
==== Front
BMJ Open
BMJ Open
bmjopen
bmjopen
BMJ Open
2044-6055
BMJ Publishing Group BMA House, Tavistock Square, London, WC1H 9JR

39237286
10.1136/bmjopen-2024-084575
bmjopen-2024-084575
Original Research
Global Health
1699
1506
Pharmaceutical intervention for hypertension in a rural district of the Republic of Zambia: a model-based economic evaluation
Yokobori Yuta 1y-yokobori@it.ncgm.go.jp

http://orcid.org/0000-0002-0921-6970
Deidda Manuela 2manuela.deidda@glasgow.ac.uk

Manca Francesco 2francesco.manca@glasgow.ac.uk

1 Bureau of International Health Cooperation, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
2 Health Economics and Health Technology Assessment division, University of Glasgow, Glasgow, UK
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

None declared.

2024
05 9 2024
14 9 e08457523 1 2024
02 8 2024
Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Abstract

Objectives

In Zambia, 19.1% of the adult population had elevated blood pressure. Hence, the Ministry of Health in Zambia designated the improvement of hypertension (HTN) care services as a priority policy. However, there are limited data on cost-effective interventions to address HTN and their budget impact in sub-Saharan Africa. The objective of this paper is to investigate the cost-effectiveness of primary-level interventions for HTN (pharmaceutical treatments) compared with no treatment, and the budget impact, in the Chongwe District, rural Zambia.

Methods

A cost–utility analysis was undertaken from the perspective of healthcare provider, employing a cohort Markov model with a lifetime horizon. The model was developed and populated with evidence from the literature, including novel locally collected cost data. The analysis was run for the overall population aged 40 years and above and for subpopulations stratified by three levels of risk and gender in Chongwe District by using cost data directly collected. A probabilistic analysis was performed to assess the probability of cost-effectiveness.

Results

The dominant treatment for the general population was a combination therapy of diuretics and calcium blockers. The incremental cost-effectiveness ratio was US$1114 compared with no treatment. This was the most cost-effective first-line medication for HTN for all subgroup populations, except for the subgroups classified as low-risk defined by WHO. The estimated annual budget impact was US$1 015 605 in total if all HTN patients in Chongwe District received the most cost-effective treatment. Considering only material costs, the annual total budget was US$29 435.

Conclusion

The most cost-effective first-line medication for HTN in rural Zambia was the combination therapy of diuretics and calcium blockers for the general population. From the perspective of budget impact, local government could need to secure approximately US$30 000 to facilitate the delivery of the most cost-effective HTN medications to the entire population over 40 years in need.

Hypertension
Cardiovascular Disease
HEALTH ECONOMICS
http://dx.doi.org/10.13039/100012319 National Center for Global Health and Medicine 21A04
==== Body
pmcSTRENGTHS AND LIMITATIONS OF THIS STUDY

A cost–utility analysis comparing medical treatments for hypertension was undertaken for the first time in Zambia.

We use direct cost data specific to the Zambia context.

Utility values, transition probability between health statuses and case fatality rate were not available for the Zambia context; thus, we used secondary data and tested the sensitivity of results to the chosen parameters.

The model focuses only on first-line pharmaceutical interventions at the primary level and does not consider preventive or other kinds of interventions.

Introduction

Although hypertension (HTN) can be easily detected through blood pressure (BP) measurements and is often treated effectively using medications, it is estimated that 700 million cases remain untreated globally.1 2 With 62% of cerebrovascular diseases and 49% of ischaemic heart diseases estimated to be attributable to suboptimal BP control,3 4 HTN treatment is a key topic of interest among researchers and practitioners.57 The NCD Global Monitoring Framework coordinated by the WHO uses the proportion of individuals taking antihypertensive treatment or counselling among those at a higher risk of cardiovascular disease (CVD) to monitor progress in reducing the disease burden associated with Noncommunicable disease (NCD) in each country.8

In Zambia, one of the sub-Saharan African countries, the demand for quality HTN services is rising.9 10 According to the latest WHO STEP wise approach to surveillance,11 a large number of people has been diagnosed with HTN: 19.1% of the adult population (20.5% of men and 17.6% of women) had elevated BP, defined as systolic BP (SBP) ≥140 mm Hg and/or diastolic BP≥90 mm Hg. Other studies reported higher morbidity levels; the prevalence of HTN in adults ranged between 25.8% and 32.8% in rural areas12 13 and 34.8% in urban areas.14 Considering this, the improvement of health services to prevent and treat HTN has been identified by the Zambian Ministry of Health (MoH) as one of the key priority in the National Health Strategic Plan 2022–2026.15 While there is a promising policy agenda, the cost-effectiveness of HTN treatment has never been evaluated in Zambia. The evidence on the cost-effectiveness of treatment for HTN in sub-Saharan Africa is mixed.1627 Most of the studies suggested that pharmaceutical treatment should be cost-effective compared with no treatment,172123 25 especially among people with moderate and severe HTN. However, there is no consensus on which pharmaceutical intervention is the most cost-effective, with high levels of uncertainty related to specific assumptions regarding the cost data. For example, the unit cost of outpatient department (OPD) visits per patient is US$7.1 and US$29–US$55 for medication in Tanzania,17 28 compared with US$4.3 and US$1–US$7 in Zambia, respectively, found in our previous study.29 Similarly, the admission cost for CVD differs significantly between South Africa (US$563616) and Zambia (US$120–US$14129).

