Efficacy Of Lipid-lowering Therapy Research Articles

Dyslipidaemia in patients with chronic kidney disease - a neglected cardiovascular risk factor.

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). In addition, CKD itself is a coronary artery disease equivalent due to its atherogenic potential. Despite the role of CKD in ASCVD and recommendations to control lipid levels aggressively, landmark lipid studies have often excluded patients with advanced CKD. Furthermore, there is a scarcity of data on the use and efficacy of lipid-lowering therapy (LLT) in those with CKD in South Africa (SA). To determine the prevalence and control of dyslipidaemia in a cohort of SA patients with CKD. A retrospective, cross-sectional observational study of 250 patients with CKD attending the Charlotte Maxeke Johannesburg Academic Hospital renal clinic from 1 July 2019 to 31 July 2020 was carried out. Lipograms, the use of LLT and achievement of target lipid levels were examined. The median (interquartile range) age of this cohort was 58 (46 - 69) years; 50.4% were males and 64.4% black African. Dyslipidaemia was prevalent in 83.6% (n=209) of patients. A total of 169 (67.6%) patients were on LLT, and of these only 28 (16.6%) achieved the recommended low-density lipoprotein cholesterol (LDL-C) target. Of those not on LLT, 51 (63%) were eligible for LLT and almost all were classified as either very high risk (64.2%) or high risk (28.4%) for ASCVD. Of those on LLT, all were on statin therapy, of which simvastatin at a mean dose of 20 mg daily was the most commonly prescribed LLT. This cohort comprised a large proportion of patients classified as high or very high risk for ASCVD. Despite this, the use of LLT was inadequate, and <20% of patients were at target LDL-C levels. These data suggest a greater need for awareness of initiating LLT to achieve recommended target LDL-C levels in patients with CKD.

Effects of Lipid Lowering Therapies on Vulnerable Plaque Features: An Updated Narrative Review of the Literature.

The clinical evidence on the efficacy of lipid lowering therapy in patients with coronary artery disease (CAD) is unequivocally established. However, the effects of these therapies on plaque composition and stability are less clear. The use of intracoronary imaging (ICI) technologies has emerged as a complement to conventional angiography to further characterize plaque morphology and detect high-risk plaque features related to cardiovascular events. Along with clinical outcomes studies, parallel imaging trials employing serial evaluations with intravascular ultrasound (IVUS) have shown that pharmacological treatment has the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved. Subsequently, the introduction of high-intensity lipid lowering therapy led to much lower levels of low-density lipoprotein cholesterol (LDL-C) levels than achieved in the past, resulting in greater clinical benefit. However, the degree of atheroma regression showed in concomitant imaging trials appeared more modest as compared to the magnitude of clinical benefit accrued from high-intensity statin therapy. Recently, new randomized trials have investigated the additional effects of achieving very low levels of LDL-C on high-risk plaque features-such as fibrous cap thickness and large lipid accumulation-beyond its size. This paper provides an overview of the currently available evidence of the effects of moderate to high-intensity lipid lowering therapy on high-risk plaque features as assessed by different ICI modalities, reviews data supporting the use of these trials, and analyse the future perspectives in this field.

Adherence to lipid-lowering therapy and reaching treatment goals in youth seen in a preventive cardiology clinic.

The efficacy of lipid-lowering therapy in reducing cardiovascular disease in adults is well-established. Unfortunately, it is also well-established that adults have inadequate adherence to lipid-lowering therapy, which is associated with increased costs and mortality. However, the adherence patterns of youth prescribed lipid-lowering therapy is not well-described. We analyzed data that was prospectively collected from patients <27 years-old who were referred to a large regional preventive cardiology clinic from 2010 to 2017. Adherence to lipid-lowering therapy was self-reported at the patient's most recent clinic visit and categorized as either adequate adherence (≥80%) or inadequate adherence (<80%). We compared adherence rates by demographic factors, class of lipid-lowering therapy, length of time on lipid-lowering therapy, family history, lipid parameters, and laboratory measures of adverse effects. In our cohort, we had 318 patients prescribed a lipid-lowering medication over a seven-year period. Of those, 235 (75%) had adequate adherence. Those with adequate adherence had an improved LDL-C (123mg/dL [standard deviation (SD) 32.3] vs. 167mg/dL [SD 50.4], p<0.05), total cholesterol (198mg/dL [49.5] vs. 239mg/dL [SD 53.2]), and non-HDL-C (148mg/dL [SD 38.7] vs. 193mg/dL [SD 43.9]). In addition, patients with adequate adherence were more likely to reach goal LDL-C of <130mg/dL than those with inadequate adherence (130 vs. 25, p<0.01). The relationship between LDL-C and adherence remained statistically significant after controlling for age, gender, and the length of time on therapy (β=-0.66, p<0.01). Adherence level did not differ by gender, class of lipid-lowering therapy, length of time on lipid-lowering therapy, or presence of a family history of an atherosclerotic event. The findings were similar when we only analyzed those prescribed a statin. Self-reported adherence to lipid-lowering therapy in youth is excellent and was associated with achieving goal LDL-C goals. Obtaining adherence data from patients may help more patients reach LDL-C goals.

