Adherence and blood pressure control in patients with primary aldosteronism.

PURPOSE: The aim of our study was to evaluate the adherence to mineralocorticoid receptor (MR) antagonists and other antihypertensive therapy and blood pressure control in conservatively treated patients with primary aldosteronism (PA). MATERIALS AND METHODS: Conservatively treated subjects with previously confirmed PA (n-50, 64.5 ± 9 years of age, 24% women) were investigated via our outpatient hypertension clinic. All subjects underwent regular examinations in our clinic. In addition to basic laboratory and clinical parameters, 24 h ambulatory blood pressure monitoring (ABPM) (Spacelabs) was evaluated. Unplanned blood sampling for assessment of serum antihypertensive drug concentrations by the means of liquid chromatography-mass spectrometry was performed in all patients. In case of spironolactone, its active metabolite canrenone was also evaluated. Total non-compliance was then defined as the absence of all measured antihypertensive drugs. Partial non-compliance was calculated as the absence of serum levels of at least one, but not all antihypertensive drugs prescribed. RESULTS: Good blood pressure control was detected (mean 24 h systolic/diastolic BP 130 ± 12/77 ± 9 mmHg). The average number of antihypertensive drugs was 3.9 ± 1.5. All subjects were treated by MR antagonists. 44% of patients received spironolactone (average daily dose 45 ± 20 mg) and in the remaining 56% of subjects eplerenone was administered (average daily dose 80 ± 30 mg) due to spironolactone side effects. Assessment of antihypertensive drug concentrations revealed full adherence in 80% of all subjects, partial nonadherence was noted in the remaining 20% of subjects. MR antagonist levels were detected in almost all subjects (49 out of 50). CONCLUSIONS: Good blood pressure control and adherence to therapy were detected in conservatively treated patients with PA. Eplerenone had to be used quite often as male subjects did not tolerate dose escalation due to spironolactone side effects.

Therapy of hypertension in elderly population and its potential risks.

Arerial hypertension is comon in subjects 65 years old and includes in majority of subjects systolic/diastolic form or isolated systolic hypertension. Basic therapeutic principles to the therapy of hypertension of elderly subjects are summarized. Slow and careful uptitration of antihypertensive therapy is recommended. Potential complications and caveats of therapy are also discussed, which are especially related to older frail subjects. Pharmacotherapy of hypertension in elderly is in vast majority of subjects highly beneficial with decrease of cardiovascular (CV) events and CV mortality.

A putative placebo analysis of the effects of sacubitril/valsartan in heart failure across the full range of ejection fraction.

AIMS: The PARADIGM-HF and PARAGON-HF trials tested sacubitril/valsartan against active controls given renin-angiotensin system inhibitors (RASi) are ethically mandated in heart failure (HF) with reduced ejection fraction and are used in the vast majority of patients with HF with preserved ejection fraction. To estimate the effects of sacubitril/valsartan had it been tested against a placebo control, we made indirect comparisons of the effects of sacubitril/valsartan with putative placebos in HF across the full range of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We analysed patient-level data from the PARADIGM-HF and PARAGON-HF trials (n = 13 194) and the CHARM-Alternative and CHARM-Preserved trials (n = 5050, candesartan vs. placebo). The rate ratio (RR) of sacubitril/valsartan vs. putative placebo was estimated by the product of the RR for sacubitril/valsartan vs. RASi and the RR for RASi vs. placebo. Total HF hospitalizations and cardiovascular death were analysed using the negative binomial method. Treatment effects were estimated using cubic spline methods by ejection fraction as a continuous measure. Across the range of LVEF, sacubitril/valsartan was associated with a RR 0.54 [95% confidence interval (CI) 0.45-0.65] for the recurrent primary endpoint compared with putative placebo (P < 0.001). Treatment benefits of sacubitril/valsartan vs. putative placebo varied non-linearly with LVEF with attenuation of effects observed at LVEF above 60%. When analyzing data from PARADIGM-HF and CHARM-Alternative, the estimated risk reduction of sacubitril/valsartan vs. putative placebo was 48% (95% CI 35-58%); P < 0.001. When analyzing data from PARAGON-HF and CHARM-Preserved (with LVEF ≥ 45%), the estimated risk reduction of sacubitril/valsartan vs. putative placebo was 29% (95% CI 7-46%); P = 0.013. Across the full range of LVEF, consistent effects were observed for time-to-first endpoints: first primary endpoint (RR 0.72, 95% CI 0.64-0.82), first HF hospitalization (RR 0.67, 95% CI 0.58-0.78), cardiovascular death (RR 0.76, 95% CI 0.64-0.89), and all-cause death (RR 0.83, 95% CI 0.71-0.96); all P < 0.02. CONCLUSION: This putative placebo analysis reinforces the treatment benefits of sacubitril/valsartan on risk of adverse cardiovascular events across the full range of LVEF, with most pronounced effects observed at a LVEF up to 60%.

