Managing Menopausal Symptoms in Young Women With Breast Cancer: When Medicine Is Not All. The Take Care Project.

In the last decade, endocrine therapy strategies in perimenopausal women with hormone-responsive early breast cancer (BC) have changed and now ovarian function suppression (OFS) is recommended for the majority of patients. Side effects of OFS mimic menopausal symptoms, including hot flushes, sweats, weight gain, and sexual dysfunction, which may negatively impact quality of life (QoL). Aims of the Take Care Project are the education of physicians and patients to have all the information (medical and nonmedical) they need to manage menopausal symptoms by distributing educational materials useful to face menopause. Four different areas have been identified by surveys conducted among physicians and young patients: for each area, interventions and tools have been elaborated by a doctor and nonphysician professionals of these identified areas, to offer the widest information available. Clinical and practical suggestions have been provided. Based on the evidence given, we strongly suggest setting up a multidisciplinary team for the treatment planning of young patients with BC, which could help patients to face and manage their new menopause condition. The reduction of side effects and the improvement in QoL should be the best ally to treat young patients with BC.

May Measurement Month 2018: an analysis of blood pressure screening results from Italy.

Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness and blood pressure (BP) control are still unsatisfactory. In 2017, 30.6% of a >10 000 individual sample who took part in the May Measurement Month (MMM) campaign in Italy was found to have high BP. To raise awareness on the hypertension issue and to report BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2018. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Screenings were conducted in multiple sites by health care personnel. Among the 5554 people screened (females: 48.3%, mean age 58 ± 17 years) mean BP was 127/77 mmHg, and after imputations, 1462 (26.3%) participants were found to have high BP levels. Body mass index >25 was associated with higher systolic BP and diastolic BP (DBP), while diabetes was associated with high DBP only. Our data provide a nation-wide snapshot of BP control in a sample of individuals participating in a national health care campaign, and confirm the power of this kind of healthcare-related activities in reaching a significant number of people to raise awareness on health topics. The apparent positive trend in BP control compared to available data from other similar campaigns carried out during the past years needs to be confirmed with more methodologically robust studies.

Central Sympathetic Inhibition: a Neglected Approach for Treatment of Cardiac Arrhythmias?

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Overactivation of the sympathetic nervous system (SNS) plays an important role in the pathogenesis of comorbidities related to AF such as hypertension, congestive heart failure, obesity, insulin resistance, and obstructive sleep apnea. Methods that reduce sympathetic drive, such as centrally acting sympatho-inhibitory agents, have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. Moxonidine acts centrally to reduce activity of the SNS, and clinical trials indicate that this is associated with a decreased AF burden in hypertensive patients with paroxysmal AF and reduced post-ablation recurrence of AF in patients with hypertension who underwent pulmonary vein isolation (PVI). Furthermore, device-based approaches to reduce sympathetic drive, such as renal denervation, have yielded promising results in the prevention and treatment of cardiac arrhythmias. In light of these recent findings, targeting elevated sympathetic drive with either pharmacological or device-based approaches has become a focus of clinical research. Here, we review the data currently available to explore the potential utility of sympatho-inhibitory therapies in the prevention and treatment of cardiac arrhythmias.

A Prospective Study for Introducing Insulin Pens and Safety Needles in a Hospital Setting. The SANITHY Study.

BACKGROUND: to assess costs and safety of insulin pen devices and safety needles as compared to vial/syringes in hospitalized patients requiring insulin therapy in a General Hospital in Northern Italy. MATERIALS AND METHODS: in a prospective 9-month study, consecutive patients admitted to three Hospital Units received insulin therapy through either a traditional disposable syringe method, or pen/safety needles with dual-ended protection, or disposable safety syringes. We compared the median direct (insulin and devices) and indirect (insulin supply at discharge, insulin wastage) costs of a 10-day in-hospital insulin treatment in the 3 study groups, additionally accounting for the costs related to the observed needlestick injury rate. Patients' safety during in-hospital stay (hypo- and hyperglycemia episodes) and satisfaction were also assessed. RESULTS: N=360 patients (55% men, mean age 75.6 years, 57% with DM since ≥10 years) were recruited in the study. Insulin pens had higher median direct cost than both traditional syringes (43 vs. 18 ε/patient, p<.0001) and safety syringes (21.5 ε/patient, p<.0001). However, when also indirect and injuries costs were taken into account, the estimated savings for using pens over traditional syringes were as high as 32 ε/patient (45.8 vs. 77.6 ε/patient, p-value <.0001). No differences in patients' safety were observed. 74% and 12% of patients using pens and syringes would like to continue the method at home, respectively (p<0.0001). DISCUSSION: A selective use of individual pre-filled pens/safety needles for patients who are likely to continue insulin therapy at home may strongly reduce hospital diabetes treatment related costs.

