Initiation of hypertension treatment with a fixed-dose combination or its monocomponents -- does it really matter?

Despite efforts to diagnose and treat hypertension effectively, the goal of lowering blood pressure (BP) levels is rarely achieved, as treatment is often initiated with a single antihypertensive agent. The aim of this study was to assess the safety and efficacy of a first-line fixed-dose combination treatment compared with treatment with its monocomponents over a period of 4 weeks. Patients (n = 149) with essential hypertension were randomised to receive 2.

Microalbuminuria and tubular proteinuria as risk predictors of cardiovascular morbidity and mortality in essential hypertension: final results of a prospective long-term study (MARPLE Study)*.

Objective: To evaluate the impact of microalbuminuria (MAU) or tubular proteinuria (TPU) on cardiovascular and cerebrovascular events and all-cause mortality, and to assess whether a normalization of MAU and/or TPU induced by angiotensin-converting enzyme-inhibitor-based antihypertensive treatment with ramipril improves cerebrovascular prognosis in essential hypertensive patients without diabetes mellitus.

Method: A prospective, controlled, multicenter study was performed involving 3529 hypertensive participants (average follow-up 42.5 months).

Cost effectiveness of ramipril in patients at high risk for cardiovascular events : economic evaluation of the HOPE (Heart Outcomes Prevention Evaluation) study for Germany from the Statutory Health Insurance perspective.

Background: In the HOPE (Heart Outcomes Prevention Evaluation) trial, ramipril (compared with placebo) significantly reduced cardiovascular death and all-cause mortality as well as the incidence of costly cardiovascular events, such as myocardial infarction, revascularisation, stroke, cardiac arrest, hospitalisation due to heart failure and worsening angina pectoris, new-onset diabetes mellitus and microvascular diabetic complications.

Objective: Data from the HOPE study were used in a cost-effectiveness analysis to determine the additional cost per life-year gained (LYG) when the ACE inhibitor ramipril was added to the current medication of patients at high risk for cardiovascular events. The aim was to establish the incremental cost-effectiveness ratio (ICER) of ramipril versus placebo from the perspective of the Statutory Health Insurance (SHI) provider in Germany, for both the study population as a whole and for the subgroup of patients with diabetes.

High-dose furosemide for established ARF: a prospective, randomized, double-blind, placebo-controlled, multicenter trial.

Background: The effect of furosemide on the survival and renal recovery of patients presenting with acute renal failure (ARF) is still debated.

Methods: Three hundred thirty-eight patients with ARF requiring dialysis therapy were randomly assigned to the administration of either furosemide (25 mg/kg/d intravenously or 35 mg/kg/d orally) or matched placebo, with stratification according to severity at presentation. The primary end point was survival.

Therapeutic effects of angiotensin II inhibition or blockade on the progression of chronic renal disease.

Experimental and clinical research has supported the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in diabetic, hypertensive and proteinuric nephropathies. This review will evaluate the role of angiotensin II in the progression of renal damage in kidney diseases; the diagnostic value of microalbuminuria as an early clinical sign of renal damage and the possibility of preventing its further progression; the clinical results obtained with ACE inhibitors and/or ARBs in diabetic and non-diabetic nephropathies; and the therapeutic possibilities of ACE inhibitors and ARBs in renal transplantation. Based on available clinical data, ACE inhibitors can be considered to be the gold standard in reducing and/or preventing albuminuria, and thereby decreasing the percentage of patients who will progress to end-stage renal disease and death.

[ACE inhibitor or AT1 antagonist. Is there a differential therapy?].

ACE-inhibitors and AT, receptor antagonists play an important role in the treatment of cardiovascular and renal diseases. The criteria of evidence-based medicine indicate that ACE-inhibitors (in appropriate combinations with other cardiovascular agents) continue to represent the treatment of first choice in chronic heart failure, post-myocardial infarction with compromised ventricular function, high cardiovascular risk, and diabetic (type 1) nephropathy. It is here that the AT1 antagonists should be used--in particular when ACE-inhibitors are not tolerated.

Use of ramipril in preventing stroke: double blind randomised trial.

Objective: To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke.

Design: Randomised controlled trial with 2x2 factorial design.

Setting: 267 hospitals in 19 countries.

Cost effectiveness of ramipril in patients with non-diabetic nephropathy and hypertension: economic evaluation of Ramipril Efficacy in Nephropathy (REIN) Study for Germany from the perspective of statutory health insurance.

