Abstract
Background
Hypertension is a prevalent global health issue with far-reaching consequences. It impacts millions of individuals worldwide and poses significant risks to overall health. We aimed to explore and compare the cost-effectiveness and clinical efficacy of single, dual, and triple antihypertensive therapies in the management of blood pressure.
Method
This retrospective observational study evaluated the cost effectiveness of antihypertensive therapy from the inpatient records of hypertensive urgency patients from January 2022 to December 2022. Data was extracted from the medical records including crucial information such as MR number, name, gender, weight, dates of admission and discharge, co-morbidities, therapy type, prescribed drugs and doses, and blood pressure readings. Employing standard costing techniques, the study calculated direct medical costs associated with the patient’s stay, medical care, nursing, and medication charges, considering the timeframe of August 2023. Data was analyzed using SPSS and Microsoft Excel. Mann Whitney and Kruskall Walis test was performed for statistical analysis.
Results
Out of 120 patients, the majority were male 55% and between the age group 61–80 years i.e., 45%. The analysis revealed a statistically significant impact on systolic blood pressure across the different therapies. Monotherapy resulted in a higher median systolic BP (140.0 mmHg [IQR 6.27]) compared to dual therapy (136.7 mmHg [IQR 6.7]) and triple therapy (133.3 mmHg [IQR 10.0]), with a significant difference (p = 0.000). In terms of cost-effectiveness, triple therapy demonstrated the lowest average cost-effectiveness ratio (ACER) for systolic BP control PKR 1803, while dual therapy was the most cost-effective for diastolic BP management with PKR 2438.
Conclusion
The study concluded triple therapy as the most cost effective strategy for reducing systolic blood pressure, demonstrating its efficacy in blood pressure management. Conversely, dual therapy proved optimal for controlling diastolic blood pressure.
Registration
IRB # 0126 − 23 Dated: 24 July 2023.
Keywords: Cost effectiveness, Antihypertensive, Mono, Dual, Triple therapy, Average cost effectiveness, Incremental cost effectiveness ratio
Background
Hypertension is the most prevalent health issue with worldwide implications. It has a profound impact on millions of people globally leading to severe health related complications and associated with an increased risk of developing cardiovascular diseases, strokes, and kidney problems [1]. The primary etiological factors of elevated blood pressure are multifaceted; they may arise from an array of determinants including genetic predisposition, lifestyle factors, and age-related issues [2]. Hypertensive urgency is rather a more serious condition with a rapid surge in blood pressure without any potential damage to the organ. In this condition, a patient needs urgent medical attention to prevent any further damage as the patient is at high risk of organ damage [3]. Hypertensive urgency and hypertensive emergency are differentiated by end-organ damage, in the latter one, end-organ damage occurs while hypertensive urgency being significantly more common [4]. It’s been reported to have 6 hypertensive crisis cases out of every 1,000 individuals. Among these cases, most of the people almost 71.7% presented with hypertensive urgency, while 19.1% experienced hypertensive emergency. Additionally, 9.2% of these cases were identified as hypertensive pseudo-crises [5]. If prompt medical attention is not provided it can worsen into a Hypertensive emergency, to ensure no organ damage timely and appropriate treatment is paramount [3]. Chronic condition can damage various organs such as increased workload on the heart, as a result coronary artery disease, heart failure, and left ventricular hypertrophy can occur [6].
It is more commonly observed in patients with a previous history of uncontrolled hypertension, because of inconsistent management, medication non adherence, and inadequate BP monitoring [7]. Age-related changes that occur in the body with time such as changes in blood vessel elasticity is another potential risk [8]. Socioeconomic status demographic factors, and ethnicity may play a key role in susceptibility, it is because some ethnic groups are genetically prone while those with lower socioeconomic status may face difficulty in properly managing hypertension with limited resources and finance [9, 10].