Primary Aldosteronism and Pregnancy.

OBJECTIVE: Primary aldosteronism (PA) may present at younger age and may thus complicate pregnancy. Our aim was to identify female patients in whom PA was diagnosed after pregnancy complicated with hypertension and to analyze possible hypertension-related complications during pregnancy. METHODS: We performed retrospective analysis of female patients with PA diagnosed and treated at our Department who were pregnant before the diagnosis of PA. RESULTS: We found 14 patients with PA (age at diagnosis 32.2 ± 4.2 years, hypertension duration 5.4 ± 3.6 years) suffering from hypertension 3 (IQR 0, 4) years before pregnancy (6 patients had hypertension diagnosed during pregnancy). Three subjects were pregnant twice, and 1 patient had been pregnant three times before the final diagnosis of PA was made. Ten subjects delivered by Caesarean section (in 3 cases due to early-onset preeclampsia and 2 subjects due to significantly increased blood pressure), and 9 cases spontaneously (1 subject complicated twice due to late-onset preeclampsia). Preterm delivery occurred in 5 cases - the earliest one in the sixth month of gestation. Subsequent diagnosis of PA (sometimes with a long delay up to a maximum of 12 years) was made on the basis of significantly low potassium values (2.7 ± 0.4 mmol/L; 2 subjects even suffered from muscle cramps) and hypertension (mostly moderate), elevated plasma/serum aldosterone (54.1 ± 20.2 ng/dL) and suppressed plasma renin activity (0.4 ± 0.2 ng/mL/h) or plasma renin (1.9 ± 1.6 ng/L). Thirteen subjects underwent laparoscopic adrenalectomy (in all but 2 cases, diagnosis of a large cortical adenoma [16 ± 5.9 mm] was made), and 1 subject was classified with bilateral hyperplasia according to adrenal venous sampling. Operation normalized BP in 10 subjects and improved BP control in the remaining 3 subjects. Two patients became pregnant after adrenalectomy, and their pregnancies were uneventful. CONCLUSION: PA is associated with a high rate of pregnancy-related complications. The most frequent complication is preeclampsia, in some cases leading to preterm delivery. The optimal prevention of these complications is early diagnosis of PA, and in these particular hypertensive cases, the awareness of hypokalemia.

Primary aldosteronism in a general population sample. The Czech post-MONICA study.

Purpose: Primary aldosteronism (PA) is considered the most common form of secondary hypertension, however, its prevalence, particularly in a general population, is still a matter of debate. The aim of our study was to evaluate the prevalence of PA in a randomly selected general population sample.Materials and methods: A total of 1940 individuals (1% population random sample) aged 25-64 years were screened for major cardiovascular risk factors in six districts of the Czech Republic. Hypertension was defined as a mean of two blood pressure readings ≥140/90 mmHg at one visit or taking antihypertensive medication. Within this population, 740 individuals were labelled as hypertensives and 650 of them sampled for the analysis of direct plasma renin and serum aldosterone. The diagnosis of PA was based on elevated serum aldosterone, low plasma renin and high aldosterone/renin (ARR) ratio and was also verified by a confirmatory test with saline infusion.Results: Positive ARR was found in 52 (8%) individuals (64% women, 36% men, however, due to substatntial proportion of reluctatnt participants to undergo a further work-up (27%), we could confirm the diagnosis of PA only in 13 of them (2%). Aldosterone-producing adenoma was found in one case only, seven patients had idiopathic type and five individuals refused potential surgical treatment therefore, adrenal venous sampling was not performed.Conclusion: Elevated serum aldosterone together with low renin and high ARR were found in 52 (8%) of hypertensives selected from a general population sample, however, the diagnosis of PA was confirmed only in 13 of them (2%). This study based on a general population survey highlighted the difficulty of conducting epidemiological studies on primary aldosteronism in a relatively healthy cohort part of whom did not provide the level of collaboration that is necessary to assess the true prevalence of this condition.

