be an individual one.
Evidence indicates that the net benefit of aspirin use in this group is small. Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit.
Adults age 60 years or older
The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults age 60 years or older.
*Note: The American College of Cardiology/American Heart Association (ACC/AHA 10-year CVD risk calculator is recommended is LINK to estimate 10-year risk of CVD.
Annual bleeding events in individuals without risk factors for increased bleeding are rare but increases modestly with advancing age. Risk factors for increase bleeding are history of gastrointestinal bleeding risk, history of peptic ulcer disease, male sex, diabetes, liver disease, elevated blood pressure and smoking. Certain medications, including non-steroidal anti-inflammatory drugs, steroids, and anticoagulants, also increase the risk of bleeding.
For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. The net benefits, however, become smaller with advancing age because of an increased risk for bleeding, so modelling data suggest that it may be reasonable to consider stopping aspirin use around age 75 years.
Decisions about initiating aspirin use should be based on shared decision making between clinicians and patients about the potential benefits and harms. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin use. Persons who place a higher value on the potential harms or on the burden of taking a daily preventive medication than the potential befits may choose not to initiate low-dose aspirin use.