Maurizio Destro

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 telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients

The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide (HCTZ) vs lisinopril/HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. A total of 160 patients, 76 men and 84 women, aged 61–75 years, with sitting diastolic blood pressure (DBP) >90 mmHg and <110 mmHg and systolic blood pressure (SBP) >140 mmHg were randomized to receive temisartan 80 mg/HCTZ 12.5 mg o.d. or lisinopril 20 mg/HCTZ 12.5 mg o.d. for 24 weeks, according to a prospective, open-label, blinded end point, parallel-group design. At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed and cognitive function was evaluated through six different tests (verbal fluency, Boston naming test, word-list memory, word-list recall, word-list recognition and Trails B). Both treatments significantly reduced ambulatory BP. However, the telmisartan/HCTZ combination produced a greater reduction in 24-h, day-time and night time ABPM values. Lisinopril/HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study, whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score (+17.1 and +15.7%, respectively, P<0.05 vs baseline), the word-list recall score (+13.5 and +16.9%, P<0.05) and the Trails B score (−33 and −30.5%, P<0.05). These results suggest that in elderly hypertensive patients treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP than lisinopril/HCTZ combination and, unlike this latter, improves some of the components of cognitive function, particularly episodic memory and visuospatial abilities.

Effect of Benazepril plus Amlodipine vs Benazepril Alone on Urinary Albumin Excretion in Hypertensive Patients with Type II Diabetes and Microalbuminuria

SummaryTo compare the effect of the combination of benazepril and amlodipine on urinary albumin excretion (UAE) with that of benazepril alone, 45 patients with hypertension and type II (non-insulin-dependent) diabetes mellitus and microalbuminuria were randomised to receive benazepril 10mg plus amlodipine 5mg once daily, or benazepril monotherapy (10mg once daily), for 6 months. Before and after 3 and 6 months of therapy, sitting blood pressure and heart rate, bodyweight, UAE, plasma creatinine and creatinine clearance, glycosylated haemoglobin and plasma levels of glucose, electrolytes, uric acid and nitrogen were evaluated. Both benazepril alone and benazepril plus amlodipine significantly reduced blood pressure values without affecting heart rate and glucose homeostasis, but combination therapy was more effective in lowering both systolic and diastolic blood pressure. At 3 months, there was a similar reduction in UAE in the patients treated with benazepril alone and in those treated with benazepril plus amlodipine, but at 6 months UAE tended to show a greater decrease with the combination (−24.6%, p < 0.02) than with monotherapy (−19.7%, p < 0.04). Creatinine clearance significantly increased during combination therapy (p < 0.02), but was unchanged during benazepril monotherapy.In conclusion, compared with benazepril monotherapy, benazepril plus amlodipine tended to produce a greater reduction in UAE, and increased creatinine clearance.

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 telmisartans 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.

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 All receptor antagonists, at clinically comparable dosages, may be associated with differences in anti hypertensive efficacy.

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.

Hydrochlorothiazide added to valsartan is more effective than when added to olmesartan in reducing blood pressure in moderately hypertensive patients inadequately controlled by monotherapy

This study was undertaken to evaluate the effects on blood pressure of hydrochlorothiazide (HCTZ) 12.5 mg added to valsartan 160 mg or to olmesartan 20 mg in hypertensive patients. After a 2-wk placebo period, 130 patients, aged 35 to 75 y, with diastolic blood pressure (DBP) ≥99 and <110 mm Hg were randomly assigned to olmesartan 20 mg once daily or to valsartan 160 mg once daily according to a prospective, parallel-arm study design. After 4 wk of monotherapy, patients whose BP was not controlled (DBP ≥90 mm Hg) were given combination treatment with HCTZ 12.5 mg for an additional 4 wk. At the end of the placebo period and at the end of each treatment period, clinical and ambulatory BP measurements were recorded. At the end of the combination therapy period, venous blood samples were drawn 2, 4, and 24 h after drug intake for evaluation of HCTZ plasma concentrations. Both combinations induced a greater ambulatory BP reduction than monotherapy. However, mean reduction from baseline in the valsartan/HCTZ-treated patients (-21.5/-14.6 mm Hg for 24 h, -21.8/-14.9 mm Hg for daytime, and -20.4/-13.7 mm Hg for nighttime systolic blood pressure [SBP]/DBP) was greater than in the olmesartan/HCTZ-treated patients (-18.8/-12.3 mm Hg for 24 h, -19.3/-12.8 mm Hg for daytime, and -17.4/-10.6 mm Hg for nighttime SBP/DBP). The difference between the effects of the 2 treatments was significant (P<.01). In particular, compared with monotherapy, the add-on effect of HCTZ 12.5 mg was significantly greater in the valsartan group than in those treated with olmesartan; the difference was more evident for nighttime BP values. Plasma concentrations of HCTZ were significantly greater with valsartan than with olmesartan at each determination time (P<.05). These findings suggest that the addition of HCTZ 12.5 mg to valsartan 160 mg monotherapy produces a greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 mg monotherapy.

Effects of Amlodipine vs Enalapril on Microalbuminuria in Hypertensive Patients with Type II Diabetes

SummaryThe effects of once-daily amlodipine 10mg or enalapril 20mg on urinary albumin excretion (UAE) were evaluated over 12 months, in a randomised trial of 50 hypertensive patients with type II (non-insulin-dependent) diabetes mellitus and microalbuminuria. Both drugs significantly reduced systolic and diastolic blood pressure without affecting heart rate or glucose homeostasis. UAE was significantly reduced after 3 months of treatment with enalapril, and 6 months of therapy with amlodipine. The percentage reduction in UAE significantly correlated with the decrement in systolic blood pressure and duration of hypertension in both treatment groups. Creatinine clearance was unaffected by enalapril, but was significantly increased by amlodipine. Long term treatment with either amlodipine or enalapril was therefore effective in reducing UAE in hypertensive patients with type II diabetes and microalbuminuria.

Losartan and amlodipine on myocardial structure and function: a prospective, randomized, clinical trial

Diabet. Med. (2011) 29, 24–31 (2012)