In this study, we investigate the cost-effectiveness of HTN treatment by using the cost data collected independently in the local health facilities, focusing on the first-line pharmaceutical interventions at the primary level in rural Zambia. The results from this study will provide the government and MoH with evidence-based recommendations to assess the feasibility and affordability of HTN health policies.

Methods

A cost–utility analysis was undertaken from the perspective of healthcare providers to compare the cost-effectiveness of interventions for HTN in the adult population in Zambia. The economic evaluation methods and results were reported following the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards.30

The Chongwe District in Zambia was selected as the setting and location to conduct the economic analysis due to the availability of unit cost, health service data for cardiovascular diseases (CVDs) from previous studies29 31 . This data was obtained as part of the activities in the Project for Strengthening Basic Health Care Services Management for Universal Health Coverage conducted by the Japanese International Cooperation Agency. The Chongwe District is a typical rural district in Zambia, located next to the capital city. According to the latest Census,32 the population’s average age was 21.1 (SD: 0.25) in 2010. The age distribution was similar between the Chongwe District and the national total. The average prevalence of HTN was 19.1% (95% CI 17.5% to 20.6%).11 The CVD risk distribution at the age of 40 was different across genders (26% low risk, 21% moderate risk and 12% high risk for males and 21%, 15%, and 5% for females).31 All detailed data on age distribution, HTN and CVD risks for both genders are provided in online supplemental table S1–16.

Population

The target population for this study was patients from the Chongwe District aged ≥40 years with HTN, as the WHO recommends routine BP screening for individuals in this age group due to their higher risk of CVD.3335 Zambia’s 2016 Standard Treatment Guideline (STG) aligns with this recommendation.36 HTN is defined as SBP≥140 mm Hg and/or DBP≥90 mm Hg, according to the HEART technical package.34 It was assumed that people are eligible for preventive cardiology intended as the practice of early, primary and secondary prevention of all CVDs37 at the age of 40 years and that thereafter they receive treatment for their remaining life spans. This assumption is in line with the WHO package34 that proposed the routine screening of HTN among persons aged >40 years, as a high-risk population for CVDs, as well as the clinical protocol in Zambia36 that promotes a screening for HTN for this population subgroup.

A hypothetical cohort of 1000 male and female patients according to gender distribution in the district (online supplemental table S4) was entered into the model for the treatment of HTN. The starting age in the model was 40 years (in accordance with the aforementioned WHO and Zambian STG recommendations3336). To provide a relevant policy message, the Zambian guidelines do not suggest different treatments for different levels of risk or sex; hence, the main findings of this study relate to the general population in the Chongwe District. However, an exploratory analysis was performed on clinically relevant subpopulations based on the three risk levels (low, moderate and high) and sex, resulting in a total of six subgroup analyses.

Intervention and comparators

A Markov model assessed the cost-effectiveness of intervention (ie, drug combination to treat HTN recommended by the WHO HEARTS technical package34 and Zambia STG,36 as listed in table 1) versus comparator (no pharmaceutical intervention). The type, name and recommended dose of each drug available for HTN in Zambia38 are presented in online supplemental table S1.

Table 1 List of interventions

Intervention number	Combination of drugs	
1	Monotherapy of diuretics	
2	Monotherapy of CCB	
3	Monotherapy of ACEI or ARB	
4	CCB+diuretics	
5	Diu+ACEI or ARB	
6	CCB+ACEI or ARB	
ACEIACE inhibitorARBangiotensin receptor blockerCCBcalcium channel blocker

Cycle length and time horizon

A lifetime horizon was chosen to capture and evaluate the full costs and effects over a lifetime, in line with the National Institute for Health and Care Excellence (NICE) recommendations39 and ISPOR good practices.40 Specifically, the time horizon was set at 30 years because the life expectancy was 29.5 years at the age of 40 years for both genders, according to the 2010 census life table.32 The lehgthe of each sycle was a 1-year.17

Discount and currency rates

An annual discount rate of 3.5% rate was applied to costs and utilities as recommended by NICE.39 The currency rate adopted was US$1=ZK10.59 in 30 June 2019.

Model structure

The CVD prevention model is a probabilistic Markov-type model representing long-term costs and outcomes associated with treatments and comparator, considering a hypothetical Zambian population. The model (figure 1) was adapted from a previous study17, which investigated the cost-effectiveness of first-line pharmaceutical interventions for HTN in the Tanzanian population. Six mutually exclusive health states were considered: ‘no history of CVD,’ ‘history of myocardial infarction or congestive heart disease (CHD)’ and ‘history of stroke’. Finally, ‘death’ was modelled as an absorbing state, and stroke was modelled in three different health states based on severity: ‘mild,’ ‘moderate’ or ‘severe,’ to be consistent with disability weights reported in the Global Burden of Disease (GBD) 2010.41 In the model, a cohort starts from healthy individuals aged 40 (ie, ‘no history of CVD’). The cohort transitioned between different health states according to age-specific risks for each type of clinical event and considering also risk reduction from the interventions. Each health state is associated with a specific cost and disutility (as detailed in table 2). After each cycle, patients can stay in their state or change state in line with the model transition probabilities. We assume that if an individual experienced several CVD events, we used the cost and disutility related to the most severe event. Also, our model assumes that patients can either stay in their health state or move to a more severe status. A 70-year time horizon was considered to reflect life expectancy at the age of 40 years in Zambia, according to the 2010 census life table.32 In each model, ‘no treatment’ was the baseline strategy, which was compared with different interventions for the primary prevention of CVD. To explore the effects of the interventions in different populations, three distinct submodels were created to represent three CVD risk levels: low risk, moderate risk and high risk, according to the WHO CVD risk chart at the age of 40 years.42

Figure 1 Model structure. CHD, congestive heart disease.

