Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with left ventricular hypertrophy (LVH), mainly due to a highly significant 25% reduction in the relative risk of stroke compared with an atenolol-based regimen, for a similar reduction in blood pressure. The aim of this economic evaluation was to estimate the cost-effectiveness of losartan compared with atenolol from a UK national health system perspective. Quality-adjusted survival and direct medical costs were modelled beyond the trial using the within-trial incidence of stroke. Survival with stroke, study medication use and quality of life by stroke status were taken directly from the LIFE trial. The LIFE data were supplemented with UK data on lifetime direct medical costs of stroke and life expectancy in individuals without stroke. No additional stroke events or use of study treatment were assumed beyond the trial. Costs and benefits were discounted using current UK Treasury rates. In the base-case analysis, the reduction in stroke-related costs (by 968 sterling pound) offset 86% of the increase in study medication costs (1128 sterling pound) among losartan-treated patients. The incremental cost-effectiveness ratio (ICER) for losartan versus atenolol in hypertensive patients with LVH was 2130 sterling pound per quality-adjusted life year (QALY) gained (3195 Euro/QALY), and this increased to 11,352 sterling pound per QALY gained (16,450 Euro/QALY) when the costs of stroke beyond the first 5 years were excluded. Thus, the clinical benefit of losartan was achieved at a cost well within reported thresholds for cost-effectiveness.

Why not prescribe the best drugs for hypertension now?

As Westernised societies have become more affluent, the attitudes of the population have become more risk-aware. People are now intolerant of small risks as well as the physical or mental discomforts from drug side effects. Safety and tolerability are now major forces driving the development of new medicines for the treatment of chronic illnesses and the prevention of increasingly rare events. For example, over the past decades, lower and lower treatment thresholds have been recommended in hypertension. Public perception of risk strongly influences the acceptability of lifetime treatment, especially for mild hypertension. This era has also witnessed great advances in the development of antihypertensive drugs that combine efficacy with unsurpassed tolerability. However, the philosophy of Scottish teachers of Materia medica still appears to be followed-'never be the first or the last to prescribe a new drug'. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists are as safe and as efficacious as other antihypertensive medications and better tolerated. Large trials (HOT, HOPE, UKPDS and PROGRESS) point to the need for rigorous control of blood pressure particularly in high-risk individuals. Antihypertensive drugs that act on the renin-angiotensin system will probably impact significantly on achieving optimal blood pressure levels. Should it not now be accepted that high-risk patients should have ACE inhibitors and angiotensin II receptor antagonists prescribed as first-line agents? We review the evidence for the use of ACE inhibitors and angiotensin II receptor antagonists as antihypertensive agents.

Integrated approaches to management of hypertension: promoting treatment acceptance.

Overwhelming trial evidence indicates that the treatment of hypertension is beneficial, but in practice, less than 50% of treated hypertensive subjects have blood pressure well controlled. The success of treatment relies on acceptance by the patient. Treatment acceptance may be affected by the efficacy and tolerability of drug therapy, its effects on quality of life, and other important but less well-recognized influences such as the expectations and preconceived ideas of the physician and the patient. This report briefly reviews the factors affecting patient concordance with antihypertensive treatment and the role these factors play in the development of an integrated treatment plan. Nonconcordance with drug therapy is common: Only one third of patients always take treatment, one third take it sometimes, and one third never take their prescribed medication. With poor concordance, control of blood pressure and the consequent benefits are less likely to be realized. The factors that influence concordance are ill understood. Although drug side effects and convenience of dosing regimens are contributors, the attitudes of patients, physicians, and their interactions are likely to be of considerable importance. Concordance may be improved by involving the patient in the treatment plan, setting explicit targets, following a clear treatment plan, motivating the patient to comply with treatment, paying attention to the concerns and particular needs of the individual patient, and by ensuring frequent contacts between patients and health care professions. Successful integrated approaches to the management of hypertension must address all the factors that affect treatment acceptance.

Investigation of the mechanism of beta 2-agonist-induced activation of the renin-angiotensin system.

1. We have previously described activation of the renin-angiotensin system in asthma, and also by high-dose nebulized beta 2-agonists. In this study we sought to determine the mechanism responsible. 2. The influence of the angiotensin-converting enzyme inhibitor, lisinopril, on the response of the renin-angiotensin system and serum potassium to nebulized salbutamol was investigated in a randomized, double-blind, crossover study in eight healthy volunteers using a factorial block design. On study days, subjects received lisinopril 20 mg orally or identical placebo tablets followed 3 h later by nebulized salbutamol or placebo inhalation; plasma renin, angiotensin II, serum angiotensin-converting enzyme and potassium were measured at intervals for 120 min after inhalation. 3. Following salbutamol, plasma renin and angiotensin II concentrations were increased significantly compared with placebo [mean (SEM) plasma renin of 61.7 (15.6) mu-units/ml and angiotensin II of 17.7 (5.4) pg/mol 15 min after salbutamol, P < 0.05 versus placebo]. Baseline plasma renin concentrations were increased [160.1 (20.6) mu-units/ml] and baseline plasma angiotensin II concentrations were reduced [1.4 (0.1) pg/ml] by lisinopril, P < 0.05 versus placebo in each case. Inhibition of angiotensin-converting enzyme completely inhibited this salbutamol-induced rise in plasma angiotensin II [mean (SEM) plasma angiotensin II of 1.5 (0.4) pg/ml 15 min after salbutamol, P < 0.05 versus placebo] but had no effect on the changes in plasma renin concentrations after the beta 2-agonist [mean (SEM) plasma renin of 198.4 (18.9) mu-units/ml 15 min after salbutamol].(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of aldosterone antagonists in healthy man.

The development of methods to allow the quantitative comparison of aldosterone antagonists in healthy men is reviewed. Pharmacological action is measured against a background of mineralocorticoid excess, induced either by administration of exogenous mineralocorticoid (usually aldosterone or fludrocortisone), or by stimulation of endogenous mineralocorticoid using salt restriction, diuretic administration, or a combination of the two. Use of fludrocortisone as the exogenous mineralocorticoid has proved convenient and useful, but the influence of aldosterone antagonists on potassium metabolism has proved somewhat inconstant in this experimental model. Repeated administration of a medium-potency diuretic appears to provide a clinically relevant situation in which the effect of aldosterone antagonists on potassium metabolism can be assessed. We describe these experimental methods in detail, discuss their applications, and make some suggestions for further research.

Bumetanide and frusemide: a comparison of dose-response curves in healthy men.

1 Log dose-responses for the loop diuretics bumetanide and frusemide in healthy subjects deviated significantly from parallelism as regards urine volume and sodium excretion. Ignoring the nonparallelism the best estimate of natriuretic potency (bumetanide: frusemide) was 46:1 in the bumetanide dose range 0.5-2 mg. 2 For a given natriuresis the urinary potassium excretion following bumetanide was significantly lower than that for frusemide within this dose range. 3 The data illustrate the limitations of studies comparing diuretics at a single dose level. Extrapolation of the observed log dose-response curves provides one possible explanation for the relative potency (bumetanide: frusemide) of 20:1 reported when the drugs are used at high dosage in patients with renal failure.