Evo Alemao

Cholesterol reduction yields clinical benefits: meta-analysis including recent trials

BACKGROUND Previous meta-analyses reported by Gould et al found significant decreases of 15% in the risk for coronary heart disease (CHD)-related mortality and 11 % in risk for all-cause mortality per decrease of 10% in total cholesterol (TC) level. OBJECTIVE To evaluate the effects of reducing cholesterol on clinical events after including data from recent clinical trials. METHODS Using a literature search (MeSH key terms, including: bezafibrate, coronary disease, efficacy, gemfibrozil, hydroxymethylglutaryl-CoA reductase inhibitors, hypercholesterolemia, niacin [nicotinic acids], randomized controlled trials, and treatment outcome; years: 1999-2005), we identified trials published in English that assessed the effects of lipid-modifying therapies on CHD end points, including CHD-related death, myocardial infarction, and angina pectoris. We also included all studies from the previously published meta-analysis. Using the same analytic approach as previously, we determined the effects of net absolute reductions (1 mmol/L [38.7 mg/dL]) in TC and low-density lipoprotein cholesterol (LDL-C) on the relative risks (RRs) for all-cause mortality, CHD-related mortality, any CHD event (mortality or nonfatal myocardial infarction), and non-CHD-related mortality. RESULTS We included 62 studies involving 216,616 patients, including 126,474 from 24 randomized controlled trials the findings of which were published since the previous meta-analysis (1998). Among all patients, for every 1-mmol/L decrease in TC, there was a 17.5 reduction in RR for all-cause mortality; 24.5 %, for CHD-related mortality; and 29.5% for any CHD event. Corresponding reductions for every 1-mmol/L decrease in LDL-C were 15.6%, 28.0%, and 26.6%, respectively. Similar relationships were observed in patients without CHD. No significant relationship was found between lipid reduction and non-CHD-related mortality risk. CONCLUSIONS The results from the present analysis support conclusions from previous meta-analyses that cholesterol lowering is clinically beneficial in patients with CHD or at elevated CHD risk. These results also support the previous finding that non-CHD-related mortality is unrelated to lipid reductions.

Lipid-modifying therapy and attainment of cholesterol goals in Europe: the Return on Expenditure Achieved for Lipid Therapy (REALITY) study

ABSTRACT Background: Few studies have been conducted in actual clinical practice settings to evaluate the ways in which dyslipidemia is managed using lipid-modifying therapies. Objective: To determine lipid-modifying therapy practices and their effects on low-density lipoprotein cholesterol (LDL‐C) and/or total cholesterol (TC) goal attainment in Europeans based on prevailing guidelines at the time of therapy in each country. Methods: Retrospective cohort analysis involving 58 223 patients initiated on lipid-modifying therapies in 10 European countries, with a median patient follow-up on lipid-modifying therapy of 15.3 months. Data on prescriptions of lipid-modifying therapies, laboratory data including LDL‐C and TC, achievement of cholesterol goals for LDL‐C and/or TC, and hospitalizations were obtained from healthcare administrative databases and/or patient chart reviews. Results: Across Europe, statin monotherapy was the initial lipid-modifying treatment in 51 786 (89.3%) of 58 009 patients with available data. In addition, 38 853 (89.5%) of 43 410 patients with available follow-up statin potency data were initiated on statin regimens of medium or lower equipotency. Low-equipotency regimens include atorvastatin 5 mg, simvastatin 10 mg, and pravastatin 20 mg, whereas medium-equipotency regimens include atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg. Regimens were adjusted to higher equipotency via either up-titration or switches to combination regimens in 16.2% of patients. On average, 40.5% of patients across Europe who were not initially at guideline recommended cholesterol goals (either LDL‐C or TC) and had follow-up data attained recommended cholesterol levels, including < 30% of patients in Spain, Italy, or Hungary. In many countries, the likelihood of goal attainment was inversely associated with baseline cardiovascular risk and/or LDL‐C levels. Conclusions: Lipid management strategies in Europe during the study period were dominated by statin monotherapy. Even after prolonged follow-up on lipid-modifying therapy, approximately 60% of Europeans studied did not achieve guideline recommended cholesterol goals. Future emphasis must be placed on subsequent lipid panel monitoring, as well as the use of more efficacious, well-tolerated lipid-modifying therapies such as dual cholesterol inhibitors to enable more European patients to attain their recommended cholesterol goals.

