enalapril and eprosartan

Eprosartan is an angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) used in the treatment of hypertension. In large, randomized trials, eprosartan (with or without hydrochlorothiazide [HCTZ]) demonstrated superior antihypertensive efficacy to that of placebo and, when administered at comparable dosage regimens, had similar blood pressure-lowering effects to enalapril. Eprosartan was generally well tolerated in clinical trials and had a lower incidence of persistent dry cough than enalapril. Eprosartan has a neutral effect on metabolic parameters, such as serum lipid levels and glucose homeostasis, and a low propensity for pharmacokinetic drug interactions. The use of eprosartan or other ARBs in combination with HCTZ tends to reverse the potassium loss associated with thiazide diuretics. Independent of its antihypertensive effects, eprosartan was associated with improved clinical outcomes (primary composite endpoint of all causes of mortality and all cardiovascular and cerebrovascular events, including all recurrent events) compared with nitrendipine in a randomized, secondary prevention trial in hypertensive patients with previous cerebrovascular events (MOSES trial). Eprosartan also reduced blood pressure and was associated with a modest improvement in cognitive function in a large observational study in patients > or =50 years of age with newly diagnosed hypertension (OSCAR study). In both of these trials, additional antihypertensive therapy, such as HCTZ, was permitted. Therefore, eprosartan is a useful treatment option in the management of a broad range of patients with hypertension, and its use with HCTZ provides a rational combination regimen.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Clinical Trials as Topic; Cough; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Incidence; Nitrendipine; Randomized Controlled Trials as Topic; Receptors, Angiotensin; Recurrence; Risk Factors; Sodium Chloride Symporter Inhibitors; Thiophenes; Treatment Outcome

Hypertension means a basic public health problem in many countries in the world. The therapeutic attempts of the last years did not fulfill the hopes pinned on them, and most of the patients live with blood pressure above the goal value. This is why there is a need for new, more efficient antihypertensive drugs. On the 1st of July, 2001 irbesartan (Aprovel) was introduced in practice in Hungary. The drug belongs to the family of the angiotensin II receptor inhibitors. Several clinical studies were made with irbesartan in order to evaluate its efficiency, tolerability and safety. In other studies it was compared with other antihypertensive treatments and it was found that irbesartan decreases the systolic and diastolic blood pressure as effectively as other first line medicaments. The author summarizes the most important characteristics of irbesartan as well as the results of those clinical studies which show evidence that irbesartan deserves a special place among antihypertensive drugs.

Topics: Acrylates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Atenolol; Benzimidazoles; Benzoates; Biological Availability; Biphenyl Compounds; Controlled Clinical Trials as Topic; Drug Administration Schedule; Enalapril; Half-Life; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Telmisartan; Tetrazoles; Thiophenes; Valine; Valsartan

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor antagonists have received increased therapeutic recognition in the treatment of hypertension. Although the overall effects of the ACE inhibitors and AT1 receptor antagonists may seem superficially similar, there are important differences between the two classes in terms of neurohumoral activation, concomitant bradykinin potentiation, and inhibition of angiotensin II, derived not only from the classical ACE pathway, but also from alternative pathways. The AT1 receptor antagonist eprosartan has been shown to lower blood pressure effectively in hypertensive patients. When taken in the recommended dose range, 600-800 mg once daily, eprosartan is effective in patients with all grades of hypertension, regardless of age, sex or race. In several clinical studies, the blood-pressure-lowering effect of eprosartan has been shown to be at least as great as that of the ACE inhibitor enalapril. With respect to tolerability, eprosartan is superior to ACE inhibitor therapy and comparable to placebo. The pharmacological and therapeutic profiles of the expanding array of AT1 receptor antagonists differ in a number of respects. Most of these agents are biphenyl tetrazole, non-competitive antagonists, and some have active metabolites. Eprosartan differs from other AT1 receptor antagonists in that it is a non-biphenyl, non-tetrazole competitive antagonist without active metabolites. Several large-scale, ongoing clinical research programmes (e.g. LIFE, SCOPE and VALUE) are expected to provide information on the extent to which AT1 receptor antagonists, in comparison with other therapeutic regimens, reduce cardiovascular morbidity and mortality in different groups of hypertensive subjects. Meanwhile, current evidence suggests that the AT1 receptor antagonists provide a new approach to the management of hypertension and that they merit a fuller assessment in other cardiovascular diseases.

