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Lege Artis Medicinae

APRIL 18, 2020

[Digitally-assisted treatment planning in precision oncology]

PETÁK István, VÁLYI-NAGY István

[The progress of molecular information based on personalized precision medicine has reached a new milestone. Actually, about 6 million mutations of 600 genes may be related to the development of cancer, and on average, 3-4 of these “driver” mutations are present in each patient. Due to the progress in molecular diagnostics, we can now routinely identify the molecular profile of tumors in clinical settings. By clinical translation, there are actually available more than 125 targeted pharmaceuticals and hundreds of such therapies are under clinical trial. As a result, we have many first-line and licenced treatment options to be elected by molecular information as the optimal one for every patient. There is an increasing need for complex informatics solutions by medical software. Geneticists, molecular biologists, molecular pathologists, molecular pharmacologists are already using bioinformatics and interpretation software on their daily work. Today, online digital tools of artificial intelligence are also available for physicians for assisted treatment planning. Telemedicine, videoconferencing provide solutions for interdisciplinary virtual molecular tumor boards, which democratizes the access to precision oncology for all doctors and patients. ]

Lege Artis Medicinae

MARCH 10, 2020

[Primary care strategy of antihypertensive treatment of very elderly and frail patients]

TORZSA Péter, KALABAY László, CSATLÓS Dalma, HARGITTAY Csenge, MÁRKUS Bernadett, MOHOS András, SZIGETI Mátyás, FERENCI Tamás, MARJOLEIN Verschoor, ROZSNYAI Zsofia, JACOBIJN Gussekloo, ROSALINDE K. E. Poortvliet, SVEN Streit

[BACKGROUND - When treating very el­der­ly and frail hypertensive patients, there have to be taken in account the general health condition and frailty of patients, the present cardiovascular diseases (CVD) and values of the systolic blood pressure (SBP). Goals - In a clinical study performed in 29 countries, we aimed to analyse differences in practical antihypertensive therapy of family doctors among patients older than 80 years; further we sought to answer how much was influenced their therapeutic choice by frailty of the old age. The other goal of our study was to compare Hungarian versus international outcomes. Methodology - As part of an online survey, family practitioners had to decide about necessity of starting antihypertensive treatment among very elderly patients according to different patterns of frailty, SBP and CVD. The ratio of specific cases with positive treatment decision of family practitioners was compared in all 29 countries. We used a logistic mixed model analysis to multivariately model the role of frailty. Results - 2543 family practitioners participated in the cross-national study; 52% were female; 51% practised in urban environment. In 61% of practices, there was the ratio higher than 10% of very elderly patients. Hungary participated with 247 family practitioners in the study; 52.3% were female; 63.1% practised in urban environment. In 48.8% of practices the ratio of very elderly patients was higher than 10%. In 24 out of the 29 countries (83%), frailty was associated with GPs’ negative decision about starting treatment even after adjustment for SBP, CVD, and GP characteristics (odds ratio [OR 0.53]), 95% CI: 0.48-0.59; ORs per country 0.11-1.78). The lowest treatment ratio was in the Netherlands (34.2%; 95% CI: 32.0-36.5%) and the highest one in Ukraine (88.3%; 95% CI: 85.3-90.9%). In Hungary’s treatment ratio ranged 50-59%. This country ranked on the 27th place since Hungarian family practitioners chose rather to start antihypertensive treatment despite the frailty of the patient (OR=1.16; 95% CI: 0.85-1.59). Hungarian family practitioners started pharmacotherapy of elderly patients more frequently if they were males (OR= 1.45; 95% CI: 0.81-2.61), were working in their practice for less than 5 years (OR=2.41; 94% CI: 0.51-11.38), and if they had many patients aged over 80 years in their practice (OR=2.18; 95% CI: 0.70-6.80), however these differences were sta­­tistically not significant. Among Hun­ga­rian family practitioners starting therapy was significantly influen­ced by cardiovascular disease (OR=3.71; 95% CI: 2.64-5.23) and a SBP over 160 mmHg (OR=190.39; 95% CI: 106.83-339.28). Conclusions - In our study, there was significant difference between countries in starting antihypertensive treatment for very elderly patients. However, Hungary was among the countries where family practitioners preferred to treat their frail patients. The patients’ frailty did not have any impact on starting the therapy; rather cardiovascular disease and a SBP over 160 mmHg decided. It is an important message of the study that there is continuous need to educate family practitioners and trainees about the treatment of frail, elderly hypertensive patients.]

