Cost-effectiveness analysis comparing single-pill combination of perindopril/amlodipine/indapamide to the free equivalent combination in patients with hypertension from an Italian national health system perspective.

OBJECTIVE: To evaluate the cost-effectiveness of a single-pill combination (SPC) of perindopril/amlodipine/indapamide versus its free equivalent combination (FEC) in adults with hypertension in Italy. METHODS: A Markov model was developed to perform a cost-utility analysis with a lifetime horizon and an Italian healthcare payer's perspective. In the model, the additional effect of the SPC on blood pressure level compared with the FEC was translated into a decreased risk of cardiovascular events and CKD, which was modeled via Framingham risk algorithms. Difference in persistence rates of SPC and FEC were modeled via discontinuation rates. RESULTS: A perindopril/amlodipine/indapamide SPC is associated with lower cost and better health outcomes compared to its FEC. Over a lifetime horizon, it is associated with a 0.050 QALY gain and cost savings of €376, resulting from lower cardiovascular event rates. In the alternative scenario, where different approach for modeling impact of adherence was considered, incremental gain of 0.069 QALY and savings of €1,004 were observed. Results were robust to sensitivity and scenario analyses, indicating that use of this SPC is a cost-effective strategy. CONCLUSIONS: The findings indicate that a perindopril/amlodipine/indapamide SPC is a cost-saving treatment option for hypertension in Italy, compared to its FEC.

Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus.

Discontinuation of angiotensin-converting enzyme (ACE) inhibitor is recommended if patients experience ≥30% acute increase in serum creatinine after starting this therapy. However, the long-term effects of its continuation or discontinuation on major clinical outcomes after increases in serum creatinine are unclear. In the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation), 11 140 diabetes mellitus patients were randomly assigned to perindopril-indapamide or placebo after a 6-week active run-in period. The current study included 11 066 participants with 2 serum creatinine measurements recorded before and during the active run-in period (3 weeks apart). Acute increase in creatinine was determined using these 2 measurements and classified into 4 groups: increases in serum creatinine of <10%, 10% to 19%, 20% to 29%, and ≥30%. The primary study outcome was the composite of major macrovascular events, new or worsening nephropathy, and all-cause mortality. An acute increase in serum creatinine was associated with an elevated risk of the primary outcome ( P for trend <0.001). The hazard ratios were 1.11 (95% CI, 0.97-1.28) for those with an increase of 10% to 19%, 1.34 (1.07-1.66) for 20% to 29%, and 1.44 (1.15-1.81) for ≥30%, compared with <10%. However, there was no evidence of heterogeneity in the benefit of randomized treatment effects on the outcome across subgroups defined by acute serum creatinine increase ( P for heterogeneity=0.94). Acute increases in serum creatinine after starting perindopril-indapamide were associated with greater risks of subsequent major clinical outcomes. However, the continuation of angiotensin-converting enzyme inhibitor-based therapy reduced the long-term risk of major clinical outcomes, irrespective of acute increase in creatinine. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00145925.

[Effect of different doses of perindopril on myocardial energy expenditure in patients with heart failure following myocardial infarction].

OBJECTIVE: To investigate the changes of myocardial energy expenditure in patients with heart failure following myocardial infarction after treatment with different doses of perindopril. METHODS: Sixty-three patients with heart failure after myocardial infarction were treated with perindopril for 12 months at the doses of 4 mg (group N) and 8 mg (group H). Doppler imaging was used to measure the structural and systolic functional parameters before and after the treatment, and the circumferential end-systolic wall stress (cESS) and myocardial energy expenditure (MEE) were calculated. The biochemical indicators including serum creatinine and plasma NT-proBNP were detected before and after the treatment. RESULTS: The two groups had similar measurements before treatment. After 12 months of perindopril treatment, the patients in group N showed higher LA, LV, RA, RV, LVIDs, AD, cESS, lgNT-proBNP, and MEE with lower LVFS and LVEF than those in group H. Compared to those before treatment, LVFS and LVEF were increased and LA, LV, RA, RV, AD, LVIDs, LVMI, lgNT-proBNP and MEEm lowered after the 12-month treatment in group H. Significant changes were also found in the measured parameters except for PWTs, LVET, LVSV and LVFS in group N after the treatment. Bivariate analysis showed a significant positive correlation between MEE and lgNT-proBNP (r=0.513, P<0.01). CONCLUSION: A 12-month treatment with perindopril can suppress myocardial remodeling, improve left ventricular systolic function, and lower NT-proBNP and myocardial energy expenditure in patients with heart failure after myocardial infarction, and a higher dose can produce better results.

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.

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.