Efficacy and safety of inclisiran in patients with cerebrovascular disease: ORION-9, ORION-10, and ORION-11

Köenig, Wolfgang; Ray, Kausik K.; Landmesser, Ulf; Leiter, Lawrence A.; Schwartz, Gregory G.; Wright, R. Scott; Conde, Lorena Garcia; Han, Jackie; Raal, Frederick J.

doi:10.1016/j.ajpc.2023.100503

Cited by 10 publications

(4 citation statements)

References 26 publications

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“…Четырехлетний период наблюдения пациентов из исследований ORION-1 и ORION-3 показал долгосрочную безопасность удержания низкого уровня ХС ЛНП (менее 1 ммоль/л), достигавшегося на фоне терапии инклисираном [10]. Терапия инклисираном также не влияет на риск внутричерепного кровоизлияния у пациентов, уже имеющих цереброваскулярную болезнь: результаты субанализа по оценке терапии инклисираном у 202 пациентов в исследованиях ORION-9, ORION-10 и ORION-11 позволяет сформулировать именно такое утверждение [11].…”

Section: Discussionunclassified

New possibilities for lipid level control using inclisiran — prospects for interaction between a cardiologist and a neurologist

Skiba,

Menzorov,

Puchek

et al. 2023

Racionalʹnaâ farmakoterapiâ v kardiologii

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Dyslipidemia is one of the most significant modifiable cardiovascular risk factors. The change in the modern paradigm for dyslipidemia treatment from high-intensity statin therapy to high-intensity lipid-lowering therapy makes it possible to more often use new drug classes to achieve the target level of low-density lipoprotein cholesterol. The article presents two case reports on the use of inclisiran as part of combination lipid-lowering therapy for secondary prevention in patients at very high cardiovascular risk. Based on the presented cases, following clinical aspects of the management of cardiovascular patients are discussed: the safety of achieving low-density lipoprotein cholesterol levels below 1 mmol/l in a patient with asymptomatic cerebral infarction, the need for adequate dyslipidemia treatment after revascularization, the strategic importance of prescribing lipid-lowering therapy in patients with cerebrovascular disease to reduce the cardiovascular risk, adherence to therapy as a significant aspect of effective dyslipidemia control.

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Section: Discussionunclassified

New possibilities for lipid level control using inclisiran — prospects for interaction between a cardiologist and a neurologist

Skiba,

Menzorov,

Puchek

et al. 2023

Racionalʹnaâ farmakoterapiâ v kardiologii

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“…Consequently, inclisiran has been considered an attractive therapeutic option, particularly for non-adherent patients [ 91 ]. What the impact of inclisiran on reducing lipoproteins and MACE is, has been largely investigated in the ORION/VICTORION studies [ 90 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ], which evidenced a decrease in LDL-C over 1 year of 29.5–38.7% and 29.9–46.4% after a single dose and after two doses, respectively ( p < 0.001). Moreover, Lp(a) has been shown to significantly decrease.…”

Section: Lipid-lowering Therapy (Llt)mentioning

confidence: 99%

Appropriateness of Dyslipidemia Management Strategies in Post-Acute Coronary Syndrome: A 2023 Update

