Lege Artis Medicinae

[ACE-INHIBITORS IN THE SECONDARY PREVENTION OF CORONARY ARTERY DISEASE]

SÁRSZEGI Zsolt

JULY 14, 2007

Lege Artis Medicinae - 2007;17(06-07)

[The beneficial effects of angiotensin-converting enzyme inhibitors on biochemical and vascular markers have been proven by many experimental studies. Reduction of the angiotensin-II level has a positive effect on oxidative stress, lipid peroxidation, apoptosis, inflammatory and prothrombotic processes. Two large multicentric trials, EUROPA and HOPE, showed that perindopril and ramipril significantly reduce mortality and the risk of both fatal and non-fatal cardiovascular events in patients with atherosclerosis, thereby making them the base drugs of secondary prevention of coronary artery disease.]

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Lege Artis Medicinae

[Coalition pathology]

FRENKL Róbert

Lege Artis Medicinae

[THE IMPORTANCE OF ATTITUDES TO MEDICATION IN LIPID-LOWERING THERAPY PATIENT CO-OPERATION - PERSISTENCE AND COMPLIANCE]

NAGY László

[Controlled clinical studies on statins have produced evidence that the aggressive lowering of LDL-cholesterol (LDL-C) level reduces the mortality rate of ischaemic heart disease. About 40% of treated patients achieve the cholesterol target level. The observance of medication instructions on a daily basis (compliance) and willingness for long-term taking of the drug (persistence) are crucially important to avoid severe complications. In the long term, patients take only about 50% of their medicines according to the instructions. As a result of the generally poor compliance and persistence in taking the medications, the decrease in morbidity and mortality observed in clinical studies do not occur under real-life conditions. Patients with poor compliance (<80%) will experience only a minimal health benefit and the cost-effectiveness of the therapy will markedly decrease. For patients with poor persistence who discontinue their treatment before benefits at the clinical endpoints could manifest, the resources invested into the therapy will be lost. Both compliance and persistence deteriorate as the number of concurrently taken medicines increases. Since less than 50% of the programmes aimed at improving patient co-operation are successful, therapeutic decisions should preferably be made by taking into consideration the expected compliance/persistence already at the time of choosing the medication. By widening the use of fixed-dose combination therapies, the efficiency of treatment can substantially be increased in patients who concurrently take several medicines and require aggressive lowering of blood pressure or LDL-C level.]

Lege Artis Medicinae

[THE SAFETY OF TREATMENT WITH PEGYLATED INTERFERON-ALPHA-2A AND RIBAVIRIN IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION, BASED ON HUNGARIAN EXPERIENCE]

WERLING Klára, DALMI Lajos, GERVAIN Judit, HORVÁTH Gábor, NAGY István, NEMESÁNSZKY Elemér, RIBICZEY Pál, TELEGDY László, VARGA Márta, TORNAI István, TULASSAY Zsolt

[INTRODUCTION - Adverse effects of treatment for chronic C virus hepatitis present an important problem both for the patient and the clinician. The reduction of drug doses or the suspension of therapy lessen the likelihood of recovery. PATIENTS, METHODS - Between 2001 and 2004, 66 patients with chronic hepatitis C received 180 μg pegylated interferon-alpha-2a per week and 800-1200 mg ribavirin per day, 6 of whom for 24 weeks and 60 patients for 48 weeks. During treatment, patients were closely followed in order to recognize any adverse effects early. RESULTS - Of the patients treated for 48 weeks, 48.3% developed adverse effects, with changes in the differential in 41.7%, and anaemia, low platelet count, neutropenia in similar rates. Further side effects included cardiac complications, skin symptoms, persisting high fever, autoimmune thyroiditis and liver failure, altogether in 9 cases. Dose reduction or temporary suspension of pegylated interferon-alpha-2a was necessary in 21 cases (31.7%), while complete cessation of this treatment was decided in 7 cases, most of them because of blood count changes. The 1000 to 1200 mg per day ribavirin had to be reduced in 30.8% of patients, while treatment was stopped in 3 cases. Long-term virological remission occurred in 48% of patients who received treatment for 48 weeks, whereas no such result was observed among any of those treated for 24 weeks. CONCLUSION - Adverse effects of variable severity developed in nearly half of the patients with chronic hepatitis C infection who received antiviral treatment for 48 weeks, but treatment had to be stopped in only a small proportion of this group. Early treatment of adverse effects can prevent the need to cease therapy and may improve its efficiency.]

