László Márk

Lipid-modifying therapy and attainment of cholesterol goals in Hungary: the return on expenditure achieved for lipid therapy (REALITY) study.

AbstractBackground and objective: Cardiovascular disease is a leading cause of death in Eastern Europe. Few studies on cholesterol goal achievement have been conducted in Hungarian clinical settings. This study set out to evaluate lipid-modifying therapy practices and their effects on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) goal attainment in Hungarian patients with coronary heart disease (CHD), CHD risk equivalents, or ≥2 coronary risk factors. Methods: This multicentre observational study involved patients receiving lipid-modifying therapy who were under the care of general practitioners (n = 300) or specialists (n = 140). Physician questionnaires were used to collect data on baseline patient characteristics, including laboratory parameters. Using validated cardiovascular risk assessment measures, patients were stratified into high-risk (10-year absolute coronary risk >20%; n = 367) and lower risk groups (n = 73). Cholesterol goals were TC <4.5 mmol/L (<175 mg/dL) and LDL-C <2.5 mmol/L (<100 mg/dL) for the high-risk group and TC <5.0 mmol/L (<193 mg/dL) and LDL-C <3.0 mmol/L (<117 mg/dL) for those at lower risk. Results: Among 440 patients (n = 312 with CHD or CHD risk equivalents), 374 (85%) were initiated on HMG-CoA reductase inhibitors (statin monotherapy), 44 (10%) received fibric acid derivatives and 22 (5%) received combination regimens. Although >50% of patients needed >35% TC lowering to reach goal, <10% of patients received high or very high potency lipid-modifying regimens or combination regimens initially. A total of 116 (26.4%) patients achieved their TC goals after ≥1 year of treatment, including 27.9% of patients with CHD/risk equivalents and 22.7% of those with risk factors only. Sixty-six (15%) patients achieved goal on initial lipid-modifying regimens, while a further 50 (11.4%) achieved goal following treatment changes, including upward dosage adjustments. Conclusion: Approximately 74% of Hungarian patients receiving lipid-modifying therapy in our study did not achieve cholesterol goals. The proportion of patients realising their TC goals was higher in those treated by specialists but still did not exceed one-third.

Changes in attainment of lipid goals by general practitioners and specialists in patients at high cardiovascular risk in Hungary during 2004-2008

Introduction Lipid-lowering therapy should achieve target levels. We assessed the change of the achievement of targets and the mean low-density lipoprotein cholesterol (LDL-C) levels in high-risk Hungarian patients. Material and methods Six studies performed with patients of general practitioners (GPs) and specialists between 2004 and 2008 were evaluated: 9,508 patients from GPs and 2809 from specialist practices (total 12,317). Results During this 4-year period the LDL-C level decreased by 0.73 mmol/l and the LDL-C goal achievement rate increased from 14 to 32% in patients treated by GPs. LDL-C showed a decrease of 0.48 mmol/l and the goal achievement rate changed from 20 to 43% in patients treated by specialists. In the majority of the patients not achieving the LDL-C goal (57% for specialists and 89% for GPs) there was no modification in the current therapy. In addition to emphasizing the priority of LDL-C lowering, we should also strive for residual risk reduction, which means raising high-density lipoprotein cholesterol (HDL-C) and lowering triglyceride levels. There was no significant improvement in HDL-C or triglyceride levels during the examined period. Conclusion More attention needs to be paid to changing treatment of patients to achieve target levels.

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.

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.

An attempt to make lipid-lowering therapy more effective in Hungary. The results of MULTI GAP 2010 and the PLUS Program.

Introduction The primary goal of lipid-lowering therapy is the attainment of low-density lipoprotein cholesterol (LDL-C) target levels. Material and methods The MULTI GAP (MULTI Goal Attainment Problem) 2010 is a part of surveys started a few years ago, in which the lipid results of 1540 patients treated by general practitioners (GPs) and specialists were measured. The data were compared to the results of similar studies involving 15,580 patients between 2004 and 2009. Results In 2010 the mean LDL-C level (± SD) of patients treated by GPs was found to be 3.01 ±1.0 mmol/l. The target of 2.50 mmol/l was achieved by 32%, with a mean LDL-C level of 2.84 ±1.0 mmol/l and an achievement rate of 39% in patients treated by specialists. The results of comparisons starting from 2004 showed a marked improvement every year in the beginning, but in the last 3 years stagnation was observed. In 2010 in addition to the MULTI GAP main study, a group of physicians took part in special training called the Plus Program. As a result of this, the LDL-C level was 0.18 mmol/l lower in 114 of the GPs’ patients (p = 0.088) and 0.27 mmol/l (p < 0.0001) lower in 313 of the specialists’ patients, with a significantly better, 42% (p = 0.045) and 50% (p = 0.001), goal attainment rate, respectively. Conclusions The 2010 MULTI GAP study shows that the quality of lipid-lowering therapy in Hungary seems to be in stagnation. The results of the PLUS Program suggest that continuous training of doctors is the key to further improvement.

