Table 2.
Anti-inflammatory agents in atherosclerosis
| Target Drug |
Preclinical studies | Clinical studies | ||||
|---|---|---|---|---|---|---|
| Animal model | Outcomes | Result | Population | Outcomes | Result | |
| IL-1β Canakinumab |
Rats | Reduction of carotid neointima formation after injury190 | ✓ | 17,200 patients with MI 189 patients with type 2 diabetes mellitus and pre-existing vascular disease |
First occurrence of MACE, change in carotid plaque burden (ongoing)163 No effect on vascular structure and function, but trend towards retarded progression of atherosclerosis by MRI164 |
– |
| Recombinant IL-1ra | Apoe−/− mice | Reduction in fatty lesion formation191 | ✓ | NA | NA | NA |
| Tumour necrosis factor Etanercept, infliximab |
Apoe−/− Tnf−/− mice | Reduction in atherosclerosis plaque progression192 | ✓ | 2,126 patients with rheumatoid arthritis (meta-analysis) | Trend towards reduction in all cardiovascular events193 | ✓ |
| IL-12 subunit p40 Ustekinumab |
Apoe−/− Il12−/− mice | Reduction in atherosclerosis194 | ✓ | 3,117 patients with psoriasis (pooled analysis) | Overall cardiovascular events were similar between treatment and placebo groups195 | – |
| IL-17A Secukinumab |
Apoe−/− mice | Reduction in atherosclerosis lesion area196 | ✓ | 3,993 patients with psoriasis (pooled analysis) | Overall cardiovascular events were similar between treatment and placebo groups197 | – |
| p38 MAPK (Losmapimod) | Ldlr−/− mice | Reduction in foam cell formation and expression of CCL2 and VCAM1198 | ✓ | 99 patients with atherosclerosis receiving stable statin therapy | Reduction in vascular inflammation in most inflamed areas and reduction in inflammatory biomarkers199 | ✓ |
| CC-chemokines 35K protein to inactivate CC-chemokines |
Apoe−/− mice | Reduction in atherosclerosis, macrophage content, and lipid content in plaque200 | ✓ | NA | NA | NA |
| P-selectin Inclacumab |
Rabbits | Reduced intimal hyperplasia after injury201 | ✓ | 380 patients with saphenous vein graft disease | No effect on saphenous vein graft disease progression202 | – |
| VCAM1 | Apoe−/− mice | Reduction in plaque formation and reduced infiltration of CD45+ cells203 | ✓ | NA | NA | NA |
| sPLA2 Varespladib |
Apoe−/− mice | Reduction in atherosclerosis204 | ✓ | 5,145 patients after ACS | Significant increase in the risk of AMI, no reduction in risk of recurrent events205 | X |
| LpPLA2 Darapladib |
Pigs | Reduction in atherosclerosis206 | ✓ | 15,828 patients with stable CAD | No reduction in the primary end point of cardiovascular death, myocardial infarction, or stroke207 | – |
| Serine protease inhibition | Rabbits | Reduction in plaque growth after injury208 | ✓ | NA | NA | NA |
| Colchicine | Rabbits | Reduction in lipid deposition in aortic plaque209 | ✓ | 532 patients with stable coronary disease | Significant reduction in major cardiac events210 | ✓ |
| Methotrexate | Rabbits | Reduction in neoatheroma formation and intimal thickening211 | ✓ | 7,000 patients with stable CAD and diabetes mellitus or metabolic syndrome | Effects on nonfatal MI, nonfatal stroke, and death (ongoing)212 | – |
ACS, acute coronary syndrome; AMI, acute myocardial infarction; CAD, coronary artery disease; CCL2, C-C chemokine 2 (also known as monocyte chemoattractant protein 1); LpPLA2, lipoprotein-associated phospholipase A2; MACE, major adverse cardiovascular event; MAPK, mitogen-activated protein kinase; MI, myocardial infarction, sPLA2, secretory phospholipase A2; VCAM1, vascular cell adhesion molecule 1.