Lege Artis Medicinae

MARCH 20, 2019

[How can we reach more effective antihypertensive treatment in diabetic patients with hypertension?]

BENCZÚR Béla, TORZSA Péter

[Hypertension is the leading “silent killer” accounting for 10 million deaths worldwide. It frequently occures together with other metabolic risk factors, including type-2 diabetes mellitus and dyslipidemia augmenting the global cardiovascular risk of patients. Their treatment and reaching target blood pressure means a real challenge for practising physicians. According to the recent hypertension guidelines RAAS-inhibitors are the first choice agents which can be excellently combined with diuretics. RAAS-inhibitor based therapy frequently needs to be completed with Ca-antagonist to which statin should be added in the presence of metabolic risk factors. The benefits of amlodipin/atorvastatin fixed combination are multiple: both agents are capable to inhibit the progression of atherosclerosis and to reach blood pressure and LDL target values. In addition the well-known poor statin-adherence can be improved with fixed combination which can contribute to the reduction of risk of these high-risk subjects. ]

Lege Artis Medicinae

OCTOBER 20, 2019

[Thiazide- or thiazide-like diuretics should be used in the treatment of patients with hypertension? Particularities of the situation in Hungary]

VÁLYI Péter

[Diuretics have remained the cornerstone of the antihypertensive treatment since their widespreading in the 1960s. According to the 2018 ESC/ESH Guidelines for the management of arterial hypertension, in the absence of evidence from direct comparator trials and recognizing that many of the approved single-pill combinations are based on hydrochlorothiazide, this drug and thiazide-like indapamide can be considered suitable antihypertensive agents. In the 2018 Hungarian guidelines indapamide is named as the most efficacious diuretic in the treatment of patients with hypertension. The aim of the publication is redefining thiazide- and thiazide-like diuretic use in the treatment of hypertensive patients, with particular attention to presently available hydrochlorothia­zide and indapamide, and their combination drugs in Hungary.]

Hypertension and nephrology

OCTOBER 23, 2019

[Blood pressure management for stroke prevention and in the acute stroke. The new guideline of European Society of Hypertension (ESH, 2018), European Society of Cardiology and Hungarian Society of Hypertension (HSH, 2018)]

JENEI Zoltán

[Hypertension is the leading modifiable risk factor for stroke. Its prevalence amongst stroke patient is about 60-70% and the benefit of blood pressure (BP) lowering therapy on stroke risk reduction is well established. However the optimal BP targets for preventing stroke and reducing stroke consequences have been controversial. The new European (ESC/ESH) and Hungarian (HSH) hypertension guideline published in 2018 highlighted the primary and secondary prevention of stroke and the BP management in the acute stroke care as well. According results from ACCORD, SPRINT, HOPE-3, and other metaanalysis the systolic blood pressure (SBP) lowering < 120 mmHg has not favourable effect, thus in hypertensive patients < 65 years the SBP should be lowered to a BP range of 120-129 mmHg. In older patients ≥ 65 years the SBP should be targeted to a BP range of 130-139 mmHg (IA). In patients with acute intracerebral haemorrhage careful acute BP lowering with iv. therapy, to <180 mmHg should be considered only in case of SBP ≥ 220 mmHg (IIaB). In patients with acute ischaemic stroke who are eligible for iv. thrombolysis, BP should be carefully lowered and maintained to < 180/105 mmHg for at least the first 24 h after thrombolysis (IIaB). If the patient is not eli gible for lysis and BP ≤ 220/110 mmHg, routine BP lowering drug therapy is not recommended inside 48-72 h (IA). In patients with markedly elevated BP > 220/110 mmHg who do not receive fibrinolysis, drug therapy may be considered, based on clinical judgement, to reduce BP by 15% during the first 24 h after the stroke onset (IIbC). After 72 h of acute stroke in case of hypertensive patients < 65 years the SBP should be lowered to a BP range of 120-129 mmHg (IIaB). In older patients ≥ 65 years the SBP should be targeted to a BP range of 130-139 mmHg (IA). If BP < 140/90 mmHg after stroke, the BP lowering should be considered (IIbA). It is recommended to initiate an antihypertensive treatment with combination, preferably single pill combination of renin-angiotensin system blockers plus a calcium channel blocker and/or a thiazide like diuretics (IA). Lowering SBP < 120 mmHg is not recommended due to advers events regardless of age and type of stroke either in primary or secondary stroke prevention.]

