Istvan Reiber

Attaining United States and European Guideline LDL-cholesterol Levels with Simvastatin in Patients with Coronary Heart Disease (the GOALLS Study)

Summary The effectiveness and safety of simvastatin in reducing low-density lipoprotein cholesterol (LDL-C) to target levels in patients with coronary heart disease (CHD) were evaluated in the GOALLS (Getting to Appropriate LDL-C Levels with Simvastatin) study. This multinational, multicentre, prospective, open-label, study consisted of a six-week diet washout period followed by a 14-week titrate-to-goal treatment period with simvastatin. One hundred and ninety-eight men and women with documented CHD and a fasting LDL-C level between 115 mg/dl (3.0 mmol/l) and 180 mg/dl (4.7 mmol/l) and triglycerides (TGs) ≤ 400 mg/dl (4.5 mmol/l) were enrolled. The patients were started on 20 mg simvastatin with dose titration up to 80 mg if the LDL-C remained above 100 mg/dl at weeks 6 and 10. The key efficacy parameters were the percentage of patients achieving US and European LDL-C goals [≤ 100 mg/dl (2.6 mmol/l) and ≤ 115 mg/dl (3.0 mmol/l), respectively]. Safety was evaluated by monitoring laboratory tests and recording adverse events. After 14 weeks of simvastatin (20–80 mg) treatment, approximately 90% of the patients achieved LDL-C goals according to US (87%) and European (94%) guidelines. Most patients (72–93%) achieved target LDL-C levels on 20 mg simvastatin. An estimated 14% of the patients required titration to the 80 mg dose. Treatment with simvastatin (20–80 mg) produced statistically significant improvements in all measured lipid variables by the end of the study. The mean reductions in total cholesterol and LDL-C, and the median reduction in TG, were 28%, 41% and 16%, respectively. The increase in high-density lipoprotein cholesterol and apolipoprotein A-1 were 5% and 4%, respectively. Simvastatin was well tolerated across the dosage range. In conclusion, simvastatin, 20–80 mg/day, was safe and highly effective at reducing LDL-C levels. The recommended US and European LDL-C treatment goals were achieved in approximately 90% of the patients. These goals were similarly achieved for a variety of high-risk sub-groups (hypertensives, diabetics and elderly patients).

Association of plasma lipid levels with apolipoprotein E polymorphism in Type 2 diabetes

OBJECTIVE To evaluate the distribution of apolipoprotein E polymorphism in patients with Type 2 diabetes and their impact on plasma lipid levels. SUBJECTS Unrelated Type 2 diabetic patients (n = 298) treated by diet and sulfonylurea and not receiving lipid-lowering regimens, elderly (n = 98) and young (n = 101)unrelated healthy control subjects in Hungary. METHODS Apolipoprotein E genotypes were identified by PCR amplification and subsequent restriction endonuclease digestion. RESULTS The distribution of the most frequent genotypes in the diabetes group was E2/3 8.7%, E3/3 78.2%, E3/4 12.8%, in the elderly group E2/3 9.2%, E3/3 78.6%, E3/4 12.2% and in the young group E2/3 11.9%, E3/3 62.4%, E3/4 24.8%. The frequencies of allele e4 in the diabetes and in the elderly control group were significantly lower than in the young control group (both P < 0.05). Associations were found between the e4 allele and increased triglyceride level in the diabetes group, the e2 allele and decreased total cholesterol and LDL-cholesterol levels both in the elderly and young control groups (both P < 0.01). CONCLUSION The lower frequency of allele e4 in both the elderly and diabetes groups, may be explained by an increased morbidity and mortality in middle-aged carriers of apo e4 allele. The increased risk of e4 carriers in Type 2 diabetes may be partly mediated by a higher triglyceride level.