Determinants of nurse satisfaction using insulin pen devices with safety needles: an exploratory factor analysis.

BACKGROUND: A paucity of data exists to examine nurses' satisfaction with the use of insulin pens with safety needles in hospitalized patients with diabetes. We investigated major determinants of nurses' preference of the method of insulin administration in the context of a General Hospital in Northern Italy. METHODS: Consecutive patients admitted to three hospital units of different care intensity requiring insulin received insulin therapy through either the vial/syringe method (October to December 2012) or pen/safety needles with dual-ended protection method (January to March 2013). Before the implementation of insulin pens, floor nurses received a specific training program for proper insulin pen injection technique including individual testing of the devices (pen/safety needles). At the end of the study, nurses completed the Nursing Satisfaction Survey Questionnaire. Cronbach's alpha was used to determine the internal consistency and reliability of the questionnaire. Major determinants of satisfaction were investigated through an exploratory factor analysis. The association between each retained factor and time spent to teach patients how to self-inject insulin with pen devices was also investigated. RESULTS: Fifty-three out of 60 nurses (mean age ± SD 36.2 ± 8.5 years, 85 % women, 57 % with 10+ years of working experience) returned the questionnaire. Internal consistency of the questionnaire was satisfactory (Cronbach's alpha > 0.9). Three months after their introduction, about 92 % of nurses considered pen devices an "improvement" over the vial/syringe method. Two factors explained 85 % of nurses' satisfaction, one related to convenience and ease of use, and the other to satisfaction/time spent for dose preparation and administration. The latter factor was inversely correlated with time spent on patients' training tasks. CONCLUSIONS: Nurses' satisfaction with pen devices was higher than previously reported, possibly reinforced by safety needles with dual-ended protection. Perceived workload was a major determinant of nurse satisfaction using pen devices with safety needles. To facilitate the introduction of insulin pens in the hospital setting, it should be specifically addressed during training programs in the switch-over period.

Blood pressure control and treatment adherence in hypertensive patients with metabolic syndrome: protocol of a randomized controlled study based on home blood pressure telemonitoring vs. conventional management and assessment of psychological determinants of adherence (TELEBPMET Study).

BACKGROUND: Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patient's therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated. METHODS/DESIGN: The purpose of this open label, parallel group, randomized, controlled study is to assess whether, in patients with high cardiovascular risk (treated or untreated essential arterial hypertension--both in the office and in ambulatory conditions over 24 h--and metabolic syndrome), long-term (48 weeks) blood pressure control is more effective when based on HBPT and on the feedback to patients by their doctor between visits, or when based exclusively on blood pressure determination during quarterly office visits (conventional management (CM)). A total of 252 patients will be enrolled and randomized to usual care (n = 84) or HBPT (n = 168). The primary study endpoint will be the rate of subjects achieving normal daytime ambulatory blood pressure targets (< 135/85 mmHg) 24 weeks and 48 weeks after randomization. In addition, the study will assess the psychological determinants of adherence and persistence to drug therapy, through specific psychological tests administered during the course of the study. Other secondary study endpoints will be related to the impact of HBPT on additional clinical and economic outcomes (number of additional medical visits, direct costs of patient management, number of antihypertensive drugs prescribed, level of cardiovascular risk, degree of target organ damage and rate of cardiovascular events, regression of the metabolic syndrome). DISCUSSION: The TELEBPMET Study will show whether HBPT is effective in improving blood pressure control and related medical and economic outcomes in hypertensive patients with metabolic syndrome. It will also provide a comprehensive understanding of the psychological determinants of medication adherence and blood pressure control of these patients. TRIAL REGISTRATION: Clinical Trials.gov: NCT01541566.

