**3.2 Antisense therapy for cardiovascular diseases**

The first antisense drug, mipomersen, is approved by the FDA as an adjunct therapy for homozygous familial hypercholesterolemia, which reduces apolipoprotein B mRNA levels [16]. Apolipoprotein C III (apoCIII) plays a critical role in the metabolism of triglyceride-rich lipoproteins, and decreased expression is associated with a lower risk of cardiovascular disease [16, 17]. The clinical trial of volanesorsen, an antisense drug, is designed to reduce apoCIII mRNA levels, and the drug is currently being investigated in placebo-controlled phase III clinical trials for the treatment of familial chylomicronemia syndrome and familial partial lipodystrophy. It has been shown that severe factor XI deficiency provides protection against deep vein thrombosis and therefore cardiovascular morbidity and mortality [6]. The antisense drug IONIS-FXIRx can lower the factor XI levels and has the potential to be more effective than conventional anti-thrombotics. A phase II study with IONIS-FXIRx/BAY 2306001 is ongoing to investigate the drug's effects in patients with end-stage renal disease on hemodialysis [6, 18, 19].