et al. 2023

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It has been consistently demonstrated that circulating lipids and particularly low-density lipoprotein cholesterol (LDL-C) play a significant role in the development of coronary artery disease (CAD). Several trials have been focused on the reduction of LDL-C values in order to interfere with atherothrombotic progression. Importantly, for patients who experience acute coronary syndrome (ACS), there is a 20% likelihood of cardiovascular (CV) event recurrence within the two years following the index event. Moreover, the mortality within five years remains considerable, ranging between 19 and 22%. According to the latest guidelines, one of the main goals to achieve in ACS is an early improvement of the lipid profile. The evidence-based lipid pharmacological strategy after ACS has recently been enhanced. Although novel lipid-lowering drugs have different targets, the result is always the overexpression of LDL receptors (LDL-R), increased uptake of LDL-C, and lower LDL-C plasmatic levels. Statins, ezetimibe, and PCSK9 inhibitors have been shown to be safe and effective in the post-ACS setting, providing a consistent decrease in ischemic event recurrence. However, these drugs remain largely underprescribed, and the consistent discrepancy between real-world data and guideline recommendations in terms of achieved LDL-C levels represents a leading issue in secondary prevention. Although the cost-effectiveness of these new therapeutic advancements has been clearly demonstrated, many concerns about the cost of some newer agents continue to limit their use, affecting the outcome of patients who experienced ACS. In spite of the fact that according to the current recommendations, a stepwise lipid-lowering approach should be adopted, several more recent data suggest a "strike early and strike strong" strategy, based on the immediate use of statins and, eventually, a dual lipid-lowering therapy, reducing as much as possible the changes in lipid-lowering drugs after ACS. This review aims to discuss the possible lipid-lowering strategies in post-ACS and to identify those patients who might benefit most from more powerful treatments and up-to-date management.

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“…In the meantime, a prespecified analysis of ORION-9, ORION-10, and ORION-11 showed the potential of inclisiran to reduce composite MACE by 26% ( OR : 0.74; 95%CI 0.58–0.94), but not fatal and non-fatal myocardial infarction ( OR : 0.80; 95%CI 0.50–1.27) or fatal and non-fatal stroke ( OR : 0.86; 95%CI 0.41–1.81) [ 54 ]. Further pooled post hoc analyses of these three studies further highlighted the superiority of inclisiran (given as a twice-yearly dosing) vs placebo to reduce LDL-C consistently in patients with polyvascular [ 57 ] and cerebrovascular diseases [ 58 ].…”

Section: Inclisiran To Lower Pcsk9mentioning

confidence: 99%

Updates in Small Interfering RNA for the Treatment of Dyslipidemias

Carugo,

Sirtori,

Gelpi

et al. 2023

Curr Atheroscler Rep

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Purpose of Review Atherosclerotic cardiovascular disease (ASCVD) is still the leading cause of death worldwide. Despite excellent pharmacological approaches, clinical registries consistently show that many people with dyslipidemia do not achieve optimal management, and many of them are treated with low-intensity lipid-lowering therapies. Beyond the well-known association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular prevention, the atherogenicity of lipoprotein(a) and the impact of triglyceride (TG)-rich lipoproteins cannot be overlooked. Within this landscape, the use of RNA-based therapies can help the treatment of difficult to target lipid disorders. Recent Findings The safety and efficacy of LDL-C lowering with the siRNA inclisiran has been documented in the open-label ORION-3 trial, with a follow-up of 4 years. While the outcome trial is pending, a pooled analysis of ORION-9, ORION-10, and ORION-11 has shown the potential of inclisiran to reduce composite major adverse cardiovascular events. Concerning lipoprotein(a), data of OCEAN(a)-DOSE trial with olpasiran show a dose-dependent drop in lipoprotein(a) levels with an optimal pharmacodynamic profile when administered every 12 weeks. Concerning TG lowering, although ARO-APOC3 and ARO-ANG3 are effective to lower apolipoprotein(apo)C-III and angiopoietin-like 3 (ANGPTL3) levels, these drugs are still in their infancy. Summary In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium to tackle dyslipidaemias for ASCVD risk reduction.

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Efficacy and safety of inclisiran in patients with cerebrovascular disease: ORION-9, ORION-10, and ORION-11

Cited by 10 publications

References 26 publications

New possibilities for lipid level control using inclisiran — prospects for interaction between a cardiologist and a neurologist

New possibilities for lipid level control using inclisiran — prospects for interaction between a cardiologist and a neurologist

Appropriateness of Dyslipidemia Management Strategies in Post-Acute Coronary Syndrome: A 2023 Update

Updates in Small Interfering RNA for the Treatment of Dyslipidemias

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