Abstract P62: Efficacy of Ezetimibe 2.5 Milligrams Utilizing a Novel Tablet Splitting Strategy

Author(s):  
Lawrence Baruch ◽  
Bhanu Gupta ◽  
Ann Haynos ◽  
Sanjay Agarwal ◽  
Swapna Johnson ◽  
...  

Background: Ezetimibe's excellent tolerability and approximately 20% LDL lowering effect have made it the most commonly prescribed 2 nd line lipid lowering agent after statins. Ezetimibe is available only in a 10 mg form, either as a stand-alone tablet or in combination with simvastatin as ezetimibe/simvastatin (Vytorin). During clinical development, a wide range of ezetimibe doses were evaluated, including 0.25, 1, and 5 mg. A 2.5 mg dose of ezetimibe was never evaluated. Prospective and retrospective studies have demonstrated that splitting a 10 mg ezetimibe tablet, which provides approximately 5 mg of ezetimibe, is clinically equivalent to a whole 10 mg tablet. On the basis of these results, along with others that demonstrated 1 mg of ezetimibe significantly lowered LDL by approximately 13 to 15%, we prospectively randomized patients to either a simvastatin 20 mg tablet or an ezetimibe/simvastatin 10/80 tablet (10 mg ezetimibe plus 80 mg simvastatin) split into 4 to yield an estimated daily dose of ezetimibe 2.5 mg and simvastatin 20 mg. The efficacy of the two strategies on lipid parameters was compared. We selected ezetimibe/simvastatin 10/80 as a means of obtaining 2.5 mg of ezetimibe, as this tablet size can be readily split into 4 relatively equal parts with a commercially available tablet splitter. Study design: Thirty three subjects were randomized to either simvastatin 20 mg or an ezetimibe/simvastatin 10/80 tablet divided into 4. Lipid panels were collected at baseline and after 6 weeks of therapy. Results: Twenty nine of the 33 subjects successfully completed the study. Conclusion: From a comparative effectiveness perspective, ezetimibe 2.5 mg, delivered by splitting an ezetimibe/simvastatin10/80 tablet into 4, provides the greatest value and delivers LDL lowering comparable to full dose ezetimibe 10 mg. This novel tablet splitting strategy may be applicable to other medications and provide significant additional cost-reduction. Lipid Value (mg/dL) ES 2.5/20 * (n=14) Simvastatin 20 (n=15) P (between groups) % change from baseline (p ** ) % change from baseline (p ** ) Low density lipoprotein -44.7 ± 19.0% (<.001) -27.1 ± 22.4% (<.001) 0.03 High density lipoprotein -5.1 ± 7.4% (<.05) -0.7 ± 9.3% (ns) 0.17 Triglycerides -23.3 ± 3.8% (<.01) -11.9 ± 6.0% (.03) 0.18 Total cholesterol -34.2 ± 13.0% (<.001) -19.9 ± 14.6% (<.001) 0.001 Data is expressed as mean ± SD. * ES: Ezetimibe/simvastatin 10/80 tablet split into 4 parts, supplying ezetimibe 2.5 and simvastatin 20. ** P-value for the change in the lipid parameter from the baseline value.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Lee ◽  
S R Lee ◽  
E K Choi ◽  
K D Han ◽  
S Oh

Abstract Background High levels of lipids and lipid variability are established risk factors for atherosclerotic cardiovascular disease. We investigated their roles in the development of atrial fibrillation (AF). This is the largest cohort study yet on the association between lipid levels and AF, and the first study on the association between lipid variability and AF. Methods A nationwide population-based cohort of 3,828,652 adults (mean age 43.9 years) from the Korean National Health Insurance Service database without prevalent AF, not on lipid-lowering medication, and with at least 3 measurements of each lipid parameter at 1–2 year intervals over a 4-year period were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured, and lipid variability was calculated using variability independent of mean. The cohort was divided into quartiles by baseline lipid levels and lipid variability, and followed up for incident AF. Results During median 3.4 years of follow-up, AF was newly diagnosed in 13,240 (0.35%). AF development was inversely associated with TC and LDL-C levels (for top vs. bottom quartile; TC, hazard ratio [HR] 0.76, 95% confidence interval [95% CI] 0.72–0.80); LDL-C, HR 0.78, 95% CI 0.74–0.82) in both sexes, and with TG levels in men (HR 0.85, 95% CI 0.80–0.90). Meanwhile, AF development was associated with higher LDL-C and HDL-C variability (for top vs. bottom quartile; LDL-C, HR 1.16, 95% CI 1.10–1.22; HDL-C, HR 1.08, 95% CI 1.03–1.14) in both sexes, and with TC variability in men (HR 1.16, 95% CI 1.10–1.22). Conclusions Lower cholesterol levels (TC, LDL-C) and higher cholesterol variability (LDL-C, HDL-C) were associated with higher risk for AF. Low TG levels and high TC variability were also associated with AF incidence in men. These findings support the “cholesterol paradox” in AF, and suggest that cholesterol variability is also a risk factor for AF development.


