Dyslipidemia is one of the main risk factors leading to cardiovascular disease (CVD). The standard of therapy, administration of statins, in conjunction with lifestyle and habit changes, can improve high cholesterol levels in the majority of patients. However, some patients with familial hypercholesterolemia (FH) need low-density-lipoprotein cholesterol (LDL-C) apheresis, as the available medications fail to reduce LDL-C levels sufficiently even at maximum doses. Intense research on cholesterol reducing agents and rapid progress in drug design have yielded many approaches that reduce cholesterol absorption or inhibit its synthesis. Antisense oligonucleotides (ASOs) targeting the production of apolipoprotein B-100 (apoB-100), inhibitors of proprotein convertase subtilisin/kexin type 9, microsomal triglyceride transfer protein inhibitors, squalene synthase inhibitors, peroxisome proliferator-activated receptor agonists, and thyroid hormone receptor agonists are some of the evolving approaches for lipid-lowering therapies. We provide an overview of the apoB ASO approach and its potential role in the management of dyslipidemia. Mipomersen (ISIS-301012, KYNAMRO™) is a synthetic ASO targeting the mRNA of apoB-100, which is an essential component of LDL particles and related atherogenic lipoproteins. ASOs bind to target mRNAs and induce their degradation thereby resulting in reduced levels of the corresponding protein levels. Mipomersen has been investigated in different indications including homozygous and heterozygous FH, as well as in high-risk hypercholesterolemic patients. Recent phase II and III clinical studies have shown a 25-47% reduction in LDL-C levels in mipomersen-treated patients. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for high-risk populations.

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U sually caused by progressive atherosclerosis and associated thrombosis, peripheral arterial disease (PAD) is characterized by a reduced blood flow to the lower limbs, leading to ischemia during physical exertion and intermittent claudication as clinical presentation. 1 Intermittent claudication, classically defined by pain and muscle cramps when walking, results in a greatly reduced walking capacity and functional status. 2,3 This functional decline lowers patient quality of life and willingness to engage in physical activity, which further worsens the risk of cardiovascular disease 4 and premature mortality. 5 For these reasons, improving walking capacity is now considered a priority for the treatment of PAD. 6 Aerobic exercise, typically in the form of walking, is considered a first-line treatment in this population. 7 Scientific evidence supports the existing guidelines that recommend ≥3/wk of supervised exercise sessions of intermittent walking, according to the pain threshold (3-4/5), for 30-45 min/ session, for ≥3 mo. [7][8][9] Recent meta-analyses and clinical trials have shown an increase in maximum walking distance (MWD) on treadmill tests after supervised exercise therapy (SET) in patients with symptomatic PAD. [10][11][12][13] Although home-based exercise has shown encouraging results, the magnitude of these results was inferior to SET. 14 According to the American Heart Association, the optimal SET modality still needs to be determined for patients with PAD. 15 Accumulating data indicate that other types of SET, such as Nordic walking, underwater exercise, and resistance training, could also be effective in improving walking capacity in patients with PAD. [16][17][18][19] Recently, a meta-analysis 8 suggested that other modes of exercise (without any distinction between them) could improve walking ability similar to supervised intermittent walking. Although this