Arterial hypertension and COVID-19 infections: A brief commentary.

The issue of hypertension/antihypertensive treatment in patients with COVID-19 infection is discussed in the commentary.

[COSYREL - an efficient fixed combination for treatment of hypertension, stable ISHD and heart failure]. / COSYREL - úcinná fixní kombinace pro lécbu hypertenze, stabilní ICHS a srdecního selhání.

Fixed combinations of two or three drugs are being frequently used in cardiovascular diseases. This approach markedly increases adherence of the patients to prolonged therapy and thus leads to better control of the diseases. Fixed combinations are often used in hypertension and coronary artery disease (CAD). Cosyrel is the first fixed combination of betablocker (bisoprolol fumarat) and ACE inhibitor (perindopril arginin) available in czech market. The advantage is availability in several concentrations (10 mg/10 mg, 10 mg/5 mg a 5 mg/10 mg a 5 mg/5 mg) , when first indicates bisoprolol dose and the second perindopril. This combination is indicated in arterial hypertension and/or in stable CAD (in patients after myocardial infarction or revascularisation) and/or in dosages 5 mg/5 mg and 5 mg/10 mg in patients with chronic heart failure with systolic dysfunction. This article aimed to evaluate briefly clinical characteristics of this fixed combination. Bisoprol and perindopril arginin have a lot of data indication their positive impact on CV risk and prognosis.Key words: bisoprolol - coronary artery disease - heart failure - hypertension - perindopril.

Should All Patients with Resistant Hypertension Receive Spironolactone?

PURPOSE OF REVIEW: Resistant hypertension is a common clinical situation. Identification of true resistant hypertension (using 24-h ambulatory blood pressure monitoring to exclude white coat phenomenon, excluding secondary causes and non-adherence to treatment) is important mostly because of the application of a proper therapeutic approach and the higher cardiovascular risk of these patients. This review surveys recent studies, with a focus on mineralocorticoid receptor antagonists, including spironolactone, in the treatment of resistant hypertension. RECENT FINDINGS: A range of randomized and non-randomized studies have proved the efficacy of mineralocorticoid receptor antagonists, including spironolactone. However, long-term mortality studies are still missing for the hypertensive population. In the case of spironolactone side effects, higher doses of amiloride or eplerenone might be used. Based on available data and our own experience, spironolactone (mineralocorticoid receptor antagonists) should be involved, if tolerated, in combination therapy in true resistant hypertensive patients. Spironolactone still represents primary therapeutic modality under specific conditions of primary aldosteronism.

CHARACTERISTICS AND OUTCOMES OF METASTATIC SDHB AND SPORADIC PHEOCHROMOCYTOMA/PARAGANGLIOMA: AN NATIONAL INSTITUTES OF HEALTH STUDY.

OBJECTIVE: Overall about 10 to 20% of pheochromocytomas/paragangliomas (PHEOs/PGLs) are metastatic, with higher metastatic potential observed in succinate dehydrogenase subunit B/fumarate hydratase (SDHB/FH)-related tumors. Due to the improved availability of biochemical and genetic testing and the frequent use of anatomical/functional imaging, there is currently a higher detection rate of metastatic PHEO/PGL. METHODS: A retrospective analysis of 132 patients (27 children, 105 adults) with metastatic PHEO/PGL diagnosed and treated from 2000 to 2014 was conducted. RESULTS: Seventy-seven (58%) males and 55 (42%) females were included; 39 (30%) have died, with no sex preference. Seventy-three (55%) patients had SDHB mutations; 59 (45%) patients had apparently sporadic tumors (AST). SDHB patients had an average age at primary tumor diagnosis of 31 ± 16 years compared to 40 ± 15 years in AST patients (P<.001). The average metastatic interval (MI) decreased with increasing age in both SDHB and AST patients (P = .013 for both). Only 16% of all primary tumors were smaller than 4.5 cm. Eleven percent of patients had biochemically silent disease, more with SDHB. Of SDHB patients, 23% had metastatic tumors at first diagnosis, compared to 15% of AST patients. Five- and 10-year survival rates were significantly better for metastatic AST than SDHB patients (P = .01). Overall survival was significantly different between children and adults (P = .037); this was mostly attributed to the SDHB patients, in whom children had statistically significantly longer survival than adults (P = .006). The deceased patients all died due to the PHEO/PGL and mainly had noradrenergic phenotypes. CONCLUSION: In children, metastatic PHEOs/PGLs are mainly due to SDHB mutations; in adults they are equally distributed between in SDHB mutations and AST, with better 5- and 10-year survival rates for ASTs. In SDHB patients, children survive longer than adults. Primary metastatic tumors, most presenting as noradrenergic PGLs, are larger than 4.5 cm in >80% of patients. The frequency of metastatic tumors from primary AST increases with age, including a decreased MI compared to SDHB tumors. These results support several recommendations that are summarized in the Discussion.

