Cardiovascular disease essential medicines listing by countries: changes over time and association with health outcomes

Abstract

Background

Since national essential medicine lists guide the procurement of medicines for populations in many countries, and cardiovascular diseases are the leading cause of death globally, including cardiovascular medicines on these lists can significantly impact healthcare outcomes.

Methods

In this cross-sectional study, national essential medicines’ lists from 158 countries were analysed on whether or not they included medicines to treat ischemic heart disease, cerebrovascular disease, and hypertensive heart disease. A linear regression model was used to evaluate the association between countries’ coverage scores and amenable mortality.

Results

Listing of cardiovascular disease treatment was associated with amenable mortality from hypertensive heart disease. Health expenditure per capita was also associated with amendable mortality due to ischemic heart disease, and hypertensive heart disease.

Conclusions

Listing essential medicines for cardiovascular disease is an important aspect of healthcare quality that is associated with cardiovascular mortality.

Background

Cardiovascular disease remains the leading cause of death worldwide despite effective interventions [1]. For example, hypertension continues to be a significant yet preventable risk factor for cardiovascular disease events, contributing to 55% of deaths related to ischemic heart disease and 45% of deaths related to cerebrovascular disease [2]. Access to care and medicines varies significantly across different regions [1], and sometimes, limited accessibility and very high expenses pose significant obstacles to the utilization and compliance with essential treatments for cardiovascular diseases. For instance, a considerable portion of people in low-income and middle-income countries lack access to more than one blood pressure-lowering medicine [3]. Even when accessible, these medicines are frequently financially out of reach [3]. Such circumstances contribute to inadequate management of cardiovascular risk factors [3]. As the emergence of newer treatments for cardiovascular disease holds promise in substantially reducing cardiovascular morbidity and mortality rates, guaranteeing the affordability and accessibility of those medicines is also imperative.

Essential Medicine Lists (EMLs) represent a crucial component of national drug policies [4]. The World Health Organization (WHO), the specialized agency of the United Nations responsible for international public health, advocates for countries to maintain EMLs that prioritize treatments for prevalent health issues like cardiovascular disease. By serving as a guide, EMLs play a vital role in addressing the burden of non-communicable diseases [5].

There are usually opportunities for improvements in national EMLs as they may be outdated, either because they include obsolete medicines or because they exclude newer ones [6]. Moreover, the inclusion of a specific medication in EMLs is associated with its availability and affordability across both public and private health sectors [2].

The purpose of this study was to evaluate the relationship between the inclusion of essential medicines used to treat ischemic heart disease, cerebrovascular disease, and hypertensive heart disease, and the associated mortality rates measured by the HAQ (Healthcare Access and Quality) score. Additionally, we analyzed changes in the listing of these treatments over a six-year period.

Methods

Data sources

We employed the Global Essential Medicines (GEM) database of national EMLs that was updated in 2023. Briefly, the database was created by searching for national EMLs, having at least two researchers abstract data from each national EML and checking the data abstraction process. An algorithm was used to translate some medicine names and to assign ATC (Anatomical Therapeutic Chemical Classification) codes [7]. The database consists of a matrix listing each medicine and each country and indicates which countries list which medicines.

To identify medicines pertinent to the three specific conditions - ischemic heart disease, cerebrovascular disease, and hypertensive heart disease - we conducted a search for corresponding guidelines on the WHO website in November 2023. Three international guidelines distributed by the WHO were selected (1) Technical package for cardiovascular disease management in primary health care: Evidence-based treatment protocols 2018 [4], (2) Technical package for cardiovascular disease management in primary health care: Access to essential medicines and technology 2018 [8], and (3) Package of essential non-communicable disease interventions for primary health care 2020 [9].

We employed these guidelines, alongside reference to the WHO Model List 23rd edition [10], to identify medicines utilized in treating ischemic heart disease, cerebrovascular disease, and hypertensive heart disease. The guidelines were explored using the specific causes and their corresponding International Classification of Diseases 11th revision codes as provided by the HAQ score [11].

Data concerning population size was obtained from the United Nations [12], and data related to health expenditure was obtained from the Global Health Observatory [13], except for Somalia and Democratic People’s Republic of Korea [14, 15]. Most of the data pertained to the year 2023; if 2023 records were unavailable, information from the nearest available year to 2023 was accessed.

We employed the 2022 amenable mortality sub scores which were determined by analyzing age-standardized mortality rates related to ischemic heart disease, cerebrovascular disease, and hypertensive heart disease [11]. Amenable mortality has been defined as those premature deaths that should have not occurred in the presence of timely and effective health care [16].

Data extraction

Employing the guidelines specified for ischemic heart disease, cerebrovascular disease, and hypertensive heart disease, medicines used to manage these conditions were extracted. Whenever a guideline specified a therapeutic category of medicines, that category was comprehensively expanded to include all medicines, as medicines falling within the same chemical subgroup might be regarded as therapeutically akin. The WHO Model List acknowledges the exchangeability of certain medicines within the same therapeutic class [10]. The ATC codes [7] were utilized to determine medicines belonging to the same therapeutic class. In instances where a therapeutic class was specified along with alternatives, solely those mentioned medicines were incorporated without expanding the therapeutic class. Medicines either listed directly on the WHO Model List or cited in guidelines referenced within the WHO Model List (in a practical form for the respective conditions or causes) and marked with a square box symbol were expanded. This expansion was based on the ATC code group, the chemical subgroup of the code, encompassing all medicines included in that therapeutic class. Medicines lacking the square box symbol were not expanded. In cases where specific equivalent medicines were specified, only those identified medicines were included. A medicine coverage score was formulated by summing the count of medicines included in a country’s national EML that also appeared on our list of medicines used to treat each of the three conditions.

Data analysis

The analysis utilized Stata (16, StataCorp LLC, College Station, TX), with statistical significance set at a p-value ≤ 0.05. A linear regression model was fitted to assess the hypothesis regarding the relationship between the listing of medicines (measured as the medicine coverage score) and amenable mortality. In this analysis, the risk-standardized death rate from the HAQ dataset was the measure of amenable mortality, and the medicine coverage score served as the independent variable [11]. The regression results are presented for both unadjusted and adjusted models, with health expenditure and population size as pre-specified covariates that were included because they could be associated with both medicine coverage and amenable mortality.

Results

We identified national EMLs and HAQ scores for 158 countries (Table 1). These countries were distributed across WHO regions as follows: Eastern Mediterranean (18 countries), Europe (32 countries), Africa (47 countries), the Americas (30 countries), South-East Asia (11 countries), and the Western Pacific (20 countries) [16]. According to the 2023 World Bank categorization, the countries included encompassed diverse income levels, comprising 26 low-income countries, 50 lower-middle-income countries, 51 upper-middle-income countries, and 31 high-income countries [18].

Table 1 Country characteristics. Note: income level was extracted from website in February 2024

Overall, the most cited overall cardiovascular medicines included: morphine (listed by 153 countries), acetylsalicylic