Reduction In 24-hour Blood Pressure Research Articles

1198Women and non-diabetic patients react more strongly to radiofrequency renal sympathetic denervation

Abstract Background/Introduction Three recently published sham-controlled studies proved the efficacy of renal denervation (RDN) in hypertensive patients. However, there it is still unclear which patients should be selected for RDN. Purpose This study seeks to clarify which patient subgroups benefit most from radiofrequency RDN by analysing a nationwide multicentre registry database. Methods This is a post-hoc analysis from the multicentre Austrian Transcatheter Renal Denervation Registry hosted by the Austrian Society of Hypertension. We correlated change of systolic blood pressure (BP) after RDN to gender and presence/absence of comorbidities. Bivariate correlation and multiple linear regression analyses were performed. Results 291 patients (43% female, median age 64 years) undergoing RDN between April 2011 and September 2014 were included in this analysis. Mean baseline ambulatory 24-hour BP (systolic/diastolic) was 150±18/89±14 mmHg and mean baseline office BP was 170±16/94±14 mmHg. After RDN, mean ambulatory 24-hour BP reduction was 9±19/6±16 mmHg. The following features were associated with a good response to RDN: high baseline systolic ambulatory BP (ρ=0.53, p<0.001), high baseline diastolic office BP (ρ=0.40, p<0.001), female gender (ρ=0.10, p=0.049), absence of diabetes mellitus (DM, ρ=0.11, p=0.033), and absence of peripheral arterial disease (ρ=0.17, p=0.002). Multivariate analysis identified high baseline systolic ambulatory BP, female gender and absence of DM as independent predictors for systolic ambulatory BP reduction (systolic ambulatory BP: HR 5.83 [95% CI 4.83–6.83], p<0.001; absence of DM: HR 5.82 [2.04–9.60], p=0.003; female gender: HR 5.07 [1.46–8.68], p=0.006), although women and patients without DM had lowest baseline ambulatory BP. Furthermore, both women and patients without DM used significantly less antihypertensives after RDN (female vs male: 4.0±1.3 vs 4.4±1.3, p=0.002; no DM vs DM: 4.0±1.3 vs 4.6±1.3, p<0.001). Figure 1 Discussion Ambulatory BP reductions after RDN were substantially more pronounced in female and in non-diabetic patients despite lower baseline BP. It is concluded that in terms of efficacy female patients and non-diabetics might be more suitable for RDN. Acknowledgement/Funding The Austrian Renal Denervation Registry was funded by the Austrian Society of Hypertension.

2019 Consensus Statement of the Taiwan Hypertension Society and the Taiwan Society of Cardiology on Renal Denervation for the Management of Arterial Hypertension.

Sympathetic overactivity, an essential mechanism of hypertension, in driving sustained hypertension derives mostly from its effects on renal function. Percutaneous renal denervation (RDN) is designed to disrupt renal afferent and efferent sympathetic nerves to achieve sustained blood pressure (BP) reduction. Since 2017 onward, all three proof-of-concept, sham-controlled RDN trials demonstrated that RDN achieved consistent and clinically meaningful BP reductions [approximately 10 mmHg in office systolic BP (SBP) and 6-9 mmHg in 24-hour SBP] compared to sham operation in patients with mild to moderate or uncontrolled hypertension. There were no serious adverse events. The registry data in Taiwan showed similar 24-hour BP reductions at 12 months following RDN. The Task Force considers RDN as a legitimate alternative antihypertensive strategy and recommends 1) RDN should be performed in the context of registry and clinical studies (Class I, Level C) and 2) RDN should not be performed routinely, without detailed evaluation of various causes of secondary hypertension and renal artery anatomy (Class III, Level C). RDN could be performed in patients who fulfill either of the following BP criteria: 1) office BP ≥ 150/90 mmHg and daytime ambulatory SBP ≥ 135 mmHg or diastolic BP (DBP) ≥ 85 mmHg, irrespective of use of antihypertensive agents (Class IIa, Level B), or 2) 24-hour ambulatory SBP ≥ 140 mmHg and DBP ≥ 80 mmHg, irrespective of use of antihypertensive agents (Class IIa, Level B), with eligible renal artery anatomy and estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2. Five subgroups of hypertensive patients are deemed preferred candidates for RDN and dubbed "RDN i2": Resistant hypertension, patients with hypertension-mediated organ Damage, Non-adherent to antihypertensive medications, intolerant to antihypertensive medications, and patients with secondary (2ndary) causes being treated for ≥ 3 months but BP still uncontrolled. The Task Force recommends assessment of three aspects, dubbed "RAS" (R for renal, A for ambulatory, S for secondary), beforehand to ascertain whether RDN could be performed appropriately: 1) Renal artery anatomy eligibility assessed by computed tomography or magnetic resonance renal angiography if not contraindicated, 2) genuine uncontrolled BP confirmed by 24-hour Ambulatory BP monitoring, and 3) Secondary hypertension identified and properly treated. After the procedure, 24-hour ambulatory BP monitoring, together with the dose and dosing interval of all BP-lowering drugs, should be obtained 6 months following RDN. Computed tomography or magnetic resonance renal angiography should be obtained 12 months following RDN, given that renal artery stenosis might not be clinically evident.