Background: In the Ramipril Efficacy In Nephropathy (REIN) trial, ramipril significantly lowered the rate of reaching the combined end-point of doubling of baseline serum creatinine levels or end-stage renal failure (ESRF).

Objective: To determine the additional cost per patient-year of chronic (long term) dialysis avoided (PYCDA) when the ACE inhibitor, ramipril, was added to conventional treatment of patients with non-diabetic nephropathy and hypertension.

Study Perspective: Statutory Health Insurance (SHI) provider in Germany.

Management of hypertension and its sequelae with ACE inhibitors: biochemical, pharmacological and clinical aspects.

ACE inhibitors are a widely prescribed class of drug for the management of hypertension. Their therapeutic role in the treatment of heart failure, diabetic nephropathy and post myocardial infarction with left ventricular dysfunction is steadily increasing. Although ACE inhibitors have a similar mechanism of action--namely, inhibition of circulatory ACE, thereby decreasing the formation of angiotensin II--individual members differ in their physicochemical properties, enzyme-binding kinetics, pharmacokinetic profile, organ-specific affinity and selectivity, as well as in their bradykinin potentiating effect.

Fixed dose combinations of ACE inhibitors.

First-line antihypertensive monotherapy is effective in reducing blood pressure to within the normal range in approximately 50% of patients. Normalisation in the remaining patients may require a combination of two or more drugs. This review considers the clinical efficacy and tolerability of combinations involving angiotensin-converting enzyme (ACE) inhibitors.

Efficacy of ramipril versus enalapril in patients with mild to moderate essential hypertension.

This double-blind, randomised, cross-over study investigated the antihypertensive efficacy of ramipril and enalapril was completed by 30 patients with mild-to-moderate essential hypertension. After a four-week placebo run-in phase, the patients received either 2.5mg ramipril or 10mg enalapril once daily for four weeks.

Ramipril and felodipine: a comparison of the efficacy and safety of monotherapy versus combination therapy.

A multinational, double-blind, randomised study was conducted to investigate the efficacy and safety of a low-dose combination of the angiotensin converting enzyme inhibitor, ramipril, and the calcium antagonist, felodipine ER, in 642 patients with mild to moderate hypertension [supine diastolic blood pressure (DBP) = 95-115 mm Hg]. After a 4-week single-blind placebo run-in, patients were randomly allocated to once-daily felodipine extended release (ER; 2.5 mg), ramipril (2.

Pharmacokinetics, metabolism and biliary and urinary excretion of oral ramipril in man.

In order to evaluate the pharmacokinetics and excretion of ramipril in man, 8 cholecystectomy patients aged between 53 and 68 years received 5 mg ramipril orally as a single dose. All patients had a T-drain inserted to permit bile collection; all gave their informed consent to participate in the trial. Serum samples were collected half-hourly until 2 hours, then hourly until 6 hours, then at 8, 10, 24 and 25 hours after intake.

Multiple-dose pharmacokinetics of ramipril in patients with chronic congestive heart failure.

Thirteen patients with chronic congestive heart failure of NYHA class II-III received multiple doses (14 days) of ramipril (5 mg once daily); the concentrations of ramipril and ramiprilat in plasma, as well as ramipril, ramiprilat, glucuronides, diketopiperazine, and diketopiperazine acid in urine were measured at various times for 14 days. One patient dropped out after the first day due to hypotension and another who accidentally received another ACE inhibitor additionally was excluded, so that 11 patients completed the study. Ramipril and ramiprilat in plasma were determined by radioimmunoassay, and ramipril and its metabolites in urine were measured by gas chromatography in the laboratories of Hoechst AG.

Influence of ramipril on plasma atrial natriuretic peptide, antidiuretic hormone, angiotensin II and aldosterone in patients with chronic congestive heart failure.

Unlabelled: In an open trial 5 mg ramipril daily for 2 weeks was administered to 11 patients with congestive heart failure. 24-hour plasma profiles of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), angiotensin II (Ang II) and aldosterone (Aldo) were determined before and on days 1 and 15 of ramipril treatment, respectively. Urinary sodium excretion was also measured at the same time points.

Antihypertensive efficacy, tolerance, and safety of ramipril in young vs. old patients: a retrospective study.

The efficacy, tolerance, and safety of ramipril, an angiotensin-converting enzyme inhibitor, were assessed in 502 patients from five multicenter, double-blind studies who had mild-to-moderate essential hypertension. Each study was designed with a 4-week placebo run-in phase followed by 6 weeks of treatment with ramipril or one of five other antihypertensive treatments. A total of 412 young patients (17-65 years of age) and 90 old patients (66-87 years) in these studies received single daily doses of 5 or 10 mg of ramipril.

