A narrative review that was published in the Annals of Vascular Surgery found that patients with lower extremity peripheral artery disease (PAD) have poor lipid control. They also found a pattern of underprescribing adequate lipid-lowering medications.

PAD occurs among 5.6% of adults older than 25 years and represents more than 25% of cardiovascular disease worldwide. It has been associated with smoking, poor lifestyle, diabetes, hypertension, hypercholesterolemia, low estimated glomerular filtration rate, and Black ethnicity.

PAD is generally caused by atherosclerotic plaque in the lower limbs that reduces arterial blood flow. The condition increases risk for cardiovascular events and loss of limbs.


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The UK National Health Service guidelines recommend that patients quit smoking; improve dietary and exercise habits; manage diabetes, hypertension, and lipid levels; and begin antiplatelet therapy. In cases of severe lifestyle-limiting short-distance claudication, patients should be referred to a vascular surgeon.

The guidelines state that patients should maintain low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L. Symptomatic patients who cannot maintain recommended LDL-C levels should be prescribed high-intensity statin therapy.

A study from Canada found that only 88% of patients with PAD were on statin therapies, 43% were given moderate-intensity therapy, and 32% did not reach the LDL-C target. These trends indicate there is a pattern of inadequate statin dosing.

Patients who receive high-intensity statin doses have been associated with a 15% and 22% lower risk for mortality and amputation than patients prescribed moderate-intensity doses, respectively.

High-intensity statin therapy options include atorvastatin (³20 mg), rosuvastatin (³10 mg), or ezetimibe (10 mg) with maximal tolerated statins. The authors advocated for a “treating to target” approach for lipid-lowering therapies. This method comprises prescribing a statin and rechecking lipid levels after 3 months in order to titrate for the appropriate drug and dosing level.

Statin intolerance due to muscle toxicity or the nocebo effect occurs at a rate of 5% in clinical trials and 18% in clinical practice. Intolerance may be addressed by a de-challenge and re-challenge approach or prescription of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors.

PCSK-9 inhibitors are monoclonal antibodies that degrade the LDL receptor in hepatocytes. This therapy has been shown to decrease major adverse limb events by 42%. These monoclonal antibodies are expensive and due to costs have been made available in the UK only to patients who are at very high risk.

The review authors concluded that additional research into nonstatin lipid-reduction strategies, intolerance, and an assessment of statin adherence is needed for the PAD population. They recommend the current guidelines be audited to address the widespread pattern of underdosing and poor lipid control among patients with PAD so that the average clinical trajectory of lower limb PAD may be improved.

Reference

Sucharitkul PPJ, Jones KL, Scott DJA, Bailey MA. Lipid optimization in lower extremity peripheral arterial disease. Ann Vasc Surg. Published online May 2, 2021. doi:10.1016/j.avsg.2021.03.055