scholarly journals Inhibitors of Protein Convertase Subtilisin/Kexin 9 (PCSK9) and Acute Coronary Syndrome (ACS): The State-of-the-Art

2021 ◽  
Vol 10 (7) ◽  
pp. 1510
Author(s):  
Gabriella Iannuzzo ◽  
Marco Gentile ◽  
Alessandro Bresciani ◽  
Vania Mallardo ◽  
Anna Di Lorenzo ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Major Adverse Cardiovascular Events ◽  
Control Group ◽  
Pcsk9 Inhibitors ◽  
Coronary Syndrome ◽  
And Gender ◽  
Acute Event

Acute Coronary Syndrome (ACS) remains one of the most frequent causes of morbidity and mortality in the world. Although the age- and gender-adjusted incidence of ACS is decreasing, the mortality associated with this condition remains high, especially 1-year after the acute event. Several studies demonstrated that PCSK9 inhibitors therapy determine a significant reduction of major adverse cardiovascular events (MACE) in post-ACS patients, through a process of plaque modification, by intervening in lipid metabolism and platelet aggregation and finally determining an improvement in endothelial function. In the EVACS (Evolocumab in Acute Coronary Syndrome) study, evolocumab allows >90% of patients to achieve LDL-C < 55 mg/dL according to ESC/EAS guidelines compared to 11% of patients who only receive statins. In the EVOPACS (EVOlocumab for Early Reduction of low-density lipoprotein (LDL)-cholesterol Levels in Patients With Acute Coronary Syndromes) study, evolocumab determined LDL levels reduction of 40.7% (95% CI: 45.2 to 36.2; p < 0.001) and allowed 95.7% of patients to achieve LDL levels <55 mg/dL. In ODYSSEY Outcome trial, alirocumab reduced the overall risk of MACE by 15% (HR = 0.85; CI: 0.78–0.93; p = 0.0003), with a reduced risk of all-cause mortality (HR = 0.85; CI: 0.73–0.98: nominal p = 0026), and fewer deaths for coronary heart disease (CHD) compared to the control group (HR = 0.92; CI: 0.76–1.11; p = 0.38). The present review aimed at describing the beneficial effect of PCSK9 inhibitors therapy early after ACS in reducing LDL circulating levels (LDL-C) and the risk of major adverse cardiovascular events, which was very high in the first year and persists higher later after the acute event.

scholarly journals Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial

2020 ◽  
Vol 41 (42) ◽  
pp. 4114-4123 ◽  
Author(s):  
José Tuñón ◽  
Philippe Gabriel Steg ◽  
Deepak L Bhatt ◽  
Vera A Bittner ◽  
Rafael Díaz ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Renal Function ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Major Adverse Cardiovascular Events ◽  
Pcsk9 Inhibitors ◽  
Coronary Syndrome

Abstract Aims Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function. Methods and results ODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite intensive statin treatment. Estimated glomerular filtration rate (eGFR) &lt;30 mL/min/1.73 m2 was exclusionary. In 18 918 patients, baseline eGFR was 82.8 ± 17.6 mL/min/1.73 m2, and low-density lipoprotein cholesterol (LDL-C) was 92 ± 31 mg/dL. At 36 months, alirocumab decreased LDL-C by 48.5% vs. placebo but did not affect eGFR (P = 0.65). Overall, alirocumab reduced risk of the primary outcome (coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization) with fewer deaths. There was no interaction between continuous eGFR and treatment on the primary outcome or death (P = 0.14 and 0.59, respectively). Alirocumab reduced primary outcomes in patients with eGFR ≥90 mL/min/1.73 m2 (n = 7470; hazard ratio 0.784, 95% confidence interval 0.670–0.919; P = 0.003) and 60 to &lt;90 (n = 9326; 0.833, 0.731–0.949; P = 0.006), but not in those with eGFR &lt; 60 (n = 2122; 0.974, 0.805–1.178; P = 0.784). Adverse events other than local injection-site reactions were similar in both groups across all categories of eGFR. Conclusions In patients with recent ACS, alirocumab was associated with fewer cardiovascular events and deaths across the range of renal function studied, with larger relative risk reductions in those with eGFR &gt; 60 mL/min/1.73 m2.