Topics: Acrylates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Enalapril; Humans; Hypertension; Imidazoles; Survival Rate; Thiophenes; Treatment Outcome

The renin-angiotensin system is the major contributor to development of hypertension, atherosclerosis, and many other cardiovascular diseases. Angiotensin II, one of the main effectors of this system, contributes to the pathogenesis of hypertension and plays an important role in monocyte, platelet, and endothelium interactions. The effects on platelet and endothelial function, either by angiotensin converting enzyme inhibitors or angiotensin receptor antagonists, are still not well understood. A double-blind, randomized, prospective trial of either enalapril (10-20 mg daily) or eprosartan (400-800 mg daily) over a 10-week period was conducted in 42 patients (27 males, 15 females). Platelet activation was evaluated by measuring platelet factor 4 (PF-4), beta-thromboglobulin (beta-TG), the ratio of platelet factor 4 to beta-thromboglobulin, and endothelial function by measuring total plasma nitrate levels, von Willebrand factor (vWF) levels, and blood flow using venous occlusive plethysmography. After a 10-week treatment with enalapril or eprosartan, the sitting blood pressure in both the enalapril group (from 152.2 +/- 18.7 mmHg to 141.9 +/- 23.5 mmHg, P < 0.05) and eprosartan group (from 151 +/- 10.0 mmHg to 142.3 +/- 12.9 mmHg, P < 0.05) was significantly reduced. Significant diastolic blood pressure (DPB) reduction (from 94 +/- 8.7 to 84.5 +/- 9.6 mmHg, P < 0.05) and a greater DBP reduction response were found in the eprosartan group (63% in eprosartan versus 25% in enalapril). Additionally, dose-dependent reductions in the indices of platelet activation and endothelial dysfunction were observed in patients administered high dose treatments of eprosartan and enalapril, and the beneficial effects of these agents were not correlated with the reduction of blood pressure using both agents. Eprosartan is effective and well-tolerated in the treatment of mid-to-moderate hypertension, and the DBP response reduction to eprosartin was better than that to enalapril. A high dose of either eprosartan or enalapril significantly decreased the indices of platelet activation and endothelial dysfunction in hypertensive patients. The benefits of both agents cannot be explained solely by their antihypertensive effects and possibly may be mediated through their unique effect on angiotensin blockade.

Topics: Acrylates; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Enalapril; Endothelium, Vascular; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Platelet Activation; Prospective Studies; Thiophenes

Asymmetrical N(G), N(G)-dimethylarginine (ADMA) is associated with impaired endothelium-dependent vasodilation in humans.. Twenty young, male, mildly hypertensive subjects were included in a randomized, double-blind, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or a combination of both drugs (10 and 300 mg/day, respectively) each over 1 week, followed by a 2-week wash-out phase. After each treatment phase, ADMA concentration was measured.. ADMA concentration was 1.69+/-0.59 micromol/L in the placebo phase, and was significantly lower in the enalapril, eprosartan, and combination phases (1.41+/-0.29, 1.42+/-0.43, and 1.38+/-0.30 micromol/L, respectively; all P < 0.05 v placebo). Changes in ADMA levels were independent of the drugs' action on blood pressure (BP).. Levels of ADMA were reduced with enalapril and eprosartan therapy. Our results suggest a specific action of these drugs on ADMA levels that is independent of BP.

