p.48 抽出テキスト

............................................................................................................................................................................. 9.6 Stroke Stroke has a heterogeneous aetiology, including cardiac thromboembolism [often associated with atrial fibrillation, but also of uncertain source (embolic stroke of undetermined source)], carotid artery and proximal aortic atherosclerosis and thromboembolism, small-vessel CVD, and intracranial haemorrhage (including intracerebral and subarachnoid haemorrhage). Dyslipidaemia may play a variable role in the pathogenesis of stroke according to the particular aetiology. The relationship between dyslipidaemia and atherothrombotic events, including ischaemic stroke and TIA, is well recognized, while the association of dyslipidaemia with other types of stroke is uncertain. Notwithstanding, concomitant control of other aetiological factors, such as hypertension, is of paramount importance.

Following ischaemic stroke or TIA, patients are at risk not only of recurrent cerebrovascular events, but also of other major CV events, including MI. Secondary prevention therapy with statins reduces the risk of recurrent stroke (by 12% per mmol/L reduction in LDL cholesterol), MI, and vascular death.459,460 Statin pre-treatment at TIA onset was associated with reduced recurrent early stroke risk in patients with carotid stenosis in a pooled data analysis, supporting asearly-as-possible initiation of statins after stroke.460462 Statin therapy may yield a small increase in the risk of haemorrhagic stroke, but the evidence regarding this risk is uncertain.34,36,251,252

9.7 Heart failure and valvular diseases

9.7.1 Prevention of incident heart failure in coronary artery disease patients Cholesterol lowering with statins reduces the incidence of HF in patients with CAD (stable CAD or a history of ACS) without previous HF; this has been shown consistently in RCTs that have compared statin vs. no statin treatment463,464 as well as more-intensive vs. lessintensive statin therapy.465468 A large-scale meta-analysis of primary and secondary prevention RCTs with statins showed a modest (10%) reduction in first non-fatal HF hospitalizations with statin treatment, with no effect on HF death within the limited RCT period.469 There is no evidence that statins can prevent HF of non-ischaemic origin.

9.7.2 Chronic heart failure Two large RCTs466,470 (mainly including patients with systolic HF), as well as a meta-analysis of 24 RCTs, have shown no benefit of statin treatment on CV mortality or stroke;471 a reduction in HF hospitalizations,218,471 as well as a small reduction in MI, was observed in a pooled analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) and GISSI-HF trials.472 Based on current evidence, routine administration of statins in patients with HF without other indications for their use (e.g. CAD) is not recommended. Because there is no evidence of harm in patients on statin treatment after the occurrence of HF, there is no need for statin discontinuation for patients already on treatment.

There is no evidence regarding the effect of PCSK9 inhibition in patients with chronic HF. In the recent PCSK9 clinical outcomes trials, FOURIER119 and ODYSSEY Outcomes,120 PCSK9 inhibition in patients with atherosclerotic CVD or after an ACS did not reduce the risk of HF hospitalization. In the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study of 2174 patients with worsening HF, multivariable analysis revealed a positive linear association between PCSK9 levels and the risk of mortality, and the composite of mortality and unplanned HF hospitalization.473 Similarly, there was a negative association between LDLR levels and mortality, indicating a potential relationship between the PCSK9LDLR axis and outcomes among patients with HF that requires further investigation.473,474 Treatment with n-3 PUFAs 1 g o.d. may confer a small benefit in patients with chronic HF, as shown by a significant 9% relative risk reduction for mortality in the GISSI-HF RCT.475

9.7.3 Valvular heart diseases Aortic stenosis increases the risk of CV events and mortality, and frequently coexists with atherosclerotic CVD. Life-long high levels of LDL-C476 and Lp(a)477 have been associated with incident aortic valve stenosis and aortic valve calcification in genetic Mendelian randomization studies. Observational studies have suggested possible beneficial effects of intensive lipid lowering in slowing the progression of native valve aortic stenosis.478 However, this has not been confirmed in RCTs,266,479481 or in meta-analyses of observational and randomized trials.482,483 Three modestly sized trials479481 and one large randomized trial (SEAS, which included 1873 patients treated with simvastatin 40 mg plus ezetimibe 10 mg or placebo)266 failed to show a reduction in the clinical progression of aortic stenosis in patients with mild-to-moderate native valve aortic stenosis. In a post hoc analysis of the SEAS trial, the efficacy of lipid-lowering therapy in impeding the progression of aortic stenosis increased with higher pre-treatment LDL-C levels and lower peak aortic jet velocity (i.e. milder stenosis at baseline).484 Similarly, a post hoc analysis of three RCTs, including patients without known aortic valve stenosis at baseline [Treating to New Targets (TNT), Incremental Decrease In Endpoints Through Aggressive Lipid-lowering (IDEAL), and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL)] showed no impact of high-dose vs. usual-dose statin therapy on the incidence of aortic valve stenosis.485 In patients who underwent transcatheter aortic valve replacement, statin therapy was associated with improved outcomes in a small observational study.486 Aortic valve sclerosis (calcification of the aortic leaflets without significant transvalvular pressure gradient) is associated with an increased risk of CAD even in the absence of increased risk profiles. Whether or not statins may be useful both for aortic valve disease and CAD progression in such patients warrants further investigation.487

Recommendations for lipid-lowering therapy for the prevention of atherosclerotic cardiovascular disease events in patients with prior ischaemic stroke

Recommendations Classa Levelb

Patients with a history of ischaemic stroke or TIA are at very high-risk of ASCVD, particularly recurrent ischaemic stroke, so it is recommended that they receive intensive LDL-Clowering therapy.459,460 I A

ASCVD = atherosclerotic cardiovascular disease; LDL-C = low-density lipoprotein cholesterol; TIA = transient ischaemic attack. aClass of recommendation. bLevel of evidence. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026