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.

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 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 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.

scholarly journals Treatment Options for Hypercholesterolemia and Combined Dyslipidemia: Focus on Pitavastatin

2011 ◽  
Vol 3 ◽  
pp. CMT.S6565
Author(s):  
Yasushi Saito
Keyword(s):  
Cardiovascular Events ◽  
Treatment Options ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Multidrug Therapy ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Sustained Action ◽  
Plaque Regression

Pitavastatin is one of the most effective treatment agents for lowering serum low-density lipoprotein cholesterol (LDL-C) levels. Because pitavastatin is scarcely metabolized, the risk of drug-drug interactions during multidrug therapy is low, and the LDL-C target is achieved in the majority of patients. The incidence of adverse events associated with pitavastatin treatment has so far been comparable to or lower than that associated with other statins, and glucose metabolism is not affected by the drug. Pitavastatin promotes plaque regression and improves the plaque composition in patients with acute coronary syndrome. The serum level of high-density lipoprotein cholesterol (HDL-C) during treatment with pitavastatin was demonstrated to be inversely associated with the incidence of cardiovascular events. Because of its effective and sustained action to increase HDL-C, pitavastatin is expected to contribute to the prevention of cardiovascular events, in addition to its potent LDL-C lowering effect, especially in patients with low serum HDL-C levels.

scholarly journals Low-density lipoprotein cholesterol levels on admission and long-term outcomes in statin-naive patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Satou ◽  
Y Matsuzawa ◽  
E Akiyama ◽  
M Konishi ◽  
T Yoshii ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Coronary Syndrome ◽  
Statin Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Composite Outcomes

Abstract Introduction Dyslipidemia, especially an increase in the low-density lipoprotein cholesterol (LDL-C) has been established as one of the most important risk factors for atherosclerotic cardiovascular diseases. In contrast, some recent studies have shown that the low LDL-C level was associated with short-term poor prognosis in patients with cardiovascular disease, and this is so-called “cholesterol paradox”. However, there is few data evaluating the effects on long-term outcome of “cholesterol paradox” in patients with acute coronary syndrome (ACS). Purpose The purpose of this study was to examine whether the low LDL-C level on admission affect long-term prognosis in patients with ACS. Methods A total of 434 ACS patients who survived to hospital discharge were enrolled in this study. All patients were statin-naïve on admission, and were received statin therapy after hospitalization. Patients were divided into the low LDL-C (≤114 mg/dl) and high LDL-C (&gt;114 mg/dl) groups using the first tertile of the LDL-C level on admission. The primary endpoint was composite outcomes of all-cause death, myocardial infarction, ischemic stroke, hospitalization for congestive heart failure and unplanned revascularization. Results During a median follow-up period of 5.5 years, primary endpoint occurred in 117 patients. Overall, event-free rates differed significantly between the low and high LDL-C groups, demonstrating the lower event-free rate in patients with the low LDL-C group (38.9% in low LDL-C group versus 20.7% in high LDL-C group, p=0.0002; Figure). Even after adjustment for age, sex, body mass index, and various classical risk factors, the low LDL-C group was significantly at higher risk for primary composite outcomes compared to the high LDL-C group (adjusted hazard ratio 1.65, 95%-confidence interval 1.10–2.49, p=0.02). Conclusion In patients with ACS, the low LDL-C level on admission was significantly associated with long-term worse prognosis, regardless of statin therapy at discharge. In ACS patients with low LDL-C level, it might be necessary for elucidating the residual risk for secondary adverse event to improve their prognosis. Funding Acknowledgement Type of funding source: None

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