Topics: Acrylates; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arginine; Blood Pressure; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Enalapril; Endothelium, Vascular; Humans; Hypertension; Imidazoles; Male; Receptor, Angiotensin, Type 1; Thiophenes

Experimental data in humans on the contribution of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers to the nitric oxide system of the renal vasculature are inconsistent. Enalapril and eprosartan, alone and in combination, were used to determine their short-term effects on the renal nitric oxide system and renal hemodynamics of human subjects with essential hypertension.. Twenty male, white patients (27 +/- 1 years) with mild essential hypertension (143 +/- 11/95 +/- 6 mm Hg) were included in a double-blind, randomized, placebo-controlled, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or combination of both drugs (10 and 300 mg/day, respectively) each over a one week period followed by a two-week washout phase. After each study phase the glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined. Basal nitric oxide synthesis of the renal vasculature was assessed by the decrease in RPF after inhibition of nitric oxide synthase with NG-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg).. After one week of therapy, the combination therapy decreased casual blood pressure by 5 +/- 2/3 +/- 1 mm Hg versus placebo (P < 0.01). Neither enalapril alone (-2 +/- 2/1 +/- 2 mm Hg, NS vs. placebo) nor eprosartan alone (-1 +/- 1/0 +/- 2 mm Hg, NS vs. placebo) had a clear-cut significant effect on casual blood pressure. In the combination phase, RPF increased by 123 +/- 36 mL/min (P < 0.01). Neither enalapril alone (+59 +/- 46 mL/min, P = 0.21) nor eprosartan alone (+113 +/- 51 mL/min, P = 0.06) had a clear-cut significant effect on RPF. Changes of RPF induced by treatment correlated with the L-NMMA induced decrease in RPF in the combination (r = 0.70, P < 0.01) and eprosartan phase (r = 0.86, P < 0.001), but not in the enalapril phase (r = -0.44, P = 0.10). Renal vascular resistance was reduced by each active treatment with the most prominent reduction in the combination phase. GFR was unaffected by any treatment.. In contrast to the effects of either substance alone, a combination of half the dose of eprosartan with half the dose of enalapril had a prominent effect on renal perfusion. The effects of eprosartan on RPF are mediated, at least in part, by an increased bioavailability of nitric oxide in the renal vasculature.

Topics: Acrylates; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Blood Vessels; Double-Blind Method; Drug Combinations; Enalapril; Enzyme Inhibitors; Hemodynamics; Humans; Hypertension; Imidazoles; Male; Nitric Oxide; omega-N-Methylarginine; Receptor, Angiotensin, Type 1; Renal Circulation; Thiophenes

The objective of this study was to compare quality of life and incidence of dry persistent cough among patients treated with eprosartan and enalapril for mild-moderate hypertension. This was a randomised 26-week double-blind controlled trial carried out in clinics in nine countries of North America, Europe and South Africa. A total of 529 patients aged 18 and over with diastolic blood pressure between 95 mm Hg and 114 mm Hg were studied. Treatment comprised of eprosartan or enalapril monotherapy for 12 weeks with the option of hydrochlorothiazide addition for the remaining 14 weeks. The primary outcome measures were cough and the Psychological General Wellbeing Index (PGWB) total and subscales (anxiety, self-control, depression, general health, positive wellbeing and vitality). The results were that 17.8% of enalapril patients and 13.2% of eprosartan patients withdrew from randomised treatment. Those on enalapril were twice as likely to have gained a definite or possible cough by study end point as those on eprosartan (7.6% vs 3.2%) P = 0.099. At monotherapy end point the differences were greater (9.9% vs 2.1%) and of statistical significance, P = 0.001. Patients treated with enalapril, however, had small but significant improvements in measures of self-control and total PGWB compared with those on eprosartan. The effect sizes of 0.2 or less indicated that there were small differences. In conclusion eprosartan was associated with fewer coughs than enalapril but it performed less well on some aspects of quality of life.

