Low-density Lipoprotein Cholesterol Target Achievement Research Articles

Incremental cholesterol reduction with ezetimibe/simvastatin, atorvastatin and rosuvastatin in UK General Practice (IN-PRACTICE): randomised controlled trial of achievement of Joint British Societies (JBS-2) cholesterol targets

The aim of this study was to compare ezetimibe/simvastatin combination therapy with intensified statin monotherapy as alternative treatment strategies to achieve the Joint British Societies (JBS)-2 and National Institute for Health and Clinical Excellence low-density-lipoprotein cholesterol (LDL-C) target of < 2 mmol/l for secondary prevention or JBS-2 LDL-C target of < 2 mmol/l for primary prevention in high-risk patients who have failed to reach target with simvastatin 40 mg. This is a prospective, double-blind study conducted in 34 UK primary care centres; 1748 patients with established cardiovascular disease (CVD), diabetes or high risk of CVD who had been taking simvastatin 40 mg for > or = 6 weeks were screened and 786 (45%) with fasting LDL-C > or = 2.0 mmol/l (and < 4.2 mmol/l) at screening and after a further 6-week run-in period on simvastatin 40 mg were randomised to ezetimibe/simvastatin 10/40 mg (as a combination tablet; n = 261), atorvastatin 40 mg (n = 263) or rosuvastatin 5 mg (n = 73) or 10 mg (n = 189) once daily for 6 weeks. Rosuvastatin dose was based on UK prescribing instructions. The primary outcome measure was the proportion of patients achieving LDL-C < 2 mmol/l at the end of the study. The percentage of patients (adjusted for baseline differences) achieving LDL-C < 2 mmol/l was 69.4% with ezetimibe/simvastatin 10/40 mg, compared with 33.5% for atorvastatin 40 mg [odds ratio 4.5 (95% CI: 3.0-6.8); p < 0.001] and 14.3% for rosuvastatin 5 or 10 mg [odds ratio 13.6 (95% CI: 8.6-21.6); p < 0.001]. Similar results were observed for achievement of total cholesterol < 4.0 mmol/l. All study treatments were well tolerated. Approximately 45% of patients screened had not achieved LDL-C < 2 mmol/l after > or = 12 weeks of treatment with simvastatin 40 mg. In this group, treatment with ezetimibe/simvastatin 10/40 mg achieved target LDL-C levels in a significantly higher proportion of patients during a 6-week period than switching to either atorvastatin 40 mg or rosuvastatin 5-10 mg.

LDL-C Goal Attainment in Patients who Remain on Atorvastatin or Switch to Equivalent or Non-equivalent Doses of Simvastatin: A Retrospective Matched Cohort Study in Clinical Practice

Background: As clinical trials have shown the benefits of more intensive cholesterol control, treatment targets for low-density lipoprotein cholesterol (LDL-C) have decreased progressively. At the same time, physicians have been encouraged to contain costs by prescribing cheaper, generic statins for cholesterol management. To determine how these possibly conflicting goals are managed in clinical practice, we examined LDL-C control in patients switched from a potent, branded statin (atorvastatin) to a less potent, generic statin (simvastatin). Methods: Patients who switched from atorvastatin to simvastatin between July 2006 and January 2008 were retrospectively identified from a US medical and pharmacy claims database, and matched with controls remaining on atorvastatin. Outcomes measured were the number of switched patients receiving a simvastatin milligram dose ≥ 2 times their previous atorvastatin dose, changes in LDL-C levels, and percentage of patients achieving recommended LDL-C targets. All study variables were analyzed descriptively. Results: After applying exclusion and inclusion criteria, 1048 patients who switched from atorvastatin to simvastatin and 1048 matched controls who remained on atorvastatin were included. Among the switchers, 379 (36%) received an inappropriately low dose of simvastatin (< 2 times atorvastatin dose). In patients remaining on atorvastatin, mean LDL-C decreased from 105.7 mg/dL to 102.3 mg/dL after 44 weeks, whereas in switched patients, LDL-C remained similar, at 105.9 mg/dL on atorvastatin and 105.8 mg/dL on simvastatin. Before switching, when all patients were receiving atorvastatin, 67.4% of switchers and 69.9% of controls achieved recommended LDL-C targets. After switching, significantly fewer switchers than controls met LDL-C targets (69.1% vs 74.6%; P = 0.005). However, among patients who switched to an equivalent dose of simvastatin (≥ 2 times prior atorvastatin dose), similar proportions met LDL-C targets (72.8% vs 74.6% of controls; P = 0.402), whereas among patients who switched to inappropriate non-equivalent dose of simvastatin, a significantly lower proportion met LDL-C targets (62.5% vs 74.6% of controls; P = 0.001). Conclusions: Continuing atorvastatin was associated with lower LDL-C levels and better LDL-C target attainment compared with switching to simvastatin. Patients switched to an equivalent simvastatin dose had lower LDL-C levels and were more likely to achieve LDL-C targets than patients switched to a non-equivalent dose, suggesting physicians must consider dosage equivalence when switching statins, and should measure LDL-C and titrate statins as necessary to achieve LDL-C control.

