Prevention Beyond the Guidelines

By Amit Khera, M.D., M.Sc.
Director, Preventive Cardiology

The options for drug therapy to reduce high cardiovascular (CV) risk in those with atherosclerotic cardiovascular disease are greatly expanding. However, for both practic­ing clinicians and patients the options can be overwhelming and confusing.

To help create clarity out of this confusion, I organized and moderated a session titled “Prevention Beyond the Guidelines: What to Do Next,” in which a panel of leaders in the field dis­cussed the approach to treating high-risk second­ary prevention patients on current optimal medical therapy. Lipid-lowering therapy has advanced beyond statins to include additional agents. Given the modest LDL-C lowering of ezetimibe and high cost of PCSK9 inhibitors, ideal patients for these therapies are those at very high risk (i.e., multiple prior vascular events, CV disease and diabetes, etc.) with higher residual LDL-C despite maximal statin therapy (i.e., ≥100 mg/dL). Various agents in both the SGLT-2 inhibitor and GLP-1 receptor agonist classes of drugs have demonstrated significant reductions in CV events and should be considered for most patients with diabetes and CV disease. However, the paradigm of prescribing antidiabetic agents as CV risk-reducing therapies, rather than specifically for glucose lowering, is foreign to cardiologists and will take time to disseminate.

Extended dual antiplatelet therapy is also an option in patients with stable coronary artery disease, as is the addition of low-dose rivaroxa­ban, which demonstrated CV event reduction in the recent COMPASS trial. Antiplatelet and anticoagulant therapies always incur a bleeding penalty, which creates aversion among clinicians and requires careful patient selection to ascer­tain those at lowest bleeding risk.

Finally, there is much interest in combating the “residual inflammatory risk” of higher-risk patients with elevated hs-CRP despite opti­mal lipids and preventive therapies. While the CANTOS trial demonstrated the effect of an anti-interleukin-1 beta antibody to lower hs-CRP and CV events despite no change in lipids, the CIRT trial presented at the 2018 Scientific Sessions found no benefit of methotrexate as an anti-inflammatory agent in such patients.

Ultimately, the decision about what to do next among these options requires a preci­sion medicine approach, subphenotyping the individual patient to determine which therapies would benefit him or her the most. In addition, cost to the patient and overall cost-effectiveness are equally important considerations that need to be included in the calculus.