Glycaemic control among patients with type 2 diabetes mellitus in seven European countries: findings from the Real‐Life Effectiveness and Care Patterns of Diabetes Management (RECAP‐DM) study

Objective:  This study was undertaken to assess glycaemic control as well as changes in glycaemic control over time in patients with type 2 diabetes mellitus (T2DM) who added a sulphonylurea (SU) or thiazolidinedione (TZD) to their metformin monotherapy in typical treatment settings within seven European countries.

Current lipid management and low cholesterol goal attainment in common daily practice in Spain: The REALITY study

AbstractObjective: To evaluate prescribing patterns of lipid-lowering drugs used in management of patients at risk of coronary heart disease (CHD) in usual clinical practice in Spain and to assess low-density lipoprotein cholesterol (LDL-C) goal attainment among CHD and CHD equivalent patients (<100 mg/dL) and non-CHD patients with two or more risk factors (<130 mg/dL) who were prescribed lipid-lowering drugs. Methods: Cohort study with retrospective chart review at 23 primary care centres and 16 lipid treatment centres across Spain (59% primary care; 41% outpatient lipid centres). Physicians consecutively identified eligible patients. Adults (aged.18 years) with CHD/CHD equivalent or two or more major risk factors prior to first prescription of lipid-lowering drugs were eligible. Medical records were reviewed by physicians to collect patient characteristics, baseline and follow-up laboratory values and lipid-lowering drug treatment data. Results: 619 patients (45.5% CHD and CHD equivalent patients and 54.5% non-CHD with two or more major risk factors) were included in the study with an average study follow-up of 3.6 years. Mean age was 60.1 years (SD 10.2), and 47.8% were female. Mean baseline LDL-C was 178 mg/dL (SD 45.0) for the CHD/CHD equivalent patients and 191 mg/dL (SD 56.95) for patients with two or more risk factors. Statins were the initial lipid-lowering drugs in 90.2% of patients; 52.5% of patients were initiated on low-dose (simvastatin 10mg or lower potency) statins. Overall 20.2% of CHD/CHD equivalent and 31.4% of patients with two or more risk factors attained LDL-C goal during the study period; of patients not attaining goal, 28.7% required an additional LDL-C reduction of >30% to attain goal. In a logistic regression model for goal attainment, CHD/CHD equivalent patients (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.31, 0.72) and patients with baseline LDL-C >190 mg/dL (OR 0.53; 95% CI 0.35, 0.80) were least likely to reach cholesterol goal when compared with patients having baseline LDL-C >100 mg/dL and <130 mg/dL. Conclusion: Only 12.9% of patients attained LDL-C goal on their initial lipid-lowering drugs, and an additional 13.4% achieved goal after a change in their lipid-lowering therapy, resulting in 73.7% of patients not attaining goal after at least 3 years of follow-up, after initiation of lipid-lowering therapy. Patients who would gain the most from aggressive lipid lowering (CHD patients and patients with high baseline LDL-C) were least likely to achieve goal. More effective lipid management is needed to help these patients lower their cholesterol to goal levels or even lower.

Statins are less effective in common daily practice among patients with hypercholesterolemia: the REALITY-PHARMO study;

SUMMARY Background: To study the use and effectiveness of lipid-lowering drugs with respect to lowering of cholesterol levels in routine daily practice. Methods: 20 392 patients for whom lipid levels records were available between January 1991 and December 2001 were included in this retrospective population based cohort study. From this group of patients 1899 patients started treatment during the study period and had at least one baseline cholesterol measurement during the six months prior to the initiation of lipid lowering drugs and at least one cholesterol measurement after initiation. A patient was defined to be ‘at goal’ if the patient had a total cholesterol less than 5.0 mmol/L. Results: Our results indicate that only 30.2% of all treated patients achieved goal in the first year of treatment. After the introduction of new guidelines in 1998, recommending more aggressive treatment, the goal attainment percentage rose from 22.4% of those patients treated before 1998 to 42.3% for those in whom treatment was initiated after 1998. Conclusion: The percentage of patients achieving guideline recommended goal is low in real-life even in patients treated with high dose statins.

Cost-effectiveness of ezetimibe coadministration in statin-treated patients not at cholesterol goal: application to Germany, Spain and Norway.