Underrepresentation of ethnic and regional minorities in lipid-lowering randomized clinical trials: a systematic review and meta-analysis.

The efficacy of lipid-lowering therapies (LLT) among different ethnicities and regions remains unclear. We aimed to assess cardiovascular event reductions associated with LLT according to ethnicity and region in previously published randomized clinical trials (RCTs). Medline, EMBASE and Cochrane CENTRAL were searched for RCTs of statins, ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors comparing intensive versus less intensive low-density lipoprotein cholesterol (LDL-C) lowering. The primary endpoint was major adverse cardiovascular events (MACE) defined as the composite of cardiovascular mortality, myocardial infarction, stroke and revascularisation. Random effects meta-analysis was used to pool risk ratios (RR) with 95% confidence intervals (CI) adjusted per mmol/L reduction in LDL-C. Fifty-three trials with 329,897 participants were included. Among participants, 39.5% were from Europe, 16.0% from North America, 9.0% from Japan, 2.8% from Australasia, 1.8% from South America, 1.1% from Asia, 0.6% from South Africa and 29.2% were unspecified. Among trials reporting ethnicities, there were 60.3% White, 20.2% Japanese, 9.4% Asian, 5.5% Black and 4.7% Latin American. There was reduction in MACE with LLT in regions including Australasia (RR 0.75, 95% CI 0.67-0.85), North America (RR 0.75, 95% CI 0.69-0.83), Europe (RR 0.78, 95% CI 0.71-0.86) and Japan (RR 0.73, 95% CI 0.63-0.85), and in Black ethnicity (RR 0.55, 95% CI 0.37-0.82). Head-to-head comparisons between regions and ethnicities revealed no significant differences in MACE reduction. Despite underrepresentation in clinical trials, regional and ethnic minority groups such as Australasia and Blacks appear to derive at least as much cardiovascular benefit from LLT.

Optimal low-density lipoprotein cholesterol target level in Korean acute myocardial infarction patients (

BackgroundCurrent treatment guidelines for acute myocardial infarction (AMI) recommend lowering low density lipoprotein cholesterol (LDL-C). However, previous clinical studies among East Asian AMI patients failed to prove its clinical efficacy of lipid lowering therapy based on Western target LDL-C level. Thus, the purpose of this study is directly to compare the clinical outcomes of target LDL-C < 70 mg/dL and < 55 mg/dL and identify optimal target LDL-C level and in Korean AMI patients. Methods and resultsA total of 2198 AMI patients in Korea AMI Registry – National Institute of Health were enrolled. Patients were initially divided into LDL-C non-target group (n = 1115) and target group (n = 1083). Successful achievement of follow up target LDL-C was defined as <70 mg/dL and ≥ 50% reduction from baseline. Target group patients were additionally divided to <70 mg/dL group (n = 698) and <55 mg/dL group (n = 385). Propensity score matching analysis was done in non-target vs. target group and <70 mg/dL vs. <55 mg/dL group. In the matched population, the risk of 3 years major adverse cardiac event (MACE) (13.0% vs 9.8%, HR: 0.73; 95% CI: 0.56–0.96; p = 0.025) was higher in non-target group patients. However, the risk of MACE was similar in <70 mg/dL and < 55 mg/dL group patients (10.0% vs 8.1%, HR: 0.75, 95% CI: 0.46–1.22; p = 0.247). ConclusionIn the present study, target LDL-C level of <70 mg/dL and ≥ 50% reduction from baseline level was associated with better clinical outcomes in Korean AMI patients. However, further lowering target LDL-C level of <55 mg/dL showed no additional benefits.

