Medical Therapy for Long-Term Prevention of Atherothrombosis Following an Acute Coronary Syndrome

Gallone, Guglielmo; Baldetti, Luca; Pagnesi, Matteo; Latib, Azeem; Colombo, Antonio; Libby, Peter; Giannini, Francesco

doi:10.1016/j.jacc.2018.09.052

Cited by 72 publications

(34 citation statements)

References 138 publications

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“…Accordingly, therapies targeting the function and qualitative properties of lipoproteins could help to decrease the residual cardiovascular risk, which persists even after statin treatment [ 8 ]. Interest in using peptides has been aroused for a few years.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice

et al. 2020

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Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[113–122]apolipoprotein (apo) J (d-[113–122]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we analyzed the effect of d-[113–122]apoJ in low-density lipoprotein receptor knockout mice(LDLR-KO) on the development of atherosclerosis and lipoprotein function. Fifteen-week-old female LDLR-KO mice fed an atherogenic Western-type diet were treated for eight weeks with d-[113–122]apoJ peptide, a scrambled peptide, or vehicle. Peptides were administered subcutaneously three days per week (200 µg in 100 µL of saline). After euthanasia, blood and hearts were collected and the aortic arch was analyzed for the presence of atherosclerotic lesions. Lipoproteins were isolated and their composition and functionality were studied. The extent of atherosclerotic lesions was 43% lower with d-[113–122]apoJ treatment than with the vehicle or scramble. The lipid profile was similar between groups, but the high-density lipoprotein (HDL) of d-[113–122]apoJ-treated mice had a higher antioxidant capacity and increased ability to promote cholesterol efflux than the control group. In addition, low-density lipoprotein (LDL) from d-[113–122]apoJ-treated mice was more resistant to induced aggregation and presented lower electronegativity than in mice treated with d-[113–122]apoJ. Our results demonstrate that the d-[113–122]apoJ peptide prevents the extent of atherosclerotic lesions, which could be partially explained by the improvement of lipoprotein functionality.

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Section: Introductionmentioning

confidence: 99%

Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice

et al. 2020

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“…ACS patients have a very high risk of early cardiovascular, with over 30% of cardiovascular events and mortality occurring in the rst four days, and over 50% occurring in the rst 15 days [31]. Previous studies showed that the major cause of early ACS risks was the rupture of atherosclerotic plaques [32].Therefore, the 2019 ESC Guidelines for the Management of Dyslipidemias recommended that :for patients who present with an ACS and whose LDL-C levels are not at goal, despite already taking a maximally tolerated statin dose and ezetimibe, the addition of a PCSK9 inhibitor early after the event (during hospitalization for the ACS event if possible) should be considered, in order to obtain earlier cardiovascular bene ts [33].…”

Section: Discussionmentioning

confidence: 99%

Effect of PCSK9 Inhibitor on Lipoprotein Particles in Patients With Acute Coronary Syndromes

Cong

2020

Preprint

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Backgrounds: To assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.Methods: A total of 99 consecutive patients with ACS and poor lipid control were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140mg, q2w) and moderate statin (rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after eight weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed.Results: In the experimental group, after eight weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions (VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)) demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL 5+6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3+4) and large-sized LDL-P (LDL-P1+2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after eight weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target(P < 0.01).Conclusions: Evolocumab combination treatment for 8 weeks could significantly improve the plasma lipid profiles in ACS patients with poor lipid control, and significantly decrease the concentration of lipoprotein particles which could result in atherosclerosis.

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“…Bleeding and ischemic events following percutaneous coronary intervention (PCI) are associated with increased mortality. 1,2 The best combined strategy of stent model and dual antiplatelet (DAPT) therapy regimen is thus of maximal importance to optimize the ischemia/ bleeding event trade-off in any patient, based on the individual ischemic and bleeding risks. 3,4 In the large scale LEADERS-FREE trial, a polymer-free biolimuseluting stent (PF-BES) demonstrated improved outcomes as compared to a bare metal stent in high bleeding risk (HBR) patients, when used with a 1-month DAPT strategy.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, as high bleeding predictors largely overlap with risk factors for ischemic complications, high bleeding risk per se is an overall marker of the ischemic risk 2,31. Of note, it is interesting to note how despite the higher rate of potent P2Y12 inhibitors in patients prescribed with planned longer as compared to 1-month DAPT strategy (20.3% vs. 5.5%, p < .001), clopidogrel was the preferred choice in both groups, also among patients presenting with ACS, likely reflecting the high prevalence of HBR features in both groups.…”

mentioning

confidence: 99%

Real‐world reasons and outcomes for 1‐month versus longer dual antiplatelet therapy strategies with a polymer‐free BIOLIMUS A9‐coated stent

Gallone

D’Ascenzo

Boccuzzi

et al. 2020

Cathet Cardio Intervent

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Background A large trial established the favorable profile of a new polymer‐free biolimus A9‐eluting stent (PF‐BES) with a 1‐month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients. This is the first study comparing outcomes for a 1‐month versus longer DAPT strategies following PF‐BES‐percutaneous coronary intervention (PCI). Methods All patients undergoing PF‐BES‐PCI (January 2016 to July 2018) were included in the multicenter CHANCE registry. Patients were stratified according to DAPT strategy at discharge (planned 1‐month vs. planned >1‐month). Primary outcomes were the 390‐day estimates of a patient‐oriented and of a device‐oriented composite endpoints (POCE: death, myocardial infarction [MI] or target vessel revascularization; DOCE: cardiac death, target vessel‐MI or ischemia‐driven target lesion revascularization). Landmark analyses from 1‐month post‐PCI were carried. Results Following PF‐BES‐PCI, 328(40.3%) and 485(59.6%) patients were discharged with 1‐month and longer DAPT (12 months [6–12]), respectively. Patients with a previous or index MI were less likely to be discharged on 1‐month DAPT. Patients prescribed with 1‐month DAPT were more likely to be at HBR than those with longer DAPT (90.2% vs. 69.9%, p = .001). No between‐groups differences in the primary outcomes (planned 1‐month vs. planned >1‐month DAPT: POCE 11.9% vs. 13.2%, p = .747; DOCE: 4.8% vs. 8.1%, p = .500) were observed, also after adjusting for confoundings (POCE: adjusted‐hazard ratio [adj‐HR] 1.26, 95%CI 0.74–2.13; DOCE: adj‐HR 1.00, 95%CI 0.49–1.99). Landmark analyses showed similar results. Conclusions In a large all‐comers registry of PF‐BES PCI, no interaction of planned DAPT strategy (1‐month vs. >1‐month) with outcomes was found. This observation warrants investigation in adequately powered randomized studies (http://clinicaltrials.gov NCT03622203).

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Medical Therapy for Long-Term Prevention of Atherothrombosis Following an Acute Coronary Syndrome

Cited by 72 publications

References 138 publications

Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice

Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice

Effect of PCSK9 Inhibitor on Lipoprotein Particles in Patients With Acute Coronary Syndromes

Real‐world reasons and outcomes for 1‐month versus longer dual antiplatelet therapy strategies with a polymer‐free BIOLIMUS A9‐coated stent

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