p.10 抽出テキスト

of 40.6 month follow-up.4 A total of 13 970 patients were randomized, with approximately 70% in secondary prevention and 30% in primary prevention. Patients taking a small dose of a statin (daily dose of atorvastatin <10 mg or equivalent) were allowed and constituted 23% of the trial population. The time-averaged difference in LDL-C between the bempedoic acid and placebo arms was 0.57 mmol/L (22 mg/dL). Treatment with bempedoic acid reduced the rate of MACE, defined as a composite of death from CV causes, MI, stroke, or coronary revascularization, by 13% [hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.79–0.96; P = .004). There was no apparent effect on CV death (HR, 1.04; 95% CI, 0.88–1.24). Cardiovascular risk reduction with bempedoic acid is similar to that achieved with statins for a given absolute magnitude of LDL-C lowering.47 The rate of myalgia was similar in the two arms. Treatment with bempedoic acid increased the risk of having elevations in hepatic enzymes [>2× upper limit of normal (ULN) for either alanine aminotransferase (ALT) or aspartate aminotransferase (AST), 4.5% vs 3.0%], renal impairment (11.5% vs 8.6%), hyperuricaemia (10.9% vs 5.6%), gout (3.1% vs 2.1%), cholelithiasis (2.2% vs 1.2%), increased platelet count (7.2% vs 0.8%), and decreased haematocrit levels (2.3% vs 0.1%). Because bempedoic acid leads to a small and reversible increase in uric acid, caution is required in patients with a history of gout, even though gout does not constitute an absolute contraindication to bempedoic acid. New recommendations for the use of bempedoic acid for LDL-C lowering [complementing the recommendations for pharmacological LDL-C lowering with statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) of the 2019 ESC/EAS Guidelines1] are shown in Recommendation Table 2. Figure 2 summarizes the average percentage reduction in LDL-C levels with different pharmacological therapies, alone or in combination. It should be kept in mind that there is considerable inter-individual variability in the LDL-C-lowering response to any given lipid-lowering drug or combination, which necessitates monitoring of the treatment effects after initiation or adaptation of any LDL-C-lowering therapy. As outlined in the 2019 ESC/EAS Guidelines,1 LDL-C levels should be measured 4 to 6 weeks after initiation or intensification of lipid-lowering therapy.

Inclisiran, a small interfering ribonucleic acid (RNA) molecule that inhibits the synthesis of PCSK9, may represent an alternative approach to PCSK9 mAbs (alirocumab and evolocumab). Inclisiran has been shown in phase III trials to lower LDL-C levels by approximately 50%.48 Two CV outcome trials with inclisiran [>16 000 patients with CVD (NCT03705234) and 17 000 patients with established ASCVD (NCT05030428)] are currently ongoing and expected to report their primary outcomes in 2026 and 2027, respectively. In patients with homozygous FH, in whom statins and PCSK9 inhibitors have little efficacy and may not suffice to adequately lower LDL-C levels,49 evinacumab, an mAb against ANGPTL3 (angiopoietin-like 3), has shown potential benefits with a reduction of LDL-C close to 50%.5,50,51 Patients who are unable to take statins because of adverse effects represent a challenge in clinical practice. In such cases, the addition of a non-statin lipid-modifying agent to a maximally tolerated statin is a valuable therapeutic option.1 New evidence supporting the reduction in the risk of ASCVD events with ezetimibe in the absence of statin therapy (although not necessarily due to statin intolerance) in older persons

0 



 


















	




	





+ 
	

-10 -20 -30 -40 -50 -60 -70 -80 -90 ~30% ~50% ~20%~23% ~38% ~60%~58% ~68% ~60% ~70%~75%~75%~80% ~86%

Average LDL-C reduction (%)

Figure 2 Average reduction in low-density lipoprotein cholesterol levels with different pharmacological therapies with proven cardiovascular benefits. BA, bempedoic acid; EZE, ezetimibe; LDL-C, low-density lipoprotein cholesterol; PCSK9 mAb, proprotein convertase subtilisin/kexin type 9 monoclonal antibody. Downloaded from academic.oup.com/eurheartj/article/46/42/4359/8234482 by guest on 07 October 2026