Endpoint design for future renal denervation trials — Novel implications for a new definition of treatment response to renal denervation

BackgroundDefining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. MethodsWe compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of −5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints). ResultsWe were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. ConclusionBased on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits.

Incidence of renal artery stenosis after renal denervation in patients with resistant arterial hypertension

Catheter-based ablation of nerves in the adventitia of renal arteries (renal artery denervation [RAD]) using radiofrequency energy can reduce blood pressure (BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal artery stenosis after RAD is still an important concern. We systematically investigated the renal artery anatomy using magnetic resonance imaging (MRI) or computed tomography (CT) angiography in a consecutive series of patients 6 months after RAD. Patients with RAH were treated by RAD after exclusion of secondary causes of hypertension. RAH was defined by a mean systolic office BP >160 mm Hg. Renal artery imaging was performed 6 months after RAD by MRI angiography. In case of any contraindication for MRI, a CT angiography was performed. The primary end point was the incidence of significant renal artery stenosis (‡70% lumen diameter reduction). RAD was performed in 76 patients, and evaluation of renal artery anatomy by MRI (n [ 66; 87%) or CT angiography (n [ 10; 13%) was performed in all patients 6 months after RAD. We found no renal artery stenosis but 2 cases of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In responders, mean systolic office BP reduction was L30 mm Hg (p <0.001) and mean systolic 24-hour BP reduction was L18 mm Hg (p <0.001). In conclusion, the incidence of significant renal artery stenosis 6 months after RAD seems to be very low. However, late-onset development of nonsignificant renal artery narrowing cannot be excluded in some patients and should be anticipated in the case of RAH relapse or worsening of renal function after successful

Frequency of Renal Artery Stenosis After Renal Denervation in Patients With Resistant Arterial Hypertension

Catheter-based ablation of nerves in the adventitia of renal arteries (renal artery denervation [RAD]) using radiofrequency energy can reduce blood pressure (BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal artery stenosis after RAD is still an important concern. We systematically investigated the renal artery anatomy using magnetic resonance imaging (MRI) or computed tomography (CT) angiography in a consecutive series of patients 6months after RAD. Patients with RAH were treated by RAD after exclusion of secondary causes of hypertension. RAH was defined by a mean systolic office BP >160mm Hg. Renal artery imaging was performed 6months after RAD by MRI angiography. In case of any contraindication for MRI, a CT angiography was performed. The primary end point was the incidence of significant renal artery stenosis (≥70% lumen diameter reduction). RAD was performed in 76 patients, and evaluation of renal artery anatomy by MRI (n= 66; 87%) or CT angiography (n= 10; 13%) was performed in all patients 6months after RAD. We found no renal artery stenosis but 2 cases of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In responders, mean systolic office BP reduction was-30mm Hg (p <0.001) and mean systolic 24-hour BP reduction was-18mm Hg (p <0.001). In conclusion, the incidence of significant renal artery stenosis 6months after RAD seems to be very low. However, late-onset development of nonsignificant renal artery narrowing cannot be excluded in some patients and should be anticipated in the case of RAH relapse or worsening of renal function after successful RAD.

Renal sympathetic denervation: early impact on ambulatory resistant hypertension.

Although guidelines recommend ambulatory blood pressure (BP) monitoring (ABPM), few data are available regarding the effects of renal denervation (RDN) on 24-hour ABPM values. A total of 44 patients with mean systolic BP ≥135 mm Hg on ABPM despite adequate therapy were included. Basal systolic BP (SBP) and diastolic BP (DBP) were 154±11 mm Hg and 86±12 mm Hg, respectively. At 1 month, SBP and DBP were reduced to 146±18 mm Hg (P=.01) and 82±14 mm Hg and showed no further decrease up to 6 months. Only 55% of the patients responded to RDN (≥-5 mm Hg SBP), with a mean responder rate drop of 21/11 mm Hg. Neither the number of ablation points nor the amount of impedance drop was predictive of response. Only approximately half of patients with resistant hypertension responded to RDN. However, in these responders, a remarkable reduction of 24-hour BP occurred as early as 1 month after RDN.

