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Elevated LDL-cholesterol (LDL-C) plays a major role in atheroma formation and inflammation. Medical therapy to lower elevated LDL-C is the cornerstone for reducing the progression of atherosclerotic cardiovascular disease. Statin therapy, and more recently, other drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven efficacy in long-term lowering of LDL-C and therefore diminish cardiovascular risk. During an acute coronary syndrome (ACS), a systemic inflammatory response can destabilize other non-culprit atherosclerotic plaques. Patients with these vulnerable plaques are at high risk of experiencing recurrent cardiovascular events in the first few years post-ACS. Initiating intensive LDL-C lowering therapy in these patients with statins or PCSK9 inhibitors can be beneficial via several pathways. High-intensity statin therapy can reduce inflammation by directly lowering LDL-C, but also through its pleiotropic effects. PCSK9 inhibitors can directly lower LDL-C to recommended guideline thresholds, and could have additional effects on inflammation and plaque stability. We discuss the potential role of early implementation of statins combined with PCSK9 inhibitors to influence these cascades and to mediate the associated cardiovascular risk, over and above the well-known long-term beneficial effects of chronic LDL-C lowering.

BackgroundProprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been documented with significantly reduction in LDL cholesterol levels and cardiovascular events. However, evidence regarding the impact of PCSK9 inhibitors on coronary calcification is limited.MethodsEligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard statin therapy. Calcium score based on coronary computed tomographic angiography at baseline and follow up were compared.ResultsCompared with baseline levels, LDL cholesterol were significantly decreased in both groups, while the absolute reduction of LDL cholesterol levels were higher in patients treated with alirocumab (1.69 ± 0.52 vs. 0.92 ± 0.60, P < 0.0001). Additionally, patients in alirocumab group demonstrated a significant reduction of Lp(a) levels, whereas it was not observed in the standard statin group. Notably, greater increases in the percentage changes of CAC score (10.6% [6.3–23.3] vs. 2.9% [−6.7–8.3]; P < 0.0001) were observed in the statin group compared to the alirocumab group. Consistently, CAC progression was significantly lower in the alirocumab group than in the standard statin group (0.6 ± 2.2% vs. 2.7 ± 2.3%; P = 0.002).ConclusionsStudy indicated that administration of the PCSK9 inhibitors to statins produced significantly lower rate of CAC progression in patients with coronary artery disease. Further studies with CAC progression and their clinical outcomes are needed.Trial RegistrationClinicalTrials.gov, Identifier: NCT04851769.