[Komentár ke clánku HOPE-3: Statins Lower CV Events in Intermediate-CHD-Risk Patients]. / Studie HOPE-3: statiny snizují kardiovaskulární príhody u pacientu s intermediárním rizikem ICHS.

UNLABELLED: The HOPE-3 study focused on identifying the significance of the polypill and mini-polypill in broad clinical practice, including individuals of different gender without cardiovascular diseases with an intermediate risk of cardiovascular diseases. The authors were interested in the question whether people from various antropologhy groups including not only white people but also other antropologhy groups - the blacks, people of Asian and South American origin and more covering 6 continents, would respond in a similar way. The study mainly examined the significance of the mini-polypill, comprising the use of antihypertensive treatment (16 mg candesartan per day + 12.5 mg hydrochlorothiazide), treatment with statins (10 mg rosuvastatin per day), and their combination. The study presents a new way forward in the prevention of cardiovascular diseases, but it also entails some weaknesses which consist in rather rare medical checkups including laboratory tests. Owing to that the concept of mini-polypill has met with some reservation. But it also brings with it reduction of healthcare costs. KEY WORDS: mini-polypill - prevention of cardiovascular diseases - relevance of statins also to primary prevention.

[AT1-blockers in the treatment of hypertension: summary]. / Antagonisté receptoru pro angiotenzin II (AT1-blokátory) v lécbe hypertenze.

Angiotensin receptor antagonists (AT(1)-blockers) are considered as one of the major classes of antihypertensive drugs suitable for monotherapy as well as for combination treatment. AT(1)-blockers have comparable antihypertensive efficacy with other major classes of antihypertensive drugs. AT(1)-blockers are considered by current guidelines of Czech society of hypertension altogether with ACE-inhibitors and calcium channel blockers as universal antihypertensive drug class. AT(1)-blockers has the lowest profile of side-effects among all antihypertensive drug classes and thus very high persistence to therapy. Mechanisms of antihypertensive effects of AT(1)-blockers are discussed altogether with the results of large clinical trials and indications in the treatment of hypertension.

[The SPRINT Research. A Randomized Trial of Intensive versus Standard Blood-Pressure Control]. / Studie SPRINT. Randomizovaná studie porovnávající intenzivní kontrolu systolického tlaku s kontrolou standardní.

BACKGROUND: The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS: We randomly assigned 9 361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS: At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65 % per year vs 2.19 % per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval (CI) 0.64 to 0.89; p < 0.001). All causes mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI 0.60 to 0.90; p = 0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. CONCLUSIONS: Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. Funded by the National Institutes of Health.

[The effect of antihypertensive treatment on patients with diabetes depends on the values of blood pressure: a systematic survey and meta-analyses]. / Úcinek antihypertenzní lécby u diabetu závisí na hodnotách krevního tlaku: systematický prehled a metaanalýzy.

What was already known about these problems before the publication of the Northern Swedish study? Hypertension is the most important risk factor for mortality and cardiovascular disease on a global scale. Patients with diabetes mellitus demonstrate an increased risk for cardiovascular disease and they often also have hypertension at the same time. Antihypertensive treatment reduces the risk of cardiovascular diseases in patients with diabetes, however an optimum value of blood pressure is a matter of debate. What is the special contribution of the Swedish study? Antihypertensive treatment in patients with diabetes and a systolic pressure higher than 140 mm Hg brings with it a decreased risk of mortality and cardiovascular disease. Antihypertensive treatment in patients with dia-betes and a systolic lower than 140 mm Hg, however, brings with it an increased risk of mortality and cardiovascular disease. The interaction between systolic pressure values before the treatment and during it is significant.

Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension.

OBJECTIVE: The blood pressure (BP)-lowering effect of renal sympathetic nervous denervation (RDN) in resistant hypertension (rHT) shows large variation among studies. METHODS: We meta-analyzed summary statistics of randomized clinical trials on RDN in rHT. For continuous outcomes, we assessed heterogeneity by Cochran's Q test and used random-effect models weighted for the inverse of the variance. We assessed safety by assessing the risk of major adverse events from stratified contingency tables. RESULTS: Of 5652 patients screened in seven trials, 985 (17.4%) qualified and were randomized to control (n = 397) or RDN with SYMPLICITY(™) catheters (n = 588). Follow-up was 6 months. In both control and RDN patients, antihypertensive treatment was continued or optimized. At enrolment, age averaged 58.1 years, systolic/diastolic office and 24 h BP 168.5/93.3 mmHg and 151.8/86.1 mmHg, respectively, and estimated glomerular filtration rate (eGFR) 79.3 ml/min/1.73 m². For BP outcomes, there was heterogeneity among trials. Pooled effects (control minus RDN) were -4.9/-3.5 mmHg (95% confidence interval, -20.9 to 11.1/-8.9 to 1.9) for office BP, -2.8/-1.5 mmHg (-6.5 to 0.8/-3.3 to 0.4) for 24 h BP and 0.81 ml/min/1.73 m² (-1.69 to 3.30) for eGFR. Removing one trial at a time produced confirmatory results. Adverse events occurred in 7.4% and 9.9% of control and RDN patients, respectively (p = 0.24). CONCLUSION: In selected rHT patients maintained on antihypertensive drugs, RDN with the SYMPLICITY systems does not significantly decrease BP but is safe. Future trials with next-generation catheters should aim at identifying responders in patients with evidence of sympathetic nervous overactivity.

[Effect of spironolactone in patients with heart failure and preserved left ventricular function - TOPCAT study]. / Vliv spironolaktonu u pacientu se srdecním selháním a zachovalou funkcí levé komory - studie TOPCAT.

The TOPCAT study followed the effect of spironolactone on a chronic heart failure with a preserved left ventricular ejection fraction. The study did not find any impact on the primary goal of the study, i.e. a combination of cardiovascular mortality, managed cardiac arrest or hospitalization rate for heart failure treatment. The only finding of the study was the decrease in hospitalization rates for a heart failure. A post hoc analysis, however, identified a significant difference between patients from the Americas (USA, Canada, Argentina, Brazil) on the one hand and those from Russia/Georgia on the other. The differences were rather striking. Whereas the former manifested a significant reduction in the incidence of the primary goal, i.e. cardiovascular mortality and hospitalization with heart failure through treatment with spironolactone, the incidence of all clinical events was considerably lower in Russia/Georgia and no impact of spironolactone at all on any of the goals was identified regarding the patients from Russia/Georgia. This post hoc analysis therefore suggested a possible therapeutic effect of spironolactone in the Americas, as well as in the populations of similar characteristics. Most studies accept a definition only based on the heart failure with a preserved left ventricular ejection fraction. The study points to the need to further elaborate this definition which also has to consider changes of the left ventricular diastolic function when defining a diastolic heart failure.

[Primary hyperaldosteronism: problems of diagnostic approaches]. / Primární hyperaldosteronizmus: problémy diagnostických prístupu.

Primary hyperaldosteronism (PH) is common cause of endocrine/secondary hypertension with autonomous aldosterone overproduction by adrenal cortex. PH is typically characterized by hypertension, hypokalemia, high plasma aldosterone/renin ratio, high aldosterone, suppressed renin and nonsupressibilty of aldosterone during confirmatory tests. Diagnosis of PH can be difficult since hypokalemia is found only in 50 % of cases and measurement of the parameters of renin-angiotensin-aldosterone system can be influenced by several factors. Morphological dia-gnosis requires in majority of cases adrenal venous sampling. Early diagnostic and therapeutic measures are very important due to high prevalence of PH and potential cure. Patients with suspicion to PH should be investigated in experienced hypertensive centers due to relatively difficult laboratory and morphological diagnostic approaches.

