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The Cost-Effectiveness of Low-Cost Essential Antihypertensive Medicines for Hypertension Control in China: A Modelling Study

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      Abstract

      BackgroundHypertension is China’s leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world’s largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs.Methods and FindingsThe Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs) gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35–84 y over 2015–2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention) and for two blood pressure ranges in primary prevention (stage one, 140–159/90–99 mm Hg; stage two, ≥160/≥100 mm Hg). Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015) were considered cost-effective. Treating hypertensive adults with prior cardiovascular disease for secondary prevention was projected to be cost saving in the main simulation and 100% of probabilistic simulation results. Treating all hypertension for primary and secondary prevention would prevent about 800,000 cardiovascular disease events annually (95% uncertainty interval, 0.6 to 1.0 million) and was borderline cost-effective incremental to treating only cardiovascular disease and stage two patients (2015 Int$13,000 per QALY gained [95% uncertainty interval, Int$10,000 to Int$18,000]). Of all one-way sensitivity analyses, assuming adherence to taking medications as low as 25%, high Shanghai drug costs, or low medication efficacy led to the most unfavorable results (treating all hypertension, about Int$47,000, Int$37,000, and Int$27,000 per QALY were gained, respectively). The strengths of this study were the use of a recent Chinese national health survey, vital statistics, health care costs, and cohort study outcomes data as model inputs and reliance on clinical-trial-based estimates of coronary heart disease and stroke risk reduction due to antihypertensive medication treatment. The limitations of the study were the use of several sources of data, limited clinical trial evidence for medication effectiveness and harms in the youngest and oldest age groups, lack of information about geographic and ethnic subgroups, lack of specific information about indirect costs borne by patients, and uncertainty about the future epidemiology of cardiovascular diseases in China.ConclusionsExpanded hypertension treatment has the potential to prevent about 800,000 cardiovascular disease events annually and be borderline cost-effective in China, provided low-cost essential antihypertensive medicines programs can be implemented.

      Abstract

      In a Markov-style simulation model, Andrew Moran and colleagues estimate the reduction in cardiovascular disease and cost-effectiveness of broad provision of antihypertensive medications in China.

      Editors' Summary

      BackgroundWorldwide, in 2008, more than one billion people had high blood pressure (hypertension), a condition that is responsible for about 10 million deaths annually from heart attacks, stroke, and other cardiovascular diseases (CVDs). Hypertension, which rarely has any symptoms, is diagnosed by measuring blood pressure (BP), the force that blood circulating in the body exerts on the inside of large blood vessels. BP is highest when the heart contracts to pump blood out (systolic BP) and lowest when the heart relaxes and refills (diastolic BP). Normal adult BP is defined as a systolic BP of less than 120 millimeters of mercury (mm Hg) and a diastolic BP of less than 80 mm Hg (a BP of <120/80 mm Hg). A BP of 140–159/90–99 mm Hg indicates mild (stage one) hypertension; a BP of ≥160/≥100 mg Hg indicates severe (stage two) hypertension. Many factors affect BP, but overweight people and individuals who eat fatty or salty food are at high risk of developing hypertension. Lifestyle changes and/or antihypertensive drugs can be used to control the condition.Why Was This Study Done?Hypertension is the leading cardiovascular risk factor in China, the world’s most populous country. About 325 million adults in China have hypertension, but less than half are aware of their condition, only 34% of Chinese adults with hypertension are treated with antihypertensive drugs, and only 28% of treated individuals achieve a BP of <140/90 mm Hg. Improved hypertension control would yield enormous health gains in China, but would these gains outweigh the costs of this intervention? The World Health Organization defines a “highly cost-effective” intervention as one for which the incremental cost effectiveness ratio (ICER; in this case, the ratio of the cost difference between the intervention and no intervention to the difference in outcomes) is less than a country’s gross domestic product (GDP) per capita (a country’s total economic output divided by its number of inhabitants) per quality-adjusted life year gained (a QALY is a measure of disease burden that considers both the quality and quantity of life lived). Here, the researchers use a computer simulation model to project the cost-effectiveness of hypertension treatment in Chinese adults using the low-cost antihypertensive drugs included on the national essential medicines list. In China, most patients pay for drugs out-of-pocket, but several antihypertensive medications with affordable prices are available in government-sponsored primary health facilities.What Did the Researchers Do and Find?The researchers used a computer model called the “Cardiovascular Disease Policy Model-China” to simulate the costs of hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring, and the QALYs gained by preventing CVD in Chinese adults with untreated hypertension aged 35–84 y between 2015 and 2025. According to the model, treating hypertension for both primary prevention of CVD (reduction of hypertension in healthy individuals to prevent the development of CVD) and secondary prevention (reduction of hypertension in people who already have CVD to prevent further heart attacks or strokes) would prevent between 600,000 and a million CVD events annually. Treating only patients with CVD and patients with severe hypertension was borderline cost-effective. The ICER of this intervention was between Int$10,000 and Int$18,000 per QALY gained; China’s GDP per capita is Int$11,900.What Do These Findings Mean?These findings suggest that an expanded program of treatment for hypertension could prevent about 800,000 cardiovascular events every year in China. Such a program should be borderline cost-effective, provided low-cost essential antihypertensive drugs are used to control hypertension. As with all computer simulation studies, the numerous assumptions incorporated into the model limit the accuracy of these findings. For example, some model inputs were derived from studies of non-Chinese patients and may not accurately represent the Chinese population. Moreover, the model only considers the cost-effectiveness of using medications to control hypertension and does not consider the potential effects of lifestyle changes. Importantly, additional simulations indicate that the cost-effectiveness of the intervention would be greatly reduced if adherence to treatment were lowered or drug costs were increased. Thus, full implementation of the essential medicinesprogram and subsidized drug costs program will be needed to reap the full benefits of improved hypertension control in China.Additional InformationThis list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001860.The US National Heart Lung and Blood Institute has patient information about high BP (in English and Spanish) and a guide to lowering BP through dietThe American Heart Association provides information on hypertension and on CVDs (in several languages); it also provides personal stories about dealing with high BPThe UK National Health Service (NHS) Choices website provides detailed information for patients about hypertension (including a personal story) and about CVDThe World Health Organization provides information on CVD and controlling hypertension; "A Global Brief on Hypertension" was publi shed on World Health Day 2013; WHO-CHOICE provides information on choosing cost-effective interventionsMedlinePlus provides links to further information about high BP, heart disease, and stroke (in English and Spanish)