Table 2 Model parameters

1. Transition probability for the general populationAnnual CHD and stroke risk source: (32, 42)	
 	CHD	 Stroke	
Age (years)	Mean	Min	Max	Mean	Min	Max	
40–44	0.0070	0.0038	0.0112	0.0020	0.0013	0.0030	
45–49	0.0094	0.0055	0.0147	0.0030	0.0020	0.0043	
50–54	0.0128	0.0077	0.0195	0.0047	0.0032	0.0069	
55–59	0.0174	0.0106	0.0259	0.0070	0.0049	0.0098	
60–64	0.0234	0.0146	0.0341	0.0103	0.0075	0.0140	
65–69	0.0311	0.0201	0.0441	0.0152	0.0115	0.0198	
70–74	0.0407	0.0275	0.0558	0.0223	0.0175	0.0279	
Case fatality rate of CHD and stroke source: (17, 43, 44, 45)	
 	CHD	 Stroke	
Age (years)	Man	Woman	 Man	Woman	
40–49	0.3040	0.4070	 0.3470	0.3520	
50–59	0.3110	0.4120	 0.2480	0.1980	
60–69	0.3360	0.4300	 0.2830	0.2520	
70–79	0.3670	0.4510	 0.4200	0.4120	
80<	0.4090	0.4840	 0.6420	0.6650	
Annual background mortality rate source: (32, 44, 45)	
 	Background mortality	 Postevent (CHD or stroke) mortality	
Age	Male	Female	Total	 2×Background mortality	
40–44	0.01866	0.01394	0.01630	
45–49	0.02061	0.01341	0.01701	
50–54	0.02086	0.01474	0.01780	
54–59	0.02287	0.01569	0.01928	
60–64	0.02924	0.02017	0.02471	
65–69	0.03213	0.02523	0.02868	
70–74	0.05111	0.03984	0.04548	
75–79	0.05407	0.04896	0.05152	
80+	0.08515	0.07752	0.08134	
Probability of stroke severity at the first and subsequent event source: (17, 46, 47)	
 	Grade	 Probability	
First event	Mild	 0.29	
Moderate	 0.44	
Severe	 0.27	
Subsequent event	Mild	 0.15	
Moderate	 0.25	
Severe	 0.60	
2. Health outcome Source (32, 41)	
YLL	Life expectancy	 29.5 years at the age of 40 years for both sexes.	
YLD	Health status	 Disability weight (95% CI)	
CHD	 0.42 (0.28 to 0.57)	
Stroke (mild)	 0.02 (0.01 to 0.04)	
Stroke (moderate)	 0.08 (0.05 to 0.11)	
Stroke (severe)	 0.54 (0.36 to 0.71)	
3. Effect of drugs and costsCost (USD) and effect of HTN drugs source: (48, 49, 50)	
Type	Name	Cost per tab	Daily usage	Annual cost	Effect for CHD (95% CI)	Effect for stroke (95% CI)	
Diu	Moduretic	0.0030	Once	1.099	0.72 (0.61 to 0.84)	0.68 (0.60 to 0.77)	
CCB	Nifedipine10 mg	0.0016	Twice	1.161	0.77 (0.55 to 0.94)	0.58 (0.41 to 0.84)	
ACEI	Enalapri 10 mg	0.0027	Once	0.975	0.81 (0.70 to 0.94)	0.65 (0.52 to 0.82)	
 	Lisinopril 5 mg	0.019	Once	6.935	Same as ACEI	Same as ACEI	
ARB	Losartan 50 mg	0.0095	Once	3.468	Same as ACEI	Same as ACEI	
Unit cost without material costs for HTN per patient (USD) source: (29, 31)	
 	Consultation cost	Screening cost	Lab cost	Total cost	
Unit cost (average)	4.33	0.54	1.70	6.58	
Unit cost (range)	2.5–14.10	0.31–1.76	0.8–3.4	3.61–19.26	
Annual cost without material costs for HTN per patient source: (29, 31)	
Frequency of OPD visit	Average	Min	Max	
Every 1 month	78.90	43.35	231.15	
Every 2 months	39.45	21.68	115.58	
Every 3 months	26.30	14.45	77.05	
Costs of treatment for CVD events and post-CVD events source: (29)	
Item	Cost (USD)	
CVD event	Admission with material cost (without material cost)	Male 141.5 (132.9)	
Female 120.8 (113.4)	
Post-CVD event	ASA 75 mg	Annual cost: 20.68 (0.057/tab once daily)	
HTN treatment	Same as the intervention before the event	
ACEIACE inhibitorARBangiotensin receptor blockerASAacetylsalicylic acidCCBcalcium channel blockersCHDcongestive heart diseaseCVDcardiovascular diseaseHTNhypertensionOPDoutpatient departmentYLDyears lost due to disabilityYLLyears of life lost

Model parameters

Transition probabilities

The annual risk of acute myocardial infarction (AMI), CHD and stroke was estimated using the non-laboratory-based risk chart developed by the WHO Risk Chart Working Group42 (risk equation shown in online supplemental figure 1).

