Differential effects of angiotensin II receptor blocker and losartan/hydrochlorothiazide combination on central blood pressure and augmentation index

Abstract

Central systolic blood pressure (CSBP) may be a better predictor of cardiovascular risk than clinic brachial (B)SBP. The effects of dose increment from medium dose of angiotensin II receptor blockers (ARBs) to the maximum dose of ARBs (maximum) and changing from medium dose of ARBs to losartan 50?mg/hydrochlorothiazide 12.5?mg combination (combination) were compared in hypertensive patients in whom monotherapy with a medium ARB dose did not achieve goal home SBP (135?mmHg). Four weeks after treatment with a medium ARB dose monotherapy, those whose home SBP level was above 135?mmHg were randomized to receive the maximum ARB dose (n?=?101) or the combination (n?=?99) once daily for 8 weeks. Both regimens significantly decreased BSBP and CSBP, while a decrease in BSBP and CSBP was greater with combination. The maximum significantly decreased augmentation index (AIx), while the combination did not. The rate of a decrease in reflection to decrease in CSBP was greater in the maximum than in the combination. In the elderly subgroup, the combination more effectively lowered BSBP than the maximum, and only the combination decreased CSBP. However, in the young subgroup, the maximum decreased AIx more than combination, while both regimens lowered CSBP and BSBP to a similar extent. It is explained in part that the maximum may affect pulse wave reflection more predominantly than the combination, especially in young subjects. A weak effect on pulse wave reflection and, thus, on CSBP, of the combination may be overcome by the potent antihypertensive effect of this regimen.     

The importance of early antihypertensive efficacy: the role of angiotensin II receptor blocker therapy

Desirable features of antihypertensive agents include efficacy, tolerability, prolonged duration of action and rapid achievement of target blood pressure (BP). Recent studies have examined the relationship between the onset of antihypertensive effect and cardiovascular events. Data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE), the Study on Cognition and Prognosis in the Elderly (SCOPE), and the Systolic Hypertension in Europe (Syst-Eur) trials support the hypothesis that the time it takes to reach target BP influences cardiovascular outcomes. VALUE, which compared BP-lowering and clinical event rates between patients treated with the angiotensin II receptor blocker (ARB) valsartan or the calcium channel blocker (CCB) amlodipine as well as between those who achieved immediate or delayed BP control, provides the strongest evidence of this to date. Additional data from SCOPE and Syst-Eur suggest that delays of 3 months to 2 years in starting antihypertensive therapy can increase the risk of certain cardiovascular end points, especially stroke. These data suggest that it may be beneficial to examine the efficacy of antihypertensive agents, not only long term, but also at earlier times to assess the onset and impact of early antihypertensive effect. The ARB olmesartan medoxomil (olmesartan) and the CCB amlodipine were compared in a randomized, double-blind, placebo-controlled clinical trial, which demonstrated that the onset of antihypertensive effect of olmesartan is comparable with that of amlodipine. Another study demonstrated that more patients treated with olmesartan achieved target BPs within 2 weeks of treatment compared with the ARBs losartan, valsartan and irbesartan.     

Beneficial effect of angiotensin II type 1 receptor blocker antihypertensive treatment on arterial stiffness: the role of smoking

The purpose of the present study was to assess angiotensin receptor blocker (ARB) treatment on arterial stiffness in select hypertensive patients and define possible differences between smokers and nonsmokers. The authors evaluated 81 consecutive, nondiabetic patients (mean age, 52 years; 47 men) with uncomplicated essential hypertension with high plasma renin activity who were administered monotherapy with irbesartan, an ARB, at maximal dose. Patients were divided into smokers (n=24) and nonsmokers (n=57). Carotid-radial pulse wave velocity (PWVc-r), carotid-femoral pulse wave velocity (PWVc-f), and augmentation index (AIx) were measured before and 6 months after ARB antihypertensive treatment. All mean values of elastic effect indices were decreased after irbesartan monotherapy (AIx, from 26.3%to 21.2% [P<.01;] PWVc-f, from 7.7 m/s to 7.3 m/s [P<.05], and PWVc-r, from 8.9 m/s to 8.3 m/s [P<.001]). When comparing smokers vs nonsmokers, no difference was noted in AIx and PWVc-f change (P=not significant), while PWVc-r change was greater in smokers compared with nonsmokers (P<.05). Chronic ARB treatment may favorably affect arterial stiffness and wave reflections in hypertensive chronic smokers with elevated plasma renin levels.     