Effect of telmisartan and ramipril on atrial fibrillation recurrence and severity in hypertensive patients with metabolic syndrome and recurrent symptomatic paroxysmal and persistent atrial fibrillation.

This study evaluated the effect of telmisartan, ramipril, and amlodipine on atrial fibrillation (AF) recurrence and severity in hypertensive patients with metabolic syndrome. A total of 391 hypertensive outpatients with metabolic syndrome, in sinus rhythm but with at least 2 episodes of AF in the previous 6 months were randomized to telmisartan, ramipril, or amlodipine for 1 year. At the first AF, ventricular rate (VR) and plasma cardiac troponin I (TnI) were evaluated. P-wave dispersion (PWD) and procollagen type I carboxy-terminal peptide (PIP) were evaluated before and after 12 months of treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were similarly and significantly reduced by all treatments (P < .001). In all, 49% of patients treated with amlodipine had a recurrence of AF as did 25.5% of patients with ramipril and 12.9% of patients with telmisartan (P < .01 vs amlodipine and P < .05 vs ramipril). Ventricular rate and TnI at the first AF recurrence were significantly lower with telmisartan and ramipril than with amlodipine. P-wave dispersion was reduced by ramipril (-5.1 ms, P < .05) and even more by telmisartan (-11 ms, P < .01). Telmisartan and ramipril induced a similar PIP reduction (-52.8 and -49.8 µg/L, respectively, P < .01). These findings suggested that in these patients telmisartan was more effective than ramipril in reducing AF recurrence and severity as well as in improving PWD, despite a similar BP reduction and a similar improvement in cardiac fibrosis. This could be related to a specific effect of telmisartan on atrial electric remodeling.

Telmisartan: just an antihypertensive agent? A literature review.

INTRODUCTION: The modulation of the renin angiotensin aldosterone system (RAAS) is an important pathway in managing high blood pressure, and its overexpression plays a key role in target end-organ damage. Telmisartan is an angiotensin II receptor blocker (ARB) with unique pharmacologic properties, including the longest half-life among all ARBs; this leads to a significant and 24-h sustained reduction of blood pressure. Telmisartan has well-known antihypertensive properties, but there is also strong clinical evidence that it reduces left ventricular hypertrophy, arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection. AREAS COVERED: This paper reviews telmisartan's pharmacological properties in terms of efficacy for hypertension control and, importantly, focuses on its new therapeutic indications and their clinical implications. EXPERT OPINION: ONTARGET (ongoing telmisartan alone and in combination with ramipril global endpoint trial) demonstrated, that telmisartan confers cardiovascular protective effects similar to those of ramipril, but with a better tolerability. Moreover, recent investigations focused on the capability of telmisartan to modulate the peroxisome proliferator-activated receptor-gamma (PPAR-γ), an established target in the treatment of insulin resistance, diabetes and metabolic syndrome, whose activation is also correlated to anti-inflammatory and, finally, anti-atherosclerotic properties. Telmisartan shows peculiar features that go beyond blood pressure control. It presents promising and unique protective properties against target end-organ damage, potentially able to open a scenario of new therapeutic approaches to cardiovascular disease.

Triple combination therapy with amlodipine, valsartan, and hydrochlorothiazide vs dual combination therapy with amlodipine and hydrochlorothiazide for stage 2 hypertensive patients.