Achieving cholesterol targets by individualizing starting doses of statin according to baseline low-density lipoprotein cholesterol and coronary artery disease risk category: The CANadians Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (CanACTFAST) study

Despite an increasing body of evidence on the benefit of lowering elevated levels of low-density lipoprotein cholesterol (LDL-C), there is still considerable concern that patients are not achieving target LDL-C levels. The CANadians Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (CanACTFAST) trial tested whether an algorithm-based statin dosing approach would enable patients to achieve LDL-C and total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio targets quickly. Subjects requiring statin therapy, but with an LDL-C level of 5.7 mmol/L or lower, and triglycerides of 6.8 mmol/L or lower at screening participated in the 12-week study, which had two open-label, six-week phases: a treatment period during which patients received 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin based on an algorithm incorporating baseline LDL-C value and cardiovascular risk; and patients who achieved both LDL-C and TC/HDL-C ratio targets at six weeks continued on the same atorvastatin dose. Patients who did not achieve both targets received dose uptitration using a single-step titration regimen. The primary efficacy outcome was the proportion of patients achieving target LDL-C levels after 12 weeks. Of 2016 subjects screened at 88 Canadian sites, 1258 were assigned to a study drug (1101 were statin-free and 157 were statin-treated at baseline). The proportion of subjects who achieved LDL-C targets after 12 weeks of treatment was 86% (95% CI 84% to 88%) for statin-free patients and 54% (95% CI 46% to 61%) for statin-treated patients. Overall, 1003 subjects (80%; 95% CI 78% to 82%) achieved both lipid targets. Algorithm-based statin dosing enables patients to achieve LDL-C and TC/HDL-C ratio targets quickly, with either no titration or a single titration.

Utilization of lipid lowering medications among adults in the United States 1999–2006

ObjectiveWe examined the use of lipid lowering medications and control of dyslipidemia among US adults in 1999–2006. MethodsData were extracted from the National Health and Nutrition Examination Survey 1999–2006. ResultsThe mean low-density lipoprotein-cholesterol (LDL-C) level significantly decreased from 3.25±0.03mmol/L in 1999–2002 to 3.02±0.02mmol/L in 2003–2006 in men, and from 3.11±0.03 to 2.98±0.03mmol/L in women (p<0.001). Statins and fibrates were the most commonly used medications. Among those diagnosed with hypercholesterolemia, the proportion on treatment increased from 32.4% to 38.9% (p=0.001) in the 8-year period. The proportion of participants with a history of diabetes treated with a statin increased from 20.9±2.2% in 1999–2002 to 37.6±2.5% in 2003–2006 (p<0.001). However, only 39.9% of people with diabetes and 45.4% of people with ischemic heart disease (IHD) achieved LDL-C target levels. ConclusionsBetween 1999 and 2006, LDL-C level decreased in US adults and use of lipid lowering medications increased. More effort is still needed to detect and treat dyslipidemia in the community, particularly in people at high cardiovascular risk.

A new statin: a new standard.

Numerous studies have demonstrated that treatments designed to reduce low-density lipoprotein cholesterol (LDL-C) can reduce the risk of coronary heart disease (CHD) events in the setting of either primary or secondary prevention. The rationale for aggressive lowering of LDL-C, supported by large observational studies, is the concept that no threshold exists below which reductions fail to provide additional benefit. The statins are widely considered first-line therapy for preventing CHD events because these agents yield the greatest reductions in LDL-C. However, many patients do not achieve target LDL-C levels with the currently available statins. Newer, more effective statins may permit the benefits of aggressive LDL-C reduction to be extended to larger numbers of patients. A novel, highly efficacious statin, rosuvastatin (Crestor, AstraZeneca group of companies), is currently undergoing clinical investigation. Dose-ranging studies in hypercholesterolemic patients have shdwn that rosuvastatin produces significant, dose-dependent decreases in LDL-C when compared with placebo. Reductions have ranged from 34% at a dose of 1 mg/day to 65% at 80 mg/day. This agent has been found to be well tolerated across the range of doses studied. Phase III studies indicate that rosuvastatin is more effective than atorvastatin, pravastatin, and simvastatin in improving the atherogenic lipid profiles of hypercholesterolemic patients, and more effective than atorvastatin in improving the atherogenic lipid profiles of patients with heterozygous familial hypercholesterolemia. Overall, these findings suggest that rosuvastatin is a promising new medication for the treatment of dyslipidemias.