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[Clinical consensus conference on COPD]

TAMÁSI Lilla

Lege Artis Medicinae

[ALTERATIONS IN MYOCARDIAL CONTRACTILE PROTEIN COMPOSITION IN DIASTOLIC HEART FAILURE]

PAPP Zoltán, BORBÉLY Attila, ÉDES István

[Disturbances in ventricular relaxation may lead to the development of diastolic heart failure. The analysis of left ventricular endomyocardial biopsy specimens may help understand the underlying structural and functional changes. Such analyses have lead to the recognition that at the optimal sarcomere length of the Frank- Starling mechanism (i.e., at 2.2 μm), passive force values of the cardiomyocytes are significantly higher in individuals with diastolic heart failure than in healthy controls. As a probable explanation to this finding, increased expression of the stiffer N2B isoform of the myofilamental titin protein, at the expense of the more elastic N2BA titin isoform, has been recognized. Moreover, decreased phosphorylation of the contractile proteins was also suggested to contribute to the development of diastolic heart failure. These changes together, and along with an increase in extracellular collagen content, may greatly contribute to the relaxation disturbance observed in diastolic heart failure.]

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[THE IMPORTANCE OF THE RECOGNITION AND TREATMENT OF LIPID METABOLISM DISORDERS IN THE SECONDARY PREVENTION OF CEREBROVASCULAR DISEASES]

FOLYOVICH András, HORVÁTH Eszter

[The high world prevalence of cerebrovascular diseases, and the particularly bad morbidity rates of Hungary are well known. The physiological properties of the brain make stroke prevention outstandingly important. Effective prevention will be reflected in the reduction of the late complications that are otherwise common and expensive to treat. Because of the common simultaneous development of stroke, cardiovascular and peripheral vascular diseases, overall vascular disease prevention is preferred, even if the various vascular diseases manifest in different degrees in a patient. Hungarian data also indicate the high risk of recurrence of cerebrovascular diseases, therefore, the importance of secondary prevention is obvious. Large international studies have proven the strokepreventing effect, and, by a pleiotropic drug action, additional benefits, of the efficient treatment of blood lipid disorders. Consensus conferences in recent years defined clear and even stricter lipid-lowering target values, mostly to be reached by “double inhibition”, bile acid binding resins, fibrates and nicotinic acid derivatives, beside the most common statin treatment. Neurological and stroke departments and clinics play a pivotal role in vascular prevention.]

Lege Artis Medicinae

[Perindopril plus Indapamid CombinAtion blood preSSure reductiOn study (PICASSO)]

FARSANG Csaba

[INTRODUCTION - International and Hungarian (JNC-7, ESH/ESC2007 és 2009, MHT 2009) Guidelines suggest a target blood pressure <140/90 mmHg for hypertensive patients, and <130/80 mmHg for those with high/very high cardiovascular risk (e.g. patients with diabetes mellitus, chronic renal disease). It was proved that for achieving the most efficient antihypertensive effect and reducing side effects, thd use of drug combinations is needed in most patients. In Hungary, ACE-inhibitor plus diuretic combination is one of the most frequently used one in Hungary. The aim of the PICASSO study was to evaluate the efficacy and metabolic effects of the fixed combination of high-dose perindopril plus indapamide (Coverex-AS Komb Forte®) in clinical practice of hypertonologists, cardiologists and general practicioners. PATIENTS AND METHODS - Patients with uncontrolled, grade 1 or 2 primary hypertension, age, >18years were involved in the open, 3-month, multicentre, prospective, observational, non-interventional clinical study if the treating physician indicated a combination treatment with higher dose antihypertensive drugs. Blood pressure (also with ABPM), heart rate, metabolic parameters (plasma lipids, blood sugar, Na, K, creatinine, uric acid, GGT) were measured by routine methods, medical history and quality of life parameters were registered on a validated questionnaire. Changes in the above parameters were also separately evaluated in patients with different risk factors or with concomitant diseases. RESULTS - Data of 9683 patients were evaluated (54% women, 46% men, average age 61.8 years). By the end of the therapy used in the study, blood pressure average decreased from 159/93 to 131/80, by ABPM from 145/83 to 126/74 mmHg (24hr averages, systolic/diastolic blood pressure, respectively), the heart rate from 79 to 73 beats/min (p<0,001). Target blood pressure was achieved in 75,4% of patients with no major concomitant disease, but only in 14% of those with a concomitant disease characterised by lower target blood pressure. The diurnal index by ABPM did not change substantially. Clinically significant decreases were found in the plasma levels of total cholesterol, LDL-cholesterol, triglycerides, fasting glucose and uric acid levels, but there were no major changes in serum levels of HDL-cholesterol, Na, K, and GGT. Quality of life parameters significantly improved by the end of the study. CONCLUSIONS - Combinations of perindopril and indapamide can be successfully and safely used in everyday practice.]