OBJECTIVE: This post hoc analysis evaluated the efficacy and safety of triple therapy with amlodipine/valsartan+hydrochlorothiazide (Aml/Val+HCTZ) vs dual therapy with Aml+HCTZ in stage 2 hypertensive patients. METHODS: The analysis included patients from an eight-week, multicenter, double-blind study, randomized to Aml/Val 10/160 mg or Aml 10 mg groups, who received add-on HCTZ 12.5 mg at week 4 if mean sitting systolic blood pressure (msSBP) was >130 mmHg. RESULTS: Of the patients receiving Aml/Val+HCTZ and Aml+HCTZ, 98% (N = 133/136) and 96% (N = 200/208) completed the study, respectively. Baseline characteristics were similar across groups (Caucasians, 80.2%; diabetics, 14.8%; age, 58.6 years [28.2% ≥ 65 years]; body mass index, 31 kg/m(2); mean sitting blood pressure (msBP), 171.5/95.5 mmHg [18% msSBP ≥ 180 mmHg]). Aml/Val+HCTZ provided significantly greater msBP reductions from baseline to week 8 than Aml+HCTZ (30.5/13.8 vs 24.3/8.3 mmHg, P < 0.0001). The incremental msBP reduction (week 4 to 8) with HCTZ added to Aml/Val was greater than when added to Aml (6.9/3.5 vs 3.1/1.0 mmHg, P < 0.01). Treatments were well tolerated with similar overall incidence of adverse events (Aml/Val+HCTZ: 33.8%, Aml+HCTZ: 33.2%). CONCLUSION: Aml/Val+HCTZ provided significantly greater BP reductions than Aml+HCTZ in patients with stage 2 hypertension. Aml/Val+HCTZ triple therapy may be a suitable option for patients requiring more than two agents to reach target BP.

Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination.

The renin-angiotensin-aldosterone system (RAAS), an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs) were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs) have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination.

Effectiveness of barnidipine 10 or 20 mg plus losartan 50-mg combination versus losartan 100-mg monotherapy in patients with essential hypertension not controlled by losartan 50-mg monotherapy: A 12-week, multicenter, randomized, open-label, parallel-group study.

BACKGROUND: Increasing the dose or adding a second antihypertensive agent are 2 possible therapeutic choices when blood pressure (BP) is poorly controlled with monotherapy. OBJECTIVE: This study investigated the effectiveness and tolerability of barnidipine 10 or 20 mg added to losartan 50 mg versus losartan 100 mg alone in patients with mild to moderate essential hypertension whose BP was uncontrolled by losartan 50-mg monotherapy. METHODS: This was a 12-week, multicenter, randomized, open-label, parallel-group study. Eligible patients (aged 30-74 years) had uncontrolled hypertension, defined as office sitting diastolic BP (DBP) > or =90 mm Hg and/or systolic BP (SBP) > or =140 mm Hg, and mean daytime DBP > or =85 mm Hg and/or SBP > or =135 mm Hg. All were being treated with losartan 50 mg at enrollment. After a 1-week run-in period while taking losartan 50 mg, patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg or losartan 100-mg monotherapy. At the end of this period, patients with uncontrolled BP had barnidipine doubled to 20 mg and continued for an additional 6 weeks, whereas patients not achieving control on treatment with losartan 100 mg were discontinued. Office BP was measured at each visit, whereas 24-hour ambulatory BP monitoring (ABPM) was performed at randomization and at the final visit (ie, after 12 weeks of treatment, or at 6 weeks for patients not controlled on losartan 100 mg). The intent-to-treat population included all randomized patients who received at least one dose of study treatment and had valid ABPM recordings at baseline and the final visit. The primary end point was the change in daytime DBP between baseline and 12 weeks of treatment, compared between the combination treatment and monotherapy. Adverse events (AEs) were evaluated during each study visit. RESULTS: A total of 93 patients were enrolled (age range, 30-75 years; 60% [56/93] men). After the 1-week run-in period, 68 patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg (n = 34) or losartan 100-mg monotherapy (n = 34). A total of 53 patients were evaluable (barnidipine plus losartan, n = 28; losartan, n = 25). After 6 weeks of treatment, 18 patients in the combination treatment group (64.3%) had their dose of barnidipine doubled from 10 to 20 mg because BP was not normalized by treatment, whereas 8 patients in the losartan group (32.0%) were discontinued for the same reason. The between-treatment difference (losartan alone - combination treatment) for changes from baseline in daytime DBP was -1.7 mm Hg (95% CI, -5.8 to 2.4 mm Hg; P = NS). A similar result was observed for daytime SBP (-3.2 mm Hg; 95% CI, -8.1 to 1.7 mm Hg; P = NS). Likewise, no significant differences were found for nighttime values (mean [95% CI] DBP, 0.5 mm Hg [-3.7 to 4.7 mm Hg]; SBP, 1.5 mm Hg [-4.1 to 7.1 mm Hg]) or 24-hour values (DBP, -0.9 mm Hg [-4.8 to 2.9 mm Hg]; SBP, -1.6 mm Hg [-5.9 to 2.7 mm Hg]). Combination treatment was associated with a significantly higher rate of SBP responder patients (ie, <140 mm Hg or a reduction of > or =20 mm Hg) compared with monotherapy (82.1% [23/28] vs 56.0% [14/25]; P = 0.044). Drug-related AEs were reported in 4 patients taking combination treatment (total of 7 AEs, including 2 cases of peripheral edema and 1 each of tachycardia, atrial flutter, tinnitus, confusion, and polyuria) and in 2 patients taking losartan alone (total of 2 AEs, both tachycardia). CONCLUSIONS: This open-label, parallel-group study found that there was no significant difference in the BP-lowering effect of barnidipine 10 or 20 mg in combination with losartan 50 mg compared with losartan 100-mg monotherapy in these patients with essential hypertension previously uncontrolled by losartan 50-mg monotherapy. However, the percentage of responders for SBP was significantly higher with the combination. Both treatments were generally well tolerated. European Union Drug Regulating Authorities Clinical Trials (EudraCT) no. 2006-001469-41.

