Lege Artis Medicinae

[PErindopril-Amlodipine Reducing Blood Pressure Level Trial - The PEARL Study]

NAGY Viktor, LANTOS Éva, HABONY Norbert

AUGUST 20, 2010

Lege Artis Medicinae - 2010;20(08)

[Background and aims - In order to reach target blood pressure values more successfully and to achieve better therapeutic compliance, concomitant use of more antihypertensive agents with different mechanisms of action has gained much attention recently. In the PEARL study we investigated the antihypertensive effect of fixed dose combinations of perindopril and amlodipine (5/5, 5/10, 10/5, 10/10 mg Covercard) by measuring blood pressure values in the doctor’s office and with a 24-hour ambulatory blood pressure monitor (ABPM) in outpatients with primary, grade 1 or 2 hypertension, whose target values could not be reached with prior treatment. We also assessed changes of metabolic parameters and how patients felt themselves throughout the study. Patients and methods - In this open-label, multicentre, non-interventional, observational, 3 month long study we evaluated the data of 10 335 patients (5 483 female, 4 852 male, mean age: 61.0±12.4 years, waist circumference 99.0±13.8 cm). The mean duration of hypertension was 9.5±7.7 years. After signing the informed consent form, patients attended three visits (inclusion, months 1 and 3), and they were asked to fill in the data sheets (visit 1: gender, age, waist circumference, blood pressure and heart rate measured at the doctor’s office, duration of hypertension, risk factors, complications, accompanying diseases, previous antihypertensive treatments, complaints), laboratory blood tests and ABPM were optionally performed; visits 2 and 3: blood pressure and heart rate measured at the doctor’s office, adverse events, patient’s evaluation about the way they felt themselves, treatment, optionally performed laboratory blood tests and ABPM. Patients were asked to take perindopril-amlodipine fixed combination tablets in the mornings; the dose was increased if no normalization of blood pressure was observed. Data were analyzed with a one-sample t-test. The consistency of the different frequency distributions was tested with a Chi-square test. The two-sided level of significance was set at 5%. Results - All the parameters sensitive to treatment efficacy (blood pressure values measured on-site and with ABPM) were significantly improved with perindopril-amlodipine fixed combination treatment. Blood pressure measured at the doctor’s office reduced from 158/93 mmHg to 132/80 mmHg, while 24-hour mean blood pressure reduced from 145/84 mmHg to 128/76 mmHg (p<0.001), the diurnal index sensitive to blood pressure variability did not change and a dipper curve was observed throughout the study. Target blood pressure (<140/90 mmHg) was reached by 75.5 % of the patients. The mean dosage at the end of the study was 8 mg perindopril and 7.3 mg amlodipine. The results were consistent across subgroups of different previously received treatments and cardiovascular risks. Regarding laboratory findings, the reduction of total cholesterol from 5.67 to 5.21 mmol/L and that of LDL cholesterol from 3.18 to 2.83 mmol/L (p<0.001 for both) were of clinical importance. Eighty-five percent of the patients evaluated the way they felt themselves as excellent or improved. No serious adverse events were reported. Conclusion - Perindopril-amlodipine fixed combination can be administered effectively and safely to a large population of hypertensive patients who do not reach target blood pressure values.]



Further articles in this publication

Lege Artis Medicinae

[Tracking the Forgotten Profession]

NAGY Zsuzsanna

Lege Artis Medicinae

[Need-adjusted inequalities in the use of healthcare in Hungary]


[INTRODUCTION - The reduction of need-adjusted inequalities in the use of healthcare results in higher efficiency and fairer allocation of resources. PATIENTS AND METHODS - Data for all patients who received inpatient care (same-day or hospital treatment) in 2007 were used in the analysis. Beyond the diagnostic and diagnosisrelated group’s weight information and the number of inpatient days, the patients’ record contained data on age, sex, and postal code of residency. Besides personal data, socio-economic characteristics and general indicators of healthcare capacity have been included in the applied multilevel statistical analysis. Inequalities were estimated for all patients, and separately for those treated for malignant tumour, cardio-vascular diseases, or other diseases. RESULTS - Significant regional inequalities were observed in one-day care but an order of magnitude less in longer inpatient care. Comparing the two major diagnostic groups, the inequalities were greater among patients with cardiovascular diseases than for those with cancer. Only a small fraction of the observed inequalities was explained by the differences in the composition of population of small regions. The inequalities in the use of healthcare were largely explained by socio-economic characteristics of the regions. CONCLUSIONS - Need-adjusted inequalities in the use of healthcare supported the hypothesis that efficiency of the Hungarian healthcare system can be significantly improved by allocating the available resources according to the patients’ need.]