Effect of angiotensin-converting enzyme inhibition on human tissue renin.

This investigation was performed to assess the effect of treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril, on human tissue renin levels. A total of 41 patients were studied (32 males and 9 females, aged 48-71 years). Twenty-two of these patients received up to 5 days treatment with the ACE inhibitor ramipril (5 mg p.

Physicochemical and enzyme binding kinetic properties of a new angiotensin-converting enzyme inhibitor ramipril and their clinical implications.

After oral administration, ramipril, a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, is transformed in the liver into its active metabolite ramiprilat. Because of its pentane ring it is at least 23 times more lipophilic than enalaprilat. The in vitro affinity for ACE is 7 times higher than for enalaprilat and 47 times higher than for captopril.

A multi-centre comparative study between ramipril and enalapril in patients with mild to moderate essential hypertension.

A multi-centre, randomized, double-blind, parallel group study was undertaken in order to assess efficacy and tolerability of ramipril as compared to enalapril in mild to moderate hypertension. A 4-week placebo run-in period was followed by 4 weeks of treatment with active medication (5 mg ramipril or 10 mg enalapril in a single morning dose). In patients not responding to this dosage regimen at the end of a 4-week treatment period, the dose was doubled.

Efficacy of a fixed-dose combination of 40 mg penbutolol with 6 mg piretanide in the treatment of mild to moderate hypertension: a double-blind study against placebo.

The antihypertensive efficacy and tolerability of a fixed-dose combination containing 40 mg penbutolol (a beta-blocking agent) and 6 mg piretanide (a diuretic) in comparison to placebo was investigated in a double-blind, crossover study in 20 patients with mild to moderate essential hypertension. After a 1-week period on placebo, patients were allocated at random to receive 1 tablet daily for 4 weeks of either the combination preparation or placebo and were then crossed over to the alternative medication for a further 4 weeks. The reduction in systolic and diastolic blood pressure both at rest, during maximal ergometric exercise and isometric word load, and also in the diurnal blood pressure profile over 24 hours was significantly greater in the group treated with the fixed-dose combination than in the placebo group.

Lack of effect of piretanide (a potassium-stable diuretic) on serum magnesium.

Serum magnesium and potassium concentrations were determined in 188 patients undergoing diuretic treatment for mild to moderate hypertension in four controlled clinical trials (eleven treatment groups). Measurements were made before and after 12 weeks of treatment with piretanide monosubstance (including the retarded form) in the range 3 to 12 mg daily, with triamterene as monosubstance and in fixed dose combination with piretanide, and with amiloride in combination with hydrochlorothiazide. Eumagnesaemia and eupotassaemia were preserved at all dosage of the piretanide monosubstance.

Efficacy of a low fixed-dose combination of penbutolol with piretanide in the treatment of mild to moderate hypertension: a double-blind study against placebo.

A double-blind crossover study was carried out in 20 patients with mild to moderate essential hypertension to assess the efficacy and tolerability of a low fixed-dose combination containing 20 mg penbutolol (a beta-blocking agent) and 3 mg piretanide (a diuretic) in comparison to placebo over a period of 4 weeks. Active drug treatment in the 20 patients studied was preceded by a 1-week period of placebo. The results showed that there was an effective significant reduction in systolic and diastolic blood pressure compared with initial levels in the fixed-dose combination group, when compared to the placebo group, both at rest, during maximal ergometric and isometric work load, and also in the diurnal blood pressure profile over 24 hours.

Piretanide in the treatment of essential hypertension. A double-blind comparison versus placebo.

In a randomized, double-blind parallel group study the 24-hour hypotensive effect of piretanide and its influence on biochemical variables were compared with those of placebo in patients with mild to moderate essential hypertension. Sixty patients entered the study, all of whom met the inclusion criteria (RRdiast between 95 and 120 mmHg). There was no drop-out during the study, so that the results of all 60 patients were statistically analysed.

[Comparative study of 2 diuretic-containing combination preparations in patients with edematous heart failure].

The efficacy and tolerability of two combinations, namely 50 mg spironolactone + 20 mg furosemide (SF) or 50 mg spironolactone + 5 mg butizide (SB), were compared in a randomised intraindividual trial in 22 patients with congestive heart failure. The parameters used were: weight, ankle- and calf-circumference, blood pressure, resting pulse, resting ECG, spirometry and blood chemistry. The physicians' judgement of the success of treatment was also recorded.