Apart from individual health, hypertension has far more consequences for the economy of the country’s healthcare system, as well as globally. The cost that is associated with the management of hypertension is very significant i.e. diagnostic tests, medical appointments, medications, and potential hospitalizations [11]. Additionally, the indirect, tangible and intangible cost cannot be overlooked [12]. People with uncontrolled hypertension often face difficulty with their normal routine work. Sometimes it can be very fatal leading to the death of a person leaving families shattered and societies struggling with the loss of productive individuals [13]. Considering the current circumstances such as limited resources and rising healthcare costs, it is crucial to use resources wisely. So, we can ensure that the resources we invest result in the best possible health outcomes and economic gains [14].
The main concept of cost-effectiveness is to check whether clinical benefits outweigh the cost of the therapy. CEA (Cost-effective Analysis) is to check the cost related to the clinical outcomes by different treatment strategies [15]. The economic associations of hypertension have different factors, including direct medical costs, indirect costs resulting from reduced productivity, and intangible costs related to reduced quality of life. Therefore considering the impact of various factors and comparing different treatment options is vital [16]. Medications used for hypertension management provide a pivotal role in giving relief from BP and associated health risks, those medications comprise different classes acting on different mechanisms and can have different problems as well [17]. As the price of the drugs may vary that adds further difficulty concerning patient access and healthcare expenditures [18].
In order to identify these determinants and make informed decisions that equitably address all dimensions while seeking economically viable alternatives, a comprehensive evaluation that amalgamates clinical data with economic frameworks is essential. Furthermore, to assess the prospective health outcomes in relation to expenditures, cost-effectiveness analysis equips stakeholders with the requisite understanding necessary to enhance healthcare approaches [19]. With limited resources at stake and millions of people being affected with hypertension, understanding the CEA of antihypertensive drugs is the need of time. This study aimed to determine which antihypertensive therapy gives the best value for money, focusing on improving patient health and making the healthcare system more efficient. By measuring the cost and outcomes through CEA of different treatment strategies, a researcher provides reasonable information that enables healthcare providers and policymakers to make informed decisions and adopt patient-tailored approach with optimized resource allocation [20].
Method
Study design and setting
A retrospective observational study design was used to analyze the cost effectiveness of antihypertensive drugs. The data was collected from Shifa International Hospital Islamabad, Pakistan.
Study population
The target population for this study consisted of inpatients diagnosed with hypertensive urgency, who received medical care within the specified study period, from Jan 2022 to Dec 2022. The study enrolled all the patients of hypertensive urgency admitted during the said time period i.e., 127 out of which 120 followed the inclusion criteria. The inclusion criteria of the study include all the patients of confirmed diagnosis of hypertensive urgency, greater than 18 years of age and less than 90 years. The patients less than 18 years of age or missing or incomplete medical records were excluded.
Data collection
Demographic and clinical variables were extracted from the medical records of patient including; gender, weight, age, date of admission, date of discharge, comorbidity related to cardiovascular system, therapy type, prescribed drug and dose, and blood pressure (BP) reading. The patient’s blood pressure was measured at least three times, and the average of these readings was used. The direct medical costs, including hospital stay, medical care, nursing, and medication charges, were calculated using standard costing techniques [21, 22]. The cost was calculated based on the timeframe of August 2023.
Outcome measures
Therapeutic effectiveness
The effectiveness of each therapy in reducing systolic and diastolic blood pressure, measured as the mean reduction in mmHg following the administration of single, dual, and triple antihypertensive therapies.
Therapeutic cost
The standard costing rate was calculated for the direct medical costs associated with each patient’s hospital stay, including expenses for medicine, nursing care, and physician services. The standard cost rates for the hospital were obtained from the hospital finance department, while the rates for medicines were sourced from the hospital pharmacy. All these rates have been applied according to the data available in August 2023.
Standard costing
Standard costing is to determine a fixed or predetermined cost for each thing, in healthcare, there are fixed charges for each item, like fixed charges for a bed, fixed charges for a nurse, and fixed charges for a physician [21, 22].
Direct medical cost
Direct medical costs encompass the specific expenses directly tied to medical care, including physician fees, hospital services, medications, laboratory tests, medical equipment, and nursing care. These costs are directly associated with the diagnosis, treatment, and management of health conditions and play a crucial role in healthcare economics, cost-effectiveness analyses, and budgeting.
