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.

Population impact of losartan use on stroke in the European Union (EU): projections from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study was designed to compare losartan- vs atenolol-based antihypertensive treatment on cardiovascular morbidity and mortality in a population of 9193 hypertensive patients with left ventricular hypertrophy (LVH). In LIFE, the losartan-based treatment further reduced the primary composite end point (cardiovascular death, myocardial infarction, or stroke) by 13% (risk reduction (RR) 0.87, 95% confidence interval (CI) 0.77-0.98, P=0.021). The further reduction in stroke with losartan (RR 0.75, 95% CI 0.63-0.89, P=0.001) was the major contributing factor to the reduction in the primary end point. Our objective was to project the reduction in stroke observed with a losartan- vs an atenolol-based antihypertensive treatment regimen in the LIFE study to the European Union (EU) population. The number of stroke events averted was estimated by identifying the number of persons in the EU expected to meet the LIFE inclusion criteria, and multiplying this figure by the cumulative incidence risk difference in stroke from LIFE at 5.5 years. The age- and gender-specific prevalence of hypertension, electrocardiographically (ECG)-diagnosed LVH among those with hypertension (inclusion criteria), and heart failure among those with LVH and hypertension (exclusion criteria) were applied to the EU census estimates. We conservatively projected that an estimated 7.8 million individuals aged 55-80 years in the EU are affected by hypertension and ECG-diagnosed LVH. Use of a losartan-based antihypertensive treatment in this population is projected to prevent approximately 125 000 first strokes over a 5.5-year period. A population-wide prevention strategy of using losartan in patients with LVH and hypertension has the potential to have a major public health impact by reducing the morbidity and mortality of stroke in the EU.

Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy.

PURPOSE: This analysis evaluated whether the antiemetic efficacy of the NK1 receptor antagonist aprepitant (EMEND trade mark, Merck, Whitehouse Station, NJ) plus standard antiemetics could be sustained for up to six cycles of cisplatin-based chemotherapy. PATIENTS AND METHODS: Patients receiving cisplatin > or = 70 mg/m2 were blindly assigned to receive one of the following three regimens: (1) aprepitant 375 mg 1 hour before cisplatin on day 1 and aprepitant 250 mg on days 2 to 5 (n = 35); (2) aprepitant 125 mg before cisplatin and aprepitant 80 mg on days 2 to 5 (n = 81); or (3) placebo before cisplatin on days 2 to 5 (n = 86). All groups received ondansetron 32 mg and dexamethasone 20 mg before cisplatin, and dexamethasone 8 mg on days 2 to 5. The primary end point was complete response (no emesis and no rescue therapy) over 5 days following cisplatin in up to six cycles. A cumulative probability analysis using a model for transitional probabilities was used to analyze the data. The aprepitant 375/250-mg regimen was discontinued early in light of new pharmacokinetic data. RESULTS: In the first cycle, 64% of patients in the aprepitant group and 49% in the standard therapy group had a complete response. Thereafter, complete response rates for the aprepitant group were still 59% by cycle 6, but decreased to 34% by cycle 6 for the standard therapy group. Reasons for discontinuation were similar across treatment groups. CONCLUSION: Compared with patients who received standard therapy, those who received only the aprepitant regimen had better and more sustained protection against chemotherapy-induced nausea and vomiting over multiple cycles.

The multinational impact of migraine symptoms on healthcare utilisation and work loss.