Effects of combining azilsartan medoxomil with amlodipine in patients with stage 2 hypertension

ObjectiveThe aim of the study was to measure the effects on blood pressure (BP) of the angiotensin receptor blocker azilsartan medoxomil, in 40 and 80 mg doses, combined with 5 mg of the calcium channel blocker amlodipine and to compare these effects with placebo plus amlodipine 5 mg.MethodsThis was a randomized, controlled, double-blind study of 6 weeks’ duration in 566 patients with stage 2 hypertension. The primary endpoint was 24-h systolic BP by ambulatory monitoring.ResultsThe mean age of the participants was 58 years; men and women were equally represented, and baseline 24-h BP (153–154/93 mmHg) and clinic BP (165–166/94–95 mmHg) were similar across the three treatment groups. After 6 weeks, 24-h BP decreased by 25/15 mmHg in both the azilsartan medoxomil/amlodipine 40/5 and 80/5 mg groups. These reductions were each greater than the 14/8 mmHg decrease with placebo plus amlodipine 5 mg (P≤0.001 for both comparisons). All treatments were well tolerated, and adverse events did not increase with the azilsartan medoxomil doses. Edema or fluid retention was less common in both combination groups (2.6 and 2.7%) than with placebo plus amlodipine (7.6%).ConclusionCoadministration of azilsartan medoxomil with amlodipine was well tolerated and led to meaningful additional BP reductions compared with placebo plus amlodipine.

The Importance of 24-Hour Ambulatory Blood Pressure Monitoring in Patients at Risk of Cardiovascular Events

The accuracy of clinic blood pressure (BP) measurements is limited due to the presence of 24-hour BP variability and white-coat or masked hypertension. In contrast, 24-hour ambulatory BP monitoring (ABPM) has evolved into an accurate and reproducible tool for the assessment and management of hypertension. Various out-of-office measurements can be obtained using ABPM data, including morning, daytime, night-time and average 24-hour BP. Thus, in clinical practice, ABPM can be used to identify masked hypertension or excessive BP reduction. Furthermore, ABPM data can identify early-morning hypertension and excessive BP variability, both of which correlate with target-organ damage and cardiovascular outcomes. In large outcomes trials, ABPM sub-studies are increasingly performed to help further understand patient outcomes. However, it is evident that control of BP over the full 24-hour period, particularly during the risky early morning period, is not being achieved in general practice. In clinical trials of antihypertensive efficacy, a useful calculation is the smoothness index. This measure assesses the degree of 24-hour BP reduction, as well as its distribution pattern, throughout the 24-hour period. Importantly, the index correlates with hypertension-associated target organ damage, unlike the commonly used trough to peak ratio. Smooth BP control according to this index is achieved with long-acting drugs, such as telmisartan or amlodipine, which provide smooth 24-hour BP control, even during the early morning period. In summary, the use of ABPM is expanding, both in clinical practice and in trials, as it provides a closer correlation to prognosis than clinic BP measures. When choosing an antihypertensive agent for patients with hypertension, it is important to consider reducing BP variability by using longer acting antihypertensives, which may help to prevent cardiovascular morbidity and mortality.

Olmesartan medoxomil combined with hydrochlorothiazide improves 24-hour blood pressure control in moderate-to-severe hypertension

Background:Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has been shown to be more reliable than conventional measurements for hypertension assessment and the associated increased risk of cardiovascular events. Olmesartan/hydrochlorothiazide combination therapy has demonstrated increased blood pressure lowering over 24 hours compared with the component monotherapies. This prespecified pooled analysis of data from two trials investigated the effects of olmesartan/hydrochlorothiazide combination therapy and olmesartan monotherapy on 24-hour blood pressure control in patients with moderate-to-severe hypertension.Methods:After 8 weeks’ open-label olmesartan 40 mg monotherapy, uncontrolled patients (mean trough seated blood pressure 90–115/140–180 mmHg and 24-hour mean ambulatory diastolic blood pressure ≥80 mmHg with ≥30% of daytime ambulatory diastolic blood pressure readings >85 mmHg) were randomised to 8 weeks’ double-blind treatment with olmesartan 40 mg or olmesartan/hydrochlorothiazide 20/12.5, 40/12.5 or 40/25 mg (Study 1) or olmesartan/hydrochlorothiazide 20/25 or 40/25 mg (Study 2). This prespecified analysis of ambulatory blood pressure was performed on patients from the full analysis set of pooled studies 1 and 2, restricted to patients who provided at least one valid ABPM measurement at baseline.Results:After 8 weeks’ double-blind treatment, reductions in 24-hour, daytime and night-time blood pressure from baseline were observed for all treatment groups. These reductions were dose-dependent, with olmesartan/hydrochlorothiazide 40/25 mg demonstrating the greatest reductions in 24-hour blood pressure from baseline to Week 16 versus olmesartan monotherapy: −14.0/−8.8 vs −2.7/−2.0 mmHg, respectively; p < 0.0001.Conclusions:Adding hydrochlorothiazide to olmesartan provides more effective 24-hour blood pressure control versus olmesartan monotherapy in patients with moderate-to-severe hypertension.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00430508.Trial registration: ClinicalTrials.gov identifier: NCT00430950.