Average cost effectiveness ratio
The Average Cost-Effectiveness Ratio (ACER) is a metric used in health economics and cost-effectiveness analysis to assess the average cost associated with gaining a unit of health outcome or effectiveness.
 |
Total Cost of Intervention includes all costs associated with implementing a specific healthcare intervention, such as treatment costs, monitoring costs, and any other relevant expenses.
Average Effectiveness or Health Outcome refers to the average improvement in health or achievement of a specific health outcome attributable to the intervention. Effectiveness is often measured in terms of health metrics or units, e.g. mmHg.
Incremental cost effectiveness ratio
The Incremental Cost-Effectiveness Ratio (ICER) is a key metric in health economics and cost-effectiveness analysis. It compares the difference in costs and the difference in outcomes between two alternative interventions. The formula for calculating the ICER is:
 |
Cost of Interventions A and B are the total costs associated with implementing each of the two interventions being compared. Costs may include direct medical costs, non-medical costs, and other relevant expenses. The study has taken into account only direct medical costs.
Effectiveness of interventions A and B
This refers to the health outcomes or effectiveness associated with each intervention. The effectiveness measure could be in terms of health gains, quality-adjusted life years (QALYs), or other relevant units e.g. mmHg.
The ICER provides information on the additional cost incurred (or saved) for each additional unit of health outcome gained (or lost) when comparing two interventions. Decision-makers can use the ICER to assess the cost-effectiveness of one intervention over another [15].
Data analysis procedure
Data analysis was conducted using SPSS (Statistical Package for the Social Sciences) and Microsoft Excel. The data analysis included various statistical tests and techniques to explore the cost-effectiveness of the treatment of hypertension such as ACER (Average Cost Effectiveness Ratio) and ICER (Incremental Cost Effectiveness Ratio). Mann Whitney and Kruskal Walis test was used to statistically analyze the data. The results were presented and interpreted to draw meaningful conclusions regarding the cost-effectiveness of different treatment strategies in hypertension patients.
Results
Sociodemographic characteristics of the study population
The study included a total of 120 patients, with a slightly higher proportion of males (55%) compared to females (45%). The age distribution showed that the majority of patients were between 61 and 80 years old (45%), followed by those aged 41 to 60 years (32.5%). A smaller percentage of patients fell within the age ranges of 18 to 40 years (12.5%) and 81 to 100 years (10%). Blood pressure measurements indicated a mean systolic blood pressure of 137.8 ± 6.2 mmHg and a mean diastolic blood pressure of 81.9 ± 5.0 mmHg. The length of hospital stay varied among patients, with most (58.3%) staying for 2 to 3 days, 30.8% for 0 to 1 day, and 10.8% for 3 to 4 days. Regarding comorbidities, 55.8% of the patients had at least one comorbidity. Smoking status was less clearly defined, with only 8.3% identified as smokers, 34.2% as non-smokers, and a significant proportion (57.5%) with unknown smoking status. A detailed description is given in Table 1.
Table 1.
Sociodemographic and clinical characteristics of patients
| Variables | n (%) |
|---|---|
| Gender | |
| Male | 66 (55) |
| Female | 54 (45) |
| Age | |
| 18–40 | 15 (12.5) |
| 41–60 | 39 (32.5) |
| 61–80 | 54 (45) |
| 81–100 | 12 (10) |
| Blood pressure | |
| Systolic BP (mmHg) +-SD | 137.8 ± 6.2 |
| Diastolic BP (mmHg) +-SD | 81.9 ± 5.0 |
| Length of stay | |
| 0–1 | 37 (30.8) |
| 2–3 | 70 (58.3) |
| 3–4 | 13 (10.8) |
| Comorbidity | 67 (55.8) |
| Smoking status | |
| Smoker | 10 (8.3) |
| Non smoker | 41 (34.2) |
| Smoking status (unknown) | 69 (57.5) |
Factors affecting systolic BP, diastolic BP and cost
Patients aged above 60 years had a significantly higher median systolic blood pressure compared to those below 60 years (139.0 mmHg [IQR 8.3] vs. 136.7 mmHg [IQR 4.2], p = 0.020). However, no significant differences in systolic blood pressure were found between males and females (p = 0.285) or between patients with and without comorbidities (p = 0.905). The length of hospital stay did not significantly affect systolic blood pressure (p = 0.179), and smoking status was also not significantly associated with systolic blood pressure levels (p = 0.848). In contrast, the type of therapy administered had a statistically significant impact on systolic blood pressure, with monotherapy resulting in a higher median systolic BP compared to dual or triple therapy (140.0 mmHg [IQR 6.27] vs. 136.7 mmHg [IQR 6.7] and 133.3 mmHg [IQR 10.0], respectively; p = 0.000).
