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Michael D. Shapiro

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Jul 2026

Beyond therapeutic maximalism: Prioritization and personalization in preventive therapies.

The landscape of lipid management has transitioned from a statin-monotherapy and statin-intensification paradigm to a sophisticated, multi-axis intervention model targeting low-density lipoprotein cholesterol, triglyceride-rich lipoproteins, lipoprotein(a), and vascular inflammation. The emergence of PCSK9-targeted small interfering RNA therapies, CETP inhibitors, and Lp(a)-directed antisense and RNA based agents has enabled complementary modulation of diverse lipid pathways through distinct molecular targets. However, this increasingly multidrug approach may also increase treatment complexity, healthcare burden, and adherence challenges, particularly among high-risk patients already receiving multidrug cardiometabolic therapy. Although intensive and sustained LDL-C lowering remains foundational to preventive cardiology, the real-world effectiveness of increasingly complex treatment strategies may ultimately depend on long-term adherence, affordability, patient capacity, and implementation feasibility. We propose a Clinical Prioritization and Personalization Framework centered on individualized risk-based intensification, comprehensive residual risk management, and optimization of treatment delivery to achieve sustainable, patient-centered cardiovascular protection.

Yashendra Sethi, K. Mahajan, Michael D. Shapiro et al. · 1 citation