Beneficial effects of angiotensin II type 1 receptor blocker antihypertensive treatment on inflammation indices: the effect of smoking

The effect of long-term angiotensin II type 1 receptor blocker (ARB) therapy on inflammation indices has not been fully investigated in a hypertensive population. The authors evaluated 323 consecutive nondiabetic patients (mean age, 57 years; 176 men; 92 smokers) with high renin activity and uncomplicated essential hypertension whose blood pressure levels normalized (from 163.9/100.7 mm Hg to 131.6/82.8 mm Hg) after 4 weeks of ARB or ARB/diuretic treatment. All patients underwent full laboratory evaluation (routine examination of blood and urine, liver, kidney, thyroid function, and lipid and glucose profiles), including measurement of high-sensitivity C-reactive protein and serum amyloid A levels, at drug-free baseline, which was repeated after 6 months of ARB or ARB/diuretic treatment. A significant (P<.001) overall decrease was noted in both high-sensitivity C-reactive protein (-0.41+/-1.56 mg/dL) and serum amyloid A (-0.62+/-2.03 mg/dL), but a smaller decrease in high-sensitivity C-reactive protein and serum amyloid A change was seen in the smoker subgroup compared with nonsmokers (P<.05), indicating that the ARB or ARB/diuretic anti-inflammatory effect may be adversely affected by smoking status.     

Genomic association analysis identifies multiple loci influencing antihypertensive response to an angiotensin II receptor blocker

To identify genes influencing blood pressure response to an angiotensin II receptor blocker, single nucleotide polymorphisms identified by genome-wide association analysis of the response to candesartan were validated by opposite direction associations with the response to a thiazide diuretic, hydrochlorothiazide. We sampled 198 white and 193 blacks with primary hypertension from opposite tertiles of the race-sex-specific distributions of age-adjusted diastolic blood pressure response to candesartan. There were 285 polymorphisms associated with the response to candesartan at P<10(-4) in whites. A total of 273 of the 285 polymorphisms, which were available for analysis in a separate sample of 196 whites, validated for opposite direction associations with the response to hydrochlorothiazide (Fisher χ(2) 1-sided P=0.02). Among the 273 polymorphisms, those in the chromosome 11q21 region were the most significantly associated with response to candesartan in whites (eg, rs11020821 near FUT4, P=8.98 × 10(-7)), had the strongest opposite direction associations with response to hydrochlorothiazide (eg, rs3758785 in GPR83, P=7.10 × 10(-3)), and had the same direction associations with response to candesartan in the 193 blacks (eg, rs16924603 near FUT4, P=1.52 × 10(-2)). Also notable among the 273 polymorphisms was rs11649420 on chromosome 16 in the amiloride-sensitive sodium channel subunit SCNN1G involved in mediating renal sodium reabsorption and maintaining blood pressure when the renin-angiotensin system is inhibited by candesartan. These results support the use of genomewide association analyses to identify novel genes predictive of opposite direction associations with blood pressure responses to inhibitors of the renin-angiotensin and renal sodium transport systems.     

Beneficial effect of switching from a combination of angiotensin II receptor blockers other than losartan and thiazides to a fixed dose of losartan/hydrochlorothiazide on uric acid metabolism in hypertensive patients