In terms of cost, patients above 60 years incurred higher median treatment costs compared to those below 60 years (20,933.4 [IQR 10,617.6] vs. 20,764.6 [IQR 20,775.8], p = 0.025). There was no significant difference in costs based on gender (p = 0.633) or comorbidity status (p = 0.318). Length of hospital stay was a significant factor influencing cost, with longer stays associated with significantly higher costs (p < 0.001 for all comparisons). The type of therapy also influenced cost, with triple therapy leading to higher median costs compared to mono and dual therapy (20,989.6 [IQR 10,578.3] vs. 20,768.2 [IQR 20,769.3] and 20,810.2 [IQR 20,781.4], respectively; p = 0.034). A detailed description is given in Table 2.
Table 2.
Factors affecting systolic blood pressure, diastolic blood pressure, and cost
| Factor | Category | Systolic BP (Median [IQR]) | p-Value | Diastolic BP (Median [IQR]) | p-Value | Cost (Median [IQR]) | p-Value |
|---|---|---|---|---|---|---|---|
| Age | Below 60 | 136.7 (4.2) | 0.020 | 83.3 (5.0) | 0.645 | 20,764.6 (20,775.8) | 0.025 |
| Above 60 | 139.0 (8.3) | 83.3 (8.4) | 20,933.4 (10,617.6) | ||||
| Gender | Male | 138.3 (8.4) | 0.285 | 83.3 (8.4) | 0.477 | 20,930.8 (20,927.1) | 0.633 |
| Female | 138.3 (7.1) | 82.5 (5.0) | 20,818.5 (20,723.3) | ||||
| Comorbidities | With Comorbidities | 138.3 (6.7) | 0.905 | 83.3 (5.0) | 0.798 | 20,815.0 (20,752.2) | 0.318 |
| Without Comorbidities | 138.3 (6.7) | 83.3 (6.7) | 20,962.6 (20,884.3) | ||||
| Length of Stay | 0–1 | 138.3 (6.50) | 0.179 | 83.3 (5.0) | 0.946 | 10,380.4 (5,734.7) | 0.000 |
| 2–3 | 138.3 (8.40) | 82.5 (6.7) | 31,112.9 (10,369.8) | ||||
| 4–5 | 138.3 (7.45) | 83.3 (9.2) | 41,653.4 (5,334.9) | ||||
| Smoking | Yes | 136.7 (8.38) | 0.848 | 85.8 (7.13) | 0.303 | 10,438.6 (22,398.0) | 0.489 |
| No | 138.3 (5.70) | 83.3 (5.0) | 20,856.4 (10,429.5) | ||||
| Unknown | 138.3 (8.40) | 83.3 (6.7) | 20,898.0 (20,906.6) | ||||
| Therapy Type | Mono | 140.0 (6.27) | 0.000 | 83.3 (5.0) | 0.346 | 20,768.2 (20,769.3) | 0.034 |
| Dual | 136.7 (6.7) | 83.3 (4.15) | 20,810.2 (20,781.4) | ||||
| Triple | 133.3 (10.0) | 81.7 (8.3) | 20,989.6 (10,578.3) |
Mann Whitney test was used with a level of significance < 0.05 to assess differences in age, gender and comorbidities, while, Kruskal Wallis test with a level of significance < 0.05 was used to analyze differences in length of stay, smoking status and therapy type.
Table 3 presents post hoc analysis with no significant differences in systolic or diastolic blood pressure across different lengths of hospital stay (p > 0.05), but costs were significantly higher with increasing stay duration (p < 0.001 for all comparisons). Smoking status did not significantly affect systolic or diastolic blood pressure (p > 0.05) or costs (p > 0.05). In contrast, therapy type significantly influenced systolic blood pressure, with notable differences between mono, dual, and triple therapy (p < 0.01 for all comparisons), while diastolic blood pressure remained unaffected (p > 0.05). Costs were also significantly higher for triple therapy compared to mono and dual therapy (p < 0.05).
