Pharmacoeconomic Evaluation On Effects Of Two Initial Combination Therapy Regimens For Hypertension Using Markov Model

Chapters 1:Effects of initial therapy for hypertension with combination therapy regimen and impact on renal functionObjective To evaluate the effects and side effects of initial therapy for hypertension with a combination of low-dose amlodipine plus amiroride or low-dose amlodipine plus telmisartan regimen.Method A total of 302 hypertensive patients were included. Inclusion criteria were:essential hypertension,50-79 years of age with at least one cardiovascular risk factor and signed consent forms. Patients were randomly assigned to receive low-dose amlodipine plus amiroride (group A)or low-dose amlodipine plus telmisartan (group B). Blood pressures, side effects, metabolic parameters and renal function indexes were observed during 1-year following-up. All patients will be followed-up for 1 year.Results After 1-year treatment, mean blood pressure in group A and B were reduced to (128.1±10.3)/(76.6±8.0) mmHg and (131.5±12.3)/(77.3±9.2)mmHg from (157.1±12.0)/(91.1±9.4)mmHg and (156.4±13.6)/(91.2±9.5) mmHg(P<0.05), respectively. Blood pressure control rates reached 87.1% in group A and 76.5% in group B(P=0.024) The serum uric acid level significantly elevated from (310.59±76.32)μmol/1 to (353.71±76.77)μmmol/l(P=0.000) after treatment in group B. The serum creatinine level decreased from (85.15±21.25)μmmol/1 to (82.70±20.21)μmmol/1 (P=0.001) after treatment in group B.Conclusion Initial low-dose andodipine-based antihypertensive combination regimens could significantly decrease blood pressure level and achieve satisfactory blood pressure control rate with few side effects. Compatibility of telmisartan may provide renal protection independent of BP lowering in combination regimen.The two combination schemes could markedly improve quality of life in patients with hypertension. Chapters 2:The one-year pharmacoeconomic evaluation of two initial combination therapy regimens for hypertension using Decision-tree modelObjective To evaluate the cost-effectiveness of low-dose amlodipine plus telmisartan(group A) or amlodipine plus amiroride(group B) therapy in hypertensive patients using a decision-tree model with a time horizon of 1 year. To provide evidence on the optimal combination therapy regimens and treatment options in hypertensive patients.Method Based on the trial data, a cost-effectiveness decision-tree model was developed to assess, about 1 year period, the short-time economic effects, where the total effective rates, Blood pressure control rates and QALYs were estimated as indicators of effectiveness, respectively. Roll back, cost-effectiveness analysis, cost-utility analysis and incremental cost-effectiveness analysis wore adopted in the decision-tree model. Both one-way and two-way sensitivity analysis were earried out to determine the robustness of our baseline results.Results1. Expected values:About the average cost per patient needed with a time horizon of 1 year, group A need￥1247, group B need￥1917. About the total effective rates and blood pressure control rates, group A reached 87.6% and 80.9%, group B reached 84.0% and 70.7%. About the average QALYs per patient gained, group A were 0.046 QALYs and group B were 0.085 QALYs.2. The one year cost-effectiveness analysis showed that, the cost of effective treatment was￥1389 and￥2230 per patient in group A and group B, respectively. At the cost of blood pressure controlled for each case, group A need￥1540, and group B require Y2712. At the cost of gain 1 QALY after 1 year therapy, group A need Y26979, and group B require￥22517.The estimated ICER for group A versus group B was￥17222 per QALY gained.3. The sensitivity analysis results showed that there were no impact of variations in key model inputs on the model.Conclusion From group decision-making considerations, applying the economic benefit, the initial low-dose amlodipine plus amiloride is optimal opinion; And consider from improving the quality of Chapters 3:The long-tharm pharmacoeconomic evaluation of two initial combination therapy regimens for hypertension using Markov modelObjective Our aim was to apply Markov model to the Pharmacoeconomic evaluation of the effect with long-term low doses of amlodipine plus amiloride and amlodipine plus telmisartan antihypertensive therapy, to provide a basis for the selection of optimized combination therapy, to offer the methodological reference for the Pharmacoeconomic evaluation of the domestic hypertension Intervention.Method1. According to the natural history of hypertension, we had built Markov state transition