Antihypertensive efficacy of olmesartan medoxomil and candesartan cilexetil in achieving 24-hour blood pressure reductions and ambulatory blood pressure goals

Background. For patients with hypertension, effective 24-hour blood pressure (BP) control is vital to ensure protection against the early morning surge in BP and the associated increased risk of cardiovascular events. The aim of this analysis was to assess the 24-hour antihypertensive efficacy of olmesartan medoxomil (20 mg once daily) compared with candesartan cilexetil (8 mg once daily), with particular emphasis on BP control during the early morning period.Methods. This is an additional analysis of a previously reported randomised, double-blind study in which 635 patients with mainly mild to moderate hypertension were randomised to 8 weeks of treatment with either olmesartan medoxomil 20 mg/day or candesartan cilexetil 8 mg/day. Changes from baseline during the last 4 and 2 hours of ambulatory BP measurement (ABPM) after 1, 2 and 8 weeks of treatment were compared between the two groups. In addition, the proportions of patients who achieved various ABPM goals, including those suggested by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) [&lt;125/80 mm Hg] and the Japanese Society of Hypertension (JSH) [&lt;135/80 mm Hg], over 24 hours, during the daytime and at the last 4 and 2 hours of ABPM measurement were also compared.Results.After 8 weeks, significantly greater proportions of patients treated with olmesartan medoxomil 20 mg achieved 24-hour and daytime ABPM goals recommended by the guidelines of the ESH/ESC (25,6 % and 18,3 %, respectively) and JSH (37,5 % and 26,6 %, respectively) compared with candesartan cilexetil 8 mg (24-hour ESH/ESC goal 14,9 %,p&lt;0,001; 24-hour JSH goal 26,6 %,p=0,003; daytime ESH/ESC goal 9,6 %,p=0,002; daytime JSH goal 16,4 %,p=0,002). During the last 4 hours of 24-hour ABPM, the proportions of patients who achieved the ESH/ESC and JSH ABPM goals were significantly greater with olmesartan medoxomil (33,3 % and 39,1 %, respectively) than with candesartan cilexetil (22,9 %,p&lt;0,001 and 31,6 %,p=0,047, respectively). Similarly, during the last 2 hours of 24-hour ABPM, the proportions of patients who achieved these BP goals were either significantly greater (JSH) or approached statistical significance (ESH/ESC) with olmesartan medoxomil (26,9 % and 19,9 %, respectively), compared with candesartan cilexetil (19,6 %,p=0,028 and 14,3 %,p=0,061, respectively).Conclusion. Compared with candesartan cilexetil 8 mg, greater proportions of olmesartan medoxomil-treated patients (20 mg) achieved ESH/ESC and JSH ABPM goals over 24 hours. The superior BP control of olmesartan medoxomil was also reflected in the larger proportions of olmesartan medoxomil-treated patients who achieved the ESH/ESC and JSH ABPM goals during the early morning surge period. This not only demonstrates that olmesartan medoxomil 20 mg provides superior 24-hour BP reduction, but also suggests that olmesartan medoxomil may provide greater protection against the increased risk of cardiovascular events associated with the early morning BP surge period.