Role of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update.

The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor) and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker). Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.

New strategies and drugs in the treatment of hypertension: monotherapy or combination?

Hypertension is one of the major risk factors associated with cardiovascular diseases. A range of blood pressure-lowering agents is available including diuretics, alpha- and beta-blockers, aldosterone antagonists, calcium-channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and direct renin inhibitors (DRI). Most patients require two or more medications to control their blood pressures within normal ranges. When high blood pressure cannot be controlled by low-dose monotherapy, physicians employ either high-dose monotherapy or combination therapy. High-dose ARB monotherapy is more effective for reducing proteinuria against low-dose ARB monotherapy or CCBs. Combination therapy is recommended for hypertension patients to facilitate prompt maintenance of blood pressure. Single-pill combination therapy simplifies treatment and optimizes long-term compliance. Thiazide diuretics such as hydrochlorothiazide (HCTZ), alone or in combination are still widely used as first-line hypertension treatment. Recent studies have shown that double (CCB+ARBs) or triple (CCB+ARBs+HCTZ) combination therapies have a greater lowering efficacy and are better tolerated. Moreover, the use of DRIs has been patented and proven effective in selected categories of hypertensive patients with or without concomitant target organ damage (TOD).

Olmesartan medoxomil: recent clinical and experimental acquisitions.

Angiotensin II is a vasoactive hormone of the renin-angiotensin system and plays an important role in the pathophysiology of several organ damages. Angiotensin II receptor blockers have been shown to be effective in treating both hypertension and connected organ damages. It is well known that although the angiotensin II receptor blockers have structural and pharmacokinetic differences, few pharmacological differences separate them. One of these is the degree of binding to the angiotensin II receptor type 1 compared with the angiotensin II receptor type 2; olmesartan medoxomil exhibits more than a 12,500-fold greater affinity for the angiotensin II receptor type 1 receptor than for the angiotensin II receptor type 2, making it theoretically the second most potent agent. However, olmesartan's excellent receptor interaction is based on the combination of several specific pharmacokinetic factors. Potential advantages of this drug include once-daily dosing, a very low incidence of significant adverse reactions and/or events and a well-tolerated side effect profile. Nowadays, we have a lot of information about the pharmacology, antihypertensive efficacy and safety of olmesartan medoxomil, to further extend many clinical studies are still continuing to evaluate the potential benefits of high dosages and/or combination of this molecule.

Efficacy and safety of amlodipine/valsartan compared with amlodipine monotherapy in patients with stage 2 hypertension: a randomized, double-blind, multicenter study: the EX-EFFeCTS Study.