2015 ◽  
Vol 36 (2) ◽  
pp. 146-153 ◽  
Author(s):  
Yeoungjee Cho ◽  
Janine Büchel ◽  
Sonja Steppan ◽  
Jutta Passlick-Deetjen ◽  
Carmel M. Hawley ◽  
...  

Background The longitudinal trends of lipid parameters and the impact of biocompatible peritoneal dialysis (PD) solutions on these levels remain to be fully defined. The present study aimed to a) evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solutions on serum lipid parameters, and b) explore the capacity of lipid parameters (total cholesterol [TC], triglyceride [TG], high density lipoprotein [HDL], TC/HDL, low density lipoprotein [LDL], very low density lipoprotein [VLDL]) to predict cardiovascular events (CVE) and mortality in PD patients. Methods The study included 175 incident participants from the balANZ trial with at least 1 stored serum sample. A composite CVE score was used as a primary clinical outcome measure. Multilevel linear regression and Poisson regression models were fitted to describe the trend of lipid parameters over time and its ability to predict composite CVE, respectively. Results Small but statistically significant increases in serum TG (coefficient 0.006, p < 0.001), TC/HDL (coefficient 0.004, p = 0.001), and VLDL cholesterol (coefficient 0.005, p = 0.001) levels and a decrease in the serum HDL cholesterol levels (coefficient -0.004, p = 0.009) were observed with longer time on PD, whilst the type of PD solution (biocompatible vs standard) received had no significant effect on these levels. Peritoneal dialysis glucose exposure was significantly associated with trends in TG, TC/HDL, HDL and VLDL levels. Baseline lipid parameter levels were not predictive of composite CVEs or all-cause mortality. Conclusion Serum TG, TC/HDL, and VLDL levels increased and the serum HDL levels decreased with increasing PD duration. None of the lipid parameters were significantly modified by biocompatible PD solution use over the time period studied or predictive of composite CVE or mortality.


2021 ◽  
Vol 11 (5) ◽  
pp. 2001
Author(s):  
Magbool Alelyani ◽  
Safar Abadi Saeed Al-Saleem Alshahrani ◽  
Gaffar Sarwar Zaman ◽  
Ibrahim Hadadi ◽  
Mustafa Jafar Musa ◽  
...  

Smoking is well known to be correlated with cardiovascular abnormalities, in particular atherosclerosis and heart diseases. This article investigates the effect and relationship of smoking tobacco on the thickness of the intima–media (IMT) belonging to the common carotid arteries (CCAs), and also blood concentration of the lipid profile (LP), mainly the total cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and also triglycerides. Nineteen male tobacco smokers and thirty-five healthy male non-smoking Saudi participants were involved in this study after obtaining their informed consent. An ultrasound and a spectrophotometer were used to determine the IMTs and lipid parameters, respectively. The thicknesses of the smokers’ right (RCA) and left carotid (LCA) arteries (0.72 and 0.7 mm, respectively) were significantly greater than the thicknesses of the arteries of the non-smokers (0.58 and 0.62 mm, respectively) (p-value = 0.005 and 0.04). Insignificant differences between the means of the other parameters in the two groups were studied. Smoking is a risk factor for stroke, because it significantly increases the IMTs of both the right and left carotid arteries.


