[Evaluation of the pharmacoeconomic efficacy of prestance in the treatment of hypertensive patients on the basis of the results of the POTENTIAL program]. / Otsenka farmakoekonomicheskoi effektivnosti preparata prestans pri lechenii bol'nykh arterial'noi gipertoniei na osnove rezul'tatov programmy POTENTsIAL.

AIM: To pharmacoeconomically estimate the use of a fixed-dose combination of perindopril and amlodipine in the treatment of hypertensive patients. MATERIAL AND METHODS: A pharmacoeconomic study was conducted on the basis of the Russian postmarketing observational open program POTENTIAL, which included the estimation of direct and indirect costs associated with the addition of a fixed-dose combination of perindopril and amlodipine to conventional therapy for hypertension in patients who had not achieved adequate blood pressure (BP) control. Cost-difference, cost-effectiveness, and budget-impact analyses were carried out. RESULTS: The addition of prestance to conventional therapy for hypertension can reduce total costs by 5.-5.8 times, direct costs required to achieve 1% of patients with adequate BP control by 20.5-42.1 times, and direct costs to improve a patient's status by one visual analogue scale score by 1.03-2.11 times. Within a 5-year horizon, the administration of prestance can decrease the cost of therapy for high BP and related strokes by 1.39-1.46 times. CONCLUSION: Due its high efficacy, prestance (amlodipine + perindopril) is a pharmacoeconomically preferred alternative only to the conventional therapy for hypertension even if the least costly generics are used, in both the short and medium term.

Individualized Angiotensin-Converting Enzyme (ACE)-Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model.

BACKGROUND: Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. METHODS AND RESULTS: Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to treat ranged from as low as 29 (clinical risk score ≥10 and PGXscore of 0) to 521 (clinical risk score ≤6 and PGXscore of 2). Furthermore, our data suggest that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is cost-effective. CONCLUSIONS: Both baseline clinical phenotype, as well as genotype determine the efficacy of widely prescribed ACE inhibition in stable CAD. Integration of clinical and pharmacogenetic determinants in a combined risk prediction model demonstrated a very wide range of gradients of absolute treatment benefit.

Cost-effectiveness of lowering blood pressure with a fixed combination of perindopril and indapamide in type 2 diabetes mellitus: an ADVANCE trial-based analysis.

OBJECTIVE: To determine the cost-effectiveness of routine administration, irrespective of blood pressure (BP), of a fixed-dose combination of perindopril and indapamide to patients with type 2 diabetes mellitus. DESIGN, SETTING AND PARTICIPANTS: Prospective cost-effectiveness analysis within the Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial, an international, multicentre, randomised controlled trial of 11,140 participants with type 2 diabetes randomly allocated to receive perindopril plus indapamide (4 mg-1.25 mg/day) or placebo. MAIN OUTCOME MEASURES: Health-related quality-of-life measured by the EuroQol-5D, resource utilisation, and cost-effectiveness (cost per death averted at 4.3 years' average follow-up, and estimated cost per life-year gained, by extrapolation). RESULTS: The mean health-related quality-of-life score of survivors was 0.80 (on a 0-1 scale [death to full health]), with no difference between treatment groups. Active treatment reduced hospital admissions for coronary heart disease and coronary revascularisation by 5%. For the Australian participants, perindopril-indapamide cost A$1368 per patient during the trial period, but reduced total hospitalisation costs by A$410 and other medication costs (mainly other BP-lowering drugs) by A$332. The absolute reduction in all-cause mortality for the active treatment group was 1.1%, giving a cost per life saved of A$49,200. Lifetime extrapolation gave an estimated cost per life-year saved of A$10,040 (discounted at 5% per year). CONCLUSION: The combination of perindopril and indapamide in patients with type 2 diabetes appears to be cost-effective. TRIAL REGISTRATION: United States National Library of Medicine NCT00145925.

An economic evaluation of a perindopril-based blood pressure lowering regimen for patients who have suffered a cerebrovascular event.

