A Blurred Line: What’s the Distinction Between Primary and Secondary Prevention Today?

By Amit Khera, M.D., M.Sc.

Professor of Internal Medicine
Director, Preventive Cardiology

In an era of increasing use of coronary artery calcium (CAC) scanning, where asymptomatic individuals with high burdens of atherosclerosis are detected, what is the distinction between primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD)? That was the topic of a joint session between the American Society for Preventive Cardiology and AHA that I moderated at #AHA21.

An impetus for this topic was a recent article demonstrating that in participants from the MESA study, the 10-year risk of ASCVD events in those with a CAC score > 1,000 was comparable to the individuals with stable CAD in the placebo arm of the FOURIER PCSK9 inhibitor trial. This and other studies call into question reserving preventive therapies only for those with prior ASCVD events. In the opening debate, both the protagonist and antagonist agreed on this point, and the subsequent presentations reviewed various preventive therapies, starting with PCSK9 inhibitors. The current ACC/AHA Cholesterol Guidelines advocate for PCSK9 inhibitor use only in secondary prevention patients who are deemed “very high risk.” However, the price of these medications has come down substantially since the guideline release and additional clinical trial and clinical experience has been garnered. It seems reasonable to use these medications in those with very high CAC scores if they have residually elevated LDL-C (> 70 mg/dL) despite high-intensity statin use.

The AHA/ACC 2019 Prevention Guidelines and the recent USPSTF draft guidelines on aspirin use both endorse the more conservative use of aspirin in primary prevention, reserving it for those at higher ASCVD risk and lower bleeding risk. Our research from the Dallas Heart Study has demonstrated that when modeling the effects of aspirin, those with a CAC score > 100 and a low bleeding risk may have a net benefit from ASA in primary prevention, balancing ASCVD event reduction with major bleeding.

While there was general agreement for opportunities of both PCSK9 inhibitors and aspirin in those with very high CAC scores, there was more uncertainty about icosapent ethyl, SGLT2 inhibitors, and GLP1 receptor agonists, particularly in individuals without concomitant heart failure or diabetes. There are some conflicting data for high-dose omega 3 fatty acids in secondary prevention, and inadequate data for the latter two agents in patients without diabetes but higher ASCVD risk. Regardless of the specific therapies, this session spotlighted the imperative to consider more aggressive preventive measures in those with a high burden of subclinical atherosclerosis, given that the line between primary and secondary prevention increasingly is blurred.

Email: amit.khera@utsouthwestern.edu

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