Lege Artis Medicinae

[Clinical pharmacologic principles and problems related to the clinical use of innovative and similar biological medicines]


[The active substances in the biological medicinal products are macromolecules, primarily proteins most of which are currently produced by various biotechnological methods in different biological systems. The spatial structure of the macromolecular active substances cannot be accurately determined by the presently available methods. Therefore, both physico-chemical and biological methods are needed for the control of their quality and production. The active proteins induce immunologic reactions in the organism. The appearance of neutralizing antibodies frequently leads to the inhibition of the effect of the biological medicines. The European Medicines Agency (EMA) registers the medicinal products containing similar macromolecular active substances produced by biotechnological methods as biosimilar agents, since their chemical identity cannot be proven. The similarities and differences of their biological and immunological effects can be evaluated only in comparative non-clinical and clinical trials. The frequent exchange of biological medicines increases the appearance of antibodies in the patients, therefore the substitution of biological drugs should be done only by the treating physicians if clinically necessary.]

Lege Artis Medicinae

[An Endless Story?]


Lege Artis Medicinae

[A chance to concretize the teratogenic risk: healthy babies born to mother with isotretinoin treatment during pregnancy]


[The teratogenic risk means the probability of the occurrence of congenital abnormalities in fetuses after the exposure of teratogenic agents, mainly drugs during pregnancy. The recent highresolution ultrasound scanning may help us to concretize this teratogenic risk. The Genetic, Teratogenic and Family Planning Counseling Clinic of the authors in Budapest were visited by 10,557 couples or client between 1998 and 2007. Ten pregnant women visited this Clinic due to the isotretinoin (Roaccutan) treatment during pregnancy during the 10 years study period. At present Roaccutan is the most teratogenic drug among the medicinal products in Hungary because its teratogenic risk is 25% for a characteristic pattern of congenital abnormality syndrome including a/microtia, ventriculomegaly and contruncal cardiovascular malformation. These fetal defects are detectable by the high-resolution ultrasound scanning between 18th and 20th gestational week of pregnant women. Thus this examination was recommended for the 10 pregnant women with unintended use of isotretinoin (Roaccutan ) in early pregnancy. Six pregnant women followed our advice and the repeated ultrasound scanning was not able to detect the above-mentioned characteristic defects and all the 6 newborns were healthy after birth. In conclusion the recent highresolution ultrasound examination provides a chance for the diagnosis of certain fetal defect between 18th and 20th gestational week of pregnant women. The Hungarian law allows these pregnant women to decide the termination of pregnancy until 20th (24th) gestational week after the diagnosis of severe fetal defects. However, this approach can protect the life of the major part of fetuses in pregnant women at high risk.]

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[The importance of assessing subclinical organ damage in risk prediction of hypertensive patients]

GODINA Gabriella, JÁRAI Zoltán

[As the cardiovascular risk influences the quality and intensity of blood pressure lowering therapy, the goal blood pressure values and the frequency of medical control of hypertensive patients, as well as global risk assessment has an important role in the management of hypertension. In the last couple of years many data have been accumulated showing the poor prognostic value of traditional cardiovascular risk factors. This is the reason why recent Hungarian and international guidelines on the management of hypertension advise the screening for subclinical organ damage. Our goal was to summarize the importance of subclinical organ damage by discussing recently published literature on this topic. An overview has been made on the markers of vascular subclinical damage, like carotid atherosclerosis proved with carotid ultrasonography, peripheral arterial disease assessed with ankle-brachial pressure index measurements and vascular rigidity defined with pulse wave velocity measurements. The prognostic values of myocardial hypertrophy assessed with ECG and/or echocardiography and renal damage proved with decreased estimated glomerular filtration rate and proteinuria are also discussed. Summing up what has been said so far, the assessment of subclinical organ damage has a role in cardiovascular risk prediction, however more randomized and prospective studies have to be performed to define the most suitable (i.e. the most reliable and the most cost-effective) markers for this purpose.]

