Table 2.
Pharmacologic therapies for CVD targeting inflammatory pathway.
| Drug | Trial (Author) | Mechanism | Study findings | Comments |
|---|---|---|---|---|
| Anakinra | VCU-ART3 Abbate et al. (70) | Decrease IL-1 receptor | CRP AUC decreased with treatment in patients with STEMI (median 67 vs. 214; p <0.001) | Significantly decreased death, new onset HF or death/hospitalization for HF as well; effets short-term (rebound CRP and IL-6 upon stopping); not supported by genetic studies |
| Canakinumab | CANTOS Ridker et al. (64) | Decreasing IL-1b | Nonfatal MI, stroke or CV death decreased with the 150mg dose (HR 0.83; p = 0.005) | Independent of dyslipidemia; patients had high CRP at baseline; higher incidence of fatal infection compared to placebo; no significant impact on all-cause mortality |
| Colchicine | CALCOT Tardif et al. (71) | Decrease CRP, NLRP3 inflammasome inhibitor | CV death, resuscitated cardiac arrest, MI, stroke, or urgent hsopitalization for angina requiring coronary revascularization decreased with treatment (HR 0.77; p = 0.02) | Significant GI side effects |
| Darapladib | SOLID-TIMI 52 O'Donoghue et al. (72) | Decrease lp-PLA2 | No significant difference in major coronary events with treatment (HR 0.99; p = 0.78) | Genetic studies inconsistent; lp-PLA2 did not decrease inflammatory markers |
| Low dose IL-2 | LILACS Zhao et al. (73) | Promotes regulatory T-cells | Results pending | Effective in preclinical data; more selective T-cell regulators than Aldesleukin being developed |
| Methotrexate | CIRT Ridker et al. (74) | Dihydrofolate reducatase inhibitor | Nonfatal MI, stroke or CV death not significantly changed with treatment (HR 0.96; p = 0.91) | Treatment did not decrease inflammatory markers; pathway may not be relevant |
| Rosuvastatin | JUPITER Ridker et al. (71) | Decrease high-sensitivity CRP | MI, stroke or death from CV causes decreased with treatment (HR 0.56; p <0.00001) | Independent of dyslipidemia |
| Tocilizumab | ASSAIL-MI Broch et al. (75) | Anti-IL-6 receptor antibody | Myocardial salvage in acute STEMI larger with treatment (difference 5.6; p = 0.04) | No significant difference in infarct size between treatment and placebo; non-specific blocker of IL-6 signalling |
| Varespladib | VISTA-16 Nicholls et al. (76) | Decrease sPLA2 | CV death, nonfatal MI, nonfatal stroke and unstable angina did not significantly decrease with treatment (HR 1.25; p = 0.08) | Trial stopped early for greater risk of MI with treatment; non-specific treatment; pathway not supported by Mendelian randomization |
| Xilonix | El Sayed et al. (77) | Anti-IL-1a antibody | MACE did not significantly change with treatment (9% vs. 24%; p = 0.22) | Limited clinical data available; did not lower CRP |
AUC, area under the curve; CRP, C-reactive protein; CV, cardiovascular; GI, gastrointestinal; HF, heart failure; HR, hazard ratio; IL, interleukin; Lp-PLA2, lipoprotein-associated phospholipase A2; MACE, major adverse cardiovascular events; MI, myocardial infarction; S-PLA2, secretory phospholipase A2; STEMI, ST-segment elevation myocardial infarction.