Achieving blood pressure (BP) targets in stage 2 hypertension usually requires two or more drugs, which should be selected from different classes. This study compared the efficacy and tolerability of amlodipine/valsartan with amlodipine in patients with stage 2 hypertension. In this multicenter, randomized, double-blind, 8-week study, 646 patients with stage 2 hypertension (mean sitting systolic blood pressure [MSSBP] >/=160 mm Hg) received amlodipine/valsartan 5/160 mg or amlodipine 5 mg for 2 weeks, prior to being force-titrated to amlodipine/valsartan 10/160 mg or amlodipine 10 mg, respectively, for a further 6 weeks. Hydrochlorothiazide could be added at Week 4 if MSSBP was >/=130 mm Hg. At endpoint Week 4, reductions in MSSBP were significantly greater in patients receiving amlodipine/valsartan than in those receiving amlodipine (30.1 mm Hg vs. 23.5 mm Hg; P < .0001). Likewise, MSSBP reductions in patients with baseline MSSBP >/=180 mm Hg were also greater for amlodipine/valsartan at Week 4 (40.1 mm Hg vs. 31.7 mm Hg for amlodipine; P = .0018). Differences favoring amlodipine/valsartan were also seen for BP control. Amlodipine/valsartan was generally well tolerated. These findings support the rationale for combining agents with complementary mechanisms of action, such as amlodipine and valsartan, in the management of stage 2 hypertension.

Effectiveness of hydrochlorothiazide in combination with telmisartan and olmesartan in adults with moderate hypertension not controlled with monotherapy: a prospective, randomized, open-label, blinded end point (PROBE), parallel-arm study.

BACKGROUND: The potential combinations of antihypertensive agents are many, and making rational choices depends on the characteristics of each drug and on their complementary mechanisms of action. OBJECTIVE: The aim of this study was to evaluate the effectiveness of adding hydrochlorothiazide (HCTZ) 12.5 mg to olmesartan 20 mg or telmisartan 80 mg on blood pressure (BP) in patients with moderate hypertension. METHODS: Consecutive outpatients at the Centro per l'Ipertensione e la Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy, of both sexes aged 39 to 75 years were considered eligible for enrollment if they had a sitting diastolic BP (DBP) ->99 mm Hg and <110 mm Hg at the end of an initial 2-week washout period. Patients were random- ized to olmesartan 20 mg QD or telmisartan 80 mg QD according to a prospective, open-label, blinded end point, parallel-arm design. After 8 weeks of monotherapy, patients whose BP was not controlled (DBP ->90 mm Hg) received HCTZ 12.5 mg QD for 8 additional weeks. Clinical and ambulatory BPs were measured at the end of the washout period and at the end of both treatment periods. Adverse events (AEs) were recorded from spontaneous reports and direct inquiry from investigators. RESULTS: One hundred forty-five patients, all of whom were white, were recruited for the study. After the initial washout period, 13 patients did not meet the inclusion criteria and 6 refused to continue. A total of 126 white patients (69 men, 57 women; mean [SD] age, 60.2 [11.6] years) were randomized to receive monotherapy. Of these, 35 patients (56%) in the olmesartan group and 33 (52%) in the telmisartan group had previously received antihypertensive therapy. At the end of monotherapy, the 52 patients in the olmesartan group and the 49 patients in the telmisartan treatment group who were still in the study and had their BP inadequately controlled by treatment had HCTZ 12.5 mg QD added to their treatment regimen. Both combinations induced a greater ambulatory mean (SD) systolic BP (SBP) and DBP reduction than monothera- py (SBP: 145.3 [6.1] in the olmesartan group and 140.1 [6.4] in the telmisartan group, P < 0.05; DBP: 88.1 [5.1] in the olmesartan group and 84.9 [4.9] in the telmisartan group, P < 0.05). The mean (SD) reduction from baseline in the telmisartan/HCTZ-treated patients (21.5 [10.1]/14.6 [5.2] mm Hg for 24 hours, 21.8 [10.2]/14.9 [5.2] mm Hg for daytime, and 20.4 [10.3]/13.7 [5.9] mm Hg for nighttime; all, P < 0.001 vs baseline) was significantly greater than that observed in the olmesartan/HCTZ-treated patients (18.8 [9.8]/12.3 [4.9] mm Hg for 24 hours, 19.3 [9.8]/12.8 [4.9] mm Hg for daytime, and 17.4 [10.2]/10.6 [5.5] mm Hg for nighttime; all, P < 0.001 vs baseline), with a significant difference between the 2 treatment groups (P < 0.01). Compared with mono- therapy, the add-on effect of HCTZ 12.5 mg QD administration was significantly greater in the telmisartan group than in the olmesartan group (P < 0.05); the differ- ence being more evident for nighttime BP values (SBP, P 0.031; DBP, P 0.025). Reported AEs were similar in the olmesartan/HCTZ and the telmisartan/HCTZ groups (4 patients [7%] vs 3 patients [6%]). CONCLUSION: The addition of HCTZ 12.5 mg to telmisartan 80 mg monothera- py was associated with greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 nag monotherapy in these patients previously uncontrolled on monotherapy.