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[Effect of beta blockers in hypertension, ischaemic heart disease, heart failure and metabolic syndrome]

BENCZÚR Béla

[Beta-blockers are among the most widely used drugs for the treatment of cardiovascular diseases. In the mid-90’s, these drugs were recommended as first-line therapies of hypertension. With the introduction of new drugs, the list of first-choice drugs has been extended. The results of recently published major hypertension trials, which compared conventional agents (beta blockers and/or diuretics) with newer agents (angiotensin converting enzyme inhibitors, Caantagonists, angiotensin receptor blockers), raised concerns regarding the role of beta blockers in cardiovascular primary prevention. Subsequently, a metaanalysis of 13 trials has shown that compared with other drug types, beta-blocker therapy is less beneficial in patients with hypertension who do not have heart disease. Nevertheless, in cardiovascular indications other than hypertension (acute myocardial infarction, heart failure and arrhythmias), betablockers retain their dominant position.]

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[Secondary prevention of patients with ischaemic heart disease - The reduction of LDL cholesterol level and the regression of atherosclerosis]

BÁRCZI György, MERKELY Béla

[The authors review the options of secondary medical prevention in patients with ischaemic heart disease, stressing the need and safety of using statins. The beneficial effect of statin therapy on cardiovascular morbidity and mortality and the clinical benefit of the greatest possible reduction in LDL cholesterol level are presented. The atherosclerotic plaque regression achieved by a high-intensity statin therapy in the ASTEROID trial is also briefly reviewed.]

Lege Artis Medicinae

[Clinical impact of acetylsalicylic acid resistance in patients with cerebrovascular disease]

FEHÉR Andrea, PUSCH Gabriella, HARANG Gábor, GASZTONYI Beáta, PAPP Előd, WERLING Dóra, MENYHÁRT Marianna, KOMÁROMY Hedvig, SZAPÁRY László, FEHÉR Gergely

[INTRODUCTION - In the past few years, a number of studies have been published about acetylsalicylic acid resistance and its potential clinical consequences. PATIENTS AND METHODS - 281 patients with chronic cerebrovascular disease have been involved in our study. The patients were divided in two groups on the basis of their optical aggregometer results (acetylsalicylic acid responder vs. resistant). We compared the risk profiles, drug therapies, laboratory parameters and clinical outcomes of the two groups. RESULTS - Acetylsalicylic acid resistant patients were more likely to be women [23 (45.1%) vs. 92 (40%) (p<0.05)], to smoke (38% vs. 25%), have hypertension (92 vs. 78%), hypercholesterolaemia (5.69 vs. 4.85 mmol/l), and elevated LDL-levels (3.71 vs. 2.85 mmol/l), triglyceride levels (2.78 vs. 1.97 mmol/l) and hsCRP levels (17.89 vs. 7.09 mmol/l) (p<0.01). The use of statins was more frequent (56% vs. 36%) in the responder group (p<0.01). Platelet aggregation values (triggered by agonists) were significantly correlated with cholesterol, LDL, triglyceride and hsCRP levels (p<0.05). Adverse outcomes were reached in 13 (25.5%) acetylsalicylic acid nonresponders and 32 (13.9%) acetylsalicylic acid responder patients (p<0.01). In a multivariate analysis, however, only smoking (OR: 2.38, CI: 1.77-5.44) and increased LDL (OR: 3.01, CI: 2.34-5.67) and hsCRP levels (OR: 2.44, CI: 1.55-7.02) (p<0.05) were independent risk factors of adverse vascular outcomes. CONCLUSION - On the basis of our results, acetylsalicylic acid resistance was associated with a worse clinical outcome, but it was not an independent risk factor of future ischaemic events. Our results implicate that inappropriate prevention therapy might have a role in this phenomenon.]