scholarly journals Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial

2020 ◽  
pp. 204748732094198 ◽  
Author(s):  
Rafael Diaz ◽  
Qian H Li ◽  
Deepak L Bhatt ◽  
Vera A Bittner ◽  
Marie T Baccara-Dinet ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Absolute Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Major Adverse Cardiovascular Events ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Pcsk9 Inhibition

Aims Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment. Methods and results The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL ( P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80–0.96; 0.68, 0.49–0.94; and 0.65, 0.44–0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34–2.16; 3.16%, 0.38–5.94; 7.97%, 0.42–15.51; Pinteraction = 0.106). Conclusions PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.

5132Effect of PCSK9 inhibitors treatment on acute coronary syndrome and stroke incidence: a metanalysis of currently available clinical trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Cordero ◽  
L Facila ◽  
M Rodriguez-Manero ◽  
M Gomez-Martinez ◽  
V Bertomeu-Gonzalez ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Cochrane Collaboration ◽  
Significant Heterogeneity ◽  
Pcsk9 Inhibitors ◽  
Stroke Incidence ◽  
Coronary Syndrome ◽  
Major Cardiovascular Events

Abstract Background Proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors have demonstrated to induce large reductions in low-density lipoprotein cholesterol (LDLc) and major cardiovascular events but none of the studies was statistically powered to demonstrate reductions in specific endpoints rather than a combined end-point of major cardiovascular events. Methods We performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement using currently available studies involving PCSK9 inhibitors. The endpoint assessed were acute coronary syndrome (ACS) and stroke. Results We included 81,544 patients, 41,147 treated with a PSCK9 inhibitors: 17,179 with evolocumab; 13,718 with bococizumab and 10,250 with alirocumab (table 1). A total of 1,316 ACS were registered in the treatment group vs. 1,608 in controls, resulting in 18.0% reduction associated with PCSK9 treatment (figure 1). This result was reproduced exactly in the EBCT althougt a non-significant heterogeneity was detected (p=0.052). Metaregression analyses did not demonstrate the implication of the study (p=0.45), study drugs (p=0.26), age (p=0.89), hypertension (p=0.81) or diabetes (p=0.81) on such result. Results on stroke incidence are presented in figure 2. PCSK9 inhibitors treatment resulted in a 24% reduction of stroke when all studies were analyzed together; heterogeneity was statistically significant (p=0.021) but it was not observed in the EBCT analysis where PCSK9 inhibitors were associated with 24% stroke incidence reduction. Conclusions The meta-analysis of currently available studies demonstrates that PCSK9 inhibitors treatment reduces the incidence of ACS by 18% and stroke by 24%.

scholarly journals The Role of PCSK9 Inhibitors in the Improvement of Outcomes in Patients after Acute Coronary Syndrome: Results of ODYSSEY OUTCOMES Trial

2019 ◽  
Vol 14 (6) ◽  
pp. 922-934 ◽  
Author(s):  
Yu. A. Karpov
Keyword(s):  
Acute Coronary Syndrome ◽  
Statin Therapy ◽  
High Intensity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Pcsk9 Inhibitors ◽  
Coronary Syndrome

The aim of this review was to present the recently published results of ODYSSEY OUTCOMES trial and discuss the clinical perspective of these data. Patients with acute coronary syndrome are at very high risk of recurrent ischemic cardiovascular complications, especially during the first year after the event. The use of high-intensity statin therapy in this group of patients does not always lead to the achievement of target levels of atherogenic lipoproteins. PCSK9 inhibitors, administered in addition to statins, can provide additional reduction of low-density lipoprotein cholesterol, which leads to further improvements of outcomes in patients with atherosclerotic cardiovascular disease. According to the latest results from ODYSSEY OUTCOMES trial, among patients with recent acute coronary syndrome, who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who were treated with alirocumab then among those who received placebo. The treatment with alirocumab in patients with recent acute coronary syndrome was associated with reduction in death from any causes. The absolute risk reduction with alirocumab was the most prominent in the subpopulation of patients with low-density lipoprotein cholesterol ≥2,6 mmol/l at baseline. These results have implication for clinical practice and may play an important role for the improvement of outcomes in patients at highest cardiovascular risk after acute cardiovascular syndrome.

