Study Shows Aggressive Treatment of Cholesterol Reduces Cardiovascular Outcomes By One-Third

Recent findings presented at the American College of Cardiology’s Annual Scientific Session are reshaping the landscape of lipid management, offering pharmacists new evidence to support more aggressive treatment goals for high-risk patients. The landmark Ez-PAVE (NCT04626973) trial demonstrated that targeting a low-density lipoprotein cholesterol (LDL-C) level of less than 55 mg/dL, rather than the conventional 70 mg/dL, reduced the rate of major cardiovascular events by a staggering one-third among patients with atherosclerotic cardiovascular disease (ASCVD).^1,2

“The Ez-PAVE trial adds practical and clinically meaningful evidence by demonstrating that, in patients with ASCVD, targeting an LDL-C level of less than 55 mg/dL leads to a significantly lower 3-year risk of major cardiovascular events compared with the conventional target of 70 mg/dL, without compromising safety,” Byeong-Keuk Kim, MD, director of the cardiac catheterization and intervention department and professor in the Division of Cardiology at Severance Hospital, Yonsei University College of Medicine in Seoul, South Korea, said in a news release.²

This benefit was primarily driven by significant reductions in nonfatal heart attacks and the need for revascularization procedures. For the pharmacy team, these results provide a firm foundation for the more stringent targets now appearing in clinical guidelines, filling a critical evidence gap regarding optimal LDL-C levels in secondary prevention.

The biological imperative for these lower targets remains clear, as LDL-C is a primary contributor to the accumulation of plaque in artery walls. Although cholesterol is a necessary substance for hormone synthesis and cell membrane stability, an excess leads to reduced blood perfusion and increases the risk of plaque rupture, which triggers heart attacks and strokes. Individuals with extremely high LDL-C levels exceeding 190 mg/dL face a dramatically higher risk of cardiovascular events compared to those with levels below 130 mg/dL, yet nearly 29% of adults continue to live with elevated levels. Pharmacists are uniquely positioned to bridge this gap, especially since almost half of treatment-eligible adults are not currently taking necessary medications due to concerns about side effects, safety, or costs.³

In the Ez-PAVE trial, achieving these aggressive targets required clinicians to utilize high-intensity statin therapy, often supplemented by ezetimibe and PCSK9 inhibitors. This reflects a real-world clinical shift toward combination therapy, as evidenced by the trial's open-label design where treatment decisions were left to the discretion of the treating clinicians. Although statins remain the drug of choice for managing dyslipidemia, pharmacists must be prepared to manage the complexities of intensified regimens. Interestingly, the study found no significant difference in safety profiles between the intensive and conventional target groups, with similar rates of muscle symptoms and new-onset diabetes observed in both cohorts.^1-4

Patient education is another area where pharmacists play a vital role, particularly when addressing the use of OTC supplements. Many patients seek alternative options like fish oil, garlic, or red yeast rice, but these products often lack the robust evidence or regulatory oversight associated with prescription therapies. For example, red yeast rice contains monacolin K, which is chemically identical to lovastatin, yet its concentration can vary wildly between batches and may even contain toxic byproducts like citrinin. Furthermore, while niacin was once a popular option for raising good HDL-C, current guidelines no longer recommend it as an add-on to statins because it has failed to show a clear cardiovascular benefit in that context.³

“The consistency across the overall population and key subgroups suggests that the benefit of targeting LDL-C lower than 55 mg/dL is broadly applicable across the spectrum of patients with ASCVD and is not limited to specific patient subsets,” Kim said in the news release.¹

READ MORE: Cardiology Resource Center

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REFERENCES

1. More aggressive cholesterol-lowering improves heart outcomes. News release. American College of Cardiology. March 28, 2026. Accessed March 30, 2026. https://www.acc.org/About-ACC/Press-Releases/2026/03/28/18/27/More-Aggressive-Cholesterol-Lowering-Improves-Heart-Outcomes

2. Ez-PAVE: hitting lower LDL-C target reduces major CV events. American College of Cardiology. News release. March 28, 2026. Accessed March 30, 2026. https://www.acc.org/latest-in-cardiology/articles/2026/03/25/21/27/sat-345pm-ezpave-acc-2026

3. Su CP, Ambizas EM. Managing cholesterol. US Pharm. 2022;47(9):35-40. doi:https://www.uspharmacist.com/article/managing-cholesterol

4. Effects of ezetimibe combination therapy for patients with atherosclerotic cardiovascular disease; randomized comparison of LDL-cholesterol targeting <70 versus <55mg/​dl; Ez-PAVE trial. ClinicalTrials.gov identification: NCT04626973. November 17, 2025. Accessed March 30, 2026. https://clinicaltrials.gov/study/NCT04626973