Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials

ObjectivePatients with dyslipoproteinemia constitute the largest risk group for development of atherosclerosis and cardiovascular disease (CVD). Despite extensive statin use, many patients with CVD risk do not achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets. This pooled analysis of 27 previously published clinical trials conducted between 1999 and 2008 evaluated the lipid-altering efficacy and factors related to treatment response of ezetimibe combined with statin and statin monotherapy.MethodsPatient-level data were combined from double-blind, placebo-controlled or active comparator studies randomizing adult subjects to ezetimibe 10 mg plus statin (n = 11,714) versus statin alone (n = 10,517) for 6–24 weeks (mean = 9 weeks). Association of factors with treatment response, percent change from baseline LDL-C and other lipids, and attainment of guideline-recommended lipid and lipoprotein targets were evaluated.ResultsHigher baseline LDL-C, diabetes mellitus, Black race, greater age, and male gender were associated with small but significantly greater percent reductions in LDL-C regardless of treatment. Treatment influenced efficacy, with ezetimibe plus statin producing significantly greater reductions in LDL-C, total-cholesterol, non-HDL-C, ApoB, triglycerides, lipid ratios, hs-CRP; significantly larger increases in HDL-C and ApoA1; and significantly higher achievement of LDL-C (<70 mg/dl, <100 mg/dl), non-HDL-C (<100 mg/dl, <130 mg/dl), and ApoB (<80 mg/dl, <90 mg/dl) targets than statin monotherapy at statin potencies compared (p < 0.0001 for all). Differential treatment effects were seen with first-/second-line therapy and statin potency.ConclusionThese results suggest that patient characteristics have a limited influence on response to lipid-lowering therapy and demonstrate the consistent treatment effect of ezetimibe combined with statin and statin monotherapy across a diverse patient population.     

Prevalence and predictors of lipid abnormalities in patients treated with statins in the UK general practice

ObjectiveTo identify the prevalence and predictors of lipid abnormalities in statin-treated patients in the UK.MethodsA retrospective cohort study was performed using the UK General Practice Research Database. Patients ≥35 years of age were included if they received first-ever statin between January 2000 and December 2004, received statins for at least 6 weeks, had >2 years of pre- and 1 year of post-statin initiation database history, received no concomitant lipid lowering drugs and had at least one complete lipid profile conducted within 1 year before and after initiating statins. Predictors of each lipid abnormality were determined using random effects logistic regression.ResultsWithin 1 year of statin initiation, 34.7%, 27.4%, 68.2% and 57.6% of patients did not reach optimal levels of TC, LDL-C, HDL-C and TG, respectively. Failure to attain TC goal was explained by smoking (odds ratio = 1.13, 95% confidence interval [1.02–1.23]) and baseline TC >6.2 mmol/L (5.01, [4.58–5.48]). Failure to attain LDL-C goal was associated with smoking (1.28, [1.14–1.43]), LDL-C ≥4.1 to <4.9 mmol/L (2.72, [2.45–3.03]) and LDL-C ≥4.9 mmol/L (8.54, [7.62–9.54]). High CHD risk was associated with low HDL-C in women at follow-up (1.94, [1.51–2.48]). Elevated TG was associated with baseline TG ≥2.2 to <5.6 mmol/L (4.19, [3.81–4.59]), TG ≥5.6 mmol/L (16.10, [3.67–70.57]), smoking (1.26, [1.11–1.42]) and hypertension (1.12, [1.01–1.23]).ConclusionWhile TC and LDL-C management appear appropriate in the UK, attainment of recommended levels of HDL-C and TG remains poor. The latter remains a concern, as poor attainment of recommended levels of HDL-C and TG is associated with high CHD risk in women, smoking and hypertension.     

