Table 4.
HDL-affecting drugs for cardiovascular applications tested in clinical trials.
| Drug | Effect | Additional Information | |
|---|---|---|---|
| CETP inhibitors | ↓CETP → ↑HDLc | in most clinical trials, CETP-inhibitors failed to decrease CVD risk, trial with anacetrapib showed efficacy in reduction in coronary events but with side effects—liver steatosis, IR | [471] |
| ApoA-I mimetics | small peptides mimicking apoA-I → ↑pre-β HDLs, ↑CEC, anti-inflammatory properties of HDL | oral apoA-I mimetic D-4F was well tolerated and effectively reduced the inflammatory index of HDL particles in patients | [487] |
| Reconstituted HDL | recombinant apoA-I with phospholipids → ↑CEC | some molecules were clinically ineffective, some showed high incidence of adverse effects. Second-generation molecules with good safety profile are under investigation | [491,493,494,495] |
| ApoE mimetics | ↑clearance of cholesterol by SR-B1 and LDLR → ↑CEC and RCT, ↑PON1, ↓SAA | AEM-28 was promisingly tested in Phase I/II clinical trial as treatment for refractory hypercholesterolemia | [503,504] |
| Anti-EL monoclonal antibody | ↓EL → ↑HDLc, ↑HDL particle size, ↑cholesterol efflux, improved anti-inflammatory HDL function | MEDI5884 was succefully tested in Phase IIa study on patients with stable coronary artery disease | [508] |
| Epigenetic therapy (bromodomain and extraterminal domain (BET) inhibitor apabetalon) | ↑ApoA-I mRNA/apoA-I expression, ↑CEC | clinical trials show effective modulation of lipid profile, improvement of vascular inflammation and reduction in CVD events in T2DM patients | [510,511] |
| rhLCAT | recombinant human LCAT → ↑formation of HDL and RCT | in patients with CHD, rhLCAT increased HDLc, favourably altered HDL metabolism and trial showed also good tolerability and safety of treatment | [516] |
| LXR agonist | ↑ABCA1/G1, ↑ApoA-I mRNA, ↑RCT | the effect on ABCA1/ABCG1 expression was confirmed in a clinical trial, however, CNS-associated side effect and risk for steatosis was observed in animal models or humans | [523,524,525] |
| Rimonabant | inverse agonist of CB1 → ↑apoA-I, ↑HDL particles size, ↑HDLc | effect on HDL was confirmed in clinical practice, serious psychiatric side effects led to discontinuation of clinical usage | [527,528] |
| Lp-PLA2-inhibitors | ↓Lp-PLA2 | darapladib failed to reduce CVD events in patients | [532,533] |
| Plant polyphenols | LXR or PPAR activation, ↑apoA-I, ↑HDLc, ↑ABCA1/G1, SR-B1 → ↑RCT, ↑PON1, ↑LCAT and others… |
positive effect on HDLc and properties was confirmed in many clinical trials | [536,546,547] |
| Other plant metabolites and compounds | LXR or PPARγ activation, ↑HDLc, ↓SAA, ↑ABCA1/G1, → ↑RCT ↓CETP, ↑Gpx-3, ↑PON1 and others… |
positive effects on cardiovascular system were observed in many animal and human studies | [558,567] |
| Vitamin E | ↑CEC, ↓HDL dysfunction and peroxidation | effect observed only in Hp 2-2 but not Hp1-1 T2DM individuals | [576] |
| PUFAs | ↑RCT in apoE-HDL, ↓MPO oxidation products | Human | [577,578] |
| Probiotics and synbiotics | ↑HDLc, ↑ABCA1/G1, ↑RCT, ↑CEs in HDL = ↑LCAT? | mice, human | [588,592,593] |