Sex disparities in lipid-lowering therapy and dyslipidemia control in a coronary rehabilitation program

Abstract Introduction Lipid control is one of the most important secondary cardiovascular prevention targets. Although cardiovascular disease is the most common cause of death for both genders, several studies have consistently shown that women are less likely to receive guideline-recommended secondary prevention medications after an acute coronary syndrome (ACS). Purpose To compare sex disparities in dyslipidemia control in a secondary prevention population with ACS in light of the ESC Dyslipidemia Guidelines. Methods We retrospectively analysed all patients who participated in a Coronary Rehabilitation Program (CRP) after an ACS from January 2011 to October 2019. Clinical data was collected at presentation and during 12 months follow-up. Doses of atorvastatin ≥40 mg, rosuvastatin ≥20 mg or a combination of a statin and ezetimibe were considered high-intensity LDL-lowering therapy (HIT). Results Of a total of 881 patients enrolled, mean age 55.0±10.0 year-old, 16.1% were female. At baseline there were no differences respecting clinical features between genders. At admission, 51.4% of patients had ST-elevation myocardial infarction and, concerning to cardiovascular risk factors, 63% patients had dyslipidemia, 46% had hypertension, 19% were diabetic, 76% were smokers or previous smokers, 27% had family history of coronary disease and 12% had previous coronary disease (ACS or &amp;gt;50% coronary artery stenosis). At hospital admission, females and males had similar mean LDL-levels [120.7 vs 118.1 mg/dL, t(708)=0.691, p=0.496]. The vast majority of patients from both genders were prescribed with statins on hospital discharge (99.5%) and maintain it during follow-up (99.3%). Female patients received more HIT during follow-up (67.8% vs 53.9% at baseline, p=0.015; 75.6% vs 59.0% after CRP, p=0.003; and 79.8% vs 65.1% at 1-year-follow-up, p=0.007). During follow-up, at the end of the CRP (about 3 months after event), male patients exhibit a better control of LDL [82.0 vs 75.6 mg/dL, t(597)=2.4, p=0.016)] with 12.8% vs 16.4% below 55 mg/dL and 29.8% vs 44.5% below 70 mg/dL (p=0.008). At 1-year follow-up, both genders exhibited similar LDL-control due to a worsening control of the male population (81.9 vs 80.6 mg/dL, t(540)=0.52, p=0.605). Only 13.3% of females had LDL below 55 mg/dL (vs 12.9%, p=0.921) and 32.5% below 70 mg/dL (vs 37.0%, p=0.432). Conclusion This real-life study showed that guideline recommended LDL target is not achieved in the majority of patients, even under a structured CRP. Unlike other reports, there were more women receiving potent anti-dyslipidemic therapy. Nevertheless, women showed a poor control of LDL-concentration after three months of ACS and a similar control after 1-year; this highlights the uncertainties concerning the efficacy of lipid-lowering therapy in women, an underrepresented population in clinical trials. Funding Acknowledgement Type of funding sources: None.

Efficacy of Lipid-Lowering Therapy during Cardiac Rehabilitation in Patients with Diabetes Mellitus and Coronary Heart Disease.

Background: Cardiac rehabilitation (CR) in patients with coronary heart disease (CHD) increases adherence to a healthy lifestyle and to secondary preventive medication. A notable example of such medication is lipid-lowering therapy (LLT). LLT during CR improves quality of life and prognosis, and thus is particularly relevant for patients with diabetes mellitus, which is a major risk factor for CHD. Design: A prospective, multicenter registry study with patients from six rehabilitation centers in Germany. Methods: During CR, 1100 patients with a minimum age of 18 years and CHD documented by coronary angiography were included in a LLT registry. Results: In 369 patients (33.9%), diabetes mellitus was diagnosed. Diabetic patients were older (65.5 ± 9.0 vs. 62.2 ± 10.9 years, p < 0.001) than nondiabetic patients and were more likely to be obese (BMI: 30.2 ± 5.2 kg/m2 vs. 27.8 ± 4.2 kg/m2, p < 0.001). Analysis indicated that diabetic patients were more likely to show LDL cholesterol levels below 55 mg/dL than patients without diabetes at the start of CR (Odds Ratio (OR) 1.9; 95% CI 1.3 to 2.9) until 3 months of follow-up (OR 1.9; 95% CI 1.2 to 2.9). During 12 months of follow-up, overall and LDL cholesterol levels decreased within the first 3 months and remained at the lower level thereafter (p < 0.001), irrespective of prevalent diabetes. At the end of the follow-up period, LDL cholesterol did not differ significantly between patients with or without diabetes mellitus (p = 0.413). Conclusion: Within 3 months after CR, total and LDL cholesterol were significantly reduced, irrespective of prevalent diabetes mellitus. In addition, CHD patients with diabetes responded faster to LTT than nondiabetic patients, suggesting that diabetic patients benefit more from LLT treatment during CR.