Topics: Acrylates; Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cough; Double-Blind Method; Drug Administration Schedule; Enalapril; Europe; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Incidence; Male; Middle Aged; North America; Probability; Prospective Studies; Quality of Life; Risk Factors; Severity of Illness Index; South Africa; Thiophenes; Treatment Outcome

The objective of this study was to compare the quality of life and incidence of dry cough with the angiotensin II antagonist eprosartan, the ACE-inhibitor enalapril, and placebo, in hypertensive patients with a history of ACE-inhibitor cough. The study was a multicentre, randomised, double-blind, parallel group controlled trial. A total of 136 patients judged to have ACE-inhibitor cough during single-blind enalapril treatment which was lost during a subsequent placebo washout phase, were randomised to receive either eprosartan 300 mg twice daily, or enalapril 20 mg once daily, or placebo for 6 weeks. Self-completion questionnaires assessing quality of life and cough were examined at baseline and end of study. At study end point 23% of patients in the enalapril group and 5% in the eprosartan and placebo groups reported cough (which included definite, probable and possible coughs) (P = 0.02). After adjusting for multiple comparisons, the eprosartan group was not significantly different from either placebo or enalapril. There were no significant differences in the Psychological General Wellbeing Index (PGWB). In conclusion the incidence of self-reported cough on eprosartan was similar to that on placebo, and lower than on enalapril but this difference was not significant when adjustments were made for multiple comparisons. There were no differences in quality of life.

Topics: Acrylates; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cough; Double-Blind Method; Drug Administration Schedule; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Imidazoles; Incidence; Male; Middle Aged; Probability; Quality of Life; Reference Values; Risk Assessment; Severity of Illness Index; Thiophenes; Treatment Outcome

To compare the efficacy and safety of eprosartan and enalapril to lower systolic blood pressure in elderly patients with essential hypertension.. 334 patients >65 years with sitting systolic blood pressure (sitSBP) > or = 160 mmHg and diastolic blood pressure (sitDBP) 90-114 mmHg were randomized to 12 weeks of double-blind treatment with eprosartan, 600-800 mg once daily (o.d.) or enalapril (5-20 mg o.d.), with flexible dose titration to lower systolic blood pressure below 140 mmHg. The primary outcome measure was change in sitSBP at endpoint.. Least-squares mean changes from baseline in sitSBP were -18.0 and -17.4 mmHg in the eprosartan and enalapril groups, respectively (difference eprosartan-enalapril -0.6, 95% confidence interval, CI, -4.1 to 3.0, p = 0.76). The corresponding figures for sitDBP were -9.4 and -9.6 mmHg (difference eprosartan-enalapril 0.2, 95% CI -1.7 to 2.0, p = 0.84). Normalization and response rates were also similar in the two groups. Adverse events were recorded in 61 (35.7%) patients on eprosartan (one with dry cough) and 83 (50.9%) patients on enalapril (10 with dry cough).. Eprosartan and enalapril were equally effective in reducing sitSBP and sitDBP in elderly patients with predominantly systolic hypertension. Eprosartan was better tolerated and, in particular, lacked the propensity of enalapril to cause dry cough.

Topics: Acrylates; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Imidazoles; Male; Maximum Tolerated Dose; Therapeutic Equivalency; Thiophenes; Treatment Outcome

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200-300 mg b.i.d.) or enalapril (5-20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 +/- 0.3 and a decrease in CFR in the enalapril group to 1.3 +/- 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.

Topics: Acrylates; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Coronary Circulation; Double-Blind Method; Enalapril; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Thiophenes

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the patients under and over 65 years of age recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final 6 weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). Similar mean changes in blood pressure from baseline were evident with each treatment. The elderly subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and safe in elderly hypertensive patients. The combination of eprosartan and HCTZ is also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. Compared with eprosartan enalapril was associated with an increased risk of cough. These results suggest that, irrespective of age, patients may be less likely to discontinue treatment with eprosartan than with an ACE inhibitor.