The reason for choosing a non-laboratory-based risk chart was that laboratory testing was not necessarily available in all health facilities in the Chongwe District. The annual risks of AMI or CHD and stroke are described by the WHO CVD risk in persons aged 40 years in online supplemental table S7. Using the weights and the transition probabilities among different risk categories in online supplemental table S8–15, the transition probability was calculated for the general population in Chongwe District aged 40 years (table 2).

The case fatality rates of AMI and Stroke were extracted from the previous literature174345 and are outlined in table 3. Background mortality in Zambia was obtained from the Life Table of the 2010 Census,32and the annual mortality of people after the first event of CHD and stroke was assumed to increase according to previous studies44 45 as described in table 3. Postevent background mortality was assumed to be twice as high as the original mortality trend after a CHD and stroke event. Besides, the transition probability from stroke to the three severity levels (mild, moderate and severe) was collected from previous studies17 46 47 (table 2).

Table 3 Result of cost and effectiveness by the Markov model among the general population

Intervention	Cost	DALY	ICER	Life-year (LY)	LY saved	Dominance	
No treatment	318.5	10.88		21.43			
ACEI	1787.65	10.27	2398.99	21.9	0.47	Ex dominated	
Diu	1794.00	10.09	35.79	22.02	0.59	Ex dominated	
CCB	1794.18	10.14	−3.89	22.00	0.57	Abs dominated	
Diu+ACEI	1823.78	9.63	63.84	22.37	0.94	Ex dominated	
CCB+ACEI	1823.99	9.68	−4.37	22.34	0.91	Abs dominated	
Diu+CCB	1829.65	9.53	59.07	22.45	1.02	Undominated	
Cost-effectiveness of dominant treatment compared with no treatment	
No treatment	318.5	10.88		21.43			
Diu+CCB	1829.65	9.53	1114.65	22.45	1.02	Dominance	
Abs dominatedabsolute dominatedACEIACE inhibitorCCBcalcium channel blockersDALYdisability-adjusted life-yearEx dominatedextended dominatedICERincremental cost-effectiveness ratio

Health outcome

Disability-adjusted life-years (DALYs) were calculated using data from the GBD 201041 for years lost due to disability and Zambia age-specific life expectancy data for years of life lost.32 Table 3 summarises the data.

Effect of interventions

The relative risks (RRs) of the drug classes were retrieved from a systematic review,48 meta-analysis49and other published sources.50 The details are listed in table 3. The effects of combination interventions were calculated multiplicatively using RRs (RR1×RR2) as described in a previous study.17 The effects of each intervention are summarised in online supplemental table S15.

Treatment cost

The standard price of each HTN drug was obtained from the catalogue of Medical Store Limited,38 which was owned by the Zambian government. In the cost-effectiveness analysis, a cost estimated for the Zambia context was used. This cost is significantly lower compared with estimated cost from similar studies and context21; therefore, a sensitivity analysis considering a higher cost was performed. Table 3 lists the medications used in this study and their associated costs.

Regarding health service costs, unit costs of OPD visits and laboratory testing for HTN by different health levels were obtained from previous publications,2931 considering the Zambia context. While OPD unit costs included capital and labour costs, laboratory unit costs included capital, labour and material costs. The material cost for the OPD consultation was added to the relevant OPD unit cost, according to the selected intervention. The proportion of OPD visits per health facility level was also collected from the same previous study,31 (14.5% for first-level hospitals, 46.7% for health centres and 38.8% for health posts). Using OPD visit weights by health level, the average and range of unit costs for HTN in the entire Chongwe District were calculated. Eastern OPD visits included screening, laboratory testing and consultations. The unit cost per BP screening was OPD unit cost×0.125, and table 3 summarises the unit costs and their ranges. The frequency of follow-up recommended by the Zambian government is once every 1–3 months. For each expected frequency, the annual cost of HTN health services per patient was calculated as shown in table 3 and online supplemental table S17.

Regarding the cost of treatment for AMI, CHD and stroke, admission costs, including capital, labour and material costs, were extracted from a previous study29 (table 2). Special treatments, such as coronary artery bypass grafting, percutaneous transluminal coronary angiography and other intensive care, were not considered because these medical technologies were not available in Zambia during the study period(2019). For secondary prevention, it was assumed that a dose of 75 mg of acetylsalicylic acid was initiated for all patients in addition to HTN drugs in the intervention before the event. Table 2 summarises treatment costs after CVD events. All costs were discounted at the 2019 level according to World Bank inflation rates.51

Assumptions

Once individuals develop AMI or stroke, they continue to receive interventions for primary prevention until death. Life expectancy is estimated under poststroke or post-AMI conditions without secondary prevention.

Analytical methods

Main analysis

The incremental effect, cost and incremental cost-effectiveness ratios (ICERs) were first calculated for the six mutually exclusive interventions (table 1) in two different analyses regarding the general population and then according to the three levels of risk of HTN and between sexes. Strategies with ICERs below the GDP per capita in Zambia (approximately US$1500 in 2019)51 were considered cost-effective.

