Lipid-lowering Treatment In Patients Research Articles

Novel aspects of PCSK9 and lipoprotein receptors in renal disease-related dyslipidemia

Chronic kidney disease (CKD) is a global health problem with a profound impact on quality of life. Cardiovascular disease is established as a major cause of morbidity and mortality in patients with CKD. Dyslipidemia is frequently observed in CKD patients, suggesting a causal relation between dyslipidemia and cardiovascular disease in CKD patients. Currently, lipid-lowering drugs such as statins, are the primary choice for lipid lowering therapy in high-risk populations. Despite many studies showing CVD risk reduction with statins, CVD still remains the leading cause of the death in CKD. This underscores the need for new therapeutic approaches to reduce cardiovascular risk in CKD patients. Reduced lipoprotein lipase activity, increased very low-density lipoprotein production, increased proprotein convertase subtilisin kexin type 9 (PCSK9) expression and loss of hepatic heparan sulfate proteoglycans (HSPG) syndecan-1 have been associated with CKD-related dyslipidemia. Low-density lipoprotein receptor (LDLR), low-density lipoprotein receptor-related protein 1 (LRP-1) and syndecan-1, are the most important hepatic receptors for lipoprotein clearance. However, their contributions to the pathogenesis of dyslipidemia and cardiovascular disease in CKD remain unclear. Interestingly, in CKD, increased plasma lipid levels are associated with elevated levels of PCSK9. This promotes the proteolysis of LDLR, suggesting a role for PCSK9 in CKD-associated dyslipidemia. Fully humanized monoclonal antibodies targeting PCSK9 have been approved by the US Food and Drug Administration and the European Medicines Agency as lipid lowering treatment for patients with hypercholesterolemia. In CKD sub-group analysis, ODYSSEY COMBO I and ODYSSEY COMBO II studies demonstrated strong reduction in LDL-C by alirocumab compared to placebo and ezetimibe and when added to statins. However, their efficacy in reducing plasma TG is controversial. Therefore, further research work is need for a detailed analysis on efficacy and safety of PCSK9 antibodies in CKD groups. Interestingly, novel findings on PCSK9 interaction with HSPG might shed new insight on altered lipid metabolism in CKD. In this review, we discuss various aspects of lipoprotein metabolism and hepatic lipoprotein receptor signaling pathways along with the concept of renal disease-related dyslipidemia. Furthermore, this review highlights the drawbacks of current lipid-lowering therapies and proposes novel approaches for lipid management in CKD.

High rates of non-adherence to antidiabetic, antihypertensive and lipid lowering treatment in patients with type 2 diabetes revealed liquid chromatography-tandem mass spectrometry (lc-ms/ms) urine analysis

High rates of non-adherence to antidiabetic, antihypertensive and lipid lowering treatment in patients with type 2 diabetes revealed liquid chromatography-tandem mass spectrometry (lc-ms/ms) urine analysis

Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomised factorial trial

In patients with hypertension, the long-term cardiovascular and all-cause mortality effects of different blood pressure-lowering regimens and lipid-lowering treatment are not well documented, particularly in clinical trial settings. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy Study reports mortality outcomes after 16 years of follow-up of the UK participants in the original ASCOT trial. ASCOT was a multicentre randomised trial with a 2 × 2 factorial design. UK-based patients with hypertension were followed up for all-cause and cardiovascular mortality for a median of 15·7 years (IQR 9·7-16·4 years). At baseline, all patients enrolled into the blood pressure-lowering arm (BPLA) of ASCOT were randomly assigned to receive either amlodipine-based or atenolol-based blood pressure-lowering treatment. Of these patients, those who had total cholesterol of 6·5 mmol/L or lower and no previous lipid-lowering treatment underwent further randomisation to receive either atorvastatin or placebo as part of the lipid-lowering arm (LLA) of ASCOT. The remaining patients formed the non-LLA group. A team of two physicians independently adjudicated all causes of death. Of 8580 UK-based patients in ASCOT, 3282 (38·3%) died, including 1640 (38·4%) of 4275 assigned to atenolol-based treatment and 1642 (38·1%) of 4305 assigned to amlodipine-based treatment. 1768 of the 4605 patients in the LLA died, including 903 (39·5%) of 2288 assigned placebo and 865 (37·3%) of 2317 assigned atorvastatin. Of all deaths, 1210 (36·9%) were from cardiovascular-related causes. Among patients in the BPLA, there was no overall difference in all-cause mortality between treatments (adjusted hazard ratio [HR] 0·90, 95% CI 0·81-1·01, p=0·0776]), although significantly fewer deaths from stroke (adjusted HR 0·71, 0·53-0·97, p=0·0305) occurred in the amlodipine-based treatment group than in the atenolol-based treatment group. There was no interaction between treatment allocation in the BPLA and in the LLA. However, in the 3975 patients in the non-LLA group, there were fewer cardiovascular deaths (adjusted HR 0·79, 0·67-0·93, p=0·0046) among those assigned to amlodipine-based treatment compared with atenolol-based treatment (p=0·022 for the test for interaction between the two blood pressure treatments and allocation to LLA or not). In the LLA, significantly fewer cardiovascular deaths (HR 0·85, 0·72-0·99, p=0·0395) occurred among patients assigned to statin than among those assigned placebo. Our findings show the long-term beneficial effects on mortality of antihypertensive treatment with a calcium channel blocker-based treatment regimen and lipid-lowering with a statin: patients on amlodipine-based treatment had fewer stroke deaths and patients on atorvastatin had fewer cardiovascular deaths more than 10 years after trial closure. Overall, the ASCOT Legacy study supports the notion that interventions for blood pressure and cholesterol are associated with long-term benefits on cardiovascular outcomes. Pfizer.

P6187High rates of non-adherence to antidiabetic, antihypertensive and lipid lowering treatment in patients with Type 2 diabetes revealed by liquid chromatography-tandem mass spectrometry urine analysis

P6187High rates of non-adherence to antidiabetic, antihypertensive and lipid lowering treatment in patients with Type 2 diabetes revealed by liquid chromatography-tandem mass spectrometry urine analysis

Impact of the 2013 Cholesterol Guideline on Patterns of Lipid-Lowering Treatment in Patients with Atherosclerotic Cardiovascular Disease or Diabetes After 1 Year.

The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults emphasizes evidence-based treatment with moderate- to high-dose statins for patients at high risk for atherosclerotic cardiovascular disease (ASCVD). Whether this new guideline influenced patterns of treatment 1 year after its dissemination is unknown. To compare patterns of lipid-lowering treatment before and 1 year after the release of the 2013 cholesterol guideline in 2 high-risk groups: patients with ASCVD and patients with diabetes mellitus. Using pharmacy and medical claims from a large U.S. health insurance organization, 610,535 patients with ASCVD (n = 301,440) or diabetes mellitus (n = 309,095) were identified, and statin treatment rates and statin intensity were examined before and 1 year after the dissemination of the 2013 cholesterol guideline. A standardized difference of at least 10% was required to declare the effect size meaningful. Overall, there was no change in statin treatment rates for patients with ASCVD (48.0% before guideline vs. 47.3% after, standardized difference 1.4%) or diabetes (50% vs. 51.5% after, standardized difference 2.4%). Statin initiation rates among patients not on statins before the 2013 guideline were 10.1% in patients with ASCVD and 14.3% in patients with diabetes, but these gains were offset by 13.0% and 12.2% statin discontinuation rates among ASCVD and diabetes patients, respectively. Among patients taking statins 1 year after the guideline was issued, 80% of patients with ASCVD and aged ≤ 75 years were not on guideline-recommended high-intensity statin therapy, whereas most patients with ASCVD and aged > 75 years or patients with diabetes were on moderate- or high-intensity statin treatment. One year after dissemination of the 2013 cholesterol guideline, overall treatment rates with statins among patients with ASCVD and diabetes did not change appreciably, and many patients remained either untreated or undertreated. No outside funding supported this research. Chan is supported by grants from the National Heart Lung and Blood Institute (1R01HL123980 and K23HL102224). Tran, Stockl, Lew, and Solow are employed by Optum. Kao and Caglar were employed by Optum when this study was conducted. Chan serves as an advisor and consultant to OptumRx but received no compensation for work on this manuscript. Stockl is also employed by the Journal of Managed Care & Specialty Pharmacy. Spertus reports personal fees from United Healthcare and grants from Lilly, outside of the submitted work. None of the authors have any other financial conflicts of interest to report. Tran and Chan supervised this study, had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. Study design and concept were contributed by Tran and Chan. Tran and Kao collected the data, with analysis and interpretation performed by all the authors. Statistical analysis was performed by Caglar and Kao, and Tran and Chan drafted the manuscript. All authors were involved in the critical revision of the manuscript.