Topics: Acrylates; Age Factors; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Consumer Product Safety; Cough; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Imidazoles; Male; Thiophenes

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the effects seen on the safety profile, plasma renin activity, aldosterone and angiotensin II (A-II) in each treatment group. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final six weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, similar mean changes in blood pressure from baseline were evident with each treatment. Measurement of mean plasma neurohormone levels showed significant increases in renin activity in both groups and statistically significant A-II elevations in the eprosartan group (p < 0.05). Neither eprosartan nor enalapril significantly altered serum lipid profiles or electrolyte levels. Most adverse experiences reported throughout the study were mild or moderate in both treatment groups. Fewer patients receiving eprosartan (4.9%) than enalapril (9.1%) discontinued treatment because of adverse experiences. In conclusion, the results of this study show that eprosartan is well tolerated. Both eprosartan and enalapril significantly increased plasma renin activity while plasma A-II was elevated in the eprosartan group.

Topics: Acrylates; Adult; Aged; Aged, 80 and over; Aldosterone; Analysis of Variance; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Consumer Product Safety; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Renin; Thiophenes

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the 40 black patients recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final six weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). This trend was reflected in the black subgroup but the numbers were too small to confirm significance. At study endpoint the mean change in SitDBP was -10.5 +/- 1.9 mmHg and -9.6 +/- 2.4 mmHg for eprosartan-treated and enalapril-treated patients, respectively. The mean change in SitSBP for eprosartan-treated black patients was -18.8 +/- 3.5 mmHg and for enalapril-treated patients was -10.5 +/- 3.7 mmHg. The black subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and appears to be safe in black hypertensive patients. The combination of eprosartan and HCTZ was also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. The incidence of treatment-associated cough in the black subgroup was low, but there were no apparent differences between treatment groups.

Topics: Acrylates; Adult; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black People; Blood Pressure; Consumer Product Safety; Cough; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Thiophenes

The effects of a new angiotensin receptor antagonist, eprosartan (200 or 300 mg b.i.d.) and enalapril (5-20 mg u.i.d.) on cough and blood pressure were compared in a 26-week, double-blind, randomised, parallel-group, multicentre, international study involving 528 patients with hypertension. Uptitration of doses was based on clinic blood pressure measurements during the first 12 weeks, after which hydrochlorothiazide (12.5-25 mg/day) could be added. The frequency and intensity of cough was assessed by a standardised questionnaire administered at each clinic visit. The primary end-point was the incidence of persistent, dry cough not due to upper respiratory infection; change in sitting diastolic blood pressure and overall incidence of cough were secondary end-points. During the first 12 weeks of double-blind therapy, enalapril treatment was associated with a 3.45-fold higher risk of definite cough (14/261 vs 4/259, P = 0.018). Overall cough incidence (from spontaneous reports from patients, or investigator's observation) was also more frequent with enalapril, as compared to eprosartan. Both agents reduced blood pressure significantly compared to baseline, although the eprosartan-treated group had a slightly higher response rate (defined as sitting diastolic blood pressure <90 mm Hg, or at least a 10 mm Hg reduction from baseline), both at end of titration (70.3% vs 62.6%, P < 0.05) and after 26 weeks (81.7% vs 73.5%, P= 0.018). These data suggest that, in unselected hypertensive patients, eprosartan is associated with less cough and a somewhat higher responder rate than enalapril.

Topics: Acrylates; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cough; Diuretics; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Incidence; Male; Middle Aged; Risk Factors; Single-Blind Method; Sodium Chloride Symporter Inhibitors; Surveys and Questionnaires; Thiophenes; Treatment Outcome