AbstractBackground: Despite the growing use of statins, many hypercholesterolaemic patients fail to reach their lipid goal and remain at elevated risk of coronary heart disease (CHD). Alternative treatment strategies, such as ezetimibe coadministration and statin titration, can help patients achieve greater lipid control, and thereby lower their CHD risk. But is it cost effective to more aggressively lower cholesterol levels across a broad range of current statin users? Methods: Using a decision-analytic model based on epidemiological and clinical trials data, we project the lifetime benefit and cost of alternative lipid-lowering treatment strategies for CHD and non-CHD diabetic patients in Germany, Spain and Norway. Results: It is projected that from 40% to 76% of these patients who have failed to reach their lipid goal with their current statin treatment will be able to reach their goal with ezetimibe coadministration; this represents a gain of up to an additional absolute 14% who will be able to reach their goal compared with a ‘titrate to goal’ strategy where patients are titrated in order to reach their lipid goal (up to the maximum approved dose). For CHD patients, the estimated incremental cost-effectiveness ratio for ezetimibe coadministration is under €18 000 per life-year gained (€/LYG) and 26 000 €/LYG compared with strategies based on the observed titration rates and the aggressive ‘titrate to goal’ strategy, respectively; for non-CHD diabetic patients, these ratios are under 26 000 €/LYG and 48 000 €/LYG for ezetimibe coadministration compared with the two titration strategies. Conclusion: Compared with statin titration, ezetimibe coadministration is projected to be cost effective in the populations and countries studied.

The A-SACT (achievement in singapore of cholesterol targets) study in patients with coronary heart disease

BackgroundCardiovascular disease remains a leading cause of death worldwide, with hypercholesterolemia being a major risk factor. Evidence-based consensus guidelines have recommended consideration of increasingly stringent cholesterol-lowering goals, yet most patients do not meet these targets. Coronary heart disease (CHD) event and mortality rates and mean serum cholesterol levels have declined in Singapore in recent years; however, certain groups remain at elevated risk.ObjectiveTo determine (i) proportions of patients with CHD in Singapore who achieved goals for serum low-density lipoprotein-cholesterol (LDL-C); and (ii) factors influencing goal attainment.MethodsA historical cohort study was conducted using records from the Singapore Cardiac Databank, a national registry of CHD patients. Serum LDL-C goal attainment was assessed in 5174 survivors of acute myocardial infarction or coronary revascularization (i.e. coronary artery bypass graft surgery or percutaneous coronary interventions), of whom 3811 (73.7%) were at very high risk.ResultsAt baseline, the mean patient age was 60.3 years, mean serum value of total cholesterol was 228 mg/dL, and mean LDL-C was 163mg/dL. Of all CHD patients, approximately 70% did not achieve a serum LDL-C target of <100mg/dL. Most patients receiving HMG-CoA reductase inhibitor (statin) regimens were treated initially with low- to medium-equipotency regimens and were never titrated to stronger regimens. The vast majority (∼94%) of patients at very high risk did not achieve the stringent serum LDL-C target of <70mg/dL. Patients receiving higher potency statins were significantly more likely to achieve LDL-C goals, whereas those with higher baseline LDL-C levels or Malaysian ethnicity were less likely to achieve LDL-C goals.ConclusionsMost CHD patients in the large group of Singapore residents with CHD in the present study did not achieve recommended LDL-C targets. A more effective disease-management approach, including patient education concerning lifestyle modification (e.g. diet, physical activity), efforts to enhance medication adherence, and more effective, well tolerated therapies such as high-equipotency or high-dose statins and statin combination regimens, may be needed to improve achievement of consensus cholesterol targets. This is the first study of cholesterol goal attainment in a large group of Southeast Asians and serves as a baseline for future evaluations in Asian populations.

Development of a diabetes treatment simulation model : with application to assessing alternative treatment intensification strategies on survival and diabetes-related complications

Aims:  The objective of this analysis is to project the long‐term impacts on life expectancy and occurrence over 5, 10, and 40 years of microvascular and macrovascular complications of diabetes when using different haemoglobin A1c (HbA1c) thresholds for intensifying treatment of type 2 diabetes.

Lipid management and cholesterol goal attainment in Norway.