Table 3.
Post hoc analysis of pair-wise comparison for systolic, diastolic blood pressure and cost
| Factor | Systolic P-Value |
Diastolic P-value |
Cost P-value |
|---|---|---|---|
| Length of Stay | |||
|
0-1 2–3 0–1 4–5 2–3 4–5 |
0.104 0.807 0.214 |
1.000 0.721 0.772 |
0.000 0.000 0.000 |
| Smoking | |||
|
Yes-No Yes-Unknown No-Unknown |
0.526 0.625 0.943 |
0.431 0.146 0.373 |
0.172 0.327 0.870 |
| Therapy Type | |||
|
Mono-Dual Mono-Triple Dual-Triple |
0.002 0.000 0.005 |
0.413 0.173 0.492 |
0.956 0.025 0.019 |
Post hoc Mann Whitney test was used with the level of significance < 0.05
Average cost effectiveness
Table 4 presents a comparative analysis of different therapy types focussing mean costs, clinical efficacy in terms of systolic and diastolic blood pressure reduction, and the resulting average cost-effectiveness ratio (ACER) for both systolic and diastolic blood pressure control. The monotherapy approach revealed an average cost effectiveness of 5181 PKR for systolic and 3150 PKR for diastolic control. In comparison, the dual therapy demonstrated a reduced cost effectiveness, with values of 3920 PKR for systolic and 2438 PKR for diastolic control. Notably, triple therapy offers the greatest clinical efficacy and the most favorable cost-effectiveness ratios of 1803 PKR for systolic and 2684 PKR for diastolic blood pressure control as represented in Fig. 1.
Table 4.
Cost, clinical efficacy, and average Cost-Effectiveness of different therapy types
| Therapy type | Cost ± SD PKR | Systolic Effect Mean ± SD (mmHg) | Diastolic Effect Mean ± SD (mmHg) | ACER Systolic (PKR) | ACER Diastolic (PKR) |
|---|---|---|---|---|---|
| Mono | 23,315 ± 12,222 | 4.5 ± 4.7 | 7.4 ± 5.1 | 5181 | 3150 |
| Dual | 19,992 ± 13,237 | 5.1 ± 5.9 | 8.2 ± 4.4 | 3920 | 2438 |
| Triple | 24,161 ± 9735 | 13.4 ± 6.9 | 9.0 ± 5.3 | 1803 | 2684 |
Fig. 1.
Average cost effectiveness
Incremental cost effectiveness ratio
Table 5 provides an incremental cost-effectiveness ratio (ICER) analysis comparing the cost-effectiveness of different therapy types for both systolic and diastolic blood pressure reduction. The ICER values represent the additional cost per mmHg reduction in blood pressure when moving from one therapy to another. Switching single therapy to triple therapy gave an ICER of 95 PKR per mmHg reduction in SBP and 528 PKR per mmHg reduction in DBP. Opting for triple therapy over dual therapy resulted in an ICER of 502 PKR per mmHg reduction in SBP and 5211 PKR per mmHg reduction in DBP. Conversely, choosing dual therapy instead of a single therapeutic approach demonstrated dominance, indicating both lower costs and improved effectiveness. The ICER is not applicable in this scenario.
Table 5.
Incremental cost effectiveness ratio
| Therapy Comparison | (ICER) Systolic PKR per mmHg |
ICER Diastolic PKR per mmHg |
|---|---|---|
| Triple– Single | 95 | 528 |
| Triple– Dual | 502 | 5211 |
| Single– Dual | Dominant | Dominant |
Figures 2 and 3 is a graphical representation that uses a quadrant system to categorize different drug interventions based on their cost and effectiveness in comparison to an alternative. The four quadrants are explained as.
Fig. 2.
Therapy wise incremental cost effectiveness quadrants for systolic
Fig. 3.