Abstract 13503: Relative Efficacy of Alirocumab, Bempedoic Acid, Evolocumab, Ezetimibe and Inclisiran Added to Statins for Reduction of Low Density Lipoprotein Cholesterol - A Network Meta-Analysis of Randomized Clinical Trials

Background: Many patients with hypercholesterolemia and/or cardiovascular disease are unable to achieve sufficient low-density lipoprotein cholesterol (LDL-C) reduction with statins alone (or are statin intolerant). This is increasingly the case with clinical guidelines recommending that lower LDL-C levels are beneficial for patients. This network meta-analysis (NMA) assessed the relative efficacy of lipid lowering therapies (LLTs) added to statins for reducing LDL-C. Methods: A systematic review of randomized controlled clinical trials to May 2020 identified 48 studies for inclusion in the primary NMA. The primary NMA included studies ≥12 weeks duration in which alirocumab, bempedoic acid, evolocumab, ezetimibe, or inclisiran were added to moderate-high intensity statins (or lower intensity / no statin in statin intolerant patients). Random effects NMA was used to analyse % change in LDL-C to compare the treatment effects indirectly. Results: Over 12 weeks, all non-statin LLTs significantly reduced LDL-C from baseline versus placebo. Evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were associated with largest LDL-C reductions, which were greater than those achieved with lower/alternative doses of alirocumab, bempedoic acid (± ezetimibe), ezetimibe and inclisiran (Table). Consistent results were observed in sensitivity analyses to address heterogeneity (excluding familial hypercholesterolemia and east Asian studies), in the subgroup NMA of studies in predominantly atherosclerotic cardiovascular disease patients, and in the statin intolerant subgroup NMA. Conclusions: All agents reduced LDL-C, however, the PCSK9 inhibitors evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were the most effective LLT regimens for reducing LDL-C when added to statins.

Adherence to statin therapy in patients with high and very high cardiovascular risk in real clinical practice

Despite the proven efficacy of lipid-lowering therapy, adherence to long-term statin therapy in patients with cardiovascular disease remains low.Aim. To study adherence to long-term statin therapy and factors associated with adherence in patients with high and very high cardiovascular risk (CVR) in real clinical practice.Materials and methods. The single-center cohort study included 53 patients (mean age 68.1 ± 10.2 years) with high or very high CVR on the SCORE scale and have been taking statins for at least 3 months prior to inclusion in the study. The level of low-density lipoprotein cholesterol (LDL-C), cognitive impairment (MoCA test), anxiety and depression (HADS scale), presence of senile asthenia (FRAIL scale), M. Charlson comorbidity index were assessed. Adherence to statin therapy was assessed using the original questionnaire. The correlation between patient adherence and ordinal variables for the scores of the studied scales was studied.Results. Completely adherent to statin therapy were only 12 (22%) patients, 14 (26%) were insufficiently adherent, 27 (51%) were non-adherent. The target level of LDL-С was achieved in 13 (25%) patients. 38 (72%) patients showed a decrease in cognitive functions; a positive correlation was found between adherence and the MoCA test (r = 0.44, p = 0.04). Clinical and subclinical depression and anxiety were noted in 12 (23%) and 14 (26%) patients, respectively. A statistically significant negative correlation was found between adherence and depression (r = –0.32; p = 0.04) and a positive correlation between adherence and anxiety (r = 0.44; p = 0.04). There was no statistically significant correlation between adherence and the FRAIL fragility scale, as well as the M. Charlson comorbidity index.Conclusions. Depression and cognitive decline are associated with decreased adherence to statin therapy.