Characteristics, management and attainment of lipid target levels in diabetic and cardiac patients enrolled in Disease Management Program versus those in routine care: LUTZ registry

BackgroundSince 2002 the sick funds in Germany have widely implemented disease management programs (DMPs) for patients with type 2 diabetes mellitus (DM) and coronary heart disease (CHD). Little is known about the characteristics, treatment and target attainment lipid levels of these patients enrolled in DMPs compared to patients in routine care (non-DMP).MethodsIn an open, non-interventional registry (LUTZ) in Germany, 6551 physicians documented 15,211 patients with DM (10,110 in DMP, 5101 in routine care) and 14,222 (6259 in DMP, 7963 in routine care) over a follow-up period of 4 months. They received the NCEP ATP III guidelines as a reminder on lipid level targets.ResultsWhile demographic characteristics of DMP patients were similar to routine care patients, the former had higher rates of almost all cardiovascular comorbidities. Patients in DMPs received pharmacological treatment (in almost all drug classes) more often than non-DMP patients (e.g. antiplatelets: in DM 27.0% vs 23.8%; in CHD 63.0% vs. 53.6%). The same applied for educational measures (on life style changes and diet etc.). The rate of target level attainment for low density lipoprotein cholesterol (LDL-C) < 100 mg/dl was somewhat higher in DMP patients at inclusion compared to non-DMP patients (DM: 23.9% vs. 21.3%; CHD: 30.6% vs. 23.8%) and increased after 4 months (DM: 38.3% vs. 36.9%; CHD: 49.8% vs. 43.3%). Individual LDL-C target level attainment rates as assessed by the treating physicians were higher (at 4 months in DM: 59.6% vs. 56.5%; CHD: 49.8% vs 43.3%). Mean blood pressure (BP) and HbA1c values were slightly lowered during follow-up, without substantial differences between DMP and non-DMP patients.ConclusionPatients with DM, and (to a greater extent) with CHD in DMPs compared to non-DMP patients in routine care have a higher burden of comorbidities, but also receive more intensive pharmacological treatment and educational measures. The present data support that the substantial additional efforts in DMPs aimed at improving outcomes resulted in quality gains for achieving target LDL-C levels, but not for BP or HbA1c. Longer-term follow-up is needed to substantiate these results.

Exploring the gap between National Cholesterol Education Program guidelines and clinical practice in secondary care: results of a cross-sectional study involving over 10 000 patients followed in different specialty settings across Italy

To evaluate implementation of low-density lipoprotein cholesterol (LDL-C) control recommendations in secondary care and explore key points in the decisional workup. In a nationwide survey of secondary-care outpatients (n=11,124), we studied prevalence/predictors of (1) LDL-C value availability; (2) ongoing treatment with statins; (3) achievement of US National Cholesterol Education Program III target LDL-C values. Agreement between US National Cholesterol Education Program III risk category and physicians' personal risk assessments was also studied. LDL-C values were available for 78% evaluable patients; 71% of the patients with dyslipidema were undergoing treatment with statins; 34% patients undergoing treatment had target LDL-C values. At regression analysis, non-availability of LDL-C values was predicted by absence of diabetes, presence of normotension, and advancing age; lack of statins treatment by female sex, diabetes, overweight and northern location (southern location predicted treatment); non-achievement of target LDL-C values by age, diabetes, attending a diabetic clinic, cigarette smoking, history of cardiovascular disease, and taking less than six pills per day. Physicians provided underestimates of patients' risk (39% high-risk patients were rated as intermediate-risk patients and a further 10% as low-risk patients). Suboptimal prevention practice seems to be associated with various factors acting at different levels within the complex process running from individual risk-level ascertainment to LDL-C target achievement. Multicomponent interventions that target the different key steps need to be considered.

Ezetimibe

Ezetimibe

A case of rosuvastatin-induced rhabdomyolysis: More is not better

A 67-year-old female presented to the emergencydepartment with a 2-week history of progressivenausea, vomiting, abdominal pain, muscle cramps,and dehydration with an associated 3.6 kg weightloss. The patient had amedical history significantfor hypertension, hyperc-holesterolemia, myocardialinfarction, quadruple coro-nary artery bypass, asthma,and osteoarthritis. Medica-tions included enteric-coated acetylsalicylic acid81 mg daily, cilazapril 5 mgdaily, diltiazem CD 240 mgdaily, rosuvastatin 80 mgdaily, ezetimibe 10 mg daily,venlafaxine XL 75 mg daily,Advair (salmeterol/fluticasone) inhaler 250 mcg 1puff twice daily, Didrocal (calcium carbonate oretidronate) 1 tablet daily, glucosamine 1500 mgdaily, and ranitidine 150 mg twice daily. Vital signsat presentation included blood pressure 132/60mm Hg, heart rate 72 beats/minute, respiratoryrate 16 breaths/minute, and oxygen saturation 96%on room air. Abnormal findings on initial physicalexam indicated a mildly tender abdomen in all 4quadrants and reduced skin turgor, but the remain-der of the physical exam was unremarkable. Base-line laboratory tests indicated the following abnor-mal results: potassium 5.9 mmol/L, blood ureanitrogen 40.3 µmol/L, serum creatinine 1035µmol/L, creatine kinase (CK) 30,509 U/L, urinarymyoglobin >30,000 mcg/L, aspartate aminotrans-ferase 539 U/L, alanine aminotransferase 393 U/L,lactate dehydrogenase 1239 U/L. Urinalysis waspositive for red blood cellsand protein, and was nitritenegative, and a 12-leadelectrocardiogram indi-cated normal sinus rhythmwith no ischemic changes. Further history regard-ing the use of cholesterol-lowering agents revealedthe patient was initiated onsimvastatin 40 mg daily fol-lowing a myocardial infarc-tion 9 years previously, andwas switched to atorvas-tatin 20 mg daily 1 year later. The atorvastatin dosewas increased gradually over 4 years to 80 mg daily,but failed to achieve target low-density lipoproteincholesterol (LDL-C). Three years prior to presen-tation, ezetimibe 10 mg daily was added, whichresulted in an LDL-C reduction to 2.4 mmol/L.However, 7 months prior to presentation, atorvas-tatin 80 mg daily and ezetimibe 10 mg daily hadbeen inadequately controlling her cholesterol(LDL-C 2.9 mmol/L) and as a result atorvastatinwas switched to rosuvastatin 40 mg daily. Twomonths later, again due to inability to reach targetLDL-C, the dose of rosuvastatin was increased to