Effectiveness of Blood Lipid Management in Patients With Peripheral Artery Disease

BackgroundLow-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in peripheral artery disease (PAD). Lipid-lowering therapies (LLT) that reduce LDL-C decrease this risk.ObjectivesThe authors examined LLT use and actual achieved LDL-C in PAD.MethodsPAD patients in MarketScan from 2014 to 2018 were identified. Outcomes included LLT use, defined as high-intensity (HI) (high-intensity statin, statin plus ezetimibe, or PCSK9 inhibitor), low-intensity (any other lipid regimen), or no therapy, and follow-up LDL-C. Factors associated with LDL-C <70 mg/dl were identified with multivariable logistic regression.ResultsAmong 250,103 PAD patients, 20.5% and 39.5% were treated at baseline with HI and low-intensity LLT, respectively; 40.0% were on no LLT. Over a 15-month median follow-up period, HI LLT use increased by 1.5%. Among 18,747 patients with LDL-C data, at baseline, 25.1% were on HI LLT, median LDL-C was 91 mg/dl, and 24.5% had LDL-C <70 mg/dl. Within the HI LLT subgroup, median LDL-C was 81 mg/dl, and 64% had LDL-C ≥70 mg/dl. At follow-up, HI LLT use increased by 3.7%, median LDL-C decreased by 4.0 mg/dl, and an additional 4.1% of patients had LDL-C <70 mg/dl. HI LLT use was greater after follow-up MACE (55.0%) or MALE (41.0%) versus no ischemic event (26.1%). After MACE or MALE, LDL-C was <70 mg/dl in 41.5% and 36.1% of patients, respectively, versus 27.1% in those without an event. Factors associated with follow-up LDL-C <70 mg/dl included smoking, hypertension, diabetes, prior lower extremity revascularization, and prior myocardial infarction but not prior acute or critical limb ischemia.ConclusionsIn PAD, LLT use is suboptimal, LDL-C remains elevated, and LLT intensity is a poor surrogate for achieved LDL-C. Less aggressive lipid management was observed in PAD versus cardiovascular disease, highlighting missed opportunities for implementation of proven therapies in PAD.     

Suboptimal lipid levels in clinical practice among Portuguese adults with dyslipidemia under lipid-lowering therapy: Data from the DISGEN-LIPID study

IntroductionCardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal. Hypercholesterolemia has a causal role in atherosclerotic CVD. Guidelines recommend that cardiovascular (CV) risk reduction should be individualized and treatment goals identified. Low-density lipoprotein cholesterol (LDL-C) is the primary treatment target.MethodsDISGEN-LIPID was a cross-sectional observational study conducted in 24 centers in Portugal in dyslipidemic patients aged ≥40 years, on lipid-lowering therapy (LLT) for at least three months and with an available lipid profile in the previous six months.ResultsA total of 368 patients were analyzed: 48.9% men and 51.1% women (93.9% postmenopausal), of whom 73% had a SCORE of high or very high CV risk. One quarter had a family history of premature CVD; 31% had diabetes; 26% coronary heart disease; 9.5% cerebrovascular disease; and 4.1% peripheral arterial disease. Mean baseline lipid values were total cholesterol (TC) 189 mg/dl, LDL-C 116 mg/dl, high-density lipoprotein cholesterol (HDL-C) 53.5 mg/dl, and triglycerides (TG) 135 mg/dl. Women had higher TC (p<0.001), LDL-C (non-significant) and HDL-C (p<0.001), and lower TG (p=0.002); 57% of men and 63% of women had LDL-C>100 mg/dl (p=0.28), and 58% of men and 47% of women had LDL-C>70 mg/dl (p=0.933).ConclusionThese observational data show that, despite their high-risk profile, more than half of patients under LLT, both men and women, did not achieve the recommended target levels for LDL-C, and a large proportion also had abnormal HDL-C and/or TG. This is a renewed opportunity to improve clinical practice in CV prevention.     