Putting the Theory into Practice&amp;mdash;Maximizing Real-Life Blood Pressure Control for Hypertensive Patients by Improving Adherence to Therapy

The prevention and treatment of hypertension is a public health challenge, in part because most patients treated for hypertension do not achieve adequate blood pressure (BP) control. Noncompliance is a common cause, influenced by factors such as tolerability, tablet load, complexity, efficacy, and cost. Additionally, patients may question the need for lifetime treatment of an asymptomatic condition with medications that often reduce their quality of life. Clinical inertia, underdosing, and limited use of combination and new treatments also contribute. Strategies to improve BP control include the use of highly effective, long-acting, and well-tolerated antihypertensives that encourage adherence, with efficacy that extends beyond the 24-hour dosing period to provide lasting protection and mitigation against the effects of missed doses. Angiotensin receptor blockers (ARBs) encourage higher adherence than other antihypertensives, and the ARB telmisartan offers 24-hour BP reductions. Ultimately, successful management of hypertension requires the physician to help the patient understand the seriousness of their condition, the implications of noncompliance, and the need for lifetime treatment.

The Correct Administration of Antihypertensive Drugs According to the Principles of Clinical Pharmacology

Control of cardiovascular (CV) risk factors, particularly hypertension, is still unsatisfactory, resulting in excess CV morbidity and mortality worldwide. CV risk is linearly associated with an increase in blood pressure (BP) values, and clinical studies have clearly demonstrated that BP lowering represents the most effective means of preventing CV events. However, while BP reduction is a fairly easy target, BP normalization is much more difficult to achieve, and adequate BP control (<140/90 mmHg) is attained only in a small percentage of the hypertensive population. One of the main reasons for the lack of efficacy of antihypertensive pharmacological treatment is that very often drugs are not administered at the correct dosage. In this review, we discuss the importance of using clinical pharmacology to guide treatment of hypertension. Controlled clinical trials, including HOPE, EUROPA, and CONSENSUS, are used to guide prescribing decisions. Unfortunately, the results obtained in pivotal studies such as these have been obtained using drug dosages much higher than those usually used in clinical practice. The prescription of a drug for the treatment of hypertension should take into consideration the potency of the drug, i.e. the degree of BP reduction required, and the duration of action of the drug, i.e. the need to cover the dosing interval (possibly 24 hours) in a homogeneous way. This is especially the case for angiotensin-converting enzyme (ACE) inhibitors, compounds characterized by a flat dose-response curve. The significance of this flat dose-response curve is that a low dose of an ACE inhibitor has the same potency as a high dose but a shorter duration of action. If a low dosage is administered to a hypertensive patient it causes BP fluctuations, which have been associated with negative CV outcomes. In contrast, other drug classes, including calcium channel antagonists, diuretics, and β-adrenoceptor antagonists, can be used at different dosages in order to modulate their hemodynamic effects. Thus, it is important to be aware of the clinical pharmacology of antihypertensive drugs in order to choose not only the class or the molecule best suited to the clinical characteristics of the patient, but also the correct dosages to ensure effective and homogeneous 24-hour BP reduction.

COMBINATION THERAPY WITH ALISKIREN+HYDROCHLOROTHIAZIDE REDUCES 24-HOUR AMBULATORY BLOOD PRESSURE MORE EFFECTIVELY THAN RAMIPRIL IN OBESE PATIENTS WITH STAGE 2 HYPERTENSION: PP.5.191

Objective: Ambulatory blood pressure monitoring (ABPM) is a better predictor of cardiovascular events than clinic blood pressure (BP). Analysis of ABPM in a subset of patients in clinical trials is important to confirm observed changes in clinic BP. We previously showed in an 8-week, prospective, multicenter, randomized, double-blind study (N=380) that a single-pill combination of aliskiren (A) with hydrochlorothiazide (HCTZ) provided greater clinic BP reductions than ramipril (R) in obese patients (average body mass index = 35.3 ± 4.4 kg/m2) with hypertension (mean sitting systolic BP [SBP] >=160 mmHg and <200 mmHg). Here we present the efficacy and safety of A+HCTZ vs R on BP control in a subset of patients who underwent ABPM (n=89). Design and Methods: After a 1–4 week washout period, eligible patients received A+HCTZ 150/12.5 mg (n=45) or R 5 mg (n=44) for 1 week; force-titrated to A+HCTZ 300/25 mg or R 10 mg for 7 weeks. Results: Significantly greater reductions in both clinic BP and 24-hour ambulatory blood pressure (ABP) were observed at week 8 with A+HCTZ vs R (P < 0.05). Reductions in the hourly daytime (6AM-10PM) mean ambulatory systolic BP (maSBP), mean ambulatory diastolic BP (maDBP), and hourly nighttime (10PM-6AM) maDBP were also significantly greater for A+HCTZ vs R (Table). In the overall study, adverse event rates were similar in both groups (35.8%, A+HCTZ vs 37.3%, R), the most common being headache, nasopharyngitis, dizziness, and fatigue. Conclusion: The ABPM results suggest that A+HCTZ provides more effective and consistent 24-hour BP reductions than R in obese patients with stage 2 hypertension.