2020 ◽  
Vol 103 (9) ◽  
pp. 914-919

Background: Atorvastatin is a widely used statin, of which there are two available polymorphs: crystalline (original) and amorphous (generic). Pharmacological studies showed the similarity between both forms. However, the lipid-lowering effectiveness of the amorphous form was still uncertain. Objective: To compare the effectiveness of crystalline and amorphous form of atorvastatin. Materials and Methods: The authors conducted an observational cross-sectional analytic study by retrospectively collecting data from January 1, 2016 to December 31, 2017 of the patients at Queen Sirikit Heart Center of the Northeast where the original regimen of crystalline atorvastatin had been replaced by the amorphous atorvastatin at the same dose. Patients must have been prescribed each form of atorvastatin for at least six weeks. The lipid profiles taken at the closest to the switching point (before and after) were used. The primary outcome was changes in low-density lipoprotein (LDL) levels. The secondary outcomes were changes in total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) levels, as well as a comparison of LDL levels in patients whose tablets were split. Results: Eight hundred twenty-five patients were included in the present study. The mean age was 63.7±9.9 years. Five hundred sixty-eight patients (68.8%) were male, and 736 (89.2%) were treated as secondary prevention. The mean LDL levels during crystalline and amorphous atorvastatin use were 92.4±39.0 and 91.8±41.0 mg/dL, respectively (mean difference –0.6; 95% confidence interval [CI], –2.2 to 1.0; p=0.460). The mean TC, TG, and HDL levels during crystalline and amorphous form use were 153.1±43.3 and 152.0±48.6 mg/dL (p=0.400), 153.4±129.0 and 155.0±148.3 (p=0.740), 43.6±11.9, and 44.4±12.0 (p=0.004), respectively. Among the patients who had tablet splitting, the mean LDL levels during crystalline and amorphous atorvastatin use were 89.2±28.3 and 91.0±30.8 mg/dL, respectively (p=0.279). Side effects were recorded in nine patients, one of which was rhabdomyolysis. Conclusion: The effectiveness of amorphous atorvastatin at lowering lipids was comparable to that of atorvastatin in its crystalline form, and patients were generally able to tolerate amorphous atorvastatin. Keywords: Atorvastatin, Crystalline, Amorphous, Lipid-lowering, Low-density lipoprotein


1984 ◽  
Vol 51 (02) ◽  
pp. 186-188 ◽  
Author(s):  
A Szczeklik ◽  
R J Gryglewski ◽  
K Sladek ◽  
E Kostka-Trąbka ◽  
A Żmuda

SummaryDihomo-γ-linolenic acid (DHLA), a precursor of monoenoic anti-aggregatory prostaglandins (PGE1, PGD2), was administered for 4 weeks in a daily dose of 1.0 g into 33 patients with atherosclerosis on a basis of a double-blind trial. Comparison of treatment and placebo groups revealed elevation of DHLA in red cell lipids in DHLA-treated subjects. No differences, however, between the two groups could be observed in platelet aggregability, thromboxane A2 generation by platelets, serum cholesterol, PGE1 and PGE2 levels, and in inhibitory activity of low-density lipoproteins against prostacyclin synthetizing system in arteries. The dietary supplementation used did not lead to distinct antithrombotic effects.


2019 ◽  
Vol 20 (10) ◽  
pp. 1029-1040 ◽  
Author(s):  
Xinjie Lu

Background:One of the important factors in Low-Density Lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9) is a newly discovered serine protease that destroys LDLR in the liver and thereby controls the levels of LDL in plasma. Inhibition of PCSK9-mediated degradation of LDLR has, therefore, become a novel target for lipid-lowering therapy.Methods:We review the current understanding of the structure and function of PCSK9 as well as its implications for the treatment of hyperlipidemia and atherosclerosis.Results:New treatments such as monoclonal antibodies against PCSK9 may be useful agents to lower plasma levels of LDL and hence prevent atherosclerosis.Conclusion:PCSK9's mechanism of action is not yet fully clarified. However, treatments that target PCSK9 have shown striking early efficacy and promise to improve the lives of countless patients with hyperlipidemia and atherosclerosis.


2020 ◽  
Vol 18 ◽  
Author(s):  
Xiaohan Xu ◽  
Meng Chai ◽  
Yujing Cheng ◽  
Pingan Peng ◽  
Xiaoli Liu ◽  
...  

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.


2021 ◽  
Vol 10 (14) ◽  
pp. 3098
Author(s):  
Shota Okutsu ◽  
Yoshifumi Kato ◽  
Shunsuke Funakoshi ◽  
Toshiki Maeda ◽  
Chikara Yoshimura ◽  
...  

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08–1.58, p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Giuseppina Russo ◽  
Basilio Pintaudi ◽  
Carlo Giorda ◽  
Giuseppe Lucisano ◽  
Antonio Nicolucci ◽  
...  

Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men.Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM.Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P<0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups.Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk.


2018 ◽  
Vol 12 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Andromachi Reklou ◽  
Michael Doumas ◽  
Konstantinos Imprialos ◽  
Konstantinos Stavropoulos ◽  
Dimitris Patoulias ◽  
...  

Background: Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD). Objective: In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events. Results: In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s’ and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1β with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels. Conclusion: Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy.


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