Therapy wise incremental cost effectiveness quadrants for diastolic
Northeast Plane: Interventions falling in this quadrant are both more costly and more effective than the alternative. ICER applies in this case.
Southeast Plane: Interventions in this quadrant are more effective but also less costly than the alternative. Dominant in this case.
Northwest Plane: Interventions falling in this quadrant are less effective and more costly than the alternative. The alternative is dominant.
Southwest Plane: Interventions in this quadrant are less effective and less costly than the alternative. ICER applies.
When considering systolic & diastolic BP control Triple-dual and triple-single intervention fall in a northeast plan that is more costly and more effective while single-dual intervention falls in northwest plan indicating more costly and less effective.
Discussion
In this study, we evaluated the cost-effectiveness of therapy of antihypertensive, and the results were shown through tables and graphical representations.
Upon examining the therapy-wise comparisons, it was evident that triple therapy gave the best cost-effectiveness value when SBP control was considered, exceeding both dual and single therapy approaches. On the contrary, when considering DBP regulation dual therapy was the best option among all followed by triple therapy and then single therapy. The triple therapy approach is always considered best out of the other options as reported in literature [23, 24]. This might be due to several factors, including improved BP control and cost savings associated with improved clinical outcomes. It often involved using a combination of medications from different classes that work by different mechanisms, providing a more comprehensive approach to BP management that can be helpful for those patients with complex hypertension [25, 26]. A systematic review and meta-analysis of randomized controlled trials also supported our findings stating that adding a third medication was likely to work better without causing more side effects when compared to increasing the dose of the two medicines already being used. Starting with three medications in early phases can significantly help in controlling high BP [27]. On the contrary, a comparative study of monotherapy versus combination therapy suggested that dual therapy yields the most substantial reduction in mean SBP. Consequently, it was suggested that dual therapy should be more frequently recommended for hypertensive patients [28]. Different treatment options, medications, and combinations are available for the management of hypertension but, they may have different effects on SBP and DBP with varying efficacy. Some interventions may be effective in lowering SBP while some may provide better outcomes in lowering DBP. The choice of therapy can significantly impact cost-effectiveness [29]. However, the study has some limitations i.e. The study was conducted in a single healthcare setting, which means that the results cannot be generalized to other settings. Additionally, there is a possibility of information bias since the data was retrieved only from electronic healthcare records within a specific time frame. Furthermore, retrospective studies may not consider all potential confounding variables, which can affect the relationship between the exposure and outcome variables.
Conclusion
Triple therapy proved to be the most cost-effective strategy for reducing SBP. On the other hand, dual therapy was the optimal choice for DBP. In comparison to single therapy, triple therapy was more cost-effective for both aspects of BP management. For making an informed decision and efficient resource allocation in a healthcare setting, understanding of the cost-effectiveness of single, dual, and triple therapies is important. CEA analyses gains in health relative to the cost of therapy, enabling healthcare systems to optimize the allocation of limited resources while maximizing clinical outcomes [30].
Physicians and healthcare decision-makers can get help from these studies of cost-effectiveness by allocating resources effectively. In this way, limited healthcare budgets are optimally utilized for a larger population. Moreover, it can help in choosing the option that benefits both patients and healthcare systems. Thus, reducing financial barriers to the management of hypertension and increasing accessibility [31].
Acknowledgements
None.
List of Abbreviations
- BP
Blood Pressure
- SBP
Systolic Blood Pressure
- DBP
Diastolic Blood Pressure
- CEA
Cost-effective Analysis
- ACER
Average Cost Effectiveness Ratio
- ICER
Incremental Cost Effectiveness Ratio
Author contributions
ZA conceptualize the study design and methodology. A was responsible for drafting the article and was a major contributor in writing manuscript. Both Author Read and Approved the final Manuscript.
Funding
No funding received.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Before collecting data, we got permission from Ethnic committee and Institutional Review Board (EC&IRB) using the reference number IRB# 0126 − 23 from Shifa international Hospital and Shifa Tameer e Millat University.
Consent for publication
Although the collected data was kept anonymously, respecting privacy and confidentiality, Consent for publication was also waved off by Ethnic Committee and Institutional Review Board as the data was retrieved from Medical Records of the patient retrospectively.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.