A multicentre, open study to assess the effect of individualizing starting doses of atorvastatin according to baseline LDL-C levels on achieving cholesterol targets: the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST-2) study

ABSTRACTObjectives: ACTFAST-2 was designed to match the starting dose of a statin to the baseline low density lipoprotein-cholesterol (LDL-C) value, to allow high-risk European subjects to achieve LDL-C targets within 12 weeks with the initial dose or one up-titration.Research design and methods: This was a 12-week, prospective, open-label trial that enrolled 610 high-risk subjects from 8 European countries. Subjects with LDL-C > 2.6 mmol/L (> 100 mg/dL),but ≤ 5.7 mmol/L (≤ 220 mg/dL) were assigned a starting dose of atorvastatin (10, 20, 40, 80 mg/day) according to LDL-C level and status of statin use at baseline (either statin-free or statin-treated), with a single up-titration at 6 weeks if needed.Results: At 12 weeks, 68.0% of subjects overall, including 73.5% of statin-free and 60.5% of statin-treated subjects, achieved LDL-C target (< 2.6 mmol/L (< 100 mg/dL). The total cholesterol/high density lipoprotein-cholesterol (TC/HDL-C) ratio target was achieved by 75.2% of subjects overall, including 78.1% of statin-free and 71.2% of statin-treated subjects. In the statin-free group, LDL-C decreased by a mean of 42%. In the statin-treated group, atorvastatin led to an additional 31% reduction in LDL-C over the statin used at baseline. Mean decreases in TC/HDL-C ratio were 30% and 20% in the statin-free and statin-treated groups, respectively. The incidence of AST/ALT greater than 3 times of upper limit of normal range in all patients was 0.8% and no rhabdomyolysis was reported.Conclusion: This study confirms that use of a flexible starting dose of atorvastatin allows the large majority of high-risk subjects to achieve their LDL-C target safely within 12 weeks with an initial dose or just a single up-titration.

A Model for Assessing the Cost-Effectiveness of Atorvastatin and Simvastatin in Achieving Canadian Low-Density Lipoprotein Cholesterol Targets

Background: Elevated low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for cardiovascular (CV) disease. Statins differ in their LDL-C-lowering effects and acquisition costs. Atorvastatin and simvastatin are the 2 most commonly used statins in Canada. Objective: This analysis compared the cost-effectiveness of atorvastatin and generic simvastatin in terms of annual drug cost per patient treated to Canadian LDL-C targets. It was conducted from the perspective of the Canadian provincial drug-reimbursement plans. Methods: A hypothetical cohort of 1000 dyslipidemic patients was assigned baseline LDL-C serum concentrations and levels of risk for CV disease based on Canadian population data. Canadian data on statin dosing were combined with efficacy data from a published meta-analysis to determine the proportion of patients who would be expected to achieve LDL-C targets after treatment with atorvastatin or generic simvastatin. Statin acquisition costs were obtained from Ontario and Quebec and reported in 2005 Canadian dollars. The sensitivity of the model to changes in drug costs, effectiveness, and persistence with treatment was tested. Results: The model predicted that more patients would reach the LDL-C target with atorvastatin than with simvastatin (73% vs 57%, respectively). The mean annual drug cost per patient treated to target was $54 higher with atorvastatin ($905 vs $851). The incremental cost-effectiveness ratio, measured as annual drug cost per additional patient treated to target with atorvastatin, was $1088. The model was sensitive to drug cost and effectiveness assumptions. Incorporating real-life rates of adherence into the model had no significant impact on the results. Conclusion: In this hypothetical cohort of dyslipidemic patients, treatment with atorvastatin would allow achievement of LDL-C targets in more patients than treatment with simvastatin, at an annual incremental cost of $1088 per additional patient treated to target.

