Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines / Programa Farmácia Popular: análise do mercado farmacêutico de anti-hipertensivos do sistema renina-angiotensina

Abstract This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP), a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health) included private retail pharmacy sales volume (pharmaceutical units) and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

Resumo Este artigo visa analisar as mudanças no mercado de varejo farmacêutico, seguindo as alterações de diretiva no Programa Farmácia Popular (FP), que realiza subvenção de medicamentos no Brasil, em parceria pública privada. Foi realizada análise longitudinal retrospectiva dos medicamentos da classe terapêutica dos agentes que atuam sobre o sistema renina-angiotensina. Os dados obtidos do QuintilesIMS incluíram o varejo farmacêutico em termos do volume e valores de vendas de 2002 a 2013. Análises realizadas consideraram intervenções e reformas ocorridas no FP e seu impacto no mercado farmacêutico da classe terapêutica selecionada, devido a sua relevância para o tratamento da hipertensão. Também se examinou o comportamento do mercado tomando por base as empresas farmacêuticas produtoras. Losartan monodroga representou a maior fatia de mercado entre os antagonistas de angiotensina II. Empresas nacionais obtiveram maior volume de vendas durante o período de estudo, enquanto as empresas multinacionais exibiram maior valor de vendas. Mudanças no mercado farmacêutico coincidiram com a inclusão de produtos específicos na lista de medicamentos abrangidos pelo FP e com aumentos ou isenção de copagamento pelos pacientes.

Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease.

OBJECTIVE: There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds. METHODS: We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40-69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%. RESULTS: Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) -173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50. CONCLUSIONS: Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.

An economic evaluation of antihypertensive therapies based on clinical trials

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

Economic evaluation of irbesartan in combination with hydrochlorothiazide in the treatment of hypertension in Greece.

OBJECTIVES: Hypertension is a major risk factor for cardiovascular disease and a leading cause of morbidity and mortality. This study evaluates irbesartan in relation to commonly used alternative hypertension therapies losartan and valsartan given in combination with hydrochlorothiazide (HCTZ) in the general hypertensive population in Greece. METHODS: A Markov model with eight states of health was constructed: hypertension, myocardial infarction (MI), post-MI, angina, stroke, poststroke, heart failure, and death. The model has an annual cycle and estimates mean quality-adjusted survival and treatment cost, which reflect the hypertension treatment and managing cardiovascular events. Risk functions were used to conduct extrapolations. Data on treatment effectiveness, quality of life (QOL) and epidemiology were obtained from published clinical trials and studies. The database of the main Greek National Social Insurance Institute (IKA) was analyzed to estimate the cost of events. The analysis was done from a payer perspective. All outcomes were discounted, and prices correspond to 2008. RESULTS: The estimated patient cost per annum was stable angina euro 2,252, unstable angina euro 2,572, myocardial infarction euro 2,473, post-MI euro 1,677, stroke euro 12,233, poststroke euro 1,240, heart failure euro 2,655, coronary angiography euro 1,544, percutaneous transluminal coronary angioplasty euro 6,511, and coronary artery bypass graft surgery euro 11,514. For the baseline group (age 57 years, systolic blood pressure 147 mmHg, cholesterol 6.00 mmol/L, body mass index 29) of men with mild to moderate hypertension, for irbesartan, the total treatment cost was euro 15,146, for losartan euro 15,696 and for valsartan euro 15,613; the quality-adjusted life years (QALYs) were irbesartan 12.67, losartan 12.63 and valsartan 12.64. For the baseline group of women with mild to moderate hypertension, the total treatment cost was euro 12,945 for irbesartan, euro 13,424 for losartan and euro 13,379 for valsartan; QALYs were 14.29 for irbesartan, 14.27 for losartan and 14.27 for valsartan. For men with severe hypertension, for irbesartan and losartan, the total treatment cost was euro 18,679 and euro 21,488 and QALYs 12.47 and 12.37, respectively. For women, the total treatment cost was euro 16,202 and euro 19,099 and QALYs 14.16 and 14.09, respectively. Similar results were obtained in relation to other treatment groups in various sensitivity analysis scenarios. CONCLUSIONS: Based on efficacy data from clinical trials and lower attainment costs in various hypertensive patient populations, irbesartan in combination with HCTZ compares favorably with losartan and valsartan in combination with HCTZ in the Greek setting.