Biological variation of β-sitosterol, campesterol, and lathosterol as cholesterol absorption and synthesis biomarkers

BackgroundThe analysis of blood for β-sitosterol and campesterol is the measures of cholesterol absorption while lathosterol is a measure of cholesterol synthesis. MethodsThe biological variability of β-sitosterol, campesterol, and lathosterol was measured using liquid-chromatography tandem mass spectrometry from a cohort of 25 apparently healthy subjects, where blood was taken once every weeks for 6weeks. The analytical, intra-individual, and group inter-individual variations (CVA, CVI, and CVG, respectively) were calculated. ResultsUsing absolute values, the CVI for β-sitosterol, campesterol, and lathosterol was 11.8%, 11.8%, and 22.5%, respectively, and the CVG was 28.5%, 28.8%, and 52.0%, respectively. This produced reference change values of about 24–36% for declining values and 32–47% for increasing values. The index of individuality was between 0.41 and 0.58, indicating that population based reference values are of little use for these biomarkers. The number of points needed for a homeostatic setpoint was 5 samples for β-sitosterol and campesterol, and 19 samples for lathosterol. Similar findings were observed for values when normalized to total cholesterol. These results were higher than the biological variation for total, low density and high density cholesterol obtained from the literature. Results were essentially identical when sterol values were corrected to their respective total cholesterol concentration. ConclusionsThe establishment of the biological variation for these biomarkers enables their use in the interpretation of results from clinical trials and lipid lowering treatment of patients at risk for cardiovascular disease in clinical practice.

Lipid-lowering treatment in patients at high cardiovascular risk discharged from an Italian hospital

Atherosclerosis is the leading cause of cardiovascular morbidity and mortality in Italy. One of its principal risk factors is dyslipidemia. The aim of our study was to determine the accuracy of antihypercholesterolemic treatment in high-risk patients [low-density lipoprotein (LDL) > 100 mg/dl] discharged from hospital. Among all the patients aged 40-70 years hospitalized at S. Orsola-Malpighi Hospital, Bologna, during 2008, we selected patients who had established arterial disease (coronary artery disease, cerebrovascular disease, peripheral arterial disease) or diabetes; excluding patients with creatine kinase or transaminase alterations, renal function impairment, diagnosis of hypercholesterolemia alone or incomplete lipid profile; the final population included 999 participants. Total cholesterol, high-density lipoprotein cholesterol and triglycerides were measured on blood samples. LDL-cholesterol was obtained by the Friedwald formula. Statin use was evaluated through medical records, comparing admission and discharge. The χ(2)-test was used to compare the percentage of patients on lipid-lowering treatment at admission and discharge. Considering all 462 individuals with LDL-cholesterol levels more than 100 mg/dl, statin treatment increased from 25.5% at admission to 61.7% at discharge; however, more than 38% of patients who deserved a pharmacological therapy were not treated. In addition, we observed an improvement in lipid-lowering therapy only in 23 patients with LDL-cholesterol levels more than 100 mg/dl already under statin treatment. Our data show that dyslipidemia is generally undertreated in high-risk patients, despite the fact that hospitalization brings them in contact with specialized physicians.

