[Comments on the guidelines (2018) of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension]. / Kommentar zu den Leitlinien (2018) der Europäischen Gesellschaft für Kardiologie (ESC) und der Europäischen Gesellschaft für Hypertonie (ESH) für das Management der arteriellen Hypertonie.

Arterial hypertension represents one of the most frequent chronic diseases that can lead to complications, such as stroke, dementia, heart attack, heart failure and renal failure. By 2025 the number of hypertensive patients will increase to approximately 1.6 billion people worldwide. The new guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension replace the guidelines of the ESC/ESH from 2013. The 2018 guidelines of the ESC/ESH were adopted by the German Cardiac Society and the German Hypertension League. In these comments national characteristics are worked out and the essential new aspects of the guidelines are critically discussed. These include, for example, the definition of hypertension, the importance of out of office blood pressure measurements, revised blood pressure targets, the modified algorithm for drug treatment and the relevance of device-based hypertension treatments. Important aspects for the management of hypertensive emergencies are also presented.

Combination of amlodipine 10 mg and valsartan 160 mg lowers blood pressure in patients with hypertension not controlled by an ACE inhibitor/CCB combination.

AIMS: This multicenter, open-label, single-arm trial assessed the efficacy of the combination of amlodipine 10 mg and valsartan 160 mg to provide additional blood pressure reduction and tolerability in patients with moderate hypertension not adequately responding to the combination of ramipril 5 mg and felodipine 5 mg. RESULTS: Of 133 patients treated for 5 weeks with ramipril 5 mg and felodipine 5 mg, 105 failed to achieve mean sitting systolic blood pressure <140 mmHg. These non-responders were then treated for an additional 5 weeks with amlodipine 10 mg and valsartan 160 mg, which resulted in clinically and statistically significant additional reductions in mean sitting systolic blood pressure of 15.4 mmHg (p<0.0001) and mean sitting diastolic blood pressure of 7.0 mmHg (p<0.0001). Adverse event rates were low with both treatment regimens. CONCLUSIONS: In hypertensive patients not controlled at 5 weeks by ramipril 5 mg and felodipine 5 mg, significant additional blood pressure reductions were observed after 5 weeks of treatment with amlodipine 10 mg and valsartan 160 mg. The combination of amlodipine 10 mg and valsartan 160 mg was well tolerated.

Amlodipine Besylate versus Candesartan Cilexetil in Hypertensive Patients - Office and Self-Measured Blood Pressure : A Randomised, Double-Blind, Comparative, Multicentre Trial.

OBJECTIVE: The aim of this study was to compare the antihypertensive efficacy and tolerability of the calcium channel antagonist amlodipine besylate versus the angiotensin II type 1 receptor antagonist candesartan cilexetil in hypertensive patients. PATIENTS AND METHODS: After a 2-week placebo washout period, 326 patients with essential hypertension were randomised to receive amlodipine 5mg once daily or candesartan cilexetil 8mg once daily in a double-blind, parallel-group design with a 12-week active treatment period followed by a 4-day placebo drug-free period. The initial daily dose could be doubled at week 6 if office diastolic blood pressure (DBP) was still >/=90mm Hg. BP changes were assessed daily through patient self-measurements, and fortnightly by office BP measurements. RESULTS: A total of 294 patients (151 amlodipine and 143 candesartan cilexetil) were included in the per-protocol analysis of the primary endpoint of BP change from baseline at 12 weeks. Reductions in sitting office systolic BP (SBP) [amlodipine 24.4mm Hg, candesartan cilexetil 22.3mm Hg] and DBP (amlodipine 14.9mm Hg, candesartan cilexetil 14.8mm Hg) were statistically equivalent within the chosen range of equivalence (5mm Hg for SBP and 3mm Hg for DBP). The proportion of controlled patients (office BP <140/90mm Hg) at the end of therapy was similar in both treatment groups (amlodipine 46.9%, candesartan cilexetil 44.4%). The reduction in self-measured DBP was significantly greater (p < 0.05) for amlodipine (7.2mm Hg) compared with candesartan cilexetil (4.8mm Hg). There was no significant difference between the two treatments in the incidence of adverse events reported. CONCLUSIONS: Amlodipine besylate and candesartan cilexetil were both very effective in lowering office BP after 12 weeks of treatment. There was a trend towards a better self-measured BP reduction with amlodipine compared with candesartan cilexetil. The overall incidence of adverse events was comparable between the two treatments.

Health-related quality of life during treatment of elderly patients with hypertension: results from the Study on COgnition and Prognosis in the Elderly (SCOPE).