Sensitivity analysis

Deterministic and probabilistic sensitivity analyses were performed. A deterministic sensitivity analysis was performed on the following parameters: the effects of drugs on stroke and CHD, cost of drugs, the utility of CHD and stroke, initial treatment cost of CVD, cost of aspirin treatment after the event and cost of OPD visits. Parameter for both sensitivity analyses are fully reported in online supplemental table S18 and 19. For the deterministic sensitivity analysis, a Tornado diagram was produced, and for the probabilistic sensitivity analysis, an incremental cost-effectiveness scatter plot and cost-effectiveness acceptability curves were produced using TreeAge Pro.

Budget impact

A budget impact analysis was also performed using the results of the Markov model and the data of the HTN population of the Chongwe District (online supplemental table S3).

Results

Cost-effectiveness analysis of treatment for HTN medications among the general population

The results for the general population are presented in table 3. The dominant treatment is a combination of diuretics and calcium blockers. The estimated ICER was US$1114.65 per averted DALY, compared with no treatment. As the incremental cost-effectiveness per DALY threshold was set at US$1500 based on Zambian GDP per capita,51 this combination therapy was considered a cost-effective intervention.

Deterministic sensitivity analysis: the general population

The Tornado diagram between the no treatment and dominant intervention, which was a combination therapy of diuretics and calcium channel blockers (CCB), is shown in online supplemental figure 2. The midpoint of the ICER was US$1129.06 per averted DALY. As the cost of drugs changed from 1/10th to 10 times the standardised price, the ICER ranged from approximately US$1100–US$1350 per averted DALY. The ICER score changed from US$800 to US$1400 per averted DALY, and the parameter with the greatest impact on the ICER was the cost of OPD visits, which depended on the frequency of visits. If the frequency was less than every month, the ICERs were lower than US$1500 per averted DALY.

Probabilistic sensitivity analysis for the general population

Online supplemental figure 3 depicts the incremental cost-effectiveness scatter plot of the combination of the dominant treatment strategy (combination of diuretics and calcium blockers) for HTN compared with no treatment using 1000 Monte Carlo iterations. The dotted line represents a willingness-to-pay (WTP) threshold of US$1500. Most dots were below the WTP threshold and the ICER from the PSA analysis comparing Diu+CCB and no treatment was US$880/averted DALY. We also reported the 95% uncertainty interval estimates for ICERs from the PSA: (248–2118). Figure 2 displays the cost-effectiveness acceptability curves representing the probability of cost-effectiveness for each level of WTP. No treatment is the most cost-effective strategy if the WTP is below approximately US$1200, and combination therapy with diuretics and calcium blockers becomes the most cost-effective intervention if the WTP is beyond this value.

Figure 2 Cost-effectiveness acceptability curve among men at high risk. ACEI, ACE inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blockers.

Subgroup analysis

The target population was categorised into six groups according to sex and three CVD risks: mild, moderate or high. Online supplemental table S20 shows the cost-effectiveness results for males and females at each level of the risk subgroup. In all subgroups, the dominant treatment was a combination therapy with diuretics and calcium blockers. However, compared with the absence of treatment, this intervention was not cost-effective across all subgroups. The ICERs between combination therapy and no treatment are summarised in online supplemental table S22. The cost-effectiveness acceptability curves for the six subgroups are illustrated in online supplemental figure 4. When the cost-effectiveness threshold of ICER is set at US$1500 per averted DALY based on GDP per capita,51 combination therapy is cost-effective among both sexes with high and moderate CVD risk. However, in a population with low CVD risk, no treatment should be considered a cost-effective strategy.

Budget impact

Online supplemental table S22 shows the estimated annual budget impact if all HTN patients aged 40 years and above in Chongwe District received the most cost-effective treatment: diuretics and calcium blockers. The annual total budget impact was estimated at US$1 015 605, including labour, capital and material costs. Taking into account only material costs, the annual total budget was US$29 435.5, which needs to be covered by the Chongwe District as the national government would be responsible for labour and capital costs.

Discussion

This study examined the cost-effectiveness of several first-line HTN therapy options recommended by the WHO using novel data coming from primary care in rural Zambia. According to the findings, the most cost-effective first-line medication for HTN in a rural Zambian setting was a combination therapy with diuretics and calcium blockers for the general population. Considering subpopulations by gender and three levels of risk, this combination of therapies was still cost-effective for all high-risk individuals (male and female) and for male moderate-risk individuals. The threshold of ICER was set as US$1500, which is approximately equivalent to the GDP per capita in Zambia in 2019.51 For other subgroups (male and female low-risk and female moderate risk) ‘no treatment’ was the most cost-effective strategy. In a previous study investigating the cost-effectiveness of first-line antihypertensive drugs in Tanzania,17 the combination of ACE inhibitor+diuretic and triple therapy of ACE inhibitor+diuretic+calcium blocker was the most cost-effective interventions for populations with low to moderate risk and high to very-high risk, respectively. However, triple therapy was not included in this study because this package was not recommended as a first-line drug by WHO HEARTS guidelines.35 Thus, the results were not comparable among high-risk populations. However, in the low-risk population, our results, finding that the combination of diuretics and calcium blockers was the most cost-effective, differ from the Tansania study.17 As the drug effectiveness parameters were similar between the two studies, this discrepancy is likely due to the cost of each HTN drug. The cost of ACE inhibitor (ACEI) and CCB in another study21 in Tanzania. However, as our cost source derived from the standard prices published by the governmental medical supply organisation in Zambia36 (the annual costs of ACEI and CCB are estimated as US$29.3 and US$54.8 to US$1.16 and US$3.47, respectively), we believe that our estimates are more likely to provide robust results for the Zambian context.