Implementation of clinical practice guidelines for acute ischaemic stroke in specialist care centres

IntroductionCerebrovascular disease is associated with high morbidity and mortality. In 2008, the Spanish Ministry of Health published its Clinical Practice Guidelines for stroke prevention, but implementation of that document has not yet been assessed. Our study aims to investigate compliance with the Guidelines by analysing control over vascular risk factors, antithrombotic treatment and lipid lowering treatment in patients who had suffered an acute ischaemic stroke and who were under the care of neurologists or internists. MethodsCross-sectional study based on data from clinical reports (vascular risk factors, diagnosis and treatment), blood pressure readings and laboratory tests pertaining to 203 patients diagnosed with acute ischaemic stroke and admitted to a medium-to-long stay hospital for rehabilitation and care. ResultsThe mean patient age was 75±10 years; 56% were women. The most common risk factors were hypertension (68%) and diabetes mellitus (40%). Intravenous fibrinolytic therapy had been administered to 8.9% of the patients. Of the patients with thrombotic cerebral infarction, 91.7% received antiplatelet agents; 59.4% of patients with embolic infarction received anticoagulants. Statins were prescribed to 65% of patients with thrombotic infarction. Laboratory tests upon admission showed that 23% of patients had total cholesterol levels above 175mg/dl and 26.6% had plasma glucose levels above 126mg/dl. Of the patient total, 70% received antihypertensive therapy, but 47.5% had blood pressure levels above 130/80mm Hg. ConclusionsIn our opinion, secondary prevention of acute cerebrovascular disease could be improved, mainly by increasing the percentage of patients treated with antiplatelet or anticoagulant drugs (depending on aetiology), increasing prescription of statins, and improving blood pressure control.

Implementación de las guías de práctica clínica sobre ictus isquémico agudo en atención especializada

IntroductionCerebrovascular disease is associated with high morbidity and mortality. In 2008, the Spanish Ministry of Health published its Clinical Practice Guidelines for stroke prevention, but implementation of that document has not yet been assessed. Our study aims to investigate compliance with the Guidelines by analysing control over vascular risk factors, antithrombotic treatment and lipid lowering treatment in patients who had suffered an acute ischaemic stroke and who were under the care of neurologists or internists. MethodsCross-sectional study based on data from clinical reports (vascular risk factors, diagnosis and treatment), blood pressure readings and laboratory tests pertaining to 203 patients diagnosed with acute ischaemic stroke and admitted to a medium-to-long stay hospital for rehabilitation and care. ResultsThe mean patient age was 75±10 years; 56% were women. The most common risk factors were hypertension (68%) and diabetes mellitus (40%). Intravenous fibrinolytic therapy had been administered to 8.9% of the patients. Of the patients with thrombotic cerebral infarction, 91.7% received antiplatelet agents; 59.4% of patients with embolic infarction received anticoagulants. Statins were prescribed to 65% of patients with thrombotic infarction. Laboratory tests upon admission showed that 23% of patients had total cholesterol levels above 175mg/dl and 26.6% had plasma glucose levels above 126mg/dl. Of the patient total, 70% received antihypertensive therapy, but 47.5% had blood pressure levels above 130/80mm Hg. ConclusionsIn our opinion, secondary prevention of acute cerebrovascular disease could be improved, mainly by increasing the percentage of patients treated with antiplatelet or anticoagulant drugs (depending on aetiology), increasing prescription of statins, and improving blood pressure control

LDL-Cholesterin in der Sekundärprävention: Zielwert-Erreichung unter Lipidsenkern in Praxis und Spital in Österreich (ZIEL)