Among the angiotensin II receptor blockers (ARBs), losartan (LOS) has uricosuric action. The clinical benefits of LOS compared with those of other ARBs may be apparent when it is combined with diuretics, which have an unfavorable influence on serum uric acid (SUA). The effects of switching from combinations of ARBs other than LOS and thiazides to a fixed-dose combination comprising 50 mg LOS and 12.5 mg hydrochlorothiazide on blood pressure (BP), SUA, percent fractional excretion of UA (FEUA), and urine pH were assessed in 57 hypertensive outpatients. A significant reduction in BP was observed after 6 months (P < .01). The switching therapy significantly decreased SUA level (6.0 ± 1.3 vs. 5.7 ± 1.3 mg/dL, P < .01), which was accompanied by increases in FEUA (P < .01) and urine pH (P < .01). The change in SUA was negatively correlated with the changes in FEUA (P < .004) and estimated glomerular filtration rate (P < .05). The change in FEUA was positively correlated with the changes in urine pH (P < .05) but not with BP or estimated glomerular filtration rate. In a separate group of patients treated with ARBs other than LOS (n = 82), a significant BP reduction was observed, but no change in SUA or FEUA was observed. In conclusion, switching therapy decreased SUA level, which was accompanied by an increase in FEUA. This result may depend on the balance between LOS-induced inhibitory action of urate transporter 1 and hydrochlorothiazide-induced plasma volume reduction. The increase in urine pH plays a role in UA urinary excretion.     

Combination angiotensin receptor blocker/hydrochlorothiazide as initial therapy in the treatment of patients with severe hypertension

Patients with severe hypertension are at high risk for cardiovascular events. The authors hypothesized that initial treatment with a combination angiotensin receptor blocker/diuretic agent would be safe and more effective than initial treatment with a single agent for these patients. In this 6-week, double-blind trial, 585 patients were randomized to losartan/hydrochlorothiazide or losartan as monotherapy and titrated as needed at 2-week intervals to reach goal blood pressure (<90 mm Hg). Almost twice as many patients achieved goal at the primary end point of 4 weeks on 50 mg losartan/12.5 mg hydrochlorothiazide vs. the losartan regimen (50-100 mg; p=0.002). Additionally, almost three times as many patients achieved goal blood pressures at 6 weeks (p<0.001). Adverse experiences on losartan/hydrochlorothiazide (43%) were significantly less than with the angiotensin receptor blocker alone (52.6%). This study confirmed the efficacy and tolerability of initial use of a fixed combination of losartan/hydrochlorothiazide vs. losartan without a thiazide.     

The angiotensin II type 1 receptor blocker valsartan attenuates graft vasculopathy

Objective Transplant arteriosclerosis remains the major cause of graft failure after cardiac transplantation. Here, we investigated the effects of the angiotensin II type 1 receptor blocker valsartan on the development of transplant arteriosclerosis in a murine model of cardiac transplantation. Methods Hearts from DBA/2 (H–2^d) mice were heterotopically transplanted into B10.D2 (H–2^d) mice. Recipients were treated with oral administration of valsartan (10 mg/kg/day) or vehicle. Results Morphometrical analysis of the cardiac allografts harvested at 30 days revealed that valsartan significantly reduced the development of coronary atherosclerosis (intima/media ratio: 0.39 ± 0.05 vs. 0.66 ± 0.08, P < 0.01). At two weeks after transplantation, there was no significant difference between the two groups in expression of adhesion molecules and cytokines. Valsartan significantly reduced the number of peripheral mononuclear cells that differentiated into smooth muscle–like cells in the presence of basic fibroblast growth factor and platelet–derived growth factor BB (18.0 ± 1.5 vs. 30.3 ± 4.4 cells/HPF, P = 0.01). Conclusions These results suggest that angiotensin II plays a role in the pathogenesis of transplant arteriosclerosis and that blockade of angiotensin II type 1 receptor might be effective as a prophylactic therapy for transplant arteriosclerosis along with conventional immunosuppressive drugs.     