Effect of telmisartan-amlodipine combination at different doses on urinary albumin excretion in hypertensive diabetic patients with microalbuminuria.

BACKGROUND: Aim of this study was to evaluate the effect of the telmisartan-amlodipine combination at different doses on urinary albumin excretion rate (UAER) in hypertensive diabetic patients with microalbuminuria. METHODS: After a 2-week placebo period, 300 hypertensive patients with type 2 diabetes and microalbuminuria were treated with the 40 mg of telmisartan and 2.5 mg of amlodipine combination. After 4 weeks 210 patients whose blood pressure (BP) was not controlled (BP >130/80 mm Hg) were randomized to two-dose titration regimens, one based on increasing doses of telmisartan (up to 160 mg daily) and fixed 2.5-mg dose of amlodipine, the other based on increasing doses of amlodipine (up to 10 mg daily) and fixed 40-mg dose of telmisartan. After 12 weeks the nonresponder patients were given transdermic clonidine (0.1mg/d). After 16 weeks the patients yet not controlled were discontinued, the others were followed for 48 weeks. Office BP, UAER, creatinine clearance, plasma potassium, fasting glycemia, and glycosylated hemoglobin were assessed at the end of the telmisartan (40 mg)/amlodipine (2.5 mg) treatment period and after 48 weeks of treatment. RESULTS: Similar decrease in systolic/diastolic BP values were obtained with both regimens (-24/-21, -23/-21, and -24/-21 mm Hg, all P < .001 v baseline, with increasing telmisartan; -25/-22, -25/-21, and -25/-22 mm Hg, all P < .001 v baseline with increasing amlodipine). Reductions of UAER were 47.5% (P < .01), 65.3% (P < .001), and 77% (P < .0001) for telmisartan 80, 120, and 160 mg/amlodipine 2.5 mg daily, respectively, whereas reductions of UAER were 34% (P < .03), 37% (P < .03), and 33% (P < .03) for amlodipine 5, 7.5, and 10 mg/telmisartan 40 mg daily, respectively, The difference between the two regimens was statistically significant (P < .05, P < .01, and P < .001, respectively). CONCLUSIONS: These findings indicate that, at comparable levels of BP reduction, UAE decreased more in subjects treated with escalating doses of telmisartan.

Losartan and prevention of atrial fibrillation recurrence in hypertensive patients.

The aim of the study was to evaluate the effect of losartan as compared with amlodipine, both associated with amiodarone, in preventing the recurrence of atrial fibrillation (AF) in hypertensive patients with a history of recent paroxysmal atrial fibrillation. Two hundred and fifty mild hypertensive (SBP > 140 mm Hg and/or DBP > 90 < 100 mm Hg) outpatients in sinus rhythm but with at least two ECG-documented episodes of symptomatic atrial fibrillation in the previous 6 months and in treatment with amiodarone were randomized to losartan or amlodipine and were followed up for 1 year. Clinic blood pressure (BP) and a 24-hour ECG was evaluated every month; the patients were asked to report any episode of symptomatic atrial fibrillation and to perform an ECG as early as possible. Two hundred and thirteen patients completed the study, 107 in the losartan group and 106 in the amlodipine group. After 12 months the SBP/DBP mean values were significantly reduced by both losartan (from 151.4/95.6 to 135.5/83.7 mm Hg, P < 0.001 versus baseline) and amlodipine (from 152.3/96.5 to 135.2/83.4 mm Hg, P < 0.001 versus baseline), with no difference between the two treatments. At least one ECG-documented episode of atrial fibrillation was reported in 13% of the patients treated with losartan and in 39% of the patients treated with amlodipine. The use of losartan in combination with amiodarone seems more effective than amlodipine/amiodarone combination in preventing new episodes of atrial fibrillation in hypertensive patients with recurrent atrial fibrillation. This might be related to possible favorable impact of angiotensin II receptor blockers (ARB) on the atrial electrical and structural remodeling in this type of patients.