Efficacy and tolerability of ezetimibe 10 mg/day coadministered with statins in patients with primary hypercholesterolemia who do not achieve target LDL-C while on statin monotherapy: A Canadian, multicentre, prospective study – the Ezetrol ® Add-On Study

For patients who have above-target low-density lipoprotein cholesterol (LDL-C) levels while on statin monotherapy, coadministration of a cholesterol absorption inhibitor with the statin may decrease serum LDL-C levels and improve overall lipid profiles. To assess the effectiveness and safety of ezetimibe 10 mg/day coadministered with a statin in patients with primary hypercholesterolemia who have higher than recommended LDL-C levels while on statin monotherapy. A six-week, prospective, multicentre study of eligible patients who had above-target LDL-C levels while on monotherapy with any statin, regardless of dose, for a minimum of four weeks. All patients were treated for six weeks with 10 mg ezetimibe daily coadministered with their current statins. A total of 1141 patients were screened, 953 (83.5%) fulfilled the study inclusion criteria and 837 (87.8%) completed the study. Reasons for withdrawal included: lost to follow-up (50 patients [5.2%]); protocol violations (45 patients [4.7%]); adverse events (19 patients [2.0%]); and withdrawal of consent (two patients [0.2%]). After six weeks of treatment, statistically significant (P = 0.001) mean reductions were observed in LDL-C (30.05%), total cholesterol (20.84%), triglycerides (10.16%), apolipoprotein B (19.84%) and the total cholesterol to high-density lipoprotein cholesterol ratio (19.88%). At six weeks, 674 patients (80.5%) achieved target LDL-C levels. Fifty predominantly mild, nonserious adverse events related to ezetimibe were reported by 32 patients (3.4%). Frequently reported adverse events included constipation (n = 7 [0.7% of patients]), diarrhea (n = 4 [0.4%]) and dizziness (n = 4 [0.4%]). Ezetimibe coadministered with statins is effective in reducing LDL-C in patients who do not attain target LDL-C levels while on statin monotherapy.

Objetivos del tratamiento hipolipemiante en pacientes con alto riesgo y muy alto riesgo cardiovascular: ¿un reto posible?

The last modifications of the National Cholesterol Education Program (NCEP) indicate some lower therapeutic targets of low density protein cholesterol (LDL-c) in patients with very high vascular risk. Our study aims to establish the degree of compliance of the therapeutic targets defined by these modifications. Descriptive and cross sectional study of patients from a cardiovascular clinic. Low-density lipoprotein cholesterol (LDL-c) was calculated and targets were established according the new update of NCEP-ATP III. 836 patients, 625 (75%) with HR and 211(25%) with VHR were studied 45% of HR and 67% of VHR were receiving treatment with statins (p < 0.001) but only 38% of HR and 15% of VHR achieved target LDL-c levels. The percentage of patients who could achieve LDL-goals using the maximum approved dose of the statins plus other lipid lowering drug was calculated: The 31% of HR and 51% of VHR were unable to achieve the LDL-c targets. Only 15% of very high risk patients achieve target levels of LDL-c according to the new NCEP-ATP III recommendations. Even using maximum dose of statins in combination with other lipid lowering drugs, less than half of the patients will be able to achieve LDL-c goal (< 70 mg/dl).

Reducing residual cardiovascular risk: the relevance of raising high-density lipoprotein cholesterol in patients on cholesterol-lowering treatment

Reducing low-density lipoprotein cholesterol (LDL-C) with statin therapy represents the cornerstone of dyslipidaemia management in patients with cardiovascular disease, as reflected in current treatment guidelines. Yet even among statin-treated patients who achieve LDL-C targets (&lt; 2.59 mmol/L [100 mg/dL]), the residual risk of further cardiovascular events remains unacceptably high. Although clinical studies indicate that intensive LDL-C lowering may provide some additional benefit, this does not suppress the excess cardiovascular risk sufficiently. This European Expert Panel therefore recognises that there is an unmet clinical need in the management of these patients. Additional intervention to modify other clinically important risk factors should be viewed as a priority. A reduced level of high-density lipoprotein cholesterol (HDL-C) &lt; 1.03 mmol/L (40 mg/dL) in men and &lt; 1.29 mmol/L (50 mg/dL) in women is an important independent predictive factor for coronary heart disease. HDL-C levels are also predictive of cardiovascular risk in statin-treated patients, irrespective of their LDL-C levels. Therefore, HDL-C represents a logical therapeutic target for reducing cardiovascular risk further in statin-treated patients, including those who achieve LDL-C targets. Given that low HDL-C is common among dyslipidaemic patients with cardiovascular disease, a therapeutic strategy aimed at effectively raising HDL-C, while at the same time lowering LDL-C to target levels, would be expected to offer clinical benefit beyond that achieved through LDL-C reduction alone. Although both nicotinic acid and fibrates raise HDL-C, nicotinic acid has greater potency. Studies show that combination therapy with prolonged-release (PR) nicotinic acid and a statin has an acceptable tolerability profile, normalises an atherogenic lipoprotein profile, and is able to induce regression of atherosclerosis and reduce coronary risk in patients with established cardiovascular disease and suboptimal HDL-C levels. In conclusion, this European Expert Panel recommends that combination therapy with a statin and an HDL-C raising agent, such as PR nicotinic acid, should be considered in these patients, who remain at high residual risk despite achieving target LDL-C levels with statin monotherapy. Ongoing studies are essential to confirm the clinical outcome benefits of this approach.