OBJECTIVES: Cerebrovascular disease (or stroke) is one of the main causes of long-term disability and the second leading cause of death worldwide. The economic impact of stroke is clearly seen, as it is the largest single cause of bed occupancy in hospitals in England and accounts for 6% of hospital costs. This analysis is the first to quantify the economic consequences of a blood pressure lowering regimen based on the PROGRESS study (perindopril-based regimen), for reducing future cardiovascular events. DESIGN: A Markov decision analytical model was used to estimate the cost per quality adjusted life year (QALY) of blood pressure lowering in the treatment of patients presenting with a cerebrovascular event. The health states are based upon Barthel indices for which resource utilisation and health benefits have previously been estimated. SETTING: The participants for the economic analysis were obtained from the PROGRESS study database. 6,105 clinical study participants were recruited through both primary and secondary care centres. PARTICIPANTS: The mean age was 64 years; 70% were male in the original study. INTERVENTIONS: In the PROGRESS study, blood pressure lowering by a perindopril-based regimen was compared to standard care. MAIN OUTCOME MEASURES: Cost per quality adjusted life year for the duration of the study (4 years) and for a time span of 20 years. RESULTS: Using only direct hospital medical costs, the cost per QALY for a perindopril based regimen is pound 6,927 for the base study period and pound 10,133 for a 20-year time period. These results are sensitive to the cost of perindopril, the cost of the stroke unit, length of stay, and to a lesser extent, the cost of indapamide. CONCLUSIONS: This analysis demonstrates a cost-effective treatment for patients suffering a cerebrovascular event with a blood pressure lowering regimen. The findings of this study are in line with current decisions and guidance by the national institute for health and clinical excellence (NICE) in England.

Costs and effects of secondary prevention with perindopril in stable coronary heart disease in Poland: an analysis of the EUROPA study including 1251 Polish patients.

OBJECTIVES: To estimate the long-term impact of treatment with perindopril on costs and health effects in patients with stable coronary artery disease in Poland. METHODS: The cost-effectiveness analysis was based on data from a randomized double-blind, placebo-controlled trial. A decision-tree analysis was employed, including Monte Carlo and bootstrapping techniques. This study was a sub-study of the EUROPA (European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) trial (n = 12,218; mean follow-up 4.2 years). Resource use was based on data from Polish EUROPA study patients (n = 1251), while effectiveness was based on the whole EUROPA study. The health gain of perindopril in life-years was based on overall EUROPA study results, and the adapted Polish life expectancy of patients not dying during the trial. Costs were calculated in new Polish zloty (PLN), year 2003 values; euro1 = PLN4.053. Only direct healthcare costs related to cardiovascular events and medication use were studied. RESULTS: When observed mortality was combined with life expectancy beyond the end of the study, perindopril use showed a gain in life expectancy of 0.182 life-years (SD +/- 0.129) at a cost of PLN1983 (SD +/- 103) with discounting of 5% per annum on costs and no discounting on effects. This resulted in an incremental cost-effectiveness ratio (ICER) of PLN10 896 per life-year gained. The probability that the ICER for perindopril was below the threshold of PLN60 000 was 88%. The overall results were insensitive to discount rates for costs and life-years. CONCLUSIONS: Perindopril leads to a reduction in the risk of coronary events among patients with stable heart disease. When the expected improvement in life expectancy is combined with associated medical costs, there is a high probability that perindopril is cost effective, given the threshold of PLN60 000 per life-year gained.

Cost effectiveness of perindopril in reducing cardiovascular events in patients with stable coronary artery disease using data from the EUROPA study.

