Cardiovascular

PAD as a Marker of Systemic Atherosclerosis: A Comprehensive Review of Residual Risk and Contemporary Strategies for MACE and MALE Reduction.

Miceli G, Basso M, et al. • Medicina (Kaunas, Lithuania) • 2026

Review PubMed 42942436 DOI 10.3390/medicina62101905

TL;DR

PAD is a manifestation of systemic atherosclerosis associated with substantial risks of MACE and MALE, and the authors propose a phenotype-based approach integrating ischemic, bleeding, metabolic, functional, and limb-related risk to support individualized treatment and sustained vascular protection.

Key Findings

Background

PAD is a manifestation of systemic atherosclerosis and carries substantial risks of both major adverse cardiovascular events (MACE) and major adverse limb events (MALE).

The abstract states PAD is 'associated with substantial risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE).'
The review examines the epidemiological and pathobiological links between PAD, polyvascular disease, and residual cardiovascular and limb risk.
The abstract does not report specific effect sizes, sample sizes, or p-values for these associations.

Evidence Synthesis

The review summarizes contemporary evidence for integrated PAD management spanning multiple therapeutic domains.

Domains covered: antithrombotic therapy, intensive lipid lowering, blood pressure and diabetes management, smoking cessation, structured exercise, revascularization when indicated, and longitudinal surveillance.
The review is a comprehensive narrative synthesis; no pooled quantitative estimates are given in the abstract.

Evidence Synthesis

Particular attention is given to dual-pathway inhibition, non-statin lipid-lowering agents, and cardiometabolic therapies for reducing residual risk.

These three therapeutic areas are highlighted as focal points of the evidence synthesis.
Specific trial results or numerical benefits are not reported in the abstract.

Evidence Synthesis

The review distinguishes established PAD-specific benefits from subgroup or emerging evidence.

The authors explicitly separate evidence established in PAD populations from evidence derived from subgroups or that is still emerging.
This distinction is applied to the antithrombotic, lipid-lowering, and cardiometabolic therapies discussed.

Conclusions

The authors propose a phenotype-based approach to PAD care that integrates ischemic, bleeding, metabolic, functional, and limb-related risk.

The approach is intended to support individualized treatment and sustained vascular protection.
It is a proposed framework rather than a tested intervention; the abstract reports no outcome data for it.

What This Means

This review looks at peripheral artery disease (PAD), in which arteries in the legs become narrowed by plaque. The authors describe PAD as a sign of atherosclerosis throughout the body, not just in the legs. People with PAD face substantial risks of both heart-related events such as heart attack and stroke, and limb-related events such as serious loss of blood flow to the leg. Even with standard treatment, some risk remains, which the authors call residual risk. The authors summarize current evidence on treatments that may lower these risks. These include antithrombotic (clot-preventing) medicines, intensive cholesterol lowering, blood pressure and diabetes control, quitting smoking, supervised exercise, procedures to restore blood flow when needed, and ongoing follow-up. They give particular attention to combining two types of blood-thinning pathways, cholesterol drugs beyond statins, and newer diabetes and metabolic medicines. They also separate benefits proven specifically in people with PAD from those seen only in subgroups or still emerging. The authors propose that care be tailored to each person's profile, considering their risk of clots and cardiovascular events, risk of bleeding, metabolic health, physical function, and limb status. This research suggests that treating PAD as a whole-body condition, with individualized combinations of therapies, may offer better long-term protection. The abstract does not give numerical results, and this is a framework proposal rather than a test of a new treatment.

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Citation

Miceli G, Basso M, Cuffaro M, Marchese A, Tuttolomondo A. (2026). PAD as a Marker of Systemic Atherosclerosis: A Comprehensive Review of Residual Risk and Contemporary Strategies for MACE and MALE Reduction.. Medicina (Kaunas, Lithuania). https://doi.org/10.3390/medicina62101905

Key Findings

What This Means

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