Cálculo del impacto económico para Chile del uso de losartán en diabéticos tipo 2 con nefropatía diabética, basado en resultados del estudio RENAAL / Economic impact of Losartan use in type 2 diabetic patients with nephropathy

Background: The study RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) demonstrated that Losartan was more effective lo reduce the progression of kidney disease in diabetic patients with proteinuria and a reduction in glomerular filtration rate. Aim: To perform a cost benefit analysis of Losartan use from provider and payer points of view. Material and methods: Published data of the RENAAL study was analyzed. The costs of the use or not use of Losartan in patients with diabetic nephropathy were compared in terms of total costs of the disease including medications, hospital admissions for myocardial infarction, cerebrovascular accidents and congestive cardiac failure and the costs of chronic hemodialysis. Results: The reduction in antihypertensive medication use, hospital admissions, and the delay in dialysis requirement from a mean of 65 to 79 months induced by Losartan use, results in net savings of $7,576,135 per patient, at 3.5 years of intervention. The figure does not change using different sensitivity scenarios. Conclusions: The eventual use of Losartan in type 2 diabetic patients results in important savings.

Cost-effectiveness of losartan in diabetic nephropathy: a Greek perspective.

BACKGROUND: Diabetic nephropathy is the primary cause of end-stage renal disease (ESRD), which involves substantial economic burden. The primary objective of this study was to estimate the potential effect of losartan on the costs associated with ESRD in patients with diabetic nephropathy in a Greek setting. A secondary aim was to approximate the direct health care cost of renal replacement therapy (RRT) in Greece. METHODS: A cost-effectiveness analysis was performed to compare losartan with placebo in patients with type 2 diabetes and nephropathy. Clinical data were derived from the RENAAL study. All costs were calculated from the perspective of the Greek social insurance system, in 2003 euros. Future costs were discounted at 3%. The time horizon was 3.5 years. Extensive sensitivity analyses were performed. RESULTS: The reduction in the number of ESRD days over 3.5 years in patients treated with losartan reduced ESRD-related costs by 3,056.54 euros, resulting in net cost savings of 1,665.43 euros per patient. Net cost savings increase thereafter, increasing to 2,686.48 euros per patient over a period of 4.0 years. The results were robust under a wide range of plausible assumptions. The weighted mean daily cost of RRT was estimated at 90.97 euros per patient. The total economic burden of RRT for the year 2003 has been estimated at 304.773 million euros. CONCLUSIONS: This study demonstrated that treatment of patients with diabetic nephropathy in Greece with losartan is cost-effective, as it leads to important savings for the social insurance system by slowing the progression to ESRD.

Cost effectiveness of losartan in patients with hypertension and LVH: an economic evaluation for Sweden of the LIFE trial.

OBJECTIVE: Evaluate the cost effectiveness of losartan compared with atenolol from a Swedish national health system perspective. DESIGN: The Losartan Intervention For Endpoint reduction in hypertension study (LIFE) was a double-masked, randomized trial of losartan versus atenolol in 9193 patients with essential hypertension and left ventricular hypertrophy (LVH) ascertained by electrocardiography. Losartan reduced the primary composite end point of cardiovascular death, myocardial infarction (MI), or stroke by 13% (P = 0.021) and reduced the risk of stroke by 25% (P = 0.001), despite a comparable degree of blood pressure control. METHODS: Life years gained was estimated by combining the absolute risk reduction in stroke with the life years gained by preventing stroke. Quality-adjusted life years (QALYs) gained was estimated by combining the absolute risk reduction in stroke with the QALYs gained by preventing stroke. QALYs were estimated by weighting life years by health-related quality of life (QoL), as measured with visual analogue scale (VAS) data collected in the trial. Net costs were defined as the total of study medication cost, stroke-related costs, and costs of increased survival. Costs are in 2003 Swedish prices. All costs and effects were discounted at a 3% annual rate. RESULTS: Prevention of a stroke resulted in a gain of 5.7 life years and 4.3 QALYs. As a consequence, losartan treatment resulted in a per patient increase of 0.092 life years [95% confidence interval (CI): 0.038, 0.146] and 0.069 QALYs (95% CI: 0.028, 0.109) as compared with atenolol treatment. Losartan reduced direct stroke-related cost per patient by 1141 euros due to a lower cumulative incidence of stroke for losartan at 5.5 years (4.9%) as compared with atenolol (6.5%) (95% CI of difference: 0.7, 2.5). The reduction in stroke-related cost offset 80% of the added cost of losartan drug therapy. After inclusion of study medication cost, net cost per patient was 289 euros higher for losartan than atenolol. The net cost per QALY gained for losartan was 4188 euros (37,813 SEK), which is well within common Swedish benchmark upper values (200-500,000 SEK) for accepted cost-effective interventions. CONCLUSION: Based on the results from the LIFE trial, treatment with losartan compared with atenolol, in hypertensive patients with LVH, is a cost-effective intervention.