Combined therapy of mixed dyslipidemia in patients with high cardiovascular risk and changes in the lipid target values and atherogenic index of plasma

PurposeTo evaluate the safety and efficacy of combined lipid-modifying agents (statin + fenofibrate) on plasma lipid profile including the atherogenic index of plasma (AIP = log[TG/HDL-C]) in patients at high and very high cardiovascular (CV) risk and mixed dyslipidemia.MethodA total of 81 patients (53 males, 28 females; 60 ± 9.8 years) were included. Mixed dyslipidemia was defined as having 2 of the following 3 lipid abnormalities: LDL-cholesterol (C) >2.5 mmol/l, HDL-C <1.0 mmol/l in males and <1.3 mmol/l in females, triglycerides (TG) >1.7 mmol/l. Global CV risk was estimated according to the current European guidelines. Management with fenofibrate (160–267 mg) + atorvastatin (10–20 mg) or simvastatin (20–40 mg) was indicated for 6 months. Males and females were stratified according to the AIP risk categories: AIP <0.11 (low risk), AIP >0.21 (high risk).ResultsAbout 3/4 of high or very high CV risk patients with mixed dyslipidemia (n = 81) suffer from impaired glucose metabolism (44% had type 2 diabetes, 30% had impaired fasting glucose). Six-months combined therapy reduced LDL-C (by 29%) and TG (by 40%) significantly, but the increase of HDL-C (by 3%) was not significant. There were 47% of males and 57% of females who achieved the target LDL-C levels (<25 or <1.8 mmol/l) and 14% of males and 37% of females who received non-HDL-C <2.6 mmol/l at the end of the study. Also AIP was decreased significantly in majority of the patients (high risk AIP decreased from 87% to 47% of males and from 71% to 25% of females).ConclusionThe combined lipid-modifying therapy led to a significant improvement of the plasma lipid profile, particularly of LDL-C, TG, non-HDL-C and AIP. Atherogenic index of plasma seems to be a very useful marker of CV risk in high and very high CV risk patients with mixed dyslipidemia and glucose abnormalities. More intensive management is needed in those patients.     

Comparative prognostic value of low-density lipoprotein cholesterol and C-reactive protein in patients with stable coronary artery disease treated with percutaneous coronary intervention and chronic statin therapy

BackgroundThe comparative prognostic value of low density lipoprotein-cholesterol (LDL-C) and C-reactive protein (CRP) in patients with stable coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI) and statin therapy is poorly investigated.MethodsThe study included 7595 patients with stable CAD treated with PCI. Based on a cut-off of 100 mg/dl for LDL-C and 3 mg/L for CRP, patients were divided into 4 groups: patients with LDL-C ≤ 100 mg/dl and CRP ≤ 3 mg/L (n = 2795); patients with LDL-C > 100 mg/dl and CRP ≤ 3 mg/L (n = 2091); patients with LDL-C ≤ 100 mg/dl and CRP > 3 mg/L (n = 1296); and patients with LDL-C > 100 mg/dl and CRP > 3 mg/L (n = 1413). Statins at discharge were prescribed in all patients. The primary outcome was 1-year all-cause mortality.ResultsOne-year mortality was 2.1% (160 deaths): 1.2% (33 deaths) among patients with LDL-C ≤ 100 mg/dl and CRP ≤ 3 mg/L, 1.4% (28 deaths) among patients with LDL-C > 100 mg/dl and CRP ≤ 3 mg/L, 4.8% (60 deaths) among patients with LDL-C ≤ 100 mg/dl and CRP > 3 mg/L and 2.9% (39 deaths) among patients with LDL-C > 100 mg/dl and CRP > 3 mg/L (P < 0.001). After adjustment, CRP (hazard ratio [HR] = 1.64, 95% confidence interval [CI] 1.33–2.02, for 1 standard deviation increase in the logarithmic scale) but not LDL-C (HR = 1.03 [0.90–1.17], for 30 mg/dl increase) showed an independent association with 1-year mortality. CRP (P = 0.045) but not LDL-C (P = 0.294) increased the discriminatory power of multivariable model for prediction of mortality.ConclusionIn patients with stable CAD treated with PCI and statin therapy, CRP but not LDL-C was independently associated with increased risk of 1-year mortality.     

Rheumatoid Arthritis,Statin Indication and Lipid Goals: Analysis According to Different Recommendations

BackgroundDifferent strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA).Objectives(1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals.MethodsA cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor × 1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed.ResultsA total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals.ConclusionApplying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.     