According to the sensitivity analysis exhibited in figure 2, most of the changes in the parameters did not increase the ICERs beyond US$1500, which is Zambia’s GDP per capita. While only the costs of OPD visits could affect the selection of cost-effective interventions, combination therapy remained a cost-effective intervention if the frequency of OPD visits was less than once per month. Therefore, considering both one way and PSA (with CEAC showing the highest probability of cost-effectiveness of our dominant strategy at a WTP higher than 1300), among the general population in the Chongwe District, the results of cost-effectiveness analysis for pharmaceutical intervention for HTN seem robust.

Regarding budget impact, US$29 435.5 would be required as the annual total material costs for the district if all target populations could receive the most cost-effective pharmaceutical treatment, which is a combination of diuretics and CCB. Most material costs are derived from the cost of the drugs. According to the National Budget Book of the Ministry of Finance in Zambia,52 the annual budget for service delivery was US$241 481, excluding human resource and health system management costs. The budget impact of hypertensive drugs would account for more than 10% of the total district health office budget. Considering other health services, this appears to be a potential financial burden if the district needs to cover these investments. Support at the national or provincial level is critical for maintaining the supply of hypertensive drugs, based on the estimation of the necessary budget for HTN control so that every patient can access healthcare services.

The strength of this study is that it provides novel evidence for the cost-effectiveness analysis of HTN pharmaceutical treatments in the WHO guidelines using locally obtained data in Zambia. Consequently, building evidence on primary data from Zambia, this study is likely more robust and reliable for policy purposes in the country, as other existing evidence created on secondary data or with data from neighbouring countries. Additionally, we conducted a budget impact analysis highlighting the resources required for HTN services in rural sub-Saharan African countries. This information could contribute to create a tangible plan for the expenditure framework for comprehensive essential health services, including HTN, at the district level.

However, this study has several limitations. First, secondary prevention and special treatment for CDH, AMI and stroke were not considered because these treatments were not available in Zambia. However, as medical technologies are being developed in Zambia, these advanced interventions for CVD have to potential to be incorporated into future national guidelines. With this perspective in mind, a cost-effectiveness analysis that includes advanced treatments for CVD should be considered in the future. Second, there was limited information about the necessary parameters for economic analysis, such as utility value, transition probability between health statuses, case fatality rate related to CVD, patient costs and updated Census data since 2010 in Zambia or sub-Saharan Africa. Standardised values of these parameters specific to the sub-Saharan African setting should be investigated to identify priority areas for investment based on more reliable data. According to the deterministic analysis in figure 2 among the general population, the costs of interventions (and specifically the cost of drugs) could significantly influence the results of the cost-effectiveness analysis to calculate ICERs. Future studies should review market prices in specific sub-Saharan countries. Finally, this study did not consider other policy combined with the pharmaceutical treatment, such as reducing sodium intake, the promotion of physical activity and sensitisation to promote awareness and maintain high adherence to HTN treatment. The cost-effectiveness of comprehensive interventions, including policy-level actions, health promotion activities, pharmaceutical treatment and advanced health technology, should be investigated in future studies to assess the feasibility of introducing CVD programmes in sub-Saharan Africa, including Zambia.

Conclusions

The most cost-effective first-line medication for HTN among the six types of drug combinations in rural Zambia is the combination therapy of diuretics and calcium blockers for the general population. When analysing the subpopulation results, the most cost-effective intervention was still the combination of diuretics and calcium blockers for the subpopulations, except for men with low risk and women with moderate and low risk. Among these populations, no treatment is cost-effective. Besides, as the costs of HTN drugs are affordable, it is worth considering the promotion of delivering HTN medications even in rural areas. However, as this study analysed only first-line medications for HTN, further studies are imperative to assess the feasibility of introducing a comprehensive CVD programme in Zambia, including community sensitisation, lifestyle modification, secondary prevention and advanced treatment.

supplementary material

10.1136/bmjopen-2024-084575 online supplemental file 1

10.1136/bmjopen-2024-084575 online supplemental file 2

10.1136/bmjopen-2024-084575 online supplemental file 3

10.1136/bmjopen-2024-084575 online supplemental file 4

10.1136/bmjopen-2024-084575 online supplemental file 5

Acknowledgements

The authors wish to thank Dr Mzaza Nthele (Director, Department of Clinical Care, Diagnostic Service), Dr Consity Mwale (Lusaka Provincial Health Director), Dr Joseph Kabungo (Chongwe District Health Director), Dr Arthur Mumba (Medical Superintendent, Chongwe District Hospital), Mr. Andrew Chibangula (Planner in Chongwe District Health Office) and Mrs Tasila Sompa (Information Officer in Chongwe District Health Office) of the Ministry of Health, Zambia, for setting up the research environment. Furthermore, the authors wish to acknowledge the support from Dr John Musuku, Dr Evans Mulendele, Dr Dominique Chimanuka, Dr Nchimunya Machila and Ngosa Mumba (University Teaching Hospital in Zambia) for the development of the design, the data collection and analysis.