Effects of barnidipine on blood pressure and left ventricular diastolic function in patients with hypertension and metabolic syndrome: A 12-week, open-label noncomparison study

Background: Barnidipine is one of a new generation of dihydropyridine calcium-channel blockers. Despite evidence of favorable effects on blood pressure (BP) and insulin sensitivity, this drug has rarely been tested in hypertensive patients with metabolic syndrome (MS). Objective: The aim of this study was to evaluate the effects of barnidipine on BP and left ventricular (LV) diastolic function in patients with hypertension and MS. Methods: Consecutive subjects aged 18 to 75 years with systolic BP (SBP) of 140 to 179 mm Hg and/or diastolic BP (DBP) of 90 to 109 mm Hg and MS (based on Adult Treatment Panel III criteria) were assessed for inclusion in the study. Lifestyle changes according to current guidelines were recommended and barnidipine monotherapy 10 mg daily was initiated. All patients entered a 2-week run-in period. After a 6-week treatment period, the daily dosage was doubled for the remainder of the study in patients whose BP remained uncontrolled (≥140/≥90 mm Hg). We assessed the glycolipidic profile and LV structure and function using standard Doppler and tissue Doppler imaging (TDI) echocardiography before and after 12 weeks of treatment. Ambulatory BP records and electrocardiographic and echocardiographic tracings were coded and shipped to a central laboratory for blinded analysis. Possible adverse events (AEs) were recorded at predetermined intervals throughout the follow-up period and at unplanned intervals whenever an AE became known to the investigators. Results: Thirty-four consecutive patients were assessed for inclusion. Thirty consecutive patients (20 men, 10 women; mean {SD| age, 55.9 {10.3| years; 5 current smokers) were included in the study. At study entry, mean office SBP was 146 mm Hg, DBP was 87 mm Hg, and heart rate was 72 beats/min. At the study end, mean office SBP/DBP was <140/90 mm Hg in 20 patients (66.7%). From baseline to study end, 24-hour ambulatory BP decreased significantly by 12 and 8 mm Hg for SBP and DBP, respectively (both, P = 0.001). The smoothness index was 0.92 for SBP and 0.82 for DBP. Fasting plasma glucose concentration decreased significantly from 110 to 104 mg/dL ( P = 0.001). Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations did not change significantly. From baseline to study end, there were no significant changes in LV structure or systolic function (LV mass, 50.7 vs 50.6 g/ht 2.7; LV diastolic/systolic diameters, 47.50/29.80 vs 48.40/30.76 mm; wall motion score index, 1.0 vs 1.0; ejection fraction, 61% vs 60%), while the peak E/A velocity ratio on TDI increased from 1.078 to 1.245 ( P = 0.009). No AEs (including AEs reflected by chemistry values) either unrelated or related to treatment were noted during the 12-week duration of the study. Conclusions: In these hypertensive patients with MS, a 12-week treatment period with barnidipine in addition to lifestyle modifications was associated with significant reductions in 24-hour BP and BP variability, reduction in plasma glucose concentration, and improvement in LV diastolic relaxation. No significant changes in lipid concentrations, LV structure, or systolic function were found.

Telmisartan/Hydrochlorothiazide

Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis Plus, Micardis HCT, PritorPlus] are available in many countries for the treatment of patients with essential hypertension. Combining the angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of action. In the US and EU, telmisartan/HCTZ is approved for patients whose hypertension is not adequately controlled with telmisartan monotherapy; US labelling for the fixed-dose combination also includes inadequate control of blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once-daily telmisartan/HCTZ has been demonstrated in several large, randomized trials in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan achieved significant reductions in BP in nonresponders to telmisartan monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to or significantly greater than that of various comparator agents. Moreover, in studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent 24-hour BP reductions throughout morning, daytime and night-time periods. The BP-lowering efficacy over the entire 24-hour dose administration interval is consistent with the pharmacokinetic profile of telmisartan, which has the longest elimination half-life among currently available ARBs and a unique chemical structure. Adverse events with telmisartan/HCTZ in clinical trials were typically mild and transient, and no unexpected events occurred that had not been previously reported with either telmisartan or HCTZ. Extensive tolerability data are available for telmisartan, in particular from the ONTARGET study, the largest clinical outcomes trial with an ARB. As such, fixed-dose combinations of telmisartan/HCTZ provide an effective, rational and generally well tolerated treatment option for the management of patients with hypertension.