Statin therapy in the primary prevention of early atrial fibrillation after coronary artery bypass grafting

ObjectiveAssessment of the role of statin therapy in the prevention of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) in patients without prior atrial fibrillation.MethodsA retrospective analysis of 206 patients, aged 57.2 ± 7.9 years (mean ± SD), who underwent isolated CABG is carried out. All patients are divided into two groups. The first group (nSt-patients) includes the patients who did not receive statin therapy prior to CABG (n = 82). The second group (St-patients) includes the patients who received statin therapy prior to CABG (n = 124). Both groups received the statin therapy from the first day after CABG. The risk of occurrence of POAF is evaluated using the Cox-regression model.ResultsThe rate of POAF was 25.6% in nSt-patients and 6.5% in St-patients (P = 0.020). On the 4th day after CABG, white blood cells (WBC) count was 11.0 (9.0, 13.0) × 10⁹/mL (medians with inter-quartile ranges) in nSt-patients and 9.0 (7.6, 10.2) × 10⁹/mL in St-patients (P < 0.001). The peak WBC numbers occurred on the day of POAF onset. The Cox-regression analysis shows that only two factors (statin therapy and number of grafts) had significant influence on the POAF onset. Odds ratio of POAF event prediction by statin therapy was 0.20 (95%CI: 0.08–0.51), P < 0.001. Each subsequent graft increased the risk of POAF in 2.1 times.ConclusionStatin therapy carried out prior to the CABG is an effective approach to primary prevention of POAF in early postoperative period. Statin therapy after CABG in nSt-patients does not give prophylactic effect observed in St-patients.     

Saxagliptin efficacy and safety in patients with type 2 diabetes receiving concomitant statin therapy

AimsTo examine whether concomitant statin therapy affects glycemic control with saxagliptin 2.5 and 5 mg/d in patients with type 2 diabetes mellitus (T2DM).MethodsEfficacy and safety were analyzed post hoc for pooled data from 9 saxagliptin randomized, placebo-controlled trials with a primary 24-week treatment period (4 monotherapy, 2 add-on to metformin, 1 each add-on to a sulfonylurea, thiazolidinedione, or insulin ± metformin). Safety was also assessed in an 11-study, 24-week pool and an extended 20-study pool, which included 9 additional 4- to 52-week randomized studies. Comparisons were performed for patient groups defined by baseline statin use.ResultsSaxagliptin produced greater mean reductions in glycated hemoglobin than placebo, with no interaction between treatment and baseline statin use (P = 0.47). In patients receiving saxagliptin 2.5 and 5 mg and placebo, the proportion of patients with ≥ 1 adverse event (AE) was 78.1%, 64.0%, and 63.2%, respectively, in patients with any statin use and 70.6%, 57.9%, and 55.0% in patients with no statin use. Serious AEs, deaths, and symptomatic confirmed hypoglycemia (fingerstick glucose ≤ 50 mg/dL) were few and similar, irrespective of baseline statin use.ConclusionsSaxagliptin improves glycemic control and is generally well tolerated in patients with T2DM, irrespective of concomitant statin therapy.     

Association Between Lipid Testing and Statin Adherence in the Veterans Affairs Health System

BackgroundMeasurement with a lipid panel after statin initiation and in long-term follow-up is recommended in both 2013 and 2018 cholesterol guidelines to assess statin efficacy and adherence. We assessed whether routine laboratory evaluation with lipid panels is associated with greater statin adherence.MethodsWe identified patients with atherosclerotic cardiovascular disease within the entire Veterans Affairs (VA) health care system with at least one primary care visit between October 2013 and September 2014, who were on statin therapy (n = 813,887; n = 52,583 for new statin users). Statin adherence was determined using medication refill data and assessed by proportion of days covered (PDC). Association between number of lipid panels completed and PDC was assessed with adjusted regression models.ResultsWithin the study period, the mean number of lipid panels that were completed per patient was 1.5 ± 1.0. In the overall cohort, percentage of statin users with PDC ≥ 80% was 66.0% for patients with ≥ 1 lipid panel and 61.2% for patients with 0 lipid panels (P < .0001). Among new statin users, PDC ≥ 80% was 68.0% for patients with lipid panels completed within 4-12 weeks of therapy initiation and 59.3% for those without lipid panels completed within the timeframe (P < .0001). In adjusted analysis, number of lipid panels completed was associated with a modest but significant increase in PDC, when PDC was evaluated as a continuous (beta-coefficient 0.0054, P < .001) or categorical (PDC ≥ 80% [odds ratio (OR) 1.01; 95% confidence interval (CI), 1.00-1.01]) measure of statin adherence. The significant association was also observed in new users (beta-coefficient 0.0058, P < .001; OR 1.02; 95% CI, 1.00-1.03).ConclusionRoutine, guideline-directed completion of lipid panels in atherosclerotic cardiovascular disease patients on statins overall and among new statin users is associated with a modes6t but significant increase in statin adherence.     