The efficacy of eprosartan, a highly selective, orally-active non-biphenyl, non-tetrazole, type 1 angiotensin II (AT1) receptor antagonist, was compared with that of the angiotensin-converting enzyme (ACE) inhibitor, enalapril, with the addition of hydrochlorothiazide (HCTZ) when necessary in patients with severe hypertension (sitting diastolic blood pressure [sitDBP] > or = 115 mmHg and < or = 125 mmHg). Patients (n = 118) were randomized into an 8-week, double-blind titration phase and were started on oral eprosartan 400 mg total daily dose, given b.i.d., or oral enalapril 10 mg total daily dose, given o.d. The dose of eprosartan was increased to 600 and 800 mg daily, given b.i.d., and that of enalapril to 20 and 40 mg daily, given o.d., at weeks 2 and 4 if sitDBP was > or = 90 mmHg. If blood pressure remained uncontrolled on maximum doses of eprosartan or enalapril at week 6, HCTZ 25 mg o.d. was added to the treatment regimen. Patients whose blood pressure was deemed medically acceptable by the investigator at week 8 entered a 2-week maintenance phase on the final dose used in the titration phase. The primary efficacy measure was the difference between treatments of the mean reduction from baseline in sitDBP at the end of the study. Eprosartan and enalapril caused a similar reduction in sitDBP at study endpoint. The mean change in sitDBP at the end of the study for the eprosartan group was -20.1 mmHg vs -16.2 mmHg for the enalapril group. However, eprosartan produced significantly greater decreases in both sitting and standing systolic blood pressure (sitSBP and staSBP, respectively) than enalapril. The mean decrease in sitSBP was 29.1 mmHg for eprosartan compared with 21.1 mmHg for enalapril (p = 0.025). The mean reduction in staSBP was 27.8 mmHg for eprosartan compared with 20.0 mmHg for enalapril (p = 0.032). At the end of the study, the response rate (sitDBP < 90 mmHg or decreased from baseline by at least 15 mmHg) was 69.5% in the eprosartan group and 54.2% in the enalapril group. The proportion of patients in each treatment group who required addition of HCTZ was similar. Eprosartan was well tolerated; the overall incidence of adverse events was comparable to that in the enalapril group. These results demonstrate that in patients with severe hypertension, eprosartan is well tolerated and may be more effective than enalapril in reducing systolic blood pressure.

Topics: Acrylates; Administration, Oral; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Thiophenes

ABT-869 [N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea] is a novel multitargeted inhibitor of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinase family members. ABT-869 demonstrates tumor growth inhibition in multiple preclinical animal models and in early clinical trials. VEGF receptor inhibition is also associated with reversible hypertension that may limit its benefit clinically. To evaluate optimal therapeutic approaches to prevent hypertension with VEGF receptor inhibition, we characterized the dose-dependent effects of seven antihypertensive agents from three mechanistic classes [angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs)] on hypertension induced by ABT-869 in conscious telemetry rats. We report that ABT-869-induced hypertension can be prevented and reversed with subtherapeutic or therapeutic doses of antihypertensive drugs with a general rank order of ACEi > ARB > CCB. In SCID mice, the ACE inhibitor, enalapril (C(20)H(28)N(2)O(5) x C(4)H(4)O(4)) at 30 mg/kg, prevented hypertension, with no attenuation of the antitumor efficacy of ABT-869. These studies demonstrate that the adverse cardiovascular effects of the VEGF/PDGF receptor tyrosine kinase inhibitor, ABT-869, are readily controlled by conventional antihypertensive therapy without affecting antitumor efficacy.

Topics: Acrylates; Amlodipine; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Calcium Channel Blockers; Dose-Response Relationship, Drug; Enalapril; Humans; Imidazoles; Indazoles; Lisinopril; Male; Mice; Mice, SCID; Neoplasms; Nifedipine; Phenylurea Compounds; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Ramipril; Rats; Rats, Sprague-Dawley; Telmisartan; Thiophenes; Xenograft Model Antitumor Assays

