The efficacy and safety of valsartan and a combination of valsartan and hydrochlorothiazide in the treatment of patients with mild to moderate arterial hypertension: a subgroup analysis of the effect of valsartan and its combination with .

BACKGROUND AND AIM: The aim of the study was to establish the effect of valsartan and combination of valsartan and hydrochlorothiazide (HCTZ) on pulse wave velocity (PWV) and central blood pressure (CBP) in a large population of patients with mild to moderate arterial hypertension. METHODS: This was an international, multicentre, open-label, prospective trial. After one week of washout in previously treated patients, 74 subjects were treated with valsartan or valsartan combined with HCTZ for 16 weeks according to the protocol. Naïve patients received the treatment immediately. During the active treatment, four visits were planned for each patient to obtain data for the primary and secondary efficacy. At the beginning and at the end of the study PWV and CBP were determined with central arterial pressure waveform analysis (SphygmoCor®, Atcor Medical). This study is registered with clinicaltrialsregister.eu, EudraCT number 2012-005129-57. RESULTS: The results of the present VICTORY trial showed that valsartan and combination of valsartan and HCTZ effectively reduced the brachial blood pressure in patients with mild to moderate arterial hypertension as well as PWV, central systolic blood pressure and central diastolic blood pressure. The effects on the augmentation index were not statistically significant. CONCLUSIONS: Valsartan and valsartan/HCTZ improve arterial stiffness in patients with mild to moderate hypertension.

The efficacy and safety of valsartan and combination of valsartan and hydrochlorothiazide in the treatment of patients with mild to moderate arterial hypertension - the VICTORY trial.

BACKGROUND AND AIM: The aim of the trial was to establish the efficacy and safety of Valsacor® (valsartan) and Valsacombi® (combination of valsartan and hydrochlorothiazide) in a wide variety of patient populations with mild to moderate arterial hypertension. METHODS: We performed an international, multicentre, open-label, prospective trial. After one week of washout in previously treated patients, the patients were treated for 16 weeks according to the protocol. Naïve patients entered the treatment period immediately. During the active treatment, four visits were planned for each patient to obtain the data for the primary and secondary efficacy endpoints analysis. The principal methods were blood pressure (BP) measurement, additionally in a subgroup of patients, assessment of erectile function. The initial dosage of valsartan 80 mg/day was titrated up to 320 mg/day to achieve the BP goal, with the addition of hydrochlorothiazide (HCTZ) in a fixed-dose combination (FDC), if needed. RESULTS: Mean ± standard deviation changes from baseline at week 16 were -26.6 ± 10.4 mm Hg (systolic BP) and -14.8 ± 7.6 mm Hg (diastolic BP). A total of 91% of the patients treated with either valsartan or valsartan FDC achieved the BP goal. Adverse reactions were experienced by 7.1% of the patients, with the most common being headache (1.9%), palpitation (1.6%), dizziness (1.6%), and fatigue (1.6%), during the whole trial. CONCLUSIONS: The results of the VICTORY trial show that valsartan and valsartan FDC effectively reduce the BP in patients with mild to moderate arterial hypertension and have a good tolerability profile.

Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.

BACKGROUND AND OBJECTIVES: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. RESULTS: A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. CONCLUSION: A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

BACKGROUND AND OBJECTIVES: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. PROTOCOL DESIGN: The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125  mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8  mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. OUTCOMES: Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. SAMPLE SIZE CALCULATION: It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

Arterial hypertension as a public health issue in Slovenia.

Hypertension is an important risk factor for cardiovascular diseases. An epidemiological survey in 1985 found that the prevalence of hypertension in Slovenia was comparable to rates reported from western European countries. Awareness of hypertension was poor and only a small fraction of patients had their blood pressure under satisfactory control. Since 1985, few population studies have been completed; the results suggest that little progress has been made in the field of hypertension control. The responsibility for the situation lies partly with family physicians, who often fail to react properly to uncontrolled blood pressure. Data from the last CINDI survey conducted in 2004 are more encouraging. Apparently, physicians now provide their patients with more information on how to attain their target blood pressure, and the percentage of hypertensive patients with controlled blood pressure seems to have increased. However, these are only assumptions, which should be verified by a nationwide epidemiological study. A pilot survey involving a random sample of the Slovenian adult population (about 11,000 subjects) is in progress and will be completed by the end of the year 2005.

Autonomic nervous system and microvascular alterations in normotensives with a family history of hypertension.

Autonomic nervous system and microvascular alterations at pre-hypertensive stage of hypertension have still not been fully elucidated. We aimed at addressing central and local influences on microvascular reactivity at pre-hypertensive stage of hypertension. To that end, we studied microvascular reactivity in 59 normotensives with a family history of hypertension and 46 controls. We measured laser-Doppler flow on the finger nailfold skin in the resting condition, after an 8-min occlusion of digital arteries and during local nitroglycerin application. Finger pressure, pulse and ECG were monitored by a Finapres device. Heart rate power spectral analysis was performed using Fast Fourier transformation. Baroreflex sensitivity was estimated by the sequence method. Normotensives with a family history of hypertension showed higher systolic pressure, decreased high-frequency power of the heart rate variability spectrum and reduced baroreflex sensitivity in the resting condition as well as decreased fundamental frequency of laser-Doppler flow oscillations during nitroglycerin application. We conclude that normotensives with a family history of hypertension exhibit altered sympathovagal balance with decreased parasympathetic activity at the cardiac level as well as increased myogenic microvascular reactivity.

Autonomic nervous system activity in normotensive subjects with a family history of hypertension.

This study was designed to address alterations in autonomic nervous system activity in normotensive subjects with a family history of hypertension. We compared the autonomic nervous system activity in 59 normotensives with a family history of hypertension and 46 normotensives with no family history of hypertension. Skin blood flow was measured using laser-Doppler method on the nailfold skin in the resting condition, during systemic cooling and during upright tilting. Finger blood pressure, pulse and ECG were monitored by a finapres device. Heart rate, systolic pressure and microvascular flow power spectral analyses were performed using fast Fourier transformation. Baroreflex sensitivity was estimated with the sequence method. Compared to the control group, normotensives with a family history of hypertension showed significantly higher systolic pressure, decreased proportion and area of the high-frequency band of the heart rate variability power spectrum and reduced baroreflex sensitivity in the resting condition as well as a decreased proportion and area of the high-frequency band of the heart rate variability power spectrum during systemic cooling. We also proved a different time course of baroreflex sensitivity during upright tilting in the two groups. In contrast, we did not find any significant differences in the parameters of systolic pressure and microvascular variability power spectra between the two groups. Our results indicate that even normotensives with a family history of hypertension exhibit an increased ratio of sympathetic to parasympathetic activity at the cardiac level; however, they do not show any alteration of the vascular sympathetic reactivity.