p.45 抽出テキスト

............................................................. HTG and low HDL-C levels at baseline.421 Consistent with these findings, a meta-analysis of fibrates in the prevention of CVD in 11590 people with T2DM showed that fibrates significantly reduced the risk of non-fatal MI by 21%, but had no effect on the risk of overall mortality or coronary mortality.422 In CV outcome trials of fibrates, the risk reduction has appeared to simply be proportional to the degree of non-HDL-C lowering.50

Overall, available data indicate that diabetic patients with atherogenic dyslipidaemia may derive clinical benefits from TG-lowering therapy as an add-on to statin treatment.354 The ongoing PROMINENT trial is exploring the efficacy of pemafibrate, a new selective PPAR-a modulator, in reducing CVD outcomes in 10 000 diabetic patients with atherogenic dyslipidaemia on a statin.317,423 There are limited data on the impacts on CVD of adding omega-3 fatty acids to statin therapy in patients with high plasma TG levels who are treated with statins. The REDUCE-IT trial examined the effects of icosapent ethyl 2 g b.i.d. on CV events in 8179 high-risk patients with HTG who were taking a statin. Over a median of 4.9 years, there was a significant (P < 0.001) 25% reduction in the composite primary outcome of CV death, non-fatal MI, non-fatal stroke, coronary revascularization, or unstable angina, corresponding with an absolute reduction of 4.8%, which was offset by a 1% increased absolute risk of hospitalization for atrial fibrillation or flutter.194 The STRENGTH trial is investigating the effect of omega-3 fatty acids, in addition to a statin, in individuals with HTG and low HDL-C levels who are at high-risk for CVD. The ASCEND trial was a randomized 22 factorial design study of aspirin and omega-3 fatty acid supplements for the primary prevention of CV events in people with DM, but not specifically with HTG. Among 15 480 people randomized to omega-3 fatty acid supplements vs. placebo over a mean follow-up of 7.4 years, there was no significant effect (HR 0.97, 95% CI 0.871.08) on serious vascular events [non-fatal MI, non-fatal stroke, transient ischaemic attack (TIA), or vascular death].329,424426

9.4.3 Type 1 diabetes mellitus T1DM is associated with high CVD risk, in particular in patients with microalbuminuria and renal disease.427 Conclusive evidence supports the proposition that hyperglycaemia accelerates atherosclerosis. Emerging evidence highlights the frequent coexistence of MetS with T1DM, resulting in the so-called double diabetes increasing CVD risk.428 The lipid profile in T1DM patients with good glycaemic control is ‘supernormal’, and is characterized by subnormal TG and LDL-C levels, whereas HDL-C levels are usually within the upper normal range or slightly elevated. This is explained by subcutaneous administration of insulin that increases LPL activity in adipose tissue and skeletal muscle, and consequently the turnover rate of VLDL particles.429 However, there are potentially atherogenic changes in the compositions of both HDL and LDL particles. Consistent data have demonstrated the efficacy of statins in preventing CV events and reducing CV mortality in patients with DM, with no evidence of sex differences.430,431 A meta-analysis including 18 686 patients with DM demonstrated that a statininduced reduction of LDL-C yielded a 9% reduction in all-cause mortality and a 21% reduction in the incidence of major CV events per 1.0 mmol/L (40mg/dL) lower LDL cholesterol.418 Similar benefits were seen in patients with T1DM and T2DM. In diabetic patients with ACS, intensive statin treatment led to a reduction in all-cause mortality and CV death, and contributed to a reduction in atheroma progression.432

9.4.4 Management of dyslipidaemia for pregnant women with diabetes In both T1DM and young-onset T2DM patients, there is a paucity of evidence to indicate the age at which statin therapy should be initiated. To guide an approach, statins are not indicated in pregnancy,433 and should be avoided in both T1DM and T2DM individuals who are planning pregnancy. If diabetic individuals aged <_30 years have no evidence of vascular damage and, in particular, microalbuminuria, it seems reasonable to delay statin therapy in asymptomatic patients until the age of 30. Below this age, statin therapy should be managed on a case-by-case basis, taking into account the presence of microalbuminuria, end organ damage, and ambient LDL-C levels. Recommendations for the treatment of dyslipidaemias in DM are shown in the table below.

Recommendations for the treatment of dyslipidaemias in diabetes mellitus

Recommendations Classa Levelb In patients with T2DM at very-high riskc, an LDL-C reduction of >_50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) is recommended.34,418,432 I A In patients with T2DM at high risk,c an LDL-C reduction of >_50% from baseline and an LDL- C goal of <1.8 mmol/L (<70 mg/dL) is recommended.418 I A Statins are recommended in patients with T1DM who are at high or very-high risk.c 427 I A Intensification of statin therapy should be considered before the introduction of combination therapy. IIa C If the goal is not reached, statin combination with ezetimibe should be considered.33,299 IIa B Statin therapy is not recommended in premenopausal patients with diabetes who are considering pregnancy or are not using adequate contraception. III C Statin therapy may be considered in both T1DM and T2DM patients aged <_30 years with evidence of end organ damage and/or an LDL-C level >2.5 mmol/L, as long as pregnancy is not being planned. IIb C

LDL-C = low-density lipoprotein cholesterol; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus. aClass of recommendation. bLevel of evidence. cSee Table 6. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026