Concepts and Controversies: Lipid Management in Patients with Chronic Kidney Disease.

Atherosclerotic cardiovascular disease (ASCVD) remains an important contributor of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is recognized as an important risk enhancer that identifies patients as candidates for more intensive low-density lipoprotein (LDL) cholesterol lowering. However, there is controversy regarding the efficacy of lipid-lowering therapy, especially in patients on dialysis. Among patients with CKD, not yet on dialysis, there is clinical trial evidence for the use of statins with or without ezetimibe to reduce ASCVD events. Newer cholesterol lowering agents have been introduced for the management of hyperlipidemia to reduce ASCVD, but these therapies have not been tested in the CKD population except in secondary analyses of patients with primarily CKD stage 3. This review summarizes the role of hyperlipidemia in ASCVD and treatment strategies for hyperlipidemia in the CKD population.

Интенсификация липидснижающей терапии у пациентов с тяжелыми нарушениями липидного обмена в условиях специализированных липидных центров. Возможности применения эволокумаба

The article presents current data on the prevalence of dyslipidemia worldwide and in the Russian Federation as the main cardiovascular risk factor of developing diseases associated with atherosclerosis. The article identifies the problems of low-level detection of dyslipidemia in the population and insufficient efficacy of lipid-lowering therapy to achieve the lipid profile target values depending on the established risk. It also presents the possibilities of modern lipid-lowering therapy with the use of innovative drugs — PCSK9 inhibitors and the use of evolocumab in accordance with evidence-based medicine. Adding that, the article shows the experience of two lipid control centers (in Kemerovo and Surgut) with the postulation of the need to expand the lipid control center chain to improve methods for providing medical care to patients with severe forms of dyslipidemia. The possibilities of intensifying lipid-lowering therapy in real clinical practice are outlined on the example of patients undergoing treatment in the lipid control center of Kemerovo. Evolocumab has been shown to be highly effective: reduction of atherogenic cholesterol fractions by 67% from the baseline and high safety of such therapy.KEYWORDS: lipid metabolism disorders, statins, lipid-lowering therapy, familial hypercholesterolemia, PCSK9 inhibitors, evolocumab.FOR CITATION: Barbarash O.L., Kashtalap V.V., Fedorova N.V. et al. Intensification of lipid-lowering therapy in patients with severe lipid metabolism disorders in specialized lipid control centers. Possibilities of using evolocumab. Russian Medical Inquiry. 2020;4(7):437–444. DOI: 10.32364/2587-6821-2020-4-7-437-444.

Efficacy of lipid-lowering therapy beyond statins to prevent cardiovascular events: a meta-analysis.

Efficacy of lipid-lowering therapy beyond statins to prevent cardiovascular events: a meta-analysis.

Long-term use of a combination of atorvastatin and ezetimibe in children with homozygous familial hypercholesterolemia

Background: Homozygous familial hypercholesterolemia (HoFH) is an underdiagnosed and undertreated genetic disorder of lipoprotein metabolism associated with mortality during young age due to accelerated atherosclerosis. There is limited data on the efficacy of lipid lowering therapies in HoFH. Methods: Medical records of 3 children with HoFH who received a combination of atorvastatin and ezetimibe for a mean duration of 11.6±1.5 years were retrospectively analysed. Results: There was a significant decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) from the baseline levels (mean percent change in TC, LDL-C, TG and HDL-C of 58.5%, 56.2%, 67.5% and 29.7% respectively). Conclusions: We conclude that long-term use of a combination of atorvastatin and ezetimibe significantly lowers the plasma LDL-C concentrations in patients with HoFH without causing any significant adverse effects. Ours is the first study from India on long-term use of lipid modifying drug therapy in children with HoFH.

Lipid Lowering Therapy to Modify Plaque Microstructures.

Due to the pandemics of obesity and diabetes mellitus, especially in the Western countries, atherosclerotic cardiovascular disease (ASCVD) has become a major health burden and is expected to increase in the future. Modifying lipid targets, especially low-density lipoprotein cholesterol (LDL-C) level, has become the first-line therapy for primary and secondary prevention of ASCVD. Intravascular imaging modalities have contributed to elucidating clinical efficacy of lipid lowering therapy on atherosclerotic plaques. Optical coherence tomography (OCT) is a high-resolution imaging tool enables visualization of plaque microstructures associated with its instability. This modality has demonstrated favorable changes in plaque microstructures under lowering LDL-C level. In addition, clinical studies using OCT have suggested potential association of other lipid targets, including triglyceride and high-density lipoprotein cholesterol with plaque microstructures. Given continuing cardiovascular risks despite statin therapy, OCT will be an important imaging modality to evaluate novel therapeutic approaches that potentially modulates plaque instability.