An experience of the use of angiotensin II receptor blocker losartan in patients with metabolic syndrome and chronic kidney disease

Aim of the study--to assess efficacy and safety of one of angiotensin II receptor blockers in patients with metabolic syndrome (MS) and I-V stage chronic kidney disease. We studied cardiodynamic and renal effects of losartan in average daily dose 50 +/- 13.06 mg in 20 patients (9 men and 11 women aged 32-79 years) with MS and I-V stage chronic kidney disease. Cardiodynamic effects of losartan were assessed by office blood pressure (BP) measurements, 24-hour BP monitoring (24-HBPM), echocardiography. Laboratory investigations included biochemical analysis of the blood with measurement of creatinine levels, lipid blood composition, fasting glucose, and glucose under conditions of oral glucose tolerance test. Renal function was assessed by glomerular filtration rate and microalbuminuria (MAU). Parameters of quality of life were analyzed with the use of questionnaires "Quality of life of patients with hypertensive disease" and EuroQol EQ-5D VAS thermometer. Duration of follow up was 12 weeks. 24-HBPM revealed significant lowering of systolic and diastolic BP in all temporal intervals, significant decrease of elevated diurnal systolic and diastolic BP burden, tendency to lowering of variability and normalization of 24-hour BP profile. We also noted tendency to lowering of MAU from 5.60 mg/dl (median) (3.50; 9.20 [25th and 75th percentile]) to 3.25 mg/dl (0.40; 7.83); significant lowering of levels of triglycerides and glucose under conditions of glucose tolerance test; improvement of parameters characterizing quality of life namely reduction of integral assessment by the "Quality of life of patients with hypertensive disease" questionnaire and improvement of EQ-5D VAS (thermometer) score related to arterial hypertension. We conclude that losartan in patients with MS and early signs of impairment of kidney function in addition to antihypertensive action exerts favorable effect on parameters of 24-hour BP profile, has good safety profile, causes favorable metabolic effects, lowers level of MAU and improves parameters of quality of life.     

Azilsartan: a newly approved angiotensin II receptor blocker

Hypertension is a common chronic disease that leads to significant cardiovascular morbidity and mortality. Blood pressure control is essential to prevent end-organ complications, such as stroke, myocardial infarction, heart failure, or kidney disease. Azilsartan is the eighth angiotensin II receptor blocker approved for the management of hypertension, alone or in combination with other agents. At the approved dosage, it reduces systolic blood pressure by 12 to 15 mm Hg and diastolic blood pressure by 7 to 8 mm Hg. A higher dose of azilsartan (80 mg) was superior to valsartan 320 mg or olmesartan 40 mg in lowering systolic blood pressure in short-term studies. Additional blood pressure reduction is expected when azilsartan is used adjunctively with a diuretic. However, the effects of azilsartan on cardiovascular morbidity or mortality are still lacking. Azilsartan is well tolerated; the most common side effects are headache and diarrhea. No cases of hyperkalemia have been reported in 6-week clinical trials. Worsening of renal function and hypotension should be monitored, particularly in those with baseline risk factors. It is unknown whether azilsartan would join angiotensin-converting enzyme inhibitors and other angiotensin receptor blockers as the preferred hypertensive agents for end-organ protection. At this time, azilsartan should be considered as an alternative agent for mild-to-moderate hypertension, or as an adjunctive therapy when preferred agents fail to maintain optimal blood pressure control. It is also an option for those patients who have contraindications or cannot tolerate other antihypertensive agents, including dry cough induced by angiotensin-converting enzyme inhibitors.     

Significance of angiotensin II receptor blocker lipophilicities and their protective effect against vascular remodeling.

Although the lipophilicities of the various angiotensin II receptor blockers (ARBs) are very different, the relationship between lipophilicity and the protective effect against vascular remodeling is unclear. In this study, we compared the protective effects of a highly lipophilic ARB, telmisartan, and an ARB with low lipophilicity, losartan, on vascular function and oxidative stress in stroke-prone spontaneously hypertensive rats (SHR-SP). SHR-SP received oral placebo, 1 mg/kg telmisartan, or 10 mg/kg losartan for 2 weeks. The blood pressure (BP) in SHR-SP was significantly higher than that in Wistar-Kyoto (WKY) rats before treatment, and the BP was reduced equally in telmisartan- and losartan-treated SHR-SP compared to placebo-treated SHR-SP. Acetylcholine-induced vasorelaxation in isolated carotid arteries was significantly weaker in SHR-SP than in WKY rats, but in both telmisartan- and losartan-treated SHR-SP, acetylcholine-induced vasorelaxation was significantly higher than in placebo-treated SHR-SP. Moreover, acetylcholine-induced vasorelaxation in telmisartan-treated rats was significantly stronger than in losartan-treated SHR-SP. The expression of the endothelial nitric oxide synthase gene was significantly higher in telmisartan- and losartan-treated rats than in placebo-treated SHR-SP, and was significantly higher in telmisartan-treated rats than in losartan-treated rats. In contrast, the expression of the NAD(P)H oxidase subunit p22phox gene in telmisartan-treated SHR-SP was significantly lower than that in losartan-treated SHR-SP. Immunohistochemistry showed that angiotensin II expression in the aorta was significantly lower in telmisartan-treated SHR-SP than in losartan-treated SHR-SP. In conclusion, a highly lipophilic ARB, telmisartan, may be useful for preventing NAD(P)H oxidase activity, and thereby for conferring vascular protection.     

Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients

OBJECTIVES: We investigated the vascular effects of candesartan in hypertensive patients. BACKGROUND: The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The plausible mechanisms are that angiotensin II promotes superoxide anion generation, endothelial dysfunction, inflammation, and impaired fibrinolysis. The effects of candesartan on these conditions have not been clearly observed. METHODS: We administered placebo or candesartan 16 mg daily during two months to 45 patients with mild-to-moderate hypertension. This was a randomized, double-blind, placebo-controlled, crossover study in design. RESULTS: Candesartan did not significantly change lipoprotein levels. However, compared with placebo, candesartan significantly reduced plasma levels of malondialdehyde from 1.50 +/- 0.07 to 1.29 +/- 0.09 microM (p = 0.009); improved the percent flow-mediated dilator response to hyperemia from 5.17 +/- 0.24 to 6.22 +/- 0.26% (p < 0.001); and, furthermore, reduced plasma levels of monocyte chemoattractant protein (MCP-1) from 213 +/- 8 to 190 +/- 7 pg/ml (p = 0.003), tumor necrosis factor-alpha from 2.93 to 2.22 pg/ml (p = 0.026), and plasminogen activator inhibitor type 1 from 74 +/- 4 to 53 +/- 4 ng/ml (p < 0.001) but not C-reactive protein (CRP), matrix metalloproteinase protein, and fibrinogen. There were no significant correlations between these changes and reduction of systolic blood pressure (BP) (-0.247 < or = r < or = 0.195) and between these changes and reduction of diastolic BP (-0.262 < or = r < or = 0.197). There were no significant correlations between markers of inflammation and flow-mediated dilation percent or reduction of oxidant stress (-0.119 < or = r < or = 0.127). Furthermore, we observed no significant correlations between CRP and MCP-1 levels (r = -0.162). CONCLUSIONS: Inhibition of the angiotensin II type 1 (AT1) receptor in hypertensive patients reverses endothelial dysfunction, measured as an improvement in flow-mediated dilation and fibrinolysis and reduction of oxidant stress and inflammatory cytokines, suggesting that AT1 receptor blocker therapy has antiatherogenic effects.     

Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.     

Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial

Traditional randomized controlled clinical trials are designed to define the specific properties of individual antihypertensive drugs but do not provide full information about their use in clinical practice. To carry out a large-scale practice-based open-label trial to evaluate the safety and efficacy of an angiotensin receptor blocker (ARB) in controlling blood pressure (BP) in the community setting, 703 practitioners recruited 2705 hypertensive patients. There were three groups: untreated at the time of study entry with uncontrolled BP (>/=140/90 mm Hg) (N = 1957); treated but uncontrolled on current monotherapy (N = 685); and treated and controlled, but with unacceptable side effects (N = 63). After stopping any previous treatment, patients received telmisartan (40 mg daily) for 2 weeks; the dose was increased to 80 mg if BP remained >/=130/85 mm Hg. Participants were then followed for a further 4 weeks. Blood pressure decreased by 18.9/12.3 mm Hg in the untreated group, by 13.1/7.9 mm Hg in the previously treated but uncontrolled group, and increased slightly by 3.5/1.3 mm Hg in the previously controlled group. Patients not responding adequately to the 40-mg telmisartan dose had an initial BP reduction of 7.3/4.5 mm Hg; titration to 80 mg gave an additional 7.5/5.0 mm Hg reduction and controlled BP (<140/90 mm Hg) in 44% of these titrated patients. Overall, control occurred in 56% of white patients; 52% of black patients (who responded well to dose titration); 60% of patients <65 years; and 46% of patients >/=65 years. Thus, in contrast with the relatively flat dose response effects in controlled parallel group trials, this practice-based trial has demonstrated the value of titrating telmisartan to its maximum dose in patients with inadequate BP responses to the initial dose, and has shown its efficacy across major demographic groups.     