The Study on COgnition and Prognosis in the Elderly (SCOPE) was a multinational, randomised, double-blind study to assess the effects of candesartan 8-16 mg daily on cardiovascular events and cognitive function in elderly patients (aged 70-89 years) with mild to moderate hypertension. A total of 4937 patients were randomised to candesartan or placebo with other antihypertensive drugs (mostly diuretics, beta-blockers, and calcium antagonists) added as needed to control blood pressure. Only 16% of the patients in the control group received placebo alone. The mean follow-up was 3.7 years. The aim of this health-related quality of life (HRQL) substudy analysis was to investigate changes in HRQL during antihypertensive treatment, and possible differences in patients receiving candesartan-based or other antihypertensive treatment. Three validated HRQL instruments were used: the Psychological General Well-being (PGWB) Index, the Subjective Symptoms Assessment Profile (SSA-P), and the EuroQoL Health Utility Index (EuroQoL). The HRQL was generally good at baseline and well preserved during follow-up in the presence of substantial blood pressure reductions in both treatment groups. Several of the observed changes in score from baseline to last visit favoured candesartan-based compared to control treatment, particularly the changes in PGWB Anxiety (-0.5 vs -1.0, P=0.01), PGWB Positive well-being (-0.8 vs -1.1, P=0.04), SSA-P Cardiac symptoms (0.03 vs 0.10, P=0.03), and EuroQoL Current health (-3.1 vs -5.3, P=0.008). This favourable result may be related to the somewhat lower blood pressure associated with candesartan-based treatment. In conclusion, there should be no reason to withhold modern antihypertensive therapy in elderly patients due to concerns for a negative effect on HRQL.

Pulse pressure responses in patients treated with Valsartan and hydrochlorothiazide combination therapy.

In a randomized, double-blind, parallel-group study of middle-aged and elderly patients, we examined the effects of treatment with the angiotensin receptor blocker valsartan (Val) in combination with hydrochlorothiazide (HCTZ) on pulse pressure (PP). After a 2-week washout period, patients entered a 4-week single-blind Val 160 mg once daily run-in period before randomization to one of three treatment groups: Val 160 mg (n = 666), Val 160 mg/HCTZ 12.5 mg (n = 670) or Val 160 mg/HCTZ 25 mg (n = 666), once daily for eight weeks. Sitting PP at baseline was similar in all groups. From baseline to randomization, Val monotherapy reduced PP by 4.7 +/- 10.2 mmHg (mean +/- SD). At the end of the study, overall reductions in PP were 6.7 mmHg for Val 160/HCTZ 12.5 and 7.5 mmHg for Val 160/HCTZ 25. Val monotherapy reduced PP in mild-to-moderate hypertensive patients. Val combined with HCTZ provides an additional dose-related reduction in PP.

Combination therapy with AT(1)-receptor blockers.

Although current hypertension management guidelines recommend increasingly stringent blood pressure targets, these targets are seldom achieved in clinical practice. Even in patients with mild-to-moderate hypertension, monotherapy is only effective in approximately 50-70% of patients, and thus there is a clear need for combination therapy if stringent blood pressure targets are to be achieved. Drugs used in combination therapy should satisfy a number of prerequisites, including complementary mechanisms of action, enhanced efficacy in combination, and maintained (or improved) tolerability. Evidence is accumulating that combination therapy with an AT(1)-receptor blocker and a diuretic represents a rational and effective treatment option. In clinical trials, the combination of candesartan cilexetil, 16 mg, and hydrochlorothiazide, 12.5 mg, has been shown to be more effective in lowering blood pressure than either agent alone. Furthermore, this combination has been shown to reduce blood pressure to a greater extent, and control blood pressure in a higher proportion of patients, than the combination of losartan, 50 mg, and hydrochlorothiazide, 12.5 mg, both when used instead of or in addition to previous antihypertensive therapy. The placebo-like tolerability of AT(1)-receptor blockers was maintained when these drugs were used in combination with hydrochlorothiazide. The combination of candesartan and a dihydropyridine calcium antagonist has also been shown to be more effective than either component alone. Furthermore, in the Candesartan and Lisinopril Microalbuminuria (CALM) Study, the combination of candesartan and lisinopril reduced blood pressure to a greater extent than either agent alone, and tended to have a greater effect on microalbuminuria.

Potential for antihypertensive treatment with an AT(1)-receptor blocker to reduce dementia in the elderly.

Hypertension is an established risk factor for stroke and other cerebrovascular disorders. Both stroke and small lacunar infarcts or white matter lesions can cause cognitive impairment and dementia, and there is evidence that vascular risk factors play a major role in the development of both Alzheimer's disease and vascular dementia. Several large epidemiological studies have shown that raised blood pressure in midlife is a strong risk factor for dementia later in life; however, blood pressure often decreases following the development of dementia. The cognitive function hypothesis proposes that elevated blood pressure increases the risk of decline of cognitive function, and that this can be reversed by active lowering of blood pressure. Evidence in support of this hypothesis comes from the Syst-Eur Dementia project, and from a number of smaller studies. SCOPE (Study on Cognition and Prognosis in the Elderly) is a large prospective study involving almost 5000 elderly patients (age 70-89 years), who are randomised to receive candesartan cilexetil, 8-16 mg, or placebo. Candesartan was chosen for this study because it is effective and well tolerated in elderly patients. SCOPE should provide important information on the long-term effects of AT(1)-receptor blocker treatment with candesartan on morbidity-including effects on cognitive function-and cardiovascular mortality in elderly hypertensive patients.

[Ideal combination partners in therapy of hypertension. Calcium antagonists are much better than their reputation]. / Ideale Kombinationspartner in der Hochdrucktherapie. Kalziumantagonisten sind viel besser als ihr Ruf.