Hypertension and nephrology

FEBRUARY 20, 2019

[Carvedilol in chronic kidney disease]

CSIKY Botond

[Chronic kidney disease (CKD) is endemic affecting 850 million people worldwide. Adequate antihypertensive treatment slows the progression of the kidney disease and also decreases the mortality of this population. Because of the comorbidities and the high cardiovascular risk beta-blockers have to be administered frequently in these patients. Carvedilol is a 3rd generation non-selective beta-blocker with alpha- 1 receptor blocking and antioxidant properties. It is metabolically neutral, it does not increase the risk of new onset diabetes and it does not increase the patients’ body weight. In some animal models of CKD and in several human CKD studies carvedilol has shown to have nephroprotective properties and it also decreased the cardiovascular risk in combination therapies.]

Hypertension and nephrology

FEBRUARY 20, 2019

[The importance of statin therapy in hypertension]

PARAGH György, PÁLL Dénes

[Hypertension and hypercholesterolaemia often co-occur and promote early cardiovascular disease. Previous studies have shown that antihypertensive treatment may be more effective if LDL cholesterol is also reduced. This may be due to the increased expression of angiotensin-1 receptor in hypercholesterolaemia, which increases peripheral vascular resistance through angiotensin-2, and adversely affects endothelial and smooth muscle cells. Other authors indicate that high cholesterol levels increase the production of angiotensin-2 through the activation of the chymase system. High cholesterol levels increase the amount of circulating oxidized LDL which binds to the transmembrane oxidized LDL receptor (LOX- 1) also activates the angiotensin-1 receptor. In addition, angiotensin-2 has an effect on intracellular cholesterol synthesis by enhancing the key enzyme of the synthesis of intracellular cholesterol, HMG-CoA reductase. The authors present the studies that support cholesterol lowering can contribute to lowering blood pressure and other major meta-analyses in which the beneficial effects of cholesterol lowering and lipid lowering on blood pressure reductions were not proven. In the background, it may well be that these studies are not designed to evaluate the effect of cholesterol-lowering drugs on hypertension in patients with hypercholesterolaemia, and non-statin-treated patients are not randomized.]

Hypertension and nephrology

SEPTEMBER 12, 2018

[Treatment of hypertension in kidney transplant patients]