model to simulate the dynamic changes of the five states (event free, non-fatal myocardial infarction, non-fatal stroke, natural death and non-natural death) in the hypertension patients who received the two combined treatment, and a 1-year cycle length was chosen.2. We had applied Markov model using Roll back analysis,Markov cohort simulation and Monte c arlo simulation analysis to project expected life years, the expected quality-adjusted life years and the medical costs in the subsequent 40 years of life time for the hypertension patients who had been long-term treated with low dose of amlodipine plus amiloride or amlodipine plus telmisartan. Both one-way and two-way sensitivity analysis were carried out to determine the robustness of our baseline results.3. On the basis of the published study of China's population-based clinical trials, we had obtained Markov model transition probability between states, health utility values and health care costs in the states through literature review and search statistical data of China.Results1. The baseline Roll back analysis showed that after amlodipine plus amiloride antihypertensive therapy for 40 years, the average cost-effectiveness ratio was 1416 yuan/LYG and 1790 yuan/QALY respectively. Compared with the threshold criteria, amlodipine plus telmisartan regimen was dominated. Markov cohort simulation analysis showed that after 40 Markov Model cycles 84.4% patients in amlodipine plus amiloride antihypertensive therapy model cohort were natural death, 14.4% of whom were non-natural death, patients with non-fatal myocardial infarction and with non-fatal stroke accounted for 0.04% and 0.2011% respectively; cumulative costs and effects were 30203 yuan, 21.329 life years and 16.876 quality-adjusted life years gained. We had simulated 20000 cases of using amlodipine plus amiloride treatment sample populations by Monte Carlo simulation analysis. According to the analysis, the average cost-effectiveness ratio of the amlodipine plus amiloride treatment and its 95% confidence interval were 1173.1 yuan/ QALY (95% CI:1139.43 yuan/QALY～1174.72 yuan/QALY), the net monetary benefit was 364256 yuan (95% CI:361523.0 yuan～366,988.6 yuan), the net health benefit was 16.05 QALYs (95% CI:15.927QALYs ～16.168 QALYs).2. The baseline Roll back analysis after amlodipine plus telmisartan antihypertensive therapy for 40 years showed that the average cost-effectiveness ratio was 2252 yuan/LYG and 2334 yuan/QALY respectively. Compared with the threshold criteria, the amlodipine plus telmisartan program was the disadvantaged program. Markov cohort simulation analysis showed that after 40 Markov Model cycles 85.1% patients in amlodipine plus amiloride antihypertensive therapy model cohort were natural death,13.7% of whom were non-natural death, patients with non fatal myocardial infarction and with non-fatal stroke accounted for 0.09% and 0.15% respectively; cumulative costs and effects were 39680 yuan,17.618 life years and 17.001 quality-adjusted life years. We had simulated 20000 cases of using treatment sample populations by Monte Carlo simulation analysis. According to the analysis, the average cost-effectiveness ratio of the amlodipine plus telmisartan treatment and its 95% confidence interval were 1843.6 yuan/ QALY (95% CI:1,817.15 yuan/QALY～1850.00 yuan/QALY), the net monetary benefit was 354,851 yuan (95% CI:354040.2 yuan 359,382.2 yuan), the net health benefit was 15.84 QALYs (95% CI: 15.72QALYs～15.85QALYs).3. The analysis which used 1 times the 2008 per capita GDP 22698 yuan as the threshold standard and amlodipine plus amiloride antihypertensive therapy as a baseline for incremental analysis showed that the incremental cost-effectiveness ratio of telmisartan+amlodipine treatment was 75713 yuan/QALY, the incremental net monetary benefit (INMB) and the incremental net health benefit (INHB) were-7480.1 yuan (95% CI:-7804.6～-7155.6 yuan),-0.329QALYs (95% Cl:-0.343 QALYs～-0.315 QALYs). The probability that the net benefits of the Amlodipine plus amiloride treatment was greater than that of telmisartan plus amlodipine treatment was 94.5%.4. According to the sensitivity analysis, the change of key parameters in the set range did not affect the model results.Conclusion1. Two combination regimens were able to attain significant clinical effectiveness and economic Benefit, however in the case of limited resources, priority should be given to the amlodipine plus amiloride combined antihypertensive therapy as the initial program, in order to obtain better economic benefit.2. Markov model can be used for the better Economic evaluation of blood pressure intervention.