Calcium antagonists are a chemically heterogeneous group of substances that effectively reduce elevated blood pressure in all age groups and also show organoprotective properties. A number of randomized studies have revealed a reduction in morbidity, in particular stroke. These substances are the drugs of first choice in the elderly, in left-ventricular hypertrophy and in obstructive pulmonary disease. Care must be exercised when congestive heart failure or acute coronary syndrome presents. Calcium antagonists are ideal combination drugs that help achieve targeted blood pressure levels.

AT1-receptor blocker-based combination therapy in hypertension.

Despite an increase in the number of patients treated for hypertension, blood pressure control is achieved in a minority of patients. The use of rational, well-tolerated combination regimens with complementary modes of action, such as an AT1-receptor blocker administered with a low dose of a thiazide diuretic, provides an effective and well-tolerated management strategy for patients who require more than monotherapy to control blood pressure. In clinical trials in patients with mild-to-moderate hypertension, a newly available combination of candesartan cilexetil-hydrochlorothiazide (HCT) 16/12.5 mg was significantly more effective than either monotherapy. This combination was also more effective than losartan-HCT 50/12.5 mg in two double-blind, randomized studies in patients with mild, moderate or severe hypertension. Furthermore, the antihypertensive efficacy of candesartan cilexetil-HCT was evident at up to 48 h following the last dose, while the effect of losartan-HCT declined rapidly during this period. Thus, the new fixed-dose AT1-receptor blocker/diuretic combination, candesartan cilexetil-HCT 16/12.5 mg combines enhanced efficacy with excellent tolerability and sets a new standard for the treatment of hypertension requiring more than monotherapy.

[Intrapulmonary tumor cell embolism from cancer of the bladder as the cause of a subacute cor pulmonale]. / Intrapulmonale Tumorzellembolie eines Harnblasenkarzinoms als Ursache eines subakuten Cor pulmonale.

HISTORY AND CLINICAL FINDINGS: A 61-year-old man had over 3 weeks experienced increasing dyspnoea on effort and loss of appetite. He reported previous chronic pain with a "stiffened hip" treated long-term with diclofenac, and three transurethral surgical interventions. It was only at the latest admission that bladder cancer (first diagnosed 2 years previously) became known as the reason for the interventions. On admission pallor, sinus tachycardia, fever of 38 degrees C and dyspnoea on light exertion were noted, but blood pressure was normal. INVESTIGATIONS: Chest X-ray was normal, but the patient had marked respiratory insufficiency (pO2 30.8 mmHg, pCO2 31.6 mmHg) on room air. Echocardiography showed a dilated right ventricle with paradoxical septal movement. There was no evidence of thrombosis in the leg veins on ultrasound. D-dimers were normal. DIAGNOSIS, TREATMENT AND COURSE: Pulmonary artery embolism of unknown origin was suspected. Despite anticoagulation with low-molecular heparin the patient's condition deteriorated. Spiral computed tomography of the thorax did not show thrombi in the pulmonary arterial vessels. Perfusion scintigraphy demonstrated definite perfusion deficits bilaterally in the upper lobes of the lung, consistent with pulmonary embolism. As his condition gradually worsened rt-PA was started to achieve fibrinolysis, but failed to produce any change in haemodynamic and respiratory functions. He died a few hours later. Microscopic examination at autopsy revealed multiple tumour emboli with intimal fibrosis in the peripheral arteries. A poorly differentiated urothelial carcinoma of the bladder with extensive infiltration of blood vessels was found (carcinomatous haemangiosis). CONCLUSION: A malignant tumour with micro-embolization of tumour cells should be considered as a possible diagnosis when the clinical picture indicates pulmonary embolism of unknown genesis.

Efficacy and tolerability of candesartan cilexetil in special patient groups.

Patients with hypertension do not comprise a homogeneous group, and the majority present with a variety of concomitant and associated conditions. Antihypertensive therapies should therefore be effective and well tolerated in a wide range of patients and should, ideally, ameliorate the negative target-organ effects of hypertension, such as atherosclerosis, cardiovascular remodelling and renal impairment. Evidence is accumulating that the new angiotensin II type 1 receptor blocker, candesartan cilexetil, lowers blood pressure effectively and is well tolerated in a variety of patient groups, including women and the elderly. In patients with severe hypertension, a treatment schedule based on candesartan cilexetil, with the addition of diuretic and calcium antagonist therapy as needed, has been found to control blood pressure successfully. Candesartan cilexetil does not affect glucose tolerance or lipid profiles in patients with diabetes mellitus, and it is not associated with any of the side effects of other antihypertensive agents that would make it unsuitable for use in patients with pulmonary disease. Initial clinical studies have indicated that candesartan cilexetil is well tolerated and effective in patients with heart failure. Furthermore, the available evidence shows that treatment with candesartan cilexetil can reverse the negative effects of hypertension on left ventricular hypertrophy and microalbuminuria. It therefore appears that the pronounced efficacy and placebo-like tolerability of candesartan cilexetil, as demonstrated in large clinical trials of patients with mild to moderate hypertension, can be extended to a wide range of specific patient groups.