To investigate the cost-utility of eprosartan versus enalapril (primary prevention) and versus nitrendipine (secondary prevention) on the basis of head-to-head evidence from randomized controlled trials.. The HEALTH model (Health Economic Assessment of Life with Teveten for Hypertension) is an object-oriented probabilistic Monte Carlo simulation model. It combines a Framingham-based risk calculation with a systolic blood pressure approach to estimate the relative risk reduction of cardiovascular and cerebrovascular events based on recent meta-analyses. In secondary prevention, an additional risk reduction is modeled for eprosartan according to the results of the MOSES study ("Morbidity and Mortality after Stroke--Eprosartan Compared to Nitrendipine for Secondary Prevention"). Costs and utilities were derived from published estimates considering European country-specific health-care payer perspectives.. Comparing eprosartan to enalapril in a primary prevention setting the mean costs per quality adjusted life year (QALY) gained were highest in Germany (Euro 24,036) followed by Belgium (Euro 17,863), the UK (Euro 16,364), Norway (Euro 13,834), Sweden (Euro 11,691) and Spain (Euro 7918). In a secondary prevention setting (eprosartan vs. nitrendipine) the highest costs per QALY gained have been observed in Germany (Euro 9136) followed by the UK (Euro 6008), Norway (Euro 1695), Sweden (Euro 907), Spain (Euro -2054) and Belgium (Euro -5767).. Considering a Euro 30,000 willingness-to-pay threshold per QALY gained, eprosartan is cost-effective as compared to enalapril in primary prevention (patients >or=50 years old and a systolic blood pressure >or=160 mm Hg) and cost-effective as compared to nitrendipine in secondary prevention (all investigated patients).

Topics: Acrylates; Antihypertensive Agents; Cardiovascular Diseases; Cost-Benefit Analysis; Enalapril; Europe; Geography; Humans; Hypertension; Imidazoles; Male; Meta-Analysis as Topic; Middle Aged; Monte Carlo Method; Nitrendipine; Primary Prevention; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Thiophenes

Topics: Acrylates; Antihypertensive Agents; Coronary Disease; Enalapril; Humans; Hypertension; Imidazoles; Risk Factors; Stroke; Systole; Thiophenes; Treatment Outcome

Activation of the renin-angiotensin system may contribute to the derangement in renal and cardiac function in congestive heart failure. The present study evaluated the effects of eprosartan, a selective angiotensin II receptor antagonist, on renal hemodynamic and excretory parameters and on the development of cardiac hypertrophy in rats with aortocaval fistula, an experimental model of congestive heart failure. Infusion of eprosartan (1.0 mg/kg) in rats with aortocaval fistula produced a significant increase (+34%) in total renal blood flow and a sustained decrease (-33%) in the calculated renal vascular resistance. These effects on renal hemodynamics were more pronounced than those observed in sham-operated control rats and occurred despite a significant fall (-12%) in mean arterial blood pressure. Moreover, eprosartan caused a preferential increase in renal cortical blood perfusion and significantly increased glomerular filtration in rats with congestive heart failure. Chronic administration of eprosartan (5.0 mg/kg per day for 7 days through osmotic minipumps inserted intraperitoneally on the day of operation) resulted in a significant enhancement of urinary sodium excretion compared with nontreated rats with heart failure. Moreover, administration of eprosartan to salt-retaining rats with congestive heart failure resulted in a progressive increase and ultimate recovery in urinary sodium excretion. Finally, early treatment with eprosartan blocked the development of cardiac hypertrophy in rats with aortocaval fistula to a larger extent than the angiotensin-converting enzyme inhibitor enalapril. These findings emphasize the importance of angiotensin II in mediating the impairment in renal function and induction of cardiac hypertrophy in heart failure and further suggest that angiotensin II receptor blockade may be a useful treatment of these consequences in severe cardiac failure.

Topics: Acrylates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Cardiomegaly; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Heart Failure; Hemodynamics; Imidazoles; Kidney; Male; Rats; Rats, Wistar; Renal Circulation; Sodium; Thiophenes

Topics: Acrylates; Adult; Antihypertensive Agents; Black People; Enalapril; Female; Humans; Hypertension; Imidazoles; Losartan; Receptors, Angiotensin; Thiophenes

Topics: Acrylates; Acute Kidney Injury; Angiotensin I; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Captopril; Cough; Dogs; Enalapril; Female; Glomerular Filtration Rate; Imidazoles; Male; Renal Circulation; Thiophenes