OBJECTIVE: To compare self-reported healthcare resource utilisation, paid work loss, unpaid work loss and loss of effectiveness at work due to migraine in a clinic-based adult migraine population. METHODS: The Migraine Background Questionnaire (MBQ) was translated and pilot-tested for use in 25 countries. The questionnaire was then self-administered by patients at a screening visit for 3 phase III clinical trials of rizatriptan [a selective serotonin (5-hydroxytryptamine) 5-HT1B/1D receptor agonist] in 23 US and 78 non-US sites. PARTICIPANTS: Persons 18 to 65 years of age with at least a 6-month history of moderate to severe migraines prior to the screening visit were surveyed. RESULTS: A total of 2670 persons (54.7% Europe, 16.5% Latin America, 23.1% North America, 5.5% other countries) completed the MBQ and had responses which could be analysed. On average, each patient reported 2.78 doctor visits, 0.53 emergency room visits and 0.06 hospitalisations related to migraine per year. Patients self-reported being only 46% effective while on the job with migraine symptoms. Extrapolation of patient self-reported work and productivity loss for the last 4 weeks to an annual basis suggested that clinic-based patients with migraine lose 19.5 workday equivalents (8.3 days due to absenteeism, 11.2 days due to reduced workday equivalents) due to migraine per year. In the US, the annual employer cost of this total migraine-related work loss is estimated to be $US3309 (2000 values) per patient with migraine. The levels of self-reported healthcare resources utilised for migraine and work loss were generally consistent across geographic regions. CONCLUSIONS: The impact of migraine symptoms on healthcare resource utilisation and work loss was similar across most measures in Europe, Latin America, North America and other countries. Total migraine-related work loss due to absenteeism and reduced workday equivalents accounts for most of the economic burden of migraine, regardless of country, in a clinic-based migraine population.

Work and productivity loss in the rizatriptan multiple attack study.

The objective of this study was to measure the self-reported effect of acute migraine and its treatment on paid work and productivity loss. Patients self-administered a questionnaire in which the impact of a recent migraine on paid work and productivity activities was assessed. We included the questionnaire in a randomized, double-blind, placebo-controlled, crossover, out-patient study designed to examine the safety and efficacy of rizatriptan (5-HT1B/1D receptor agonist) 10 mg p.o. in patients treating four separate migraine attacks. A total of 407 patients, aged 18-65 years, suffering from moderate to severe migrainous headaches was studied. Patients receiving rizatriptan compared with placebo reported 0.7 fewer hours (P < 0.01) of paid worked missed due to absenteeism, 0.4 fewer hours (P < 0.05) of productive time lost on the job, and 1.1 fewer total hours (P < 0.01) of work loss per migraine attack. Rizatriptan compared with placebo significantly reduced migraine-related work loss associated with absenteeism and decreased effectiveness on the job.

A regression-based method for estimating mean treatment cost in the presence of right-censoring.

In many clinical trials and evaluations using medical care administrative databases it is of interest to estimate not only the survival time of a given treatment modality but also the total associated cost. The most widely used estimator for data subject to censoring is the Kaplan-Meier (KM) or product-limit (PL) estimator. The optimality properties of this estimator applied to time-to-event data (consistency, etc.) under the assumptions of random censorship have been established. However, whenever the relationship between cost and survival time includes an error term to account for random differences among patients' costs, the dependency between cumulative treatment cost at the time of censoring and at the survival time results in KM giving biased estimates. A similar phenomenon has previously been noted in the context of estimating quality-adjusted survival time. We propose an estimator for mean cost which exploits the underlying relationship between total treatment cost and survival time. The proposed method utilizes either parametric or nonparametric regression to estimate this relationship and is consistent when this relationship is consistently estimated. We then present simulation results which illustrate the gain in finite-sample efficiency when compared with another recently proposed estimator. The methods are then applied to the estimation of mean cost for two studies where right-censoring was present. The first is the heart failure clinical trial Studies of Left Ventricular Dysfunction (SOLVD). The second is a Health Maintenance Organization (HMO) database study of the cost of ulcer treatment.

The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure.

The Losartan Heart Failure ELITE Study recently found that in patients with symptomatic heart failure and a left ventricular ejection fraction of /=65 years with symptomatic heart failure. Data on health care resource utilization were collected as part of the trial. We conducted a cost-effectiveness analysis to estimate the lifetime benefits of treatment and the associated costs. We observed no differences between treatments in the number of hospitalizations, hospital days, and emergency room visits per patient over the trial period. We estimated the total cost of losartan to be USD 54 (95% CI: USD -1,717, USD 1,755) less per patient than captopril over this time frame. We also estimated that over the projected remaining lifetime of the study population, losartan compared to captopril would increase survival by 0.20 years (undiscounted) at an average cost of USD 769 (discounted) more per patient. This cost increase translated into a cost-effectiveness ratio of USD 4,047 per year of life gained for losartan relative to captopril. In patients with symptomatic heart failure, losartan compared to captopril increased survival with better tolerability at a cost well within the range accepted as cost-effective.