Retrospective review of sex differences in the management of dyslipidemia in coronary heart disease: An analysis of patient data from a Maryland-based health maintenance organization

Background: Coronary heart disease (CHD) is the leading cause of death in men and women in the United States, with a higher mortality in women, despite a lower prevalence. Statins effectively treat dyslipidemia and reduce the risk of CHD mortality. Objective: The objective of this study was to evaluate the treatment of dyslipidemia in patients with CHD and determine if sex differences exist. Methods: This was a retrospective chart review performed within a multioffice staff model health maintenance organization of ∼70,000 members. An administrative database, containing inpatient and out-patient medical claims, was used to identify patients with CHD based on diagnostic codes. Charts were randomly selected and the following information was obtained from chart review: age; sex; risk factors for CHD; diagnosis and/or prescription for depression; blood low-density lipoprotein cholesterol (LDL-C) level; and drug, dosage, and duration of prescribed lipid-lowering therapy. Exclusion criteria included missing charts and unavailable LDL-C values. LDL-C values were classified as at target if LDL-C <2.59 mmol/L (<100 mg/dL). Patients receiving statin monotherapy were categorized into 3 potency groups, based on efficacy to lower LDL-C values: high (atorvastatin 20–80 mg, lovastatin 80 mg), medium (atorvastatin 10 mg, pravastatin 40 mg, simvastatin 200 mg), and low (fluvastatin 10–40 mg, lovastatin 10–40 mg, pravastatin 10–20 mg, simvastatin 5–10 mg). Results: A total of 1487 adult patients (64.4% male with a mean (SD) age of 65.7 (11.8) years were identified, based on diagnostic codes for CHD. Three hundred twenty charts were selected for review. After exclusion, the final study cohort was 290 patients. The cohort was 66.2% male (192/290) with no significant difference in mean (SD) age between men (65.2 [9.2] years) and women (66.9 [10.5] years). Weight of women ranged from 85 to 305 lbs; 134 to 288 lbs for men. Among the study cohort, 46.2% (134/290) of the patients achieved the target LDL-C of <2.59 mmol/L (<100 mg/dL), with significantly more men (51.0% [98/192]) than women (36.7% [36/98]) reaching target ( P = 0.021). Lipid-lowering therapy was prescribed to 68.6% (199/290) of the patients, with no significant sex differences (men, 71.4% [137/192]; women, 63.3% [62/98]). Of the patients prescribed lipid-lowering therapy (primarily statins), 53.8% (107/199) achieved target LDL-C. There was no significant sex difference in the potency groups prescribed, and the rate of LDL-C target attainment was similar across potency groups. Overall, 70.3% of patients who did not receive lipid-lowering therapy had inadequately controlled LDL-C (women, 31/36 [86.1 %]; men, 33/55 [60.0%] [ P = 0.008]). Conclusions: The majority of CHD patients from a Maryland-based health maintenance organization had elevated LDL-C values, despite a lipid-lowering prescription rate of 68.6%. A significant gap in dyslipidemia treatment in these CHD patients remained, particularly for women.

AUDIT study. Evidence of global undertreatment of dyslipidaemia in patients with type 2 diabetes mellitus

The Analysis and Understanding of Diabetes and Dyslipidaemia: Improving Treatment (AUDIT) study was a confidential, web-based, cross-sectional survey involving 2,043 diabetes specialists in 50 countries. The study investigated the attitudes of physicians specialising in the treatment of patients with type 2 diabetes mellitus towards the management of dyslipidaemia and other cardiovascular risk factors in these patients. Physicians reported obtaining lipid profiles in 91% of patients with type 2 diabetes and estimated that 62% of type 2 diabetic patients have dyslipidaemia. Across all regions, stated low-density lipoprotein cholesterol (LDL-C), triglyceride and total cholesterol targets were lower for type 2 diabetic patients with than without cardiovascular disease (CVD). Fewer physicians reported having an LDL-C target of &lt; 2.6 mmol/L (≤100 mg/dL) for patients without CVD (59%) than with CVD (85%). Physicians reported that 54% of patients achieve LDL-C targets, with significantly more estimated to achieve their LDL-C goal in North America (69%) than in any other region (43—61%; p&lt;0.001). When setting targets, 58% of physicians stated that they were most influenced by lipid management guidelines, although a large proportion of physicians from Eastern Europe (54%) and Africa/Middle East (50%) cited a personal read of the literature. Patient compliance was the most commonly perceived barrier to lipid goal attainment in most regions (42—61%); financial constraints were cited most often in South America (76%), Africa/Middle East (65%) and Eastern Europe (63%). The AUDIT study revealed a disparity between lipid screening and control in type 2 diabetic patients. Physicians reported that they treated patients without CVD less intensively than patients with CVD, suggesting that type 2 diabetes was not widely considered a coronary heart disease risk equivalent. A reassessment of guideline implementation is needed for physicians worldwide to improve lipid control to decrease cardiovascular risk in type 2 diabetes.