[Treatment of hypertension in diabetes mellitus]. / Lécba hypertenze u diabetes mellitus.

Hypertension and diabetes mellitus (DM) are common diseases. Prevalence of hypertension in DM type II is 70-80 %. Goal blood pressure (BP) is around 130/80 mm Hg. RAS blockers (ACE inhibitors or AT1 blockers) are considered as the drugs of choice because of the decrease of cardiovascular risk and prevention of nephropathy. Combination antihypertensive therapy is needed in 80-90 % of pts. Combination of RAS blocker and calcium channel blocker is clinically useful. Diuretics should be part of triple-combination. Low-dose spironolactone can be recommended in severe forms of hypertension. Pharmacological approach should involve also intervention of all other risk factors including BMI reduction in obese subjects. Some of new antidiabetic drugs may lead to significant BP decrease (gliflozines).

[The new drug is much more effective than ACE inhibitors in chronic heart failure]. / Nový lék je výrazne úcinnejsí nezli inhibitory ACE u chronického srdecního selhání.

PARADIGM-HF study observed clinical outcomes after treatment by new drug LCZ696 or enalapril in patients with systolic chronic heart failure. It was randomized double-blind trial with LCZ696 (200 mg twice a day) and enalapril (10 mg twice a day). 8442 patients were enrolled with NYHA class II or III and left ventricular ejection fiction of 40% or less. Study drugs were added to other recommended medication. The trial was prematurely terminated after median follow-up of 27 months. The primary endpoint of the study was a combination of cardiovascular mortality and the first hospitalization for heart failure. LCZ696 drug, an inhibitor of angiotensin receptor and neprilysin (Arnie), has led to a reduction in the primary composite target by 20% (p <0.001). The treatment has decreased cardiovascular mortality by 20%, p <0.001 and hospitalization for worsening heart failure by 21%, p <0.001. LCZ696 has also decreased total mortality by 16%, p <0.001. The use of LCZ696 has been accompanied by frequent symptomatic hypotension and hypotension with a decrease in systolic blood pressure below 90 mm Hg, however, LCZ696 was less often associated with an increase in serum creatinine and serum potassium than enalapril. In addition, cough has occurred less frequently after LCZ696 than after enalapril. Discontinuation of therapy occurred in 746 patients (17.8%) treated with LCZ696 and in 833 patients (19.8%) treated with enalapril (19.8%) (p = 0.02). PARADIGM-HF study has also shown superiority of LCZ696 compared to ACE inhibitors in stable outpatients with chronic systolic heart failure NYHA stages II and III. Therefore, LCZ696 is more effective than ACE inhibitors (and angiotensin receptor blockers). Moreover, it is well tolerated. LCZ696 seems to replace the ACE inhibitors in mentioned patients. The authors also discuss the results of the first randomized study PARAMOUNT investigating LCZ696 efficacy in patients with chronic heart failure and good left ventricular ejection fraction.

[PATHWAY-2 Study: spironolactone vs placebo, bisoprolol and doxazosin to determine optimal treatment of resistant hypertension. Spironolactone high effective in lowering blood pressure in drug resistant hypertension]. / Studie PATHWAY-2: spironolakton vs placebo, bisoprolol a doxazosin ke stanovení optimální lécby hypertenze rezistentní na léky. Vysoká úcinnost spironolaktonu ve snízení krevního tlaku u rezistentní hypertenze.

The PATHWAY-2 study, funded by the British Heart Foundation, randomised 335 patients with resistant hypertension (already treated according to guidelines) to sequentially receive 12 weeks of spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin (4-8 mg modified release) and placebo. The study design allowed drug comparisons in each patient, with 230 patients completing all cycles. Results showed that spironolactone reduced home systolic BP by 8.70 mm Hg more than placebo (<0.001), 4.26 mmHg more than bisoprolol/doxazosin (<0.001), 4.03 mm Hg more than doxazosin (<0.001), and by 4.48 mm Hg more than bisoprolol. By the end of the trial, there would only be 15 patients considered eligible for renal denervation trials in uncontrolled hypertension. PATHWAY-2 will have significant implications for patient recruitment in to other trials.