A hospital-based screening project (HSP) in Austria found 47% of high-risk patients (LDL-C < 100 mg/dl) and 24% of very high-risk patients (LDL-C < 70 mg/dl) at goal. Separate data for the sexes were not reported. We analyze whether LDL-C goal attainment in patients with manifest atherosclerosis and/or diabetes on stable lipid-lowering treatment differs between private practice and hospital and between men and women. From September to November 2007, 49 Austrian centers (36 private practice, 13 hospitals) documented vascular morbidity, lipid levels, and lipid lowering treatment in patients with high risk (atherosclerosis or diabetes, n = 978) and very high risk (coronary heart disease and diabetes or acute coronary syndrome, n = 322). 75% and 25% of the 1300 patients were high and very high risk, respectively. LDL-C goals of < 100 and < 70 mg/dl, respectively, were attained by 45.4% and 26.4% of patients (p < 0.001). A similar percentage of patients with very high risk was found in men and women (26.4% vs. 22.9%, NS) and goal attainment was not influenced by sex (high risk: 47.2% (m) vs. 43.8% (w), NS and very high risk: 29.1% (m) vs. 22.4% (w), NS). In patients with high risk, 41.6% treated in private practice vs. 57.9% treated in the hospital were at goal (p < 0.001). In patients with very high risk, 15.9% treated in private practice vs. 45.2% treated in the hospital were at goal (p < 0.001). Lower goal-attainment in private practice occurred despite significantly more intensive lipid intervention and probably reflects higher baseline LDL-C. LDL-C > 100 mg/dl leads to a more aggressive lipid lowering in approx. 70% of patients, irrespective of whether they are treated in private practice or in the hospital. LDL-C between 70 and 100 mg/dl, however, leads to a more aggressive lipid lowering in < 5% of patients, irrespective of whether they are high or very high risk. As observed in EUROASPIRE III for other European countries, there is substantial potential for improvement in lipid control in Austrian cardiovascular high-risk patients, irrespective of whether they are treated in private practice or in the hospital.

Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus: meta-analysis of randomised controlled trials

ABSTRACTObjective: To assess the impact of lipid lowering treatment with fibrates on cardiovascular endpoints in patients with type 2 diabetes mellitus.Methods: MEDLINE (from inception to November 2005) and the Cochrane Controlled Trials Register (including Issue 3, 2005) were searched for randomised controlled trials comparing therapy with fibrates to placebo in patients with type 2 diabetes mellitus. Electronic searches were supplemented by manual searching of reference lists, reviews, conference abstracts and specialist journals. Incidence rate ratios (IRRs) were estimated using a fixed effects model. The primary endpoint was the IRR for coronary heart disease (CHD) events (a combination of non fatal myocardial infarction and death due to CHD). Secondary endpoints included: (1) death due to CHD; (2) fatal and non fatal myocardial infarction; and (3) fatal and non fatal stroke.Results: Eight trials and 12 249 patients with type 2 diabetes were included in the analyses. A total of 924 CHD events (418 and 506 in the treatment and placebo groups, respectively) occurred during a follow up of 60 395 person-years (30 106 and 30 289 in treatment and placebo groups). The combined IRR for CHD events was 0.84 (95% confidence interval [CI] 0.74–0.96, p = 0.008). The numbers needed to treat (NNTs) to prevent one CHD event over 10 years were nine and 26 for patients with and without pre-existing CHD, respectively. IRRs for death due to CHD, myocardial infarction and stroke were 0.96 (95% CI 0.77–1.20, p = 0.73), 0.88 (95% CI 0.69–1.12, p = 0.30) and 0.87 (95% CI 0.73–1.05, p = 0.14), respectively. Larger benefits were found when restricting the analysis to trials that were not confounded by unequal provision of additional lipid-lowering therapy.Conclusions: Fibrates are associated with a substantial reduction of CHD events, but their exact role in lipid lowering treatment of patients with type 2 diabetes mellitus remains to be defined.

The importance of aggressive lipid management in patients at risk: evidence from recent clinical trials.

Clinical trials that evaluate more aggressive cholesterol reduction in a broader range of patients at high risk for coronary heart disease (CHD) are needed to fill gaps in our understanding of the impact of lipid-lowering therapy on risks for clinical events and mortality. This paper briefly reviews results from recent landmark studies that have evaluated the benefits of aggressive lipid-lowering therapy in patients with, or at risk for, CHD. The Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study demonstrated that aggressive treatment with atorvastatin was significantly more effective than less aggressive therapy with pravastatin in slowing the progression of atherosclerosis in patients with symptomatic CHD. Results from two large-scale clinical end-point trials, the Heart Protection Study (HPS) and the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA), have shown that aggressive lipid-lowering treatment in patients with relatively low baseline levels of low-density lipoprotein cholesterol (LDL-C) significantly reduces CHD risk. Taken together, the results of these landmark trials not only support aggressive lipid lowering in patients at risk for CHD, but also suggest that greater LDL-C reductions may improve outcomes across a wide range of patients.

Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper for the American College of Physicians.

Cardiovascular disease is the primary complication and cause of death in patients with type 2 diabetes mellitus. Modification of cardiovascular risk factors may improve patient outcomes. To evaluate the effectiveness of pharmacologic lipid-lowering therapy on outcomes in type 2 diabetes mellitus. Review of the literature. Randomized trials evaluating clinical outcomes of lipid-lowering treatment in patients with diabetes. Studies were identified by searching the Cochrane Library, MEDLINE, meta-analyses, review articles, and inquiries to experts. The Cochrane Library and MEDLINE searches were done in September 2002. Data were abstracted onto standardized forms by a single reviewer and were confirmed by a second reviewer. Meta-analysis of 6 primary prevention studies showed that lipid-lowering medications reduced risks for cardiovascular outcomes (relative risk, 0.78 [95% CI, 0.67 to 0.89]; absolute risk reduction, 0.03 [CI, 0.01 to 0.04] in 4.3 years of treatment); 1 major cardiovascular event was prevented by treating 34 to 35 patients. Meta-analysis of 8 studies of secondary prevention showed a similar relative risk (0.76 [CI, 0.59 to 0.93]) but more than twice the absolute risk reduction (0.07 [CI, 0.03 to 0.12] in 4.9 years of treatment) and a number needed to treat for benefit of 13 to 14. Most studies compared a lipid-lowering drug with placebo but did not evaluate the effect of reaching specific cholesterol levels. The benefit of lipid lowering with a fixed dose of a statin appeared to be similar regardless of starting cholesterol levels. Target cholesterol levels and the effectiveness of dose titration (or the use of multiple agents) have not been rigorously examined. In patients with type 2 diabetes, treatment with lipid-lowering agents reduces cardiovascular risk. Most patients, including those whose baseline low-density lipoprotein cholesterol levels are below 2.97 mmol/L (<115 mg/dL), and possibly below 2.59 mmol/L (<100 mg/dL), benefit from statins. Moderate doses of these drugs suffice in most patients with diabetes.

Quality of lipid-lowering therapy in patients with ischaemic heart disease: a register-based study in 3477 patients.

To develop a method to evaluate routine management practices concerning lipid-lowering treatment in patients with ischaemic heart disease (IHD) in a large geographic area. A register-based study linking information on IHD with cholesterol levels and prescriptions on lipid-lowering medications by personal registration number. Plasma cholesterol levels were collected from the electronic laboratory information system (LIS), and information on IHD from the Danish National Hospital Register (LPR). The extent of treatment was evaluated by information on prescriptions on lipid-lowering medications from the Danish National Health Service. Evaluates treatment in both hospitals and primary care. Patients with IHD. In total 3477 patients <75 years were identified, and 43.7% had claimed prescriptions on lipid-lowering medications (01.01.2000-31.07.2000). In the whole population, 42% reached the goal for total cholesterol lower than 5 mmol L-1 set by European guidelines. In the 1521 patients treated with lipid-lowering medications 55% reached the goal. By use of registers it was possible to develop a method to evaluate and monitor current treatment practice for dyslipidaemia in a large geographic area. The method makes it possible to evaluate the impact of guidelines, changes in treatment procedures and to provide feedback to physicians. The study revealed that lipid-lowering treatment is still not sufficiently implemented in clinical practice even in patients with known IHD, and the used doses of statins are lower than those used in randomized clinical trials.

Efficacy and tolerability of fluvastatin extended-release delivery system: a pooled analysis