虚血性心疾患患者に対する脂質低下療法の有用性について

虚血性心疾患患者に対する脂質低下療法の有用性について

Atorvastatin 10 mg plus ezetimibe versus titration to atorvastatin 40 mg: attainment of European and Canadian guideline lipid targets in high-risk subjects ≥65 years

BackgroundFew clinical studies have focused on the efficacy of lipid-lowering therapies in patients ≥65 years.MethodsAfter stabilization on atorvastatin 10 mg, hypercholesterolemic subjects ≥65 years at high/very high risk for CHD and not at LDL-C <1.81 mmol/L (with atherosclerotic vascular disease [AVD]) or <2.59 mmol/L (without AVD) were randomized to ezetimibe 10 mg plus atorvastatin 10 mg or uptitration to atorvastatin 20 mg (6 weeks) followed by uptitration to 40 mg (additional 6 weeks). A post-hoc analysis compared between-group differences in percent attainment of individual and combined LDL-C, non-HDL-C and Apo B targets based on recommendations from 2012 European and Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia treatment.ResultsAtorvastatin 10 mg plus ezetimibe produced significantly greater attainment of LDL-C, non-HDL-C, and Apo B individual and dual/triple targets vs. atorvastatin 20 mg for the entire cohort and very high-risk groups at 6 weeks. After 12 weeks, very high-risk subjects maintained significantly greater achievement of LDL-C <1.8 mmol/L (47% vs. 35%), non-HDL-C <2.6 mmol/L (63% vs. 53%) and Apo B <0.8 g/L (47% vs. 38%) single targets and dual/triple targets with atorvastatin 10 mg plus ezetimibe vs. atorvastatin 40 mg, while attainment of European target for high-risk subjects was generally similar for both treatments. Achievement of Canadian targets was significantly greater with combination therapy vs. atorvastatin 20 mg (6 weeks) or atorvastatin 40 mg (12 weeks).ConclusionsAtorvastatin 10 mg plus ezetimibe provided more effective treatment than uptitration to atorvastatin 20/40 mg for attainment of most European and Canadian guideline-recommended lipid targets in older at-risk patients.Trial registrationClinicalTrials.gov identifier NCT00418834.

Lipoprotein glomerulopathy may provide a key to unlock the puzzles of renal lipidosis

Lipoprotein glomerulopathy is an inherited renal disease characterized by unique lipoprotein thrombi in the glomerulus and is associated with the APOE mutation. Hu and colleagues investigated the genetic and clinical features of a large group of patients with lipoprotein glomerulopathy who carried APOE Kyoto, a major APOE variant. Their findings suggest its descent through a founder effect. Fibrate therapy in this group showed favorable results in the patient and renal survival rates.

PCV71 Economic Evaluation of Lipid Lowering Therapy in the Secondary Prevention Setting in the Philippines

To determine the cost-effectiveness of lipid lowering therapy in the secondary prevention of cardiovascular events in the Philippines. A cost-utility analysis was performed using Markov modeling in the secondary prevention setting. The models incorporated efficacy of lipid lowering therapy demonstrated in randomized controlled trials and mortality rates obtained from local life tables. Average and incremental cost-effectiveness ratios (ACERs and ICERs) were obtained for Simvastatin, Atorvastatin, Pravastatin, and Gemfibrozil. The costs of the following were included: medications, laboratory examinations, consultation (professional fees) and related expenses and production losses. The costs were expressed in current or nominal prices as of the 1st quarter of 2010 (Philippine peso). Utility was expressed in quality-adjusted life years gained (QALYs). Sensitivity analyses were performed using variations in the cost centers, discount rates, starting age and differences in utility weights for stroke. In the analysis using the lower-priced generic counterparts, therapy using 40 mg Simvastatin daily was the most cost-effective option compared to the other therapies, while Pravastatin 40 mg daily was the most cost-effective alternative if the higher-priced innovator drugs were used. In all sensitivity analyses, Gemfibrozil was strongly dominated by the statins. In the secondary prevention setting, Simvastatin or Pravastatin were the most cost-effective options compared to Atorvastatin and Gemfibrozil in the Philippines. Gemfibrozil was strongly dominated by the statins.