Association between dyslipidemia and vascular events in patients treated with statins: Report from the UK General Practice Research Database

ObjectiveA retrospective cohort study was conducted to evaluate the association between low high-density lipoprotein cholesterol (HDL-C) and/or elevated triglycerides (TG) and cardiovascular (CV) and/or cerebrovascular (CB) events among patients with elevated low-density lipoprotein cholesterol (LDL-C) despite statin treatment.MethodsPatient demographics, clinical characteristics, laboratory data, and CV/CB events, were collected from the UK General Practice Research Database. Abnormal lipid levels were defined using US and European clinical guidelines. The association between the frequency of CV/CB events among patients with HDL-C/TG abnormalities versus patients with isolated low LDL-C was estimated using multivariate Cox proportional hazards regression.ResultsOf 19,843 statin-treated patients, 6823 had elevated LDL-C despite therapy for a mean follow-up of 1.99 ± 1.06 years. Among these patients, 3115 (45.7%) also had HDL-C/TG abnormalities. A total of 715 patients (10.5%) experienced CV/CB events. In statin-treated patients not at LDL-C goal, the relative risk of a vascular event was 24% higher in patients with HDL-C/TG abnormalities (HR = 1.24, 95% CI: 1.06–1.46, p = 0.006) than in patients without HDL-C/TG abnormalities. Additional variables that were associated with a significantly increased risk of CV/CB events included age (p < 0.0001), gender (p = 0.027), and medication possession ratio (p < 0.0001), while diabetes mellitus (p < 0.0001), hypertension (p < 0.0001), 10-year Framingham risk score > 30% (p = 0.005), statin dose (p < 0.0001), and LDL-C level at baseline (p < 0.0001) were associated with a significantly decreased risk of CV/CB events.ConclusionAmong statin-treated patients with elevated LDL-C from UK clinical practices, reduced HDL-C and/or elevated TGs were associated with a significantly increased relative risk of CV/CB events.     

The possibility of reducing the Lp-PLA2 mass level using simvastatin monotherapy and combination therapy with ezetimibe

AimTo assess the impact of combined treatment with simvastatin and ezetimibe or treatment with simvastatin only on lipoprotein-associated phospholipase A2 mass level in patients with coronary heart disease.MethodsOne hundred patients with angiographically documented coronary atherosclerosis took part in the investigation. Lp-PLA2 mass level and cholesterol fractions were determined at baseline and after 6 months of treatment. Lp-PLA2 mass was determined by PLAC Test; DiaDexus, Inc.ResultsCombined treatment with ezetimibe and simvastatin led to significantly greater declines in Lp-PLA2 and lipid profile compared with treatment only with simvastatin (P < 0.05). Combination therapy with ezetimibe and simvastatin 20 mg/day proved to be as effective as monotherapy with simvastatin 80 mg/day on the effect on Lp-PLA2 mass level and lipids (P < 0.05). Lp-PLA2 mass level was initially higher in patients with three-vessel coronary artery disease, compared with patients with one-vessel coronary artery disease while baseline levels of lipids and hs-CRP did not differ significantly.ConclusionsCombined treatment, using half the dose of simvastatin, led to greater reduction of Lp-PLA2 mass level total cholesterol and LDL-C, compared to monotherapy with simvastatin. Due to the steady decline of target levels of LDL-C, which leads to prescribing high doses of statins (and it is not always possible because of the presence of co-morbidities), combination therapy with statin and ezetimibe is a reliable alternative, which allows not only to largely reduce LDL-C but also to significantly reduce such important participants of atherosclerosis process and markers of inflammation, as Lp-PLA2 and CRP.     

