Table 1.
Inflammatory Targets With Mechanisms of Action and Pertinent Studies
| Inflammatory Target | Mechanism | Atherosclerotic Cardiovascular Disease |
Other Clinical Conditions |
||
|---|---|---|---|---|---|
| Therapeutic Agent | Pertinent Studies | Therapeutic Agent | Indication/Pertinent Studies | ||
| C5, complement cascade | Single-chain fragment of a humanized monoclonal antibody that binds to C5 preventing cleavage to C5a and C5b-9 | Pexelizumab | Phase 2: CARDINAL Program (COMPLY [15] and COMMA [16] in STEMI) Phase 3: APEX AMI (STEMI) (20), PRIMO-CABG 1 (CABG) (25), PRIMO-CABG II (CABG) (27) |
Eculizumab | Atypical hemolytic uremic syndrome (99), pregnant patients with paroxysmal nocturnal hemoglobinuria (100), macular degeneration (101) |
| sPLA2 | Nonspecific inhibitor of sPLA2 activity | Varespladib | Phase 2: FRANCIS (ACS) (37) Phase 3: VISTA-16 (ACS) (39) |
||
| Lp-PLA2 | Direct selective inhibitor of Lp-PLA2 | Darapladib | Chronic Stable Angina: STABILITY (stable CAD) (48) ACS: SOLID-TIMI (STEMI or NSTEMI) 52 (49) |
Rilapladib | Platelet aggregation inhibition (102) |
| IL-1β | Human monoclonal antibody targeted at IL-1β | Canakinumab | Phase 2 (patients with high cardiovascular risk) (61) Phase 3: CANTOS (post-ACS) |
Anakinra (IL1-RA) | Recurrent pericarditis (103) Rheumatoid arthritis (104) Severe hidradenitis suppurativa (105) |
| P-selectin | Highly specific P-selectin human recombinant monoclonal antibody | Inclacumab | Phase 2 (NSTEMI, CABG) 69, 72 | Crizanlizumab | Sickle cell pain (106) |
| P38 MAPK signaling cascade | selective inhibitor of the p38 MAPK signaling cascade | Losmapimod | Phase 1b: (NSTEMI) (85) Phase 3: (acute MI) (86) |
Doramapimod | Active Crohn’s disease (107) |
ACS = acute coronary syndromes; AMI = acute myocardial infarction; APEX AMI = Assessment of Pexelizumab in Acute Myocardial Infarction; CABG = coronary artery bypass graft; CAD = coronary artery disease; CANTOS = Canakinumab Anti-Inflammatory Thrombosis Outcomes Study; CARDINAL = Complement And ReDuction of INfarct size after Angioplasty or Lytics; COMMA = COMplement inhibition in Myocardial infarction treated with Angioplasty; COMPLY = COMPlement inhibition in myocardial infarction treated with thromboLYtics; FRANCIS = Fewer Recurrent Acute Coronary Events With Near-Term Cardiovascular Inflammation Suppression; IL = interleukin; Lp-PLA2 = lipoprotein-associated phospholipase A2; MAPK = mitogen-activated protein kinase; MI = myocardial infarction; NSTEMI = non–ST-segment myocardial infarction; PRIMO-CABG = Pexelizumab for Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery; SOLID-TIMI 52 = Stabilization of pLaques usIng Darapladib-Thrombolysis In Myocardial Infarction 52; sPLA2 = secretory phospholipase A2; STABILITY = Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy; STEMI = ST-segment elevation myocardial infarction; VISTA-16 = Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 weeks.