KOVÁCS Tibor, WAGNER László

[Most of the renal transplant recipients suffer from hypertension. Hypertension substantially contributes to the high cardiovascular mortality in this population. The recommendation of the Hungarian Society of Hypertension and the international guidelines suggest to achieve less than 130/80 mmHg as target blood pressure in these patients. Several factors may be in the background of hypertension after kidney transplantation, which can be summarized as factors from the recipient-side, the donorside and factors provoked by transplantation itself. In most of the cases early after transplantation high doses of immunosuppressive drugs (especially calcineurin inhibitors and steroids) are responsible for the increased blood pressure. There are some further special methods apart from the general recommendations which are needed during the examination of hypertension of kidney transplant patients: e.g. measurement of blood trough-level of immunosuppressive drugs, investigation of bone-mineral disorder, screening for the level and causes of anaemia, check-up of the renal graft circulation. Kidney transplant patients suffering from hypertension usually need more than two antihypertensive drugs beyond the use of non-pharmaceutical antihypertensive methods. In the early posttransplantation period calcium channel blockers are preferred antihypertensive medications, because they counterbalance the vasoconstrictive effect of calcineurin inhibitors. The administration of renin-angiotensin-aldosterone inhibitors are rather suggested after the stabilization of renal function (from the 1-3 months posttransplantation). When designing antihypertensive strategy, comorbidities and special factors should be regarded as well, especially volume overload, proteinuria, allograft function (GFR), diabetes, other cardiovascular risk factors, previous cardiovascular events. The setup of an individual therapeutical strategy is advised in view of all these factors, which is different according to the timing after transplantation: the perioperative, the early postoperative phases and from 1-3 months after transplantation have special focuses.]

Hypertension and nephrology

JUNE 10, 2018

[Antihypertensive effect of rilmenidine focusing on the Hungarian multicenter trial VERITAS]

FARSANG Csaba, FINTA Ervin

[Summary in the antihypertensive therapy, in addition to the RAS-blockers (ACE-inhibitors or ARBs), calcium antagonists and thizid-like diuretics, other antihypertensive drugs with different mechanisms of actions, such as the imidazoline I1 receptor agonists, are beneficially used. Several international and Hungarian studies showed the results of the effects of these agents. Authors emphasize the effects of the VERITAS study showing that in hypertensive patients the imidazoline I1 receptor agonist, rilmenidine significantly decreased the office blood pressure as well as the blood pressure measured by ambulatory blood pressure monitoring (ABPM). The white-coat reaction and left ventricular hypertrophy (LVH) were also decreased. In a separate study involving hypertensive subjects rilmenidine significantly increased baroreflex sensitivity. This effect may contribute - mainly during daytime - to the antihypertensive effect. Authors summarise the most important actions of rilmenidine, and the selected publications on the results of the Hungarian and international investigations.]

Hypertension and nephrology

APRIL 29, 2021

[When should antihypertensive be taken: in the morning and/or evening? Chronopharmacotherapy of hypertension in practice]

SZAUDER Ipoly

[The circadian (24-hour) variability of blood pressure (BP) is influenced by constant and variable (external and internal) factors. With this in mind and by determining the type of hypertension with a 24-hour blood pressure monitoring (ABPM), individual chronopharmacological (chronopharmacotherapy) treatment can be planned. There are significant differences in the chronokinetics of antihypertensive drugs administered at different times. Their therapeutic range and efficacy depend significantly on their circadian timing. Although the most modern antihypertensives have a 24-hour effect, they are not able to lower blood pressure at all times. Morning intake of ACE inhibitors, ARB-s, alpha-blockers mainly affect the afternoon and early evening rise, while evening intake reduces nocturnal and morning rise. Calcium channel blockers, beta-blockers (except carvedilol and labetolol), do not affect the circadian blood pressure profile. Therefore, in nondipper hypertension or in the case of morning rise, the twice daily morning and evening administration is more effective than the single morning administration. (Usually a lower dose is sufficient in the evening.) Adequate control of nocturnal or morning blood pressure elevations can be achieved with medication taken in the evening. According to the relevant studies the conclusion is that there is no convincing evidence that the administration of BP-lowering drugs in the evening provides any significant advantage in terms of quality of BP control, prevention of target organ damage or reduction of cardiovascular events, so evening intake only is not recommended. In particular the administration of antihypertensive drugs at bedtime, especially in the case of elderly patients may cause excessive BP fall at night with increased risk of silent cerebral infarct and the myocardial ischemia in patients with coronary heart disease.]