Rendimiento diagnóstico de la secuenciación de genes de hipercolesterolemia familiar en sujetos con hipercolesterolemia primaria

Introduction and objectivesOur objective was to approximate the prevalence of mutations in candidate genes for familial hypercholesterolemia (FH) in a middle-aged Spanish population and to establish the predictive value of criteria for clinical suspicion in the detection of causative mutations.MethodsUnrelated individuals aged ≥ 18 years from the Aragon Workers’ Health Study (AWHS) with high low-density lipoprotein cholesterol (LDL-C) and clinical suspicion of FH (participants with LDL-C concentrations above the 95th percentile, participants with premature cardiovascular disease and/or participants with high LDL-C [130 mg/dL] under statin therapy), assuming that any participant with FH exhibits at leats 1 trait, were selected and the LDLR, APOB, PCSK9, APOE, STAP1 and LDLRAP1 genes were sequenced by next generation sequencing technology.ResultsOf 5400 individuals from the AWHS, 4514 had complete data on lipid levels and lipid-lowering drugs, 255 participants (5.65%) met the criteria for suspicion of FH, 24 of them (9.41%) were diagnosed with hyperlipoproteinemia(a), and 16 (6.27% of those sequenced) were found to carry causative mutations in candidate genes: 12 participants carried 11 different pathogenic LDLR alleles and 4 participants carried 1 pathogenic mutation in PCSK9. LDL-C concentrations > 220 mg/dL and LDL-C > 130 mg/dL despite statin therapy showed the strongest association with the presence of mutations (P = .011).ConclusionsOur results show that the prevalence of FH in Spain is 1:282 and suggest that the combination of high untreated LDL-C and high levels of LDL-C despite statin therapy are the best predictors of a positive FH genetic test.     

Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients

ObjectiveTo study the effects of HIV-infection and protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) on the lipid and high-density lipoprotein (HDL) subpopulation profile and to relate the changes to coronary heart disease (CHD)-risk.Methods and designThe lipid and HDL subpopulation profiles of HIV-positive subjects (n = 48) were studied prospectively by comparing pre- and post-PI-HAART data as well as cross-section by comparing the profiles to HIV-negative subjects with (n = 96) and without CHD (n = 96).ResultsHIV-infected HAART-naïve subjects had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and HDL-C and higher concentration of triglycerides (TG) than healthy controls. After receiving PI-based HAART, LDL-C and TG concentrations increased, while HDL-C concentrations remained unchanged. The HDL subpopulation profiles of HAART-naïve HIV-positive patients were significantly different from those of healthy controls and were similar to those with CHD. Moreover, the HDL subpopulation profile changed unfavorably after PI-based HAART, marked with increased concentrations of the small, lipid-poor pre-β-1 HDL (32% or 3.9 mg/dl; p < 0.001), and decreased concentration of the large, cholesterol-rich α-1 HDL(9% or 1 mg/dl ns).ConclusionAn already unfavorable lipid and HDL subpopulation profile of HIV-positive HAART-naïve subjects further deteriorated after receiving PI-based treatment, which may cause increased CHD-risk in these subjects.     

Statin therapy in the prevention of atrial fibrillation in the early postoperative period after coronary artery bypass grafting: A meta-analysis