Effect of successful hypertension control by manidipine or lisinopril on albuminuria and left ventricular mass in diabetic hypertensive patients with microalbuminuria.

OBJECTIVE: The aim of this open-labelled, randomised, parallel-group study was to evaluate the effect of long-term monotherapy with manidipine or lisinopril on albumin excretion rate (AER) and left ventricular mass index (LVMI) in hypertensive patients with type-2 diabetes and microalbuminuria. METHODS: After a 4-week wash-out period, 174 patients with essential hypertension [diastolic blood pressure (DBP) >80 mmHg and <100 mmHg], type-2 diabetes and microalbuminuria were randomised to manidipine 10 mg o.d. or lisinopril 10 mg o.d.; after 8 weeks, the dose was doubled in non-responders (DBP >80 mmHg); after 3 months, treatment was discontinued in the non-responder patients and in those complaining of side effects; the remaining 121 patients continued their therapy with manidipine or lisinopril, and 99 completed the 2-year study. At the end of the wash-out period, of the titration period and after 6, 12, 18 and 24 months of treatment, BP was measured, AER, creatinine clearance, glycosylated haemoglobin (HbA1c) and body mass index (BMI) were evaluated and an echocardiographic evaluation was performed. RESULTS: The 99 patients who completed the study were statistically analysed according to a per-protocol evaluation. Manidipine and lisinopril significantly reduced systolic blood pressure (SBP) and DBP levels (at 24 months, --22.3/15.5 mmHg, P<0.001 versus baseline and --21.4/15.7 mmHg, P<0.01 versus baseline, respectively). Both drugs provided a significant decrease in AER, but it was significantly more pronounced with lisinopril (at 24 weeks, --37.2 mg/24 h, P<0.001 versus baseline) than with manidipine (--29.9 mg/24 h, P<0.05 versus baseline) and became evident earlier in the lisinopril group (after 3 months versus 6 months of treatment). Manidipine produced a greater reduction of LVMI than lisinopril (--14.9 g/m(2) versus --10.8 g/m(2) at 24 months). The effect was more pronounced in patients with left ventricular hypertrophy at baseline (--19.8 g/m(2) versus --12.8 g/m(2), P<0.05). CONCLUSION: These data suggest that, despite similar BP lowering, non-haemodynamic factors play an important role in the pharmacological reduction of AER and LVMI in diabetic hypertensive patients.

Comparative efficacy of valsartan and olmesartan in mild-to-moderate hypertension: results of 24-hour ambulatory blood pressure monitoring.

The aim of this prospective, randomized, open-label, blinded endpoint (PROBE) study was to compare the antihypertensive efficacy of 2 angiotensin II (AII) receptor antagonists with different pharmacologic profiles, valsartan and olmesartan, in patients with mild-to-moderate essential hypertension. After an initial 2-week washout period, 114 patients (64 men, 50 women; aged 35-70 years) were randomly assigned to receive valsartan 160 mg or olmesartan 20 mg once daily for 8 weeks. After the washout period and after 2 and 8 weeks of treatment, 24-hour ambulatory blood pressure monitoring (ABPM) was performed using a noninvasive device, and casual blood pressure (BP) and heart rate were measured. Both olmesartan and valsartan had a clear-cut antihypertensive effect. However, significantly earlier and more pronounced antihypertensive activity was achieved with valsartan than with olmesartan, as demonstrated by (1) significantly lower 24-hour, daytime, and nighttime ABPM values after 2 weeks with valsartan (P<.01); (2) significantly lower percentage of abnormal BP readings with valsartan; (3) significantly higher trough-peak ratio and smoothness index with valsartan, suggesting a more prolonged and homogeneous antihypertensive effect; and (4) lower 24-hour postdose clinic systolic and diastolic BP values versus olmesartan. These findings show that pharmacodynamic and pharmacokinetic differences between AII receptor antagonists, at clinically comparable dosages, may be associated with differences in antihypertensive efficacy.