Antihypertensive Efficacy of Olmesartan Medoxomil and Candesartan Cilexetil in Achieving 24-Hour Blood Pressure Reductions and Ambulatory Blood Pressure Goals

For patients with hypertension, effective 24-hour blood pressure (BP) control is vital to ensure protection against the early morning surge in BP and the associated increased risk of cardiovascular events. The aim of this analysis was to assess the 24-hour antihypertensive efficacy of olmesartan medoxomil (20mg once daily) compared with candesartan cilexetil (8mg once daily), with particular emphasis on BP control during the early morning period. This is an additional analysis of a previously reported randomised, double-blind study in which 635 patients with mainly mild to moderate hypertension were randomised to 8 weeks of treatment with either olmesartan medoxomil 20 mg/day or candesartan cilexetil 8 mg/day. Changes from baseline during the last 4 and 2 hours of ambulatory BP measurement (ABPM) after 1, 2 and 8 weeks of treatment were compared between the two groups. In addition, the proportions of patients who achieved various ABPM goals, including those suggested by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) [<125/80mm Hg] and the Japanese Society of Hypertension (JSH) [<135/80mm Hg], over 24 hours, during the daytime and at the last 4 and 2 hours of ABPM measurement were also compared. After 8 weeks, significantly greater proportions of patients treated with olmesartan medoxomil 20mg achieved 24-hour and daytime ABPM goals recommended by the guidelines of the ESH/ESC (25.6% and 18.3%, respectively) and JSH (37.5% and 26.6%, respectively) compared with candesartan cilexetil 8mg (24-hour ESH/ESC goal = 14.9%, p < 0.001; 24-hour JSH goal = 26.6%, p = 0.003; daytime ESH/ESC goal = 9.6%, p = 0.002; daytime JSH goal = 16.4%, p = 0.002). During the last 4 hours of 24-hour ABPM, the proportions of patients who achieved the ESH/ESC and JSH ABPM goals were significantly greater with olmesartan medoxomil (33.3% and 39.1%, respectively) than with candesartan cilexetil (22.9%, p < 0.001 and 31.6%, p = 0.047, respectively). Similarly, during the last 2 hours of 24-hour ABPM, the proportions of patients who achieved these BP goals were either significantly greater (JSH) or approached statistical significance (ESH/ESC) with olmesartan medoxomil (26.9% and 19.9%, respectively) compared with candesartan cilexetil (19.6%, p = 0.028 and 14.3%, p = 0.061, respectively). Compared with candesartan cilexetil 8mg, greater proportions of olmesartan medoxomil-treated patients (20mg) achieved ESH/ESC and JSH ABPM goals over 24 hours. The superior BP control of olmesartan medoxomil was also reflected in the larger proportions of olmesartan medoxomil-treated patients who achieved the ESH/ESC and JSH ABPM goals during the early morning surge period. This not only demonstrates that olmesartan medoxomil 20mg provides superior 24-hour BP reduction, but also suggests that olmesartan medoxomil may provide greater protection against the increased risk of cardiovascular events associated with the early morning BP surge period.

Characterizing variability in cardiovascular drug responses

Characterizing variability in cardiovascular drug responses

Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension

Eplerenone is a highly selective aldosterone blocking agent, which was recently approved for the treatment of hypertension and has also been shown to reduce mortality in post-myocardial infarction patients with heart failure. To assess its usefulness in patients with essential hypertension, we performed a 12-week, double-blind, placebo-controlled, parallel-arm, fixed-dose study over a range of doses using clinic and ambulatory blood pressure (BP). After single-blind placebo therapy for 3 to 4 weeks to obtain baseline measures, 400 patients were randomized to receive placebo or 1 of 4 doses of eplerenone (25, 50, 100, and 200 mg once daily). In addition, changes from baseline in serum potassium, active renin activity, and serum aldosterone were assessed. After 12 weeks of therapy, reductions in clinic BP showed a significant dose response in which 25 mg of eplerenone achieved statistical significance compared with placebo for systolic BP; maximum clinic BP reduction was achieved with the 100 mg dose. Ambulatory BP monitoring showed that all doses of eplerenone (25 to 200 mg/day) lowered BP significantly greater than placebo with a significant dose response. The 24-hour mean BP reductions ranged from 6.4/4.4 to 10.3/5.7 mm Hg on eplerenone compared with 1.3/0.8 mm Hg on placebo. One patient on placebo and 1 patient on 200 mg of eplerenone had episodes of elevated serum potassium levels (>5.5 mEq/L). Increases in serum aldosterone were related to dose but not to reductions in 24-hour BP. Side effects and withdrawal rates attributed to eplerenone were similar to those of placebo. These data show that eplerenone is an effective antihypertensive agent at doses as low as 25 mg/day. The top effective dose in stage 1 to 3 hypertension based on clinic and ambulatory BP was 100 mg once daily. The incidence of elevated serum potassium levels was not increased across doses of eplerenone in this study.

Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension

Eplerenone is a highly selective aldosterone blocking agent, which was recently approved for the treatment of hypertension and has also been shown to reduce mortality in post-myocardial infarction patients with heart failure. To assess its usefulness in patients with essential hypertension, we performed a 12-week, double-blind, placebo-controlled, parallel-arm, fixed-dose study over a range of doses using clinic and ambulatory blood pressure (BP). After single-blind placebo therapy for 3 to 4 weeks to obtain baseline measures, 400 patients were randomized to receive placebo or 1 of 4 doses of eplerenone (25, 50, 100, and 200 mg once daily). In addition, changes from baseline in serum potassium, active renin activity, and serum aldosterone were assessed. After 12 weeks of therapy, reductions in clinic BP showed a significant dose response in which 25 mg of eplerenone achieved statistical significance compared with placebo for systolic BP; maximum clinic BP reduction was achieved with the 100 mg dose. Ambulatory BP monitoring showed that all doses of eplerenone (25 to 200 mg/day) lowered BP significantly greater than placebo with a significant dose response. The 24-hour mean BP reductions ranged from 6.4/4.4 to 10.3/5.7 mm Hg on eplerenone compared with 1.3/0.8 mm Hg on placebo. One patient on placebo and 1 patient on 200 mg of eplerenone had episodes of elevated serum potassium levels (>5.5 mEq/L). Increases in serum aldosterone were related to dose but not to reductions in 24-hour BP. Side effects and withdrawal rates attributed to eplerenone were similar to those of placebo. These data show that eplerenone is an effective antihypertensive agent at doses as low as 25 mg/day. The top effective dose in stage 1 to 3 hypertension based on clinic and ambulatory BP was 100 mg once daily. The incidence of elevated serum potassium levels was not increased across doses of eplerenone in this study.

A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: The MAPAVEL study

Background: When blood pressure (BP)—lowering efficacy is assessed by measurements taken in a clinic setting, angiotensin II—receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability. A search of MEDLINE to date, however, reveals no randomized, double-blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients (>200) with essential hypertension. Objective: This study compared 24-hour BP reduction and BP control, as assessed by ABPM, in patients with mild to moderate essential hypertension treated with irbesartan or enalapril. The relative tolerability of the 2 treatments was also evaluated. Methods: This was a multicenter, randomized, double-blind study in patients with mild to moderate essential hypertension (office diastolic BP [DBP] 90–109 mm Hg or systolic BP [SBP] 140–179 mm Hg). After a 3-week, single-blind placebo washout phase, patients with a mean daytime DBP ≥85 mm Hg, as measured by ABPM between 10 am and 8 pm, were randomized to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were 150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was ≥90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was defined as a BP reading <140/90 mm Hg after 12 weeks of treatment; patients achieving a reduction in DBP of ≥10 mm Hg at 12 weeks were considered responders. The ABPM criterion for BP control, independent of clinic values, was achievement of a daytime BP <130/85 mm Hg after 12 weeks of treatment; patients achieving a reduction in 24-hour DBP ≥5 mm Hg at 12 weeks were considered responders, independent of clinic values. Results: A total of 238 patients were randomized to treatment, 115 to irbesartan and 123 to enalapril. The study population was ∼52.0% female and 48.0% male, with a mean (±SD) age of 52.7 ± 10.6 years. The study was completed by 111 patients in the irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115 patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients). BP reductions were similar in the 2 groups, both as measured in the clinic (DBP, 12.7 ± 8.8 mm Hg irbesartan vs 12.4 ± 7.4 mm Hg enalapril; SBP, 19.0 ± 14.1 mm Hg vs 17.5 ± 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 ± 8.5 mm Hg vs 8.8 ± 8.5 mm Hg; SBP, 14.7 ± 14.7 mm Hg vs 12.6 ± 13.1 mm Hg). As assessed by ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115) for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3% (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2% enalapril) was not statistically different between groups, although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan (24.6% vs 9.2%, respectively; P = 0.026), essentially because of the higher incidence of cough (8.1% vs 0.9%). Conclusions: As assessed by ABPM, irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d. Based on the number of treatment-related adverse events, irbesartan was better tolerated than enalapril.