BackgroundPostoperative atrial fibrillation (POAF) is observed in the early postoperative period in approximately every third patient after coronary artery bypass grafting (CABG). The pathogenesis of POAF is multifactorial and is not yet fully studied. In many studies, postoperative inflammatory response has been extensively investigated as a potential basic factor of POAF. It is known that statins have anti-inflammatory properties. In some studies, pre- and perioperative use of statins has shown the decrease of incidence of POAF after CABG.ObjectiveWe conducted meta-analysis of randomized and observational studies of efficiency of statin therapy for the prevention of POAF after CABG.Material and methodsThe meta-analysis included 15 clinical trials of statins in 9369 patients with performed CABG during the past 10 years. 5598 patients (59.75%) were taking statins and 3771 patients (40.25%) were not taking statins. The following outcomes observed in the early postoperative period were studied: incidence of POAF, total mortality rate, total stroke rate, and total rate of myocardial infarction. The duration of hospitalization and levels of inflammatory markers before and after CABG were also assessed.ResultsThe statin therapy reduced the incidence of POAF after CABG (OR = 0.48, 95% CI: 0.35–0.67, P < 0.001). Moreover, the statin therapy decreased the total length of hospital stay and levels of inflammatory markers in the blood serum.ConclusionThe results of our meta-analysis leave no doubt in the presence of anti-inflammatory and anti-arrhythmic effect of statin therapy. We confirmed the overall positive role of using statins before CABG for POAF prevention.     

Association between triglyceride and high-density lipoprotein cholesterol change following fibrate therapy

BackgroundDebate surrounding the role of fibrates has followed mixed outcomes from several randomised controlled trials. Subgroup analysis of even the negative trials reveals significant reduction in cardiovascular risk amongst patients with low HDL-C and high TG. We previously described factors associated with HDL-C change following fibrates. As fibrates influence both HDL-C and TG levels via their action on PPAR-α, we now wished to study TG change following fibrate therapy and any associations with baseline and change in HDL-C and TC levels.MethodsData was collected from case notes of patients started on fibrates (n = 248) between 2002 and 2008 in the lipid clinics at Heart of England NHS Foundation Trust. Regression analyses were carried out to determine factors associated with changes in TG.ResultsMultiple regression analysis revealed that TG change was associated with pre-treatment TG (p < 0.001) and TC levels (p = 0.029). The association between TG change and pre-treatment TG remained significant when all factors including gender, concurrent statin treatment, diabetes and baseline HDL-C were entered into the regression model. Our previous study demonstrated significant post-fibrate HDL-C change in the group with baseline HDL-C values <1.0 mmol/l. In our present study significant TG reduction was observed regardless of the baseline patient characteristics including HDL-C levels.ConclusionsThe actions of fibrates are considered to be mediated via PPAR-α, but our data suggest that the effects on TG and HDL-C are different. Thus, the mechanisms mediating the changes of these lipids following fibrate treatment may vary.     

Use of ezetimibe results in more patients reaching lipid targets without side effects

BackgroundEzetimibe's mechanism of action, complementary to that of statins, makes it a useful therapeutic option in patients intolerant of lipid-lowering drugs or in those not achieving target lipid levels.ObjectivesTo evaluate the efficacy and safety of ezetimibe in a longterm follow-up of lipid clinic patients with emphasis on motivation for use and the impact on achievement of target lipid levels.MethodsTwo hundred and ninety-five clinic patients who were prescribed and took ezetimibe in the 13-month period following the drug's availability in Canada were identified from our database. Patients’ history and laboratory data were collected before and at first visit after the ezetimibe therapy was started. Paired t-test and chi-square test were used for statistical comparisons of ezetimibe's effect on lipid parameters and the achievement of target lipid-levels respectively.ResultsEzetimibe treatment increased significantly the proportion of patients achieving lipid targets (by 25% for LDL-C and by 21.7% for TC/HDL-C) significantly by 18% (p < 0.001) and TC/HDL-C by 15% (p < 0.011). The effect of ezetimibe in combination with other lipid-lowering therapies was similar; LDL-C decreased by 22% (p < 0.001) and TC/HDL-C by 15.4% (p < 0.011). The same lipid-lowering effect was seen in patients with diabetes. In this subgroup, addition of ezetimibe to ongoing therapy led to three- and two-fold increase in LDL-C and TC/HDL-C target levels achievement, respectively. Only 7% of patients discontinued ezetimibe treatment due to side effects.ConclusionIn patients referred to the lipid clinic (typically because of side effects or failure to reach targets on other lipid-lowering therapy) treatment with ezetimibe significantly increased proportion of those achieving their target lipid levels. This was not accompanied by significant side effects.     

Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events : A Meta-Analysis of Statin Trials

Background

Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.

Objectives

The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk.

Methods

This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.

Results

Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB.

Conclusions

The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.