ObjectiveTo document prescribing patterns of lipid-modifying therapies in hypercholesterolemic patients, cholesterol goal attainment, and factors associated with cholesterol goal attainment in Norway.MethodThis was a retrospective, observational study using existing computerized patient records at 11 primary healthcare centers in Norway and the Norwegian Patient Register of hospital data. The study population was 3111 patients identified in the primary care database who were prescribed a lipid-modifying therapy between the dates of July 1987 and May 2003 and who were α18 years of age at the time of the first prescription. Of these patients, 1337 patients had uncontrolled lipid measures at baseline. In the analysis of goal attainment, data were available for 877 (28% of the total study population) and 1144 (37%) patients with baseline and follow-up total cholesterol (TC) and/or low-density lipoprotein-cholesterol (LDL-C) levels after 4 and 12 months’ treatment, respectively.Outcome measuresInitial lipid-modifying therapy (drug and dosage), changes in initial lipid-modifying therapy, cholesterol goal attainment, and factors related to cholesterol goal attainment. Cholesterol treatment goals were defined as LDL-C <3.0 mmol/L and/or TC <5.0 mmol/L (as per the Second Joint Task Force of European Societies on the Prevention of Cardiovascular Disease).ResultsThe initial lipid-modifying therapy was a HMG-CoA reductase inhibitor (statin) in 98% of patients, most often simvastatin (42%; mean initial dosage = 18.4 mg/day) or atorvastatin (34%; 12.7 mg/day). The median year of treatment initiation was 1999 and the mean duration of follow-up was 39 months. The initial prescription remained unchanged at year 1 for most patients (69%), whereas 17% discontinued drug treatment. Mean TC levels decreased from 7.36 mmol/L at baseline (n=1337) to 5.31 mmol/L at 12 months (n=1144; p < 0.05), whereas mean LDL-C levels decreased from 4.98 (n=847) to 3.08 mmol/L at 12 months (n=713; p < 0.05). These mean reductions occurred within 3 months of the initial prescription and did not change subsequently. A total of 32.9% of patients who were not at goal at baseline achieved cholesterol goal 12 months after initiating treatment. The factors related to cholesterol goal attainment at 12 months were: baseline TC level (odds ratio [OR] 0.64; 95% CI 0.58, 0.71), treatment with a statin (OR 8.60; 95% CI 1.13, 65.4), diagnosis of diabetes mellitus (OR 2.91; 95% CI 2.01, 4.21), and age (OR 1.02; 95% CI 1.01, 1.03).ConclusionsLipid-modifying therapy in Norway is dominated by statin monotherapy. In this analysis of primary-care patients, maximal reductions in cholesterol levels were seen within the first 3–4 months after therapy initiation. After 12 months of treatment, 67% of patients remained above recommended cholesterol levels. More effective and well tolerated treatment strategies are needed to improve the probability of patients achieving cholesterol treatment goals.

Cholesterol Goal Attainment in Patients with Coronary Heart Disease and Elevated Coronary Risk: Results of the Hong Kong Hospital Audit Study

OBJECTIVE We sought to determine 1) long-term lipid-lowering treatment patterns; 2) cholesterol goal attainment rates and possible determinants of goal achievement; and 3) effects of cholesterol goal attainment on coronary events in hospitalized Hong Kong patients. METHODS In this retrospective cohort analysis, records of two public Hong Kong hospitals were reviewed for 196 adults (69% with coronary heart disease (CHD) or CHD-risk equivalent) who received at least one lipid-lowering therapy during hospitalization. Low-density lipoprotein cholesterol (LDL-C) targets were <2.6 mmol/l (<100 mg/dL) for patients with CHD or CHD risk equivalents and <3.37 mmol/l (<130 mg/dL) for those without. RESULTS Most participants were initiated on regimens of low to midequipotency doses and never had their regimens adjusted to higher potency. Approximately 44% of patients not at LDL-C at baseline failed to achieve goal during a median follow-up of 1.9 years. Patients with higher coronary risk and/or LDL-C levels at baseline were less likely than their lower-risk counterparts to achieve goal; for each 1-mmol/l (38.7-mg/dL) increase in LDL-C at baseline, the likelihood of attaining goal declined by 64%. Patients achieving cholesterol goal had significantly longer cardiovascular event-free times. CONCLUSIONS A total of 44% of Hong Kong patients not at LDL-C goals at baseline did not achieve them over 1.9 years. More effective and well-tolerated therapies, including adjunctive regimens (e.g., ezetimibe-statin, niacin-statin), may be necessary to enhance LDL-C goal achievement and increase event-free time.