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[The new joint hypertension guidelines of the European Society of Hypertension and European Society of Cardiology will simultaneously be published in August, 2018 in the J. Hypertension and Eur. Heart J. on the diagnostics, evaluation, treatment and follow up of hypertensive patients. This guidelines put emphasis on definition, and therapeutic strategies in patients with high cardiovascular risk. In this paper I summarise the cardiovascular risk factors and put emphasis on possibilities of reduction of cardiovascular risk. ]

Clinical Neuroscience



[Objectives - The assessment, in terms of safety and efficacy, of augmenting clozapine monotherapy, as well as combined psychopharmacotherapy involving clozapine, with electroconvulsive therapy (ECT). Method - Reviewed were the charts of patients who received clozapine-ECT treatment in the Department of Psychiatry and Psychotherapy of Semmelweis University between November 1999 and December 2003. Results - During the studied period there were altogether 43 patients treated with the combination of clozapine and electroconvulsive therapy. In the schizoaffective group, the values for post-electroconvulsive therapy CGI were significantly lower than either in the catatonic (Z=-3.72, p<0.01) or in the hebephrenic (Z=-3.17, p<0.01) group. Among the groups created on the basis of the number of augmentation strategies utilized, the clozapine+3 group consisted of patients significantly older than the clozapine+1 group (Z=2.45, p=0.01). In the clozapine monotherapy group, the values for post-electroconvulsive therapy CGI were significantly lower than in any of the groups that had received a combination of augmentations (monotherapy-1 augmentation: Z=-3.01, p<0.01; monotherapy-2 augmentation: Z=-2.89, p<0.01; monotherapy- 3 augmentation: Z=-2.41, p=0.01). Conclusions - According to our examinations, the augmentation of clozapine treatment with electroconvulsive therapy should be tried primarily on schizoaffective patients, in case the clozapine monotherapy is ineffective. The simultaneous use of different augmentation strategies is expected to increase only the side effects not the efficacy of the treatment.]

Hypertension and nephrology

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[Placental growth factor (PlGF) is a member of the proangiogenic VEGF-family; it is mainly produced by throphoblast cells. During the last years numerous studies have shown that circulating PlGF-level in maternal plasma is decreased and its suluble receptor sFlt-1 shows increased expression. In the present study we examined the prognostic accuracy of Alere Triage® PlGF-Assay in hypertensive disorders of pregnancy and its relation with the length of pregnancy. 130 pregnant women were involved in this case-control study (PE: 23, HELLP-syndrome: 20, superimposed praeeclampsia: 17, chronic hypertension: 25, gestational hypertension: 18 and normal control: 27). Blood draw occured between the 22nd and 34th gestational week. PlGF levels were measured by the Alere Triage® PlGF Assay using samples from the maternal plasma. The plasma PlGF-levels of women whose pregnancies were complicated by hypertensive disorders were significantnormotoly lower compared to those who had uncomplicated pregnancies and the decrease were greater in those patients who delivered before the 35th gestational week. The PlGF-test was positive in 93,7% of those women who delivered before the 35th gestational week and in 90,5% of those who delivered before the 37. gestational week. The vast majority of preeclamptic (PE: 95,7%, SIPE: 82,4%) and HELLP-syndrome (95%) patients had positive PlGF tests, the 60% of the chronic hypertension and the 44,4% of the gestational hypertension patients have also shown positive results. The main conclusion of this study is that the PlGF levels using maternal plasma are lower in those pregnancies which are complicated by hypertension and show strong correlation with the severity of the hypertensive disorder. We perceived high sensitivity values in detecting preeclampsia, HELLP-syndrome and superimposed preeclampsia. In the future we may use this method to separate high risk women for hypertensive disorders and it may improve the perinatal outcome]