Persistence with statin therapy in Hungary

Introduction Persistence with lipid-lowering drug therapy by cardiovascular patients in Hungary has not been studied previously. This study was designed to determine the rate with which Hungarian patients with hyperlipidemia persist in taking lipid-lowering agents, and to compare this with rates reported from other countries. Material and methods This was a retrospective study that utilized data from the Institutional Database of the National Health Insurance Fund to analyze persistence rates with statins and ezetimibe. The study included data for patients who started lipid-lowering therapy between January 1, 2007, and March 31, 2009. Variables included type of lipid-lowering therapy, year of therapy start, and patient age. Main outcome measures were medians of persistence in months, percentages of patients persisting in therapy for 6 and 12 months, and Kaplan-Meier persistence plots. Results The percentage of patients who persisted with overall statin therapy was 46% after 1 month, 40.3% after 2 months, 27% after 6 months, and 20.1% after 12 months. Persistence was slightly greater for statin therapy started during 2008 than during 2007. Older patients were more persistent with therapy than younger patients. Persistence with the combination of ezetimibe-statin therapy was greater than with statin or ezetimibe monotherapy. Conclusions Persistence with statin therapy by patients in Hungary was low compared with other countries. Low persistence may have negated potential clinical benefits of long-term statin therapy.

Postprandial triglyceride levels in familial combined hyperlipidemia. The role of apolipoprotein E and lipoprotein lipase polymorphisms

The effect of apolipoprotein E genotype and polymorphisms of lipoprotein lipase gene on plasma postprandial triglyceride levels in familial combined hyperlipidemic subjects and their relatives have not been sufficiently studied. This study included sixteen familial combined hyperlipidemic parents (G1): age: 52 +/- 9 years with total-cholesterol: 7.2 +/- 1.7 mmol/L, fasting triglycerides: 2.8 +/- 1.4 mmol/L and sixteen children (G2) (twelve were normolipidemic): of age: 22 +/- 5 years with total-cholesterol: 5.2 +/- 1.1 mmol/L, fasting triglycerides: 2.06 +/- 1.8 mmol/L and twelve normolipidemic, healthy controls. Blood samples were taken fasting and 2, 4, 6, 8, 10 hr postprandially after the standard fat rich test meal. We determined lipid parameters, apolipoprotein E and lipoprotein lipase HindIII and PvuII polymorphisms as well. The 6-hr critical postprandial triglyceride values were abnormal in both G1: 5.88 +/- 2.7 mmol/L and G2: 3.53 +/- 2.7 mmol/L (p <0.001), respectively, and differed significantly (p <0.001) from each other. The subjects of familial combined hyperlipidemic families with E4 allele in both generations exhibited significantly (p <0.001) higher and extended postprandial lipemia. We did not find significant effects of lipoprotein lipase HindIII or PvuII polymorphisms on the fasting lipid values alone, however in normolipidemic subjects from the same families the homozygosity of HindIII variation was associated with higher triglyceride postprandial peak (p <0.01). The main findings of our study are that i.) normolipidemic G2 subjects in familial combined hyperlipidemic families have already abnormal postprandial status, and ii.) the 6 h postprandial triglyceride values were correlated with fasting triglyceride levels, which showed association with the apolipoprotein E4 allele.

How can we further improve the LDL-cholesterol target level achievement rate based on the Hungarian MULTI GAP 2011 study results and considering the new European dyslipidemia guidelines?

Introduction Despite the continuous improvement of the quality of lipid lowering therapy the achievement of target values is still not satisfactory, mainly in the very high cardiovascular risk category patients, where the goal of low density lipoprotein cholesterol (LDL-C) is 1.80 mmol/l. Material and methods The trends in lipid lowering treatment of 17420 patients from different studies conducted between 2004 and 2010 were compared to that of 1626 patients of MULTI GAP (MULTI Goal Attainment Problem) 2011 treated by general practitioners (GPs) and specialists. Results In MULTI GAP 2011 the mean LDL-C level ± SD) of patients treated by GPs was found to be 2.87 ±1.01 mmol/l, the target value of 2.50 was achieved by 40% of them, in the specialists’ patients the mean LDL-C level proved to be 2.77 ±1.10 mmol/l and the achievement rate was 45%. In the 2.50 mmol/l achievement rate of GPs’ patients a satisfactory improvement was observed in the studied years, but the 1.80 mmol/l LDL-C goal in 2011 was attained only in 11% of very high risk cases. There was a linear correlation between the patient compliance estimated by the physicians and the LDL-C achievement rate. Conclusions As the number of very high risk category patients has been increased according to the new European dyslipidemia guidelines, growing attention needs to be placed on attainment of the 1.80 mmol/l LDL-C level. Based on the results of the MULTI GAP studies, improving patients’ adherence and the continuous training of physicians are necessary.

The role of ezetimibe in LDL cholesterol goal attainment in very high risk patients: The rosuvastatin monotherapy looks to be insufficient

Accepted: 18 July 2011; published online: 5 September 2011 Citation: Curr Med Res Opin 2011; 27:1959–60 One of the most important components of cardiovascular prevention is the achievement of appropriate LDL cholesterol level. In this process the drugs of first choice are the statins, their favorable effect on cardiovascular events and total mortality was proved by a series of studies. This has been affirmed by the Cholesterol Treatment Trialists’ Collaboration (CTTC) meta-analysis involving data of nearly 130,000 patients, where the decrease in major vascular events per 1.0 mmol/L LDL cholesterol reduction was 21%, that of all-cause mortality 10%. At the same time in everyday lipid lowering practice it is well known that in a considerable number of cases statin monotherapy is not sufficient to achieve goals. In LDL cholesterol reduction the administration of ezetimibe proved to be an outstanding help. Its damaged prestige was restored by the result of SHARP (Study of Heart and Renal Protection) study showing that the use of a combination of ezetimibe and simvastatin 20 mg significantly reduced the occurrence of cardiovascular events (e.g. 17% decrease in the rate of major atherosclerotic events, p1⁄4 0.0022). A recent meta-analysis of CMRO (Mikhailidis et al.) assesses the beneficial effects of ezetimibe treatment based on the data from 13 studies and 5080 patients. The main message of this publication with its slightly complicated and for general clinicians hard-to-understand statistics was that the odds ratio to attain LDL-C treatment goal is 2.45 (1.95, 3.08), (p1⁄4 0.007) for adding ezetimibe to statin therapy vs. doubling the statin dose. The inefficiency of statin monotherapy (even in the case of the most potent rosuvastatin) and the usefulness of administering ezetimibe would be supported by the Hungarian CORVUS (COntrolled TaRgets for High Vascular Risk Patients Using Effective Statins) study conducted among specialists where the effect of switching to high-efficient rosuvastatin on the success of lipid lowering therapy in 1385 high risk patients was investigated. In this 3-month, multicenter, prospective, observational, non-interventional open-label study 1077 out of 1385 patients belonged to the very high risk category. During the 3month treatment period in the whole patient population the level of total

The Effect of Switching to the High-Efficient Rosuvastatin on the Success of Lipid Lowering Therapy in High Risk Patients. The CORVUS (Controlled Targets for High Vascular Risk Patients Using Effective Statins) Study

Aim: Achievement of target lipid levels is a one of the most important part of the cardiovascular risk reduction to which an obvious way is to switch from current drug to a stronger statin. Method: In a 3-month, multicenter, prospective, observational, non-interventional open-label study the change of lipid levels and the rate of target level attainment were investigated in 1385 high cardiovascular risk patients, administering, if possible, rosuvastatin in those with lipid levels over the target values. Results: During the 3-month treatment period the level of total cholesterol decreased by 25.2%, LDL-cholesterol by 35.0%, triglyceride by 21.0% and HDL-cholesterol level increased by 5.1%. At the end of the study 96% of the patients were treated with rosuvastatin in monotherapy or in combination. At the third month the rate of achieving LDL-cholesterol target level was 57.7% and that of HDL-cholesterol target level was 66.7% and in case of triglyceride level 48.2%. The majority of patients (1077 persons) belonged to the very high risk category according to theguidelines of 3rd Hungarian Cardiovascular Consensus Conference. Among them the achievement rate of an LDLcholesterol level of 1.8mmol/L was proved to be 19.0%. Conclusion: The study confirmed that more frequent use of a high-efficient statin (rosuvastatin) by specialists has a beneficial effect on lipid parameters and also facilitates a higher rate of achieving target lipid levels, but to be more efficient, mainly in the very high risk category cases, the combination therapy has to be used more often.

The good, the bad, and the atherogenic

The history of the diagnostics and therapy (management) of atherosclerosis and, in close connection with it, dyslipidemia, has reached an important stage. In the 1950s, we used the word hypercholesterinemia , but later on we began using the correct term: dyslipidemia. Today, it is clear that the

Egyre.,célratörobb" lipidterápiás szokásaink-A Magyar MULTI GAP 2010 eredményei

A korabbi vizsgalatok azt mutattak, hogy a nagy kockazatu betegek jelentős resze nem eri el az LDL-C-celertekeket, es az alkalmazott lipidcsokkentő kezeles ellenere az ajanlottnal magasabb trigliceridszinttel es alacsony HDL-C-szinttel is rendelkeznek. Celok: A szerzők a 2008. es 2009. evi felmeresekhez hasonloan, a jelen vizsgalatban is a cardiovascularis esemenyen atesett betegek dyslipidaemiajanak kezelesi strategiajat elemeztek. Modszerek: A MULTI GAP (MULTI Goal Attainment Problem) 2010 vizsgalatban standard strukturalt kerdőivek segitsegevel 2332 beteg adatai kerultek feldolgozasra. Az elemzesben az osszkoleszterin-, LDL-C- mellett a HDL-C- es atherogen koleszterin- (A-C), illetve a triglicerid-celerteket elerők aranya is kiertekelesre kerult. Eredmenyek: A vizsgalt betegek 15%-a (n = 355) nem reszesult lipidcsokkentő kezelesben. A szakorvosok altal kezelt betegek 44%-a elerte a 2,5 mmol/l LDL-C-celerteket. A HDL-C-celerteket a nagy rizikoju betegek 61%-a, mig a triglicerid-celerteket a betegek 43%-...

[Becoming more "goal-oriented" in therapy of dyslipidemias: results of the Hungarian MULTI GAP 2010].

A korabbi vizsgalatok azt mutattak, hogy a nagy kockazatu betegek jelentős resze nem eri el az LDL-C-celertekeket, es az alkalmazott lipidcsokkentő kezeles ellenere az ajanlottnal magasabb trigliceridszinttel es alacsony HDL-C-szinttel is rendelkeznek. Celok: A szerzők a 2008. es 2009. evi felmeresekhez hasonloan, a jelen vizsgalatban is a cardiovascularis esemenyen atesett betegek dyslipidaemiajanak kezelesi strategiajat elemeztek. Modszerek: A MULTI GAP (MULTI Goal Attainment Problem) 2010 vizsgalatban standard strukturalt kerdőivek segitsegevel 2332 beteg adatai kerultek feldolgozasra. Az elemzesben az osszkoleszterin-, LDL-C- mellett a HDL-C- es atherogen koleszterin- (A-C), illetve a triglicerid-celerteket elerők aranya is kiertekelesre kerult. Eredmenyek: A vizsgalt betegek 15%-a (n = 355) nem reszesult lipidcsokkentő kezelesben. A szakorvosok altal kezelt betegek 44%-a elerte a 2,5 mmol/l LDL-C-celerteket. A HDL-C-celerteket a nagy rizikoju betegek 61%-a, mig a triglicerid-celerteket a betegek 43%-...