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 Changes in circulating pro-protein convertase subtilisin/kexin type 9 levels – experimental and clinical approaches with lipid-lowering agents

2019 ◽  
Vol 26 (9) ◽  
pp. 930-949 ◽  
Author(s):  
C Macchi ◽  
M Banach ◽  
A Corsini ◽  
CR Sirtori ◽  
N Ferri ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Outcomes ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome

Regulation of pro-protein convertase subtilisin/kexin type 9 (PCSK9) by drugs has led to the development of a still small number of agents with powerful activity on low-density lipoprotein cholesterol levels, associated with a significant reduction of cardiovascular events in patients in secondary prevention. The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) studies, with the two available PCSK9 antagonists, i.e. evolocumab and alirocumab, both reported a 15% reduction in major adverse cardiovascular events. Regulation of PCSK9 expression is dependent upon a number of factors, partly genetic and partly associated to a complex transcriptional system, mainly controlled by sterol regulatory element binding proteins. PCSK9 is further regulated by concomitant drug treatments, particularly by statins, enhancing PCSK9 secretion but decreasing its stimulatory phosphorylated form (S688). These complex transcriptional mechanisms lead to variable circulating levels making clinical measurements of plasma PCSK9 for cardiovascular risk assessment a debated matter. Determination of total PCSK9 levels may provide a diagnostic tool for explaining an apparent resistance to PCSK9 inhibitors, thus indicating the need for other approaches. Newer agents targeting PCSK9 are in clinical development with a major interest in those with a longer duration of action, e.g. RNA silencing, allowing optimal patient compliance. Interest has been expanded to areas not only limited to low-density lipoprotein cholesterol reduction but also investigating other non-lipid pathways raising cardiovascular risk, in particular inflammation associated to raised high-sensitivity C-reactive protein levels, not significantly affected by the present PCSK9 antagonists.

scholarly journals Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering: ODYSSEY OUTCOMES trial

2020 ◽  
Vol 41 (44) ◽  
pp. 4245-4255 ◽  
Author(s):  
Michael Szarek ◽  
Vera A Bittner ◽  
Philip Aylward ◽  
Marie Baccara-Dinet ◽  
Deepak L Bhatt ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Coronary Revascularization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Relative Reduction ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein A ◽  
Coronary Syndrome

Abstract Aims Lipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events. Methods and results Cardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio Ptrend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median −5.0 [−13.6, 0] mg/dL) and corrected LDL-C (median −51.3 [−67.1, −34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events. Conclusion Baseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.

scholarly journals Predictive value of small dense low-density lipoprotein cholesterol for cardiovascular events in Chinese elder diabetes mellitus patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Li Xu ◽  
Xu Chen ◽  
Jingfen Lu ◽  
Yan Xu ◽  
Honglin Yang ◽  
...  
Keyword(s):  
Predictive Value ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Type 2 Dm

Abstract Background As a subcomponent of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C) has been suggested to be a better predictor of cardiovascular diseases (CVD). The aim of this research was to evaluate the predictive value of the sdLDL-C in cardiovascular events (CVs) in Chinese elderly patients with type 2 diabetes mellitus (DM). Methods A total of 386 consecutive type 2 DM patients were included into this study during December 2014 to December 2016. The serum sdLDL-C level of each subject was measured by homogeneous method. During a period of 48-month’s follow-up, the occurrence of CVs and associated clinical information were recorded. Receiver operating characteristic (ROC) curves were used to assess the predictive value of serum sdLDL-C to occurrence of major CVs. Results A total of 92 CVs occurred during the study period. The ROC curve analysis manifested that sdLDL-C in the study population had a matchable discriminatory power (AUC for sdLDL-C was 0.7366, P = 0.003). In addition, Kaplan-Meier event-free survival curves displayed an obvious increase of CVs risk for sdLDL‐C ≧ 26 mg/dL (log-rank = 9.10, P = 0.003). This phenomenon had analogous results in patients who received statins at baseline (log rank = 7.336, P = 0.007). Cox regression analysis revealed that the increase in HbA1c, glucose, LDL-C, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) and the decrease in apolipoprotein AI (ApoAI) were obviously interrelated with heightened CVs risk. Multiple Cox regression demonstrated that the increase of sdLDL-C and hemoglobin A1c (HbA1c) was significantly correlated with CVs. The results of the study indicated that high sdLDL-C level (> 10 mg/dL) was a risk factor for CVs in the multivariate model (HR 1.281, 95% CI 1.225–16.032; P < 0.01). Conclusion sdLDL-C level could be an effective predictor in predicting the future CVs for Chinese elderly patients with type 2 DM and dyslipidemia.

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines

2020 ◽  
pp. 204748732094010
Author(s):  
Konstantinos C Koskinas ◽  
Baris Gencer ◽  
David Nanchen ◽  
Mattia Branca ◽  
David Carballo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Coronary Syndromes

Aims The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes. Methods and results We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria. Conclusions In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

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