Role of the angiotensin II receptor blocker valsartan in heart failure

Despite an enormous amount of research carried out in the past 10 to 20 years, the role of the renin-angiotensin system in the development of heart failure is still not very well understood. This review looks at preclinical data on the role of angiotensin II as a circulating and local hormone, and the effects of stimulation of the respective receptors in heart tissue. Recent large scale clinical trials have begun to furnish evidence of the effects of blocking the renin-angiotensin system in patients with heart failure using angiotensin-converting enzyme inhibitors or, more recently, angiotensin II receptor blockers that act directly at the receptor level, independent of pathways for angiotensin II generation. Results so far indicate that there are benefits from optimizing the blockade, but open questions remain, such as the role of endothelin and bradykinins, and the extent of crosstalk between the different systems.     

First dose hypotension after angiotensin converting enzyme inhibitor captopril and angiotensin II blocker losartan in patients with acute myocardial infarction

BACKGROUND: First dose hypotension after the administration of an angiotensin-converting enzyme inhibitor in patients with acute myocardial infarction is one of the most important adverse events of this type of treatment. There is no information about first dose hypotension after angiotensin type 1-receptor blocker in this type of patient. Aim: To compare the first dose responses to low dose captopril and losartan in patients with acute myocardial infarction. METHODS: Single blind, randomised, multicentric, prospective study. Patients (n=320) with confirmed acute myocardial infarction, age >18 years, treated by direct percutaneous transluminal coronary angioplasty, thrombolysis and/or heparin, were randomised to receive a single dose of 6.25-12.5 mg captopril or 12.5-25 mg losartan within 24 h of hospital admission. Baseline laboratory and clinical examinations were performed before entering the study. Blood pressure monitoring started at hospital admission and continued for at least 8 h after the medication (second dose of captopril was given after 8 h). RESULTS: The maximal blood pressure fall appeared about 1 h after the first dose of captopril and 3.5 h after the first dose of losartan. Patients in the captopril group had significantly higher incidence of asymptomatic hypotension (38%) than patients treated with losartan (24%) (P<0.001). No difference in hypotension requiring a change in medication was observed. CONCLUSION: Low dose of losartan is safe for initiating therapy in patients with acute myocardial infarction within 24 h of hospital admission.     

ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension.

The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week, multinational, multicentre, randomised, double-blind, double-dummy, parallel-group study of 223 patients with mild-to-moderate hypertension, defined as clinic diastolic blood pressure (DBP) >/=95 and /=140 and /=85 mm Hg. After a 4-week single-blind placebo run-in, eligible patients were randomised to receive telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebo. Ambulatory blood pressure monitoring (ABPM) after 6 weeks of double-blind therapy showed that all active treatments produced significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placebo. During the 18-to-24 h period after dosing, the reductions in SBP/DBP with telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those observed for losartan 50 mg (6.0/3.7 mm Hg), and losartan was no better than placebo. Also for the 24-h mean blood pressure, telmisartan 40 mg and 80 mg were significantly (P< 0.05) better than losartan 50 mg. Compared with losartan, telmisartan 80 mg produced significantly (P < 0.05) greater reductions in both SBP and DBP during all monitored periods of the 24-h period, while telmisartan 40 mg produced significantly greater reductions in SBP and DBP in the night-time period (10.01 pm to 5.59 am) (P < 0.05) and in DBP in the morning period (6.00 am to 11.59 am) (P < 0.05). All treatments were comparably well tolerated. Telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension, producing sustained 24-h blood pressure control which compared favourably with losartan.