**8.2. CETP inhibitors**

CETP stands for "cholesterol ester exchange/transfer protein." It catalyzes the exchange of CE and triglycerides between VLDL or LDL and HDL. In fact, many years ago, we published that Lp(a) also serves as a substrate for CETP [35]. On theoretical grounds, CETP inhibitors should be ideal for the treatment of stroke patients that exhibit significantly elevated Lp(a) and reduced HDL levels [36]. The development of drugs containing the CETP inhibitors Torcetra‐ pib and Dalcetrapib has been stopped because of unwanted side effects. Anacetrapib and Evacetrapib, on the other hand, are currently in phase II clinical trials. Concerning Anacetrapib, it was published in several reports that it reduces Lp(a) by up to 25%, yet details of this study are still lacking.

Further medications such as Eprotirome, a thyromimetikum, Lomitapide, an MTP inhibitor from Aegerion, and Mipomersen, an antisense oligonucleotide targeting apoB, all reportedly reduce Lp(a); however, it is rather uncertain that these drugs will ever be admitted for the indication, high Lp(a).

The most promising medication, at the time being, appears to be APO(a)rx, a specific antisense drug from ISIS®. In that respect, it is noteworthy that we published in 2001 that by RNA interference, a 100% inhibition of the expression of ap(a) may be accomplished in transgene apo(a) mice [39]. ISIS®, in fact, claims from a phase I study that in patients with Lp(a) of 10– 100 mg/dl, a reduction of up to 90% was reached (http://www.isispharm.com/Pipeline/ Therapeutic-Areas/Cardiovascular.htm#ISIS-APOARx). If ISIS ® succeeds in admitting their antisense drug APO(a)rx, we consider this strategy as the most specific and effective in treating hyper-Lp(a).