Effects of Addition of Policosanol to??Omega-3 Fatty Acid Therapy on the??Lipid Profile of Patients with Type??II Hypercholesterolaemia

Policosanol is a mixture of higher aliphatic primary alcohols purified from sugar-cane wax. The mixture has cholesterol-lowering efficacy, its specific effects being to reduce serum total (TC) and low-density lipoprotein cholesterol (LDL-C), and to increase high-density lipoprotein cholesterol (HDL-C). The effects of policosanol on triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol. To investigate whether combined therapy with omega-3 FA + policosanol offers benefits compared with omega-3 FA + placebo with respect to the lipid profile of patients with type II hypercholesterolaemia. This randomised, double-blind study was conducted in 90 patients with type II hypercholesterolaemia. After 5 weeks on a cholesterol-lowering diet, patients were randomised to omega-3 FA + placebo, omega-3 FA + policosanol 5 mg/day or omega-3 FA + policosanol 10 mg/day for 8 weeks. Omega-3 FA was supplied as 1g capsules (two per day); placebo and policosanol were provided in tablet form. Physical signs and laboratory markers were assessed at baseline and after 4 and 8 weeks on therapy. Drug compliance and adverse experiences (AEs) were assessed at weeks 4 and 8. The primary efficacy variable was LDL-C reduction; other lipid profile markers were secondary variables. After 8 weeks, omega-3 FA + policosanol 5 and 10 mg/day, but not omega-3 FA + placebo, significantly reduced LDL-C by 21.1% and 24.4%, respectively (both p < 0.0001). Omega-3 FA + policosanol 5 mg/day also significantly lowered TC (12.7%; p < 0.01) and TG (13.6%; p < 0.05), and significantly increased HDL-C (+14.4%; p < 0.001). Omega-3 FA + policosanol 10 mg/day significantly decreased TC (15.3%; p < 0.001) and TG (14.7%; p < 0.01), and significantly increased HDL-C (+15.5%; p < 0.0001). Omega-3 FA + placebo significantly reduced TG (14.2%; p < 0.05) but had no significant effect on other lipid profile variables. The proportion of randomised patients in the omega-3 FA + policosanol 5 or 10 mg/day groups that achieved LDL-C targets or reductions 15% was significantly greater than in the omega-3 FA + placebo group (p < 0.001). Combined therapy with omega-3 FA + policosanol 5 or 10 mg/day resulted in significantly greater changes in LDL-C, TC and HDL-C than treatment with omega-3 FA + placebo, but did not modify the TG response compared with the omega-3 FA + placebo group. Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group). Policosanol 5 or 10 mg/day administered concomitantly with omega-3 FA 1 g/day improved LDL-C, TC and HDL-C, maintained the reduction in TG attributable to omega-3 FA monotherapy, and was well tolerated. Treatment with omega-3 FA + policosanol could be useful for regulating lipid profile in patients with type II hypercholesterolaemia, but further studies involving larger sample sizes are needed before definitive conclusions can be drawn.

The use of atorvastatin treatment in usual care environments: pooled analysis of six prospective, observational studies in 90,535 patients.