Current Therapy of Hypercholesterolemia

2015 ◽  
Vol 1 (1) ◽  
Keyword(s):  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Heart Association ◽  
Current Therapy ◽  
Pcsk9 Inhibitors ◽  
Double Blind ◽  
Coronary Syndrome ◽  
Prevention Studies ◽  
Risk Patients

Randomized, double-blind, placebo-controlled secondary prevention and primary prevention studies and observational studies have documented that statins reduce cardiovascular events in high-risk patients with hypercholesterolemia. The 2013 American College of Cardiology/American Heart Association guidelines on treatment of hypercholesterolemia support the use of statins in 4 major groups that will be discussed. The Expert Panel of these guidelines could find no data supporting the routine use of nonstatin drugs combined with statins to further reduce cardiovascular events. Since these guidelines were published, a double-blind, randomized trial of 18, 144 patients with an acute coronary syndrome demonstrated at 7-year follow-up that the incidence of cardiovascular events was 34.7% in patients randomized to simvastatin plus placebo versus 32.7% in patients randomized to simvastatin plus ezetimibe (hazard ratio = 0.936; p = 0.016). Proprotein convertase subtilisinkexin type 9 (PCSK9) inhibitors further lower serum low-density lipoprotein cholesterol by 50% to 70% in patients treated with statins and 4 phase 3 trials including more than 70, 000 patients are investigating whether these monoclonal antibodies to PCSK9 will lower cardiovascular events.

scholarly journals Intensification of lipid-lowering therapy in patients with acute coronary syndrome

2020 ◽  
Vol 8 (4S) ◽  
pp. 121-129
Author(s):  
N. V. Fedorova ◽  
D. Yu. Sedykh ◽  
V. V. Kashtalap ◽  
L. Yu. Chesnokova ◽  
O. V. Gruzdeva ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Lowering Therapy

Lipid metabolism disorders play a key role in determining cardiovascular risk. The level of low-density lipoprotein cholesterol is a significant factor in the pathophysiology of atherosclerosis and an indicator, the assessment of which reduces the risk of cardiovascular events. The prevalence of acute coronary syndrome in Russia remains at a high level. To date, the successful implementation and implementation of standards for the management of acute coronary syndrome has significantly reduced hospital mortality rates, however, secondary prevention issues remain relevant. Despite a wide range of lipid-lowering drugs, the use of which at maximum doses in acute coronary syndrome does not allow reaching the target levels of the lipid spectrum, the risk of developing repeated cardiovascular events remains high. Recently, a promising direction is the use of type 9 subtilisin/ kexin proprotein convertase inhibitors for the intensification of lipid-lowering therapy in patients with acute coronary syndrome. This article presents the clinical case of the successful use of one of the inhibitors of the proprotein convertase of subtilisin/kexin type 9, alirocoumab, in lowering low-density lipoprotein cholesterol and thereby reducing the risk of repeated cardiovascular events in a patient with acute coronary syndrome.

Anti-(apolipoprotein A-1) IgGs are associated with high levels of oxidized low-density lipoprotein in acute coronary syndrome

2008 ◽  
Vol 115 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Nicolas Vuilleumier ◽  
Emmanuel Charbonney ◽  
Lionel Fontao ◽  
Montserrat Alvarez ◽  
Natacha Turck ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Paraoxonase 1 ◽  
Control Group ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Coronary Syndrome ◽  
Apolipoprotein A ◽  
Increased Risk