Data availability statement

No additional data available.

Review Process File
05 09 2024

Funding: This study was funded by the Research Fund of the National Center for Global Health and Medicine (21A04 and 22A01) for data collection, analysis and publication.

Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2024-084575).

Provenance and peer review: Not commissioned; externally peer reviewed.

Patient consent for publication: Not applicable.

Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
==== Refs
References

1 World Health Organization Fact sheet hypertension WHO 2022 Available https://www.who.int/news-room/fact-sheets/detail/hypertension Accessed 1-Mar-2022
2 NCD Risk Factor Collaboration (NCD-RisC) Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants Lancet 2021 398 957 80 10.1016/S0140-6736(21)01330-1 34450083
3 World Health Organization Adherence to long-term therapies: evidence for action WHO 2003 Available https://iris.who.int/handle/10665/42682
4 Wirtz VJ Kaplan WA Kwan GF et al Access to Medications for Cardiovascular Diseases in Low- and Middle-Income Countries Circulation 2016 133 2076 85 10.1161/CIRCULATIONAHA.115.008722 27217433
5 Walsh KB Woo D Sekar P et al Untreated Hypertension: a Powerful Risk Factor for Lobar and Nonlobar Intracerebral Hemorrhage in Whites, Blacks, and Hispanics Circulation 2016 134 1444 52 10.1161/CIRCULATIONAHA.116.024073 27737957
6 Doyle AE Hypertension and vascular disease Am J Hypertens 1991 4 103S 106S 10.1093/ajh/4.2.103s 2021454
7 Appleton SL Neo C Hill CL et al Untreated hypertension: prevalence and patient factors and beliefs associated with under-treatment in a population sample J Hum Hypertens 2013 27 453 62 4 10.1038/jhh.2012.62 23235365
8 World Health Organization NCD global monitoring framework WHO Available https://www.who.int/nmh/global_monitoring_framework/en/ Accessed 6-Jun-2021
9 Siddharthan T Ramaiya K Yonga G et al Noncommunicable Diseases In East Africa: assessing The Gaps In Care And Identifying Opportunities For Improvement Health Aff (Millwood) 2015 34 1506 13 10.1377/hlthaff.2015.0382 26355052
10 World Health Organization Noncommunicable Diseases Country Profiles 2018 Geneva WHO 2018 Available https://apps.who.int/iris/handle/10665/274512
11 Ministry of Health in Republic of Zambia Zambia steps for non-communicable diseases risk factors, zambia report for 2017 2017 Available https://www.who.int/ncds/surveillance/steps/Zambia-NCD-STEPS-Survey-Report-2017.pdf?ua=1
12 Mulenga D Siziya S Rudatsikira E et al District specific correlates for hypertension in Kaoma and Kasama rural districts of Zambia Rural Remote Health 2013 13 2345 24050622
13 Siziya S Mulenga D Prevalence and Correlates of Hypertension among Adults Aged 25 Years or Older in a Mining Town of Kitwe, Zambia J Hypertens 2012 1 10.4172/2167-1095.1000105
14 Goma FM Nzala SH Babaniyi O et al Prevalence of hypertension and its correlates in Lusaka urban district of Zambia: a population based survey Int Arch Med 2011 4 34 10.1186/1755-7682-4-34 21974840
15 Ministry of Health in Republic of Zambia National health strategic plan 2012-2026 2022 Available https://www.moh.gov.zm/wp-content/uploads/2023/02/National-Health-Stratergic-Plan-for-Zambia-2022-to-2026-revised-February-2023-lower-resolution.pd
16 Gaziano TA Steyn K Cohen DJ et al Cost-effectiveness analysis of hypertension guidelines in South Africa: absolute risk versus blood pressure level Circulation 2005 112 3569 76 10.1161/CIRCULATIONAHA.105.535922 16330698
17 Ngalesoni FN Ruhago GM Mori AT et al Cost-effectiveness of medical primary prevention strategies to reduce absolute risk of cardiovascular disease in Tanzania: a Markov modelling study BMC Health Serv Res 2016 16 185 10.1186/s12913-016-1409-3 27184802
18 Subramanian S Hilscher R Gakunga R et al Cost-effectiveness of risk stratified medication management for reducing premature cardiovascular mortality in Kenya PLoS ONE 2019 14 e0218256 10.1371/journal.pone.0218256 31237910
19 Rosendaal NTA Hendriks ME Verhagen MD et al Costs and Cost-Effectiveness of Hypertension Screening and Treatment in Adults with Hypertension in Rural Nigeria in the Context of a Health Insurance Program PLoS ONE 2016 11 e0157925 10.1371/journal.pone.0157925 27348310
20 Gaziano TA Bertram M Tollman SM et al Hypertension education and adherence in South Africa: a cost-effectiveness analysis of community health workers BMC Public Health 2014 14 240 10.1186/1471-2458-14-240 24606986
21 Robberstad B Hemed Y Norheim OF Cost-effectiveness of medical interventions to prevent cardiovascular disease in a sub-Saharan African country--the case of Tanzania Cost Eff Resour Alloc 2007 5 3 10.1186/1478-7547-5-3 17316431
22 Ortegón M Lim S Chisholm D et al Cost effectiveness of strategies to combat cardiovascular disease, diabetes, and tobacco use in sub-Saharan Africa and South East Asia: mathematical modelling study BMJ 2012 344 e607 10.1136/bmj.e607 22389337