The impact of losartan on the lifetime incidence of ESRD and costs in Mexico / El impacto del losartan en la incidencia de por vida de la enfermedad renal de la etapa terminal y sus costos en México

Background. The RENAAL (Reduction of Endpoints in Type 2 Diabetes with the Angiotensin II Antagonist Losartan) study demonstrated that treatment with losartan reduced the risk of ESRD by 29% among hypertensive patients with type 2 diabetes and diabetic nephropathy. The objective of this study was to project the effect of losartan compared to placebo on the lifetime incidence of ESRD and associated costs from a third-party payer perspective in Mexico. Methods. A competing risks method was used to estimate lifetime incidence of ESRD, while accounting for the risk of death without ESRD. The cost associated with ESRD was estimated by combining the cumulative incidence of ESRD with the lifetime cost associated with ESRD. Total cost was estimated as the sum of the cost associated with ESRD from the three main public institutions in Mexico, the lifetime cost of losartan therapy, and other costs (non-ESRD/non-losartan) expected for patients with type 2 diabetes. Survival was estimated by weighting the life expectancies with and without ESRD by the cumulative risk of ESRD. Results. The projected lifetime incidence of ESRD for losartan patients was lower (66%) compared with placebo patients (83%). This reduction in ESRD resulted in a decrease in ESRD-related cost of M$49,737 per patient and a discounted gain of 0.697 life years per patient. After accounting for the cost of losartan and the additional cost associated with greater survival, we projected that treatment with losartan would result in a net savings of M$24,073 per patient. Conclusion. Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the within-trial incidence of ESRD but is projected to result in lifetime reductions in ESRD, increased survival, and overall cost savings to public institutions in Mexico.

Antecedentes. El estudio RENAAL (Reducción de los grados o puntos terminales en la diabetes tipo 2 con losartan, el antagonista de la anglotenslna II) demostró que el tratamiento con losartan redujo el riesgo de la ESRD (enfermedad renal de la etapa terminal) en 29% entre pacientes hipertensos con diabetes tipo 2 y neuropatía diabética. El propósito estudiado fue hacer una proyección del efecto del losartan comparándolo con el placebo en la incidencia de por vida de la ESRD y con los costos asociados de un tercer pagador en perspectiva en México. Métodos. Se utilizó un método de riesgos muy competitivo para calcular la incidencia de por vida de la ESRD, al mismo tiempo que se calculaba el riesgo de muerte sin la ESRD. El costo asociado con la ESRD se calculó confirmando la incidencia acumulativa de la ESRD en relación con el costo de por vida de la terapia con losar-tan y otros costos (sin ESRD o sin losartan) con los que se contaba para pacientes con diabetes tipo 2. La supervivencia se calculó esperando las expectativas de vida con y sin ESRD por el riesgo acumulativo de ESRD. Resultados. La proyectada incidencia de por vida de la ESRD en cuanto a los pacientes con losartan fue más baja (66%) comparada con los pacientes que tomaron placebo (83%). Esta reducción de la ESRD tuvo por resultado una disminución en el costo relacionado con la ESRD de $49,737 por paciente y una ganancia descartada de 0.697 años de vida por paciente. Luego de contabilizar el costo del losartan y el costo añadido asociado con una mayor supervivencia, llegamos a la conclusión de que el tratamiento con losartan daría por resultado un ahorro neto de $24,073 por paciente. Conclusión. El tratamiento mediante losartan en pacientes aquejados de diabetes tipo 2 y neuropatía no sólo redujo la incidencia intraexperimental de la ESRD, sino que además nos ha servido para proyectar que resulte en reducciones de por vida en la ESRD, en una supervivencia incrementada y en un ahorro total de costos en cuanto a las instituciones públicas en nuestro país.

An economic evaluation of Losartan therapy in type 2 diabetic patients with nephropathy: an analysis of the RENAAL study adapted to France.

BACKGROUND: The RENAAL study enrolled 1,513 patients with type 2 diabetes mellitus and nephropathy defined by the presence of proteinuria (urinary albumin: creatinine ratio 300 mg/g or proteinuria > 500 mg per day). Compared to placebo, losartan therapy reduced by 16% (p=0.02) the risk of a composite endpoint (doubling of baseline serum creatinine level, end stage renal disease, or death) and by 28% (p=0.002) the risk of progression to end stage renal disease (ESRD). METHODS: The objective of this study was to compare, using French economic data, the additional cost of losartan therapy with the savings in cost generated by a decrease in the number of end stage renal disease days. Prospectively collected health care resource utilization were used (N(losartan)=751, N(placebo)=762). The follow-up period was 4 years. RESULTS: The mean cumulative cost of losartan over 4 years was 1,603 euros per patient. The reduction in the number of ESRD days over 4 years in patients treated with losartan significantly decreased costs associated with ESRD by 7,438 euros per patient (CI 95%: 3,029 euros - 11,847 euros, p=0.001). Compared to the placebo group, the average cost per patient over 4 years in the losartan group was lower by 5,834 euros (CI 95%: 1,407 euros - 10,301 euros, p=0.01). CONCLUSION: In addition to the medical benefit, this analysis demonstrated the economic relevance of treatment with losartan in type 2 diabetic patients with nephropathy.