ApoA-1 (apolipoprotein A-1) is the main component of HDL (high-density lipoprotein) and stabilizes PON-1 (paraoxonase-1), which prevents lipid peroxidation and oxLDL (oxidized low-density lipoprotein) formation. Autoantibodies against apoA-1 [anti-(apoA-1) IgG] have been found in antiphospholipid syndrome and systemic lupus erythematosous, two diseases with an increased risk of thrombotic events, as well as in ACS (acute coronary syndrome). OxLDL levels are also elevated in these diseases. Whether anti-(apoA-1) IgGs exist in other prothrombotic conditions, such as APE (acute pulmonary embolism) and stroke, has not been studied and their potential association with oxLDL and PON-1 activity is not known. In the present study, we determined prospectively the prevalence of anti-(apoA-1) IgG in patients with ACS (n=127), APE (n=58) and stroke (n=34), and, when present, we tested their association with oxLDL levels. The prevalance of anti-(apoA-1) IgG was 11% in the ACS group, 2% in the control group and 0% in the APE and stroke groups. The ACS group had significantly higher median anti-(apoA-1) IgG titres than the other groups of patients. Patients with ACS positive for anti-(apoA-1) IgG had significantly higher median oxLDL values than those who tested negative (226.5 compared with 47.7 units/l; P<0.00001) and controls. The Spearman ranked test revealed a significant correlation between anti-(apoA-1) IgG titres and serum oxLDL levels (r=0.28, P<0.05). No association was found between PON-1 activity and oxLDL or anti-(apoA-1) IgG levels. In conclusion, anti-(apoA-1) IgG levels are positive in ACS, but not in stroke or APE. In ACS, their presence is associated with higher levels of oxLDL and is directly proportional to the serum concentration of oxLDL. These results emphasize the role of humoral autoimmunity as a mediator of inflammation and coronary atherogenesis.

Efficacy and Safety of Evolocumab in Reducing Low Density Lipoprotein Cholesterol Levels in Chinese Patients with Non-ST-segment Elevation Acute Coronary Syndrome

2020 ◽  
Vol 18 ◽  
Author(s):  
Xiaohan Xu ◽  
Meng Chai ◽  
Yujing Cheng ◽  
Pingan Peng ◽  
Xiaoli Liu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Chinese Patients ◽  
Lipid Lowering ◽  
Control Group ◽  
Lipid Lowering Therapy ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
St Segment

Aims: To explore early intensive lipid-lowering therapy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease. Due to many reasons, the need for early intensive lipid-lowering therapy is far from being met in Chinese NSTE-ACS patients at high-risk of recurrent ischaemic events. Objective: To evaluate the feasibility, safety and efficacy of starting evolocumab in hospital to lower LDL-C levels in Chinese patients with NSTE-ACS. Methods: In this prospective cohort study initiated by researchers, 334 consecutive patients with NSTE-ACS who had sub-standard LDL-C levels (LDL-C ≥2.3 mmol/L after regular oral statin treatment for at least 4 weeks; or LDL-C ≥3.2 mmol/L without regular oral statin treatment) were included. Patients who agreed to treatment with evolocumab (140 mg subcutaneously every 2 weeks, initiated in hospital and used for 12 weeks after discharge) were enrolled in the evolocumab group (n=96) and others in the control group (n=238). All enrolled patients received regular statin treatment (atorvastatin 20 mg/day or rosuvastatin 10 mg/day; doses unchanged throughout the study).The primary endpoint was the change in LDL-C levels from baseline to week 12. Results: Most patients (67.1%) had not received regular statin treatment before. In the evolocumab group, LDL-C levels decreased significantly at week 4 and remained stable at week 8 and 12 (all p<0.001). At week 12, the LDL-C percentage change from baseline in the evolocumab group was -79.2±12.7% (from an average of 3.7 to 0.7 mmol/L), while in the control group it was -37.4±15.4% (from an average of 3.3 to 2.0 mmol/L). The mean difference between these 2 groups was -41.8% (95% CI -45.0 to -38.5%; p<0.001). At week 12, the proportions of patients with LDL-C levels <1.8 mmol/L and 1.4 mmol/L in the evolocumab group were significantly higher than in the control group (96.8 vs 36.1%; 90.6 vs 7.1%; both p<0.001). The incidence of adverse events and cardiovascular events was similar in both groups. Conclusions: In this prospective cohort study we evaluated the early initiation of evolocumab in NSTE-ACS patients in China. Evolocumab combined with statins significantly lowered LDL-C levels and increased the probability of achieving recommended LDL-C levels, with satisfactory safety and well tolerance.

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