23 Ekwunife OI Okafor CE Ezenduka CC et al Cost-utility analysis of antihypertensive medications in Nigeria: a decision analysis Cost Eff Resour Alloc 2013 11 2 10.1186/1478-7547-11-2 23343250
24 Basu S Wagner RG Sewpaul R et al Implications of scaling up cardiovascular disease treatment in South Africa: a microsimulation and cost-effectiveness analysis Lancet Glob Health 2019 7 e270 80 10.1016/S2214-109X(18)30450-9 30528531
25 Lin JK Moran AE Bibbins-Domingo K et al Cost-effectiveness of a fixed-dose combination pill for secondary prevention of cardiovascular disease in China Lancet Glob Health 2019 7 e1346 58 31477544
26 Davari M Sorato MM Kebriaeezadeh A et al Cost-effectiveness of hypertension therapy based on 2020 International Society of Hypertension guidelines in Ethiopia from a societal perspective PLoS ONE 2022 17 e0273439 10.1371/journal.pone.0273439 36037210
27 Pozo-Martin F Akazili J Der R et al Cost-effectiveness of a Community-based Hypertension Improvement Project (ComHIP) in Ghana: results from a modelling study BMJ Open 2021 11 e039594 10.1136/bmjopen-2020-039594
28 Ngalesoni F Ruhago G Norheim OF et al Economic cost of primary prevention of cardiovascular diseases in Tanzania Health Policy Plan 2015 30 875 84 10.1093/heapol/czu088 25113027
29 Ministry of Health in Republic of Zambia Study on the unit costs of health services provided at hospitals and health centres in lusaka and southern provinces Zambia, Lusaka MoH 2018
30 Husereau D Drummond M Petrou S et al Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement Int J Technol Assess Health Care 2013 29 117 22 10.1017/S0266462313000160 23587340
31 Ministry of Health in Republic of Zambia Situation analysis of service provision for cardio-vascular disease and diabetes mellitus in chongwe district Lusaka MoH 2018
32 Central statistical office of zambia 2010 census of population and housing Lusaka CSO 2012
33 World Health Organization Package of essential noncommunicable (pen) disease interventions for primary health care in low-resource settings Geneva WHO 2010 Available https://www.who.int/nmh/publications/essential_ncd_interventions_lr_settings.pdf
34 World Health Organization HEARTS technical package 2018 2018 Available https://www.who.int/publications/i/item/hearts-technical-package
35 World Health Organization Global action plan for the prevention and control of noncommunicable diseases 2013-2020 Geneva WHO 2013
36 Ministry of Health in Republic of Zambia Standard treatment guidelines, essential medicines list and essential laboratory supplies list for Zambia Luska MoH 2013
37 German CA Baum SJ Ferdinand KC et al Defining preventive cardiology: a clinical practice statement from the American Society for Preventive Cardiology Am J Prev Cardiol 2022 12 100432 10.1016/j.ajpc.2022.100432 36425534
38 Medical Store Limited MSL calaogue Lusaka MSL 2016
39 National Institute for Health and Care Excellence Guide to the methods of technology appraisal Process and methods (PMG9) 2013
40 Caro JJ Briggs AH Siebert U et al Modeling good research practices--overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-1 Med Decis Making 2012 32 667 77 10.1177/0272989X12454577 22990082
41 Salomon JA Vos T Hogan DR et al Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010 Lancet 2012 380 2129 43 10.1016/S0140-6736(12)61680-8 23245605
42 WHO CVD Risk Chart Working Group World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions Lancet Glob Health 2019 7 e1332 45 10.1016/S2214-109X(19)30318-3 31488387
43 Truelsen T Begg S The global burden of cerebrovascular disease World Health Organization 2006
44 Johansson S Rosengren A Young K et al Mortality and morbidity trends after the first year in survivors of acute myocardial infarction: a systematic review BMC Cardiovasc Disord 2017 17 53 10.1186/s12872-017-0482-9 28173750
45 Brønnum-Hansen H Davidsen M Thorvaldsen P et al Long-term survival and causes of death after stroke Stroke 2001 32 2131 6 10.1161/hs0901.094253 11546907
46 Garbusinski JM van der Sande MAB Bartholome EJ et al Stroke presentation and outcome in developing countries: a prospective study in the Gambia Stroke 2005 36 1388 93 10.1161/01.STR.0000170717.91591.7d 15947255
47 Heikinheimo T Chimbayo D Kumwenda JJ et al Stroke outcomes in Malawi, a country with high prevalence of HIV: a prospective follow-up study PLoS ONE 2012 7 e33765 10.1371/journal.pone.0033765 22479439
48 Wright JM Musini VM Gill R First-line drugs for hypertension Cochrane Database Syst Rev 2018 4 CD001841 10.1002/14651858.CD001841.pub3 29667175
49 Law MR Morris JK Wald NJ Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies BMJ 2009 338 b1665 10.1136/bmj.b1665 19454737
50 ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Hypertension 2003 42 239 46 10.1161/01.HYP.0000086521.95630.5A 12925554
51 World Bank GDP per capita (current US$) - Zambia 2019 Available https://data.worldbank.org/indicator/NY.GDP.PCAP.CD?locations=ZM
52 Ministry of Finance Z Yellow book for 2017 budget Lusaka MoF 2017