Background: At high doses, the pharmacokinetics of fluvastatin immediate-release (IR) are nonlinear, possibly due to saturation of hepatic uptake. Fluvastatin delivery to the liver in a slower but sustained fashion would be expected to avoid hepatic saturation without elevating systemic drug levels. Objective: This pooled analysis compared the efficacy and tolerability of extended-release (XL) 80-mg and IR 40-mg formulations of fluvastatin in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and raising high-density lipoprotein cholesterol (HDL-C) levels in patients with hypercholesterolemia. Methods: Data were pooled from 3 double-blind, randomized, active-controlled, multicenter, parallel-group studies that compared changes in lipid and apolipoprotein levels with fluvastatin XL 80 mg at bedtime (HS) with changes in fluvastatin IR 40 mg HS or BID in patients aged ≥18 years with primary hypercholesterolemia (consistently elevated LDL-C level [≥160 mg/dL] and plasma TG levels ≤400 mg/dL). The primary efficacy variable was percent change in LDL-C from baseline. Results: The pooled analysis provided an intent-to-treat efficacy study population of 1674 patients. At 4 weeks, fluvastatin XL 80 mg HS reduced LDL-C levels by a mean of 36.3% (median 38%), significantly greater than a mean reduction of 25.9% (median 27%) seen with fluvastatin IR 40 mg HS, and an incremental additional mean reduction in LDL-C of 10.4% ( P < 0.001). At 4 and 24 weeks, fluvastatin XL 80 mg HS provided an LDL-C reduction equivalent to fluvastatin IR 40 mg BID ( P < 0.001 for noninferiority). Significant, dose-related changes in HDL-C, LDL-C:HDL-C ratio, total cholesterol, TG, and apolipoprotein A-I and apolipoprotein B levels also occurred. Mean HDL-C level increased by 8.7% and median TG level decreased by 19% with fluvastatin XL 80 mg HS ( P < 0.001 and P < 0.05 vs fluvastatin IR 40 mg HS, respectively). Maximum mean increases in HDL-C level (21%) and median decreases in TG level (31%) with fluvastatin XL 80 mg HS occurred in patients with type IIb dyslipidemia and the highest baseline TG. Adverse events were mild, with similar frequency in all treatment groups. Conclusions: Once-daily administration of fluvastatin XL 80 mg provides enhanced efficacy with an additional 10.4% reduction in LDL-C levels compared with fluvastatin IR 40 mg HS, and superior increases in HDL-C levels, particularly in patients with elevated TG levels ( P < 0.05 vs fluvastatin IR 40 mg HS). Fluvastatin XL 80 mg HS has a good tolerability profile and is effective as starting and maintenance lipid-lowering treatment in patients with type II hypercholesterolemia.

149 Prevalence of macrovascular complications and its consequences for lipid lowering treatment in patients with diabetes mellitus type II

149 Prevalence of macrovascular complications and its consequences for lipid lowering treatment in patients with diabetes mellitus type II

1006-45 Regression of Infarct-Related Coronary Lesions on Aggressive Lipid Lowering Treatment in Patients After Recovery from Acute Myocardial Infarction

Considering of remained active nature of infarct-related lesion (IRL) early after recovery from acute myocardial infarction (AMI), a prospective study was undertaken to determine whether IRL exhibits more regression on aggressive lipid lowering treatment. Fifty patients (pts), 34 hyperlipemic (HL) and 16 normal lipids (NL), aged ≤65 year with coronary diameter stenosis &gt;25% were followed monthly. LDL-cholesterol (LDL-C) level was aimed to control below 130 mg/dl in HL patients on strict diet and pravastatin 10–30 mg/day, also LDL-apheresis in a patient with familier hyperlipemia. Repeat coronary angiography was performed in average 14 months after AMI onset, and altogether 142 lesions from 34 HL and 16 NL were analyzed quantitatively using cinedensitometry. Lesions which PTCA wire crossed were separately assessed. Average serum LDL-C levels improved from 166 to 117 mg/dl on drug and diet (p &lt; 0.001) in HL. Seven out of 92 non-IRL (7.6%) exhibited progression defined as ≥0.5 mm decrease of minimum lesion diameter, and 9 IRL (9.8%) did regression ≥0.5 mm increase. Whereas thirty five IRL showed significantly more incidence of regression (9 sites, 25.7% p = 0.021) and similar rate of progression (3 pts, 8.6%). An improvement of LDL-C/HDL-C ratio was more prominent in patients with IRL regression compared with those showing progression or no change (p &lt; 0.05). Thus the IRL was found in favor of more regression than non-IRL, and the magnitude of lesion regression can be expected according to the effect of lipid lowering treatment in patients after AMI.

Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease

The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50–60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30–40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K 2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K 2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.