The angiotensin II (AII) receptor antagonist, DuP 753 (10 mg/kg intraduodenal), produced a sustained and long-lasting antihypertensive effect in conscious renin-dependent hypertensive rats. Blood pressures were still reduced markedly 24 to 72 hr after administration of a single dose of DuP 753. However, pressor responses elicited by either angiotensin I or AII were not blocked at these times despite the continued antihypertensive effect of DuP 753. In a model of orthostatic hypotension, DuP 753 and the selective alpha-1 adrenoceptor antagonist prazosin produced a marked orthostatic hypotension response in renin-dependent hypertensive rats as demonstrated by potentiation of the decrease in blood pressure induced by a 90 degrees tilt. The nonpeptide AII receptor antagonist SK&F 108566 (10 mg/kg intraduodenal) did not produce orthostatic hypotension and the angiotensin converting enzyme inhibitor enalapril produced only a slight orthostatic response to tilting. In conscious spontaneously hypertensive rats (SHR), allowed 3 to 4 days to recover from surgery, administration of either enalapril (1 mg/kg i.v.) or SK&F 108566 (10 mg/kg i.v.) did not significantly effect blood pressure. In SHR tested within 24 hr of surgery, enalapril was effective in lowering blood pressure. In contrast, in surgically recovered SHR, DuP 753 (10 mg/kg i.v.) produced an antihypertensive effect that was slow in onset, sustained and extremely long in duration. Blood pressures did not return to predrug levels until 48 hr after administration of DuP 753. Stimulation of the thoracolumbar sympathetic outflow in pithed rats produced frequency-dependent pressor responses that were significantly potentiated by continuous infusion of a subpressor dose of AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acrylates; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Biphenyl Compounds; Captopril; Decerebrate State; Enalapril; Imidazoles; Losartan; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Receptors, Angiotensin; Spinal Cord; Tetrazoles; Thiophenes

It has been reported that high protein intake or amino acid infusion-induced glomerular hyperfiltration are accompanied by an elevation of plasma renin activity and renal renin mRNA. We therefore investigated the effect of inhibition of the renin-angiotensin system by SK&F 108566, a novel, nonpeptide angiotensin II (AII) receptor antagonist, or by enalapril, an angiotensin converting enzyme inhibitor, on glycine-induced hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate clearances in conscious chronically instrumented rats. Glycine infusion (3.7 mg/min i.v.; n = 8) significantly increased GFR by 27% (from 1.09 +/- 0.53 to 1.38 +/- 0.08 ml/min.100 g), ERPF by 22% (2.96 +/- 0.30 to 3.61 +/- 0.32 ml/min.100 g) and significantly decreased effective renal vascular resistance by 22% [from 25.4 +/- 2.9 to 20.8 +/- 2.5 mm Hg/(ml/min.100 g)]. SK&F 108566 (30 micrograms/kg.min) or enalapril (1 mg/kg), at doses which inhibited the pressor effects of AII or AI, respectively, but had no significant influence on base-line GFR and ERPF, significantly attenuated the glycine-induced glomerular hyperfiltration and hyperemia. In the presence of SK&F 108566 or enalapril, glycine resulted in only small, statistically insignificant changes in GFR (from 1.07 +/- 0.03 to 1.10 +/- 0.04 and from 1.19 +/- 0.03 to 1.21 +/- 0.08 ml/min.100 g, respectively), ERPF (from 3.27 +/- 0.21 to 3.53 +/- 0.26 and from 3.57 +/- 0.11 to 3.41 +/- 0.38 ml/min.100 g, respectively) and effective renal vascular resistance [from 21.2 +/- 1.9 to 19.2 +/- 1.6 and from 18.4 +/- 0.9 to 20.2 +/- 2.2 mm Hg/(ml/min.100 g], respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acrylates; Angiotensin Receptor Antagonists; Animals; Enalapril; Glomerular Filtration Rate; Glycine; Imidazoles; Infusions, Intravenous; Male; Rats; Rats, Inbred Strains; Renal Circulation; Renin-Angiotensin System; Thiophenes