We investigated the pattern of use as well as the efficacy and safety of atorvastatin in unselected inpatients and outpatients in routine clinical practice in Germany. Six prospective, observational studies with a similar design were pooled. The studies lasted for up to 12 weeks and data from 90,535 patients (7,287 inpatients, 83,248 outpatients) were collected. The studies were performed in Germany in 2000 and 2001. Hospital or office-based physicians selected hyperlipemic patients with or without coronary heart disease (CHD) for once daily treatment with atorvastatin. Information on demographics, atorvastatin dosage, concomitant medication, concomitant diseases, cardiovascular risk factors, lipid profile as well as adverse events (AEs) and serious adverse events (SAEs) were obtained at 2-3 visits and descriptively analyzed. Absolute and relative changes in lipid parameters, percentage of patients with low-density lipoprotein cholesterol (LDL-C) values within target ranges according to the National Cholesterol Education Program (NCEP) criteria, and frequencies of AEs. On average, patients were treated for 22.4 days (inpatients) and 106.0 days (outpatients), respectively. The overall mean atorvastatin dose of 14.4 mg/day was well tolerated by a heterogeneous patient population with a variety of concomitant diseases and medications. Overall, 0.8% of patients suffered from one or more AEs, 0.6% were considered as treatment-related. The corresponding figures for SAEs and treatment-related SAEs were 0.1% (131 patients) and 0.01% (13 patients), respectively. Subgroup analyses did not reveal a particular safety concern in any subgroup. In total, 99% of patients judged the tolerability of atorvastatin as very good or good. The mean percentages of reduction in LDL-C at the final visit ranged between 24.8% and 28.5%. Overall, 26.3% of patients reached the NCEP LDL-C goal compared to 4.9% at baseline. Inpatients achieved the target range for LDL-C more frequently than outpatients (35.3% vs 25.6%). An underuse of atorvastatin titration in clinical practice in Germany was apparent, particularly in outpatients. The use of atorvastatin in usual care environments is effective and safe. There is a gap between treatment guidelines and clinical practice in Germany as reflected by the number of patients outside the target range for LDL-C. A major opportunity exists to increase the number of patients who achieve LDL-C target ranges by appropriate dose titration and/or giving patients a higher initial dose. Available guidelines need to be implemented more stringently.

Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome

SUMMARYObjective: To conduct a post-hoc assessment of the lipid-modifying effects of adding the cholesterol absorption inhibitor, ezetimibe, to on-going statin therapy in patients with diabetes mellitus (DM) or metabolic syndrome (MetS).Research design and methods: This was a post-hoc analysis of data from a randomized, double-blind, placebo-controlled trial designed to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy and safety of adding ezetimibe 10 mg/day versus placebo to ongoing, open-label statin treatment for 8 weeks in hypercholesterolemic patients. Qualifying LDL-C levels and target LDL-C goals were based on National Cholesterol Education Program risk categories. The DM subgroup were patients who entered the study with a prior diagnosis of DM. Patients were classified as having MetS if they met 3 or more of the following criteria at baseline: triglycerides (TG) ≥ 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol (HDL-C) < 40 mg/dL (1.04 mmol/L) for men or < 50 mg/dL (1.29 mmol/L) for women; fasting serum glucose (FSG) ≥ 110 mg/dL (≥ 6.1 mmol/L); a diagnosis of hypertension or taking hypertension medication or blood pressure ≥ 130/ ≥ 85 mmHg; waist circumference > 88 cm (women) or > 102 cm (men). DM patients were excluded from the MetS subgroup analysis.Main outcome measures: The objectives were to assess the effects of treatment on plasma concentrations of LDL-C and other lipid variables, and on the percentage of patients achieving LDL-C target levels at the end of the study.Results: Of 769 patients enrolled in the original study, there were 191 (24.8%) with DM and 195 (25.4%) with MetS. Regardless of subgroup, ezetimibe + statin was significantly more effective than statin alone at lowering plasma levels of LDL-C, non-HDL-C, total cholesterol, apolipoprotein B, and triglycerides (between-group p < 0.001 for all). For all lipid parameters, the relative treatment effects were generally consistent regardless of DM or MetS status. Significantly more ezetimibe than placebo patients in all subgroups achieved prespecified LDL-C goals ( p < 0.001 for all), and although more patients in the DM and MetS groups, respectively, achieved the goal compared with their non-DM and non-MetS counterparts [83.6% (DM) versus 67.2 (non-DM) and 71.8% (MetS) versus 65.6% (non-MetS)], these differences were not significant after adjusting for differences in baseline LDL-C levels. Ezetimibe was well-tolerated and had a favorable safety profile in all subgroups.Conclusions: The co-administration of ezetimibe with statins, a therapeutic regimen that inhibits both the absorption and synthesis of cholesterol, offers a well-tolerated and efficacious treatment to lower LDL-C in patients with DM and MetS.

Reducing low-density lipoprotein cholesterol ? treating to target and meeting new European goals

Many hypercholesterolaemic patients fail to achieve target low-density lipoprotein cholesterol (LDL-C) levels in clinical practice. In part, this failure is related to inadequate efficacy of commonly used statins in reducing LDL-C and to difficulties inherent in dose titration. The availability of statins that produce large decreases in LDL-C at starting doses could significantly improve treatment of patients by facilitating achievement of LDL-C goals. The multi-national MERCURY I trial has shown that rosuvastatin at its starting 10-mg dose enables more patients to reach target LDL-C levels and reduces LDL-C more than starting or higher doses of other commonly used statins. In addition, post hoc analyses of data from trials comparing rosuvastatin with atorvastatin, simvastatin and pravastatin indicate that rosuvastatin enables more hypercholesterolaemic patients to reach the newly published LDL-C goals in the Third Joint Task Force European guidelines, including the most aggressive goals, than do other statins at starting doses and across dose ranges. Improved goal achievement at starting doses, as well as the concomitant greater reduction in LDL-C, may constitute an important advantage in clinical practice.