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      Most cited references 34

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      2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).

      Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.
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        Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.

        The age-specific relevance of blood pressure to cause-specific mortality is best assessed by collaborative meta-analysis of individual participant data from the separate prospective studies. Information was obtained on each of one million adults with no previous vascular disease recorded at baseline in 61 prospective observational studies of blood pressure and mortality. During 12.7 million person-years at risk, there were about 56000 vascular deaths (12000 stroke, 34000 ischaemic heart disease [IHD], 10000 other vascular) and 66000 other deaths at ages 40-89 years. Meta-analyses, involving "time-dependent" correction for regression dilution, related mortality during each decade of age at death to the estimated usual blood pressure at the start of that decade. Within each decade of age at death, the proportional difference in the risk of vascular death associated with a given absolute difference in usual blood pressure is about the same down to at least 115 mm Hg usual systolic blood pressure (SBP) and 75 mm Hg usual diastolic blood pressure (DBP), below which there is little evidence. At ages 40-69 years, each difference of 20 mm Hg usual SBP (or, approximately equivalently, 10 mm Hg usual DBP) is associated with more than a twofold difference in the stroke death rate, and with twofold differences in the death rates from IHD and from other vascular causes. All of these proportional differences in vascular mortality are about half as extreme at ages 80-89 years as at ages 40-49 years, but the annual absolute differences in risk are greater in old age. The age-specific associations are similar for men and women, and for cerebral haemorrhage and cerebral ischaemia. For predicting vascular mortality from a single blood pressure measurement, the average of SBP and DBP is slightly more informative than either alone, and pulse pressure is much less informative. Throughout middle and old age, usual blood pressure is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg.
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          2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

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            Author and article information

            Affiliations
            [1 ]Department of Epidemiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
            [2 ]National Center for Cardiovascular Diseases, Beijing, China
            [3 ]Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America
            [4 ]Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
            [5 ]Division of General Medicine, University of California at San Francisco, San Francisco, California, United States of America
            [6 ]Division of General Medicine, Columbia University Medical Center, New York, New York, United States of America
            [7 ]School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
            [8 ]Department of Epidemiology, Capital Medical University Beijing Anzhen Hospital and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
            [9 ]Columbia University College of Physicians and Surgeons, New York, New York, United States of America
            Stanford University, UNITED STATES
            Author notes

            The authors have declared that no competing interests exist.

            Conceived and designed the experiments: AEM DG JH. Performed the experiments: AEM PGC PWR AT CH KYT. Analyzed the data: AEM PGC JX MW CH AT. Contributed reagents/materials/analysis tools: AEM MW PGC. Wrote the first draft of the manuscript: AEM. Contributed to the writing of the manuscript: AEM DG JH DZ LG PGC. Agree with the manuscript’s results and conclusions: AEM DG JH DZ LG PGC JX MW PWR AT CH KYT. Designed and programmed the CVD Policy Model-China: AEM LG PGC MW DZ. All authors have read, and confirm that they meet, ICMJE criteria for authorship.

            Contributors
            Role: Academic Editor
            Journal
            PLoS Med
            PLoS Med
            plos
            plosmed
            PLoS Medicine
            Public Library of Science (San Francisco, CA USA )
            1549-1277
            1549-1676
            4 August 2015
            August 2015
            : 12
            : 8
            26241895
            4524696
            10.1371/journal.pmed.1001860
            PMEDICINE-D-14-02811
            (Academic Editor)

            This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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            Funding
            AEM was supported by a Career Development Award (K08 HL089675-01A1) and a research grant (R01 HL107475-01) from the US National Heart, Lung, and Blood Institute. DG and CH were supported by grants from the Ministry of Science and Technology of China (2011BAI09B03 and 2011BAI11B03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Categories
            Research Article
            Custom metadata
            All results data are shown in the manuscript. Model data inputs are described in the manuscript and appendix and are available (either in academic journals or provided by governmental or nongovernmental agencies). Investigators interested in working with the CVD Policy Model software can contact Dr. Moran, one of the corresponding authors by email. Interested authors can submit a brief (1-2 page) research proposal and collaboration plan by email that will be considered by the CVD Policy Model team. The CVD Policy Model team will interact with interested researchers in order to assess the feasibility of collaboration and clarify any questions about the research question, particularly whether the CVD Policy Model is designed to address the question. The CVD Policy Model has established a Creative Commons agreement for the purpose of establishing rules for collaborations with outside researchers. The commons allows for outside researchers to use the software, ensures that the software is used appropriately, and asks collaborators to share modifications and improvements to the software with the CVD Policy Model team. A copy of the Creative Commons agreement will be available online as a supplementary file. If interested researchers propose an analysis and sign our Creative Commons agreement, and the proposal is approved by the CVD Policy Model team, the software will be shared.

            Medicine

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