The following are key points to remember about reducing inflammation to reduce atherothrombotic risk:

1. Many patients sustain life-threatening cardiovascular (CV) events despite control of conventional risk factors.
2. Inflammation, measured by high-sensitivity C-reactive protein (CRP) or interleukin (IL)-6, is strongly associated with future vascular events.
3. The inflammatory biomarker high-sensitivity CRP predicts CV risk with magnitude of effect comparable to low-density lipoprotein (LDL) or high-density lipoprotein; IL-6 measurement is not clinically available.
4. The recent multicountry CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) showed for the first time that reducing inflammation by targeting IL-1 beta reduces vascular events in proportion to high-sensitivity CRP reduction without lowering LDL cholesterol.
5. CANTOS included 10,061 stable post-myocardial infarction patients with high-sensitivity CRP levels ≥2 mg/l (mean 4.2 mg/dl) despite aggressive statin use, antiplatelet agents, and renin-angiotensin inhibitors. Median LDL was 82 mg/dl. Participants were randomized to placebo or 50, 150, or 300 mg of canakinumab subcutaneously every 3 months.
6. During the followup period (median 3.7 years), those on 150 mg showed a significant 15% reduction in major adverse cardiac events (MACE) (nonfatal myocardial infarction, nonfatal stroke, and CV death) and a 17% reduction in MACE+ (MACE plus unstable angina requiring urgent coronary revascularization). Virtually identical effects occurred with 300 mg (but without reaching prespecified statistical significance level of 0.01058). In patients with high-sensitivity CRP level <2 mg/l after the first dose, 26% reduction in MACE and 31% reduction in CV and all-cause mortality occurred (all p < 0.001). The risk reductions were smaller and not statistically significant in those without such a response.
7. Clinicians should distinguish between patients with residual cholesterol risk and residual inflammatory risk.
8. Residual inflammatory risk, defined as high-sensitivity CRP level >2 mg/l despite aggressive LDL cholesterol lowering, is common even with LDL cholesterol levels as low as 20-30 mg/dl.
9. A simple method to predict long-term benefit with canakinumab is to administer a single dose and then treat long-term only those whose high-sensitivity CRP reduced >50% or to <2 mg/l on treatment.
10. During canakinumab treatment, high-sensitivity CRP should be monitored because benefit tracks directly with level of high-sensitivity CRP reduction achieved.
11. The benefit of canakinumab is not established in acute coronary syndrome.
12. The author affirms “the inflammation hypothesis of atherothrombosis neither conflicts nor competes with the lipid hypothesis.”
13. An individualized approach to therapy should be utilized. A patient may also have residual thrombotic risk, residual triglyceride risk, and/or residual lipoprotein(a) risk. For each, proven therapy exists, or major trials are in progress or planned.

Keywords: Inflammation, Thrombosis, Antibodies, Monoclonal, Biomarkers, Pharmacological, Lipoproteins, HDL, Cholesterol, LDL, Cholesterol, Myocardial Infarction, Angiotensins, Platelet Aggregation Inhibitors

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