The comparative efficacy of ezetimibe added to atorvastatin 10 mg versus uptitration to atorvastatin 40 mg in subgroups of patients aged 65 to 74 years or greater than or equal to 75 years

BackgroundCoronary heart disease (CHD) risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients > 65 years. The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 mg + ezetimibe 10 mg (EZ/Atorva) vs. increasing the atorvastatin dose to 40 mg.MethodsPatients ≥ 65 years with atherosclerotic vascular disease (LDL-C ≥ 1.81 mmol/L) or at high risk for coronary heart disease (LDL-C ≥ 2.59 mmol/L) were randomized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 mg for 6 wk followed by atorvastatin 40 mg for 6 wk. The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk.ResultsEZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients ≥ 75 years (n = 228), generally consistent with patients 65–74 years (n = 812). More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients ≥ 75 years at 12 wk. At 12 wk, more patients ≥ 75 years achieved LDL-C targets with monotherapy vs. combination therapy. EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients ≥ 75 years, generally consistent with the findings in patients 65–74 years.ConclusionsOur results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and ≥ 75 years of age.

Effects of Ezetimibe Added to Atorvastatin Versus Atorvastatin Up-Titration on Attainment of Single and Dual Levels for Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, or High-Sensitivity C-Reactive Protein in Older Adults with High Coronary Heart Disease Risk

Synopsis: Few clinical studies have focused on the efficacy of lipid-lowering therapies in the growing population of men and women 65 years and older. Purpose: This post-hoc analysis evaluated the effect of ezetimibe added to atorvastatin versus atorvastatin up-titration on the attainment of suggested single/dual levels of low-density lipoprotein cholesterol (LDL-C; <70, <100 mg/dL) and non-high-density lipoprotein cholesterol (HDL-C; <100, <130 mg/dL) or apolipoprotein B (apoB; <80, <90 mg/dL) in patients ≥65 years of age with hypercholesterolemia, high coronary heart disease (CHD) risk, and LDL-C levels greater than prespecified targets during atorvastatin 10 mg/day therapy (<70 mg/dL for patients with atherosclerotic vascular disease [AVD], <100 mg/dL for patients without AVD). hs-CRP is a CHD risk marker, and attainment of levels <2 mg/L either alone or together with LDL-C was also assessed. Methods: A multicenter, 12-week, randomized, double-blind, parallel-arm study of 1053 participants stabilized on atorvastatin 10 mg/day for 6 weeks, and then randomly assigned to 1 of 2 treatment regimens: (1) addition of ezetimibe 10 mg/day for 12 weeks (E+A10); (2) doubling atorvastatin to 20 mg/day (A20) for 6 weeks followed by quadrupling to 40 mg/day (A40) for an additional 6 weeks. Results: Significantly more patients achieved single LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and apoB <80 mg/dL levels and dual LDL-C and non-HDL-C, LDL-C and apoB, and LDL-C and hs-CRP < 2mg/L levels with E+A10 than up-titration to either A20 or A40. The proportion of patients reaching hs-CRP <2 alone was similar for all therapies (range, 58.4%–61.5%). Attainment of less aggressive single targets (LDL <100 mg/dL, non-HDL-C <130 mg/dL, and apoB <90 mg/dL) were significantly greater with E+A10 versus A20, whereas comparison with A40 was similar. Dual attainment of LDL-C <100 and non-HDL-C <130 was significantly greater with E+A10 than A20 or A40. Attainment of LDL-C <100 mg/dL and apoB <90 with E+A10 was significantly greater than A20, and comparable with A40. Dual attainment of LDL-C <100 mg/dL and hs-CRP <2 mg/L was similar for both treatment comparisons. Conclusions: Coadministration of ezetimibe with atorvastatin 10 mg improved attainment of single/dual treatment levels of LDL-C and non-HDL-C or apoB compared with either doubling or quadrupling the atorvastatin dose, especially when evaluating the levels that are the most appropriate for the highest-risk patient. These results suggest that addition of ezetimibe to low dose atorvastatin may be a useful treatment option for dyslipidemia in elderly patients at high risk for CHD.