BACKGROUND: The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) trial has recently reported. OBJECTIVE: To assess the cost effectiveness of perindopril in stable coronary heart disease in the UK. METHODS: Clinical and resource use data were taken from the EUROPA trial. Costs included drugs and hospitalisations. Health-related quality of life values were taken from published sources. A cost-effectiveness analysis is presented as a function of the risk of a primary event (non-fatal myocardial infarction, cardiac arrest or cardiovascular death) in order to identify people for whom treatment offers greatest value for money. RESULTS: The median incremental cost of perindopril for each quality-adjusted life year (QALY) gained across the heterogeneous population of EUROPA was estimated as 9700 pounds(interquartile range 6400-14,200 pounds). Overall, 88% of the EUROPA population had an estimated cost per QALY below 20,000 pounds and 97% below 30,000 pounds. For a threshold value of cost effectiveness of 30,000 pounds per QALY gained, treatment of people representing the 25th, 50th (median) and 75th centiles of the cost effectiveness distribution for perindopril has a probability of 0.999, 0.99 and 0.93 of being cost effective, respectively. Cost effectiveness was strongly related to higher risk of a primary event under standard care. CONCLUSIONS: Whether the use of perindopril can be considered cost effective depends on the threshold value of cost effectiveness of healthcare systems. For the large majority of patients included in EUROPA, the incremental cost per QALY gained was lower than the apparent threshold used by the National Institute for Health and Clinical Excellence in the UK.

Is multidisciplinary care of heart failure cost-beneficial when combined with optimal medical care?

BACKGROUND: Multidisciplinary care (MDC) of heart failure (HF) can significantly reduce rates of unplanned hospitalisation, the major cost component of HF care. AIMS: This prospective, randomised, controlled study examines the cost-benefits of MDC of HF in the setting of optimal medical care. METHODS: 98 NYHA class IV HF patients (mean age 70.8+/-10.5 years) were randomised to MDC (n=51) or routine care (RC; n=47) of HF. A direct intervention cost was calculated from contact time (scheduled and unscheduled) spent by the MDC team. Unplanned hospitalisation costs for HF were calculated at a daily rate of 242. Outcomes were determined in monetary terms, i.e. the cost of the service per hospitalisation prevented and net costs/savings at 3 months. RESULTS: The direct intervention cost of the MDC team was 5860, with an average cost per patient of 113 (95% Cl: 97-128). At 3 months, there were a total of 12 unplanned HF readmissions in the RC group (25.5% rate, 195 days) compared to 2 in the MDC group (3.9% rate, 17 days). The number needed to treat to prevent one hospitalisation for HF was 6 over 3 months. The cost of the service per hospitalisation prevented was 586. The intervention produced a net cost saving of 37,216 for 51 patients treated over 3 months. Sensitivity analyses using 50% variation in costs and lower relative risk reductions confirmed the cost-benefits of the intervention. CONCLUSION: MDC of HF remains cost-beneficial when combined with optimal, medical care. The significant clinical and cost-benefits suggest that this intensive approach to MDC and medical management should become the standard of care for HF.

Perindopril + indapamide: new preparation. Simple trick.

(1) The combination of perindopril 4 mg + indapamide 1.25 mg is approved for second-line treatment of hypertension after failure of perindopril alone. (2) The other combination, of a low dose of an angiotensin-converting-enzyme inhibitor (2 mg of perindopril) and a diuretic (0.625 mg of indapamide), is being promoted as first-line treatment of hypertension. (3) The clinical files for both preparations are limited to the strict minimum. (4) A dose-finding study showed that the perindopril 4 mg + indapamide 1.25 mg dose combination offered the best risk-benefit ratio by comparison with combinations containing the same perindopril dose but other indapamide doses. (5) A double-blind trial suggests that the antihypertensive activity of the perindopril 4 mg + indapamide 1.25 mg combination is equivalent to that of the captopril 50 mg + hydrochlorothiazide 25 mg and enalapril 20 mg + hydrochlorothiazide 12.5 mg combinations. The safety profile was the same for the three combinations. (6) The 2-mg perindopril combination has not been compared with perindopril monotherapy at the usual dose of 4 mg, or with indapamide monotherapy at a mean dose of 2.5 mg. (7) The two combinations are costlier than their competitors.