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.

A change of attitude in lipidology, achievement of target levels. What comes next?

One of the greatest challenges of cardiovascular prevention is to minimize the risk of cardiovascular events through the achievement of target lipid levels. Its importance is suggested by the comprehensive meta-analyses of large scale clinical trials and the therapeutic guidelines determining everyday clinical practice. The attainment of target levels is often emphasized, nevertheless, there is a gap between theory and practice. The authors compare the goal attainment rate based on Hungarian medical literature and their own data, and analyze the possibilities of further improvement. The CEL Program evaluated the achievement rate of target total cholesterol levels in more than 10 000 patients of general practitioners in 2004, 2005 and 2006, and the ratio increased from 12% to 30% within 3 years. According to the results of the Hungarian REALITY study the rate of patients achieving the target total cholesterol levels was 21% in 2004, and it increased to 27% during a 3-year period. To this very low improving rate also belongs the fact that in 2007, when only one fourth of patients were on target levels, 87% of general practitioners and 56% of specialists reconciled themselves to it and did not propose any modification in the therapy of patients not achieving the target levels. The surveys conducted at the department of internal medicine with cardiological profile of the county hospital in Gyula proved a considerable increase in the last 7 years in the administration of drugs improving the life expectancy of cardiovascular patients (aspirin, beta-blockers, ACE-inhibitors and statins) due to the widespread application of clinical guidelines and the special attention; nowadays the administration rate is above 90% in all four groups. Nevertheless, the rate of patients achieving the LDL-cholesterol goals was 37% in the high risk and 18% in the very high risk groups in December 2007 and January 2008. The fact that in the latter group only 21% of patients received combination therapy indicates that improving this ratio may be the next step. A greater emphasis should be placed on the achievement of target levels and regular revision of applied medical therapy, particularly in the high and very high risk patients as these groups can benefit the most from it.

To What Extent are National Cardiovascular Disease Preventive Guidelines Accomplished in Hungary? The Goal Attainment Program (GAP)

Purpose: Improving the management of cardiovascular disease in Hungary represents an important clinical challenge. This article assesses the achievement of national consensus total cholesterol goals among Hungarian patients of physicians educated about the consensus guidelines and assisted in cardiovascular risk assessment. Methods and results: A total of 320 general practitioners provided data on 15,404 eligible patients. Among these individuals, 14,018 (91%) had documented atherosclerosis and the remaining 9% had ≥ 2 risk factors. Despite this, less than half of all patients received lipid-lowering therapy. Only 12% of high-risk patients attained the consensus total cholesterol target of < 4.5 mmol/L (< 175 mg/dL) and 31% of individuals at low-moderate risk achieved the consensus goal of < 5.0 mmol/L (< 194 mg/dL) at the first visit. Among patients in the high-risk group whose total cholesterol levels were above the consensus goal at the first visit, 54% received no lipid-lowering therapy and 46% receiv...

Diabeteses dyslipidaemia és atherosclerosis

The incidence and the public health importance of diabetes mellitus are growing continuously. Despite the improvement observed in recent years, the leading cause of morbidity and mortality of diabetics are cardiovascular diseases. The diagnosis of diabetes mellitus constitutes such a high risk as the known presence of vascular disease. Diabetic dyslipidaemia is characterised by high fasting and postprandial triglyceride levels, low HDL level, and slightly elevated LDL-cholesterol with domination of atherogenic small dense LDL. These are not independent components of the atherogenic dyslipidaemia, but are closely linked to each other. Beside the known harmful effects of low HDL and small dense LDL, recent findings confirmed the atherogenicity of the triglyceride-rich lipoproteins and their remnants. It has been shown that the key of this process is the overproduction and delayed clearance of triglyceride-rich lipoproteins in the liver. In this metabolism the lipoprotein lipase has a determining role; its function is accelerated by ApoA5 and attenuated by ApoC3. The null mutations of the ApoC3 results in a reduced risk of myocardial infarction, the loss-of-function mutation of ApoA5 was associated with a 60% elevation of triglyceride level and 2.2-times increased risk of myocardial infarction. In case of diabetes mellitus, insulin resistance, obesity, metabolic syndrome and chronic kidney disease the non-HDL-cholesterol is a better marker of the risk than the LDL-cholesterol. Its value can be calculated by subtraction of HDL-cholesterol from total cholesterol. Target values of non-HDL-cholesterol can be obtained by adding 0.8 mmol/L to the LDL-cholesterol targets (this means 3.3 mmol/L in high, and 2.6 mmol/L in very high risk patients). The drugs of first choice in the treatment of diabetic dyslipidaemia are statins. Nevertheless, it is known that even if statin therapy is optimal (treated to target), a considerable residual (lipid) risk remains. For its reduction treatment of low HDL-cholesterol and high triglyceride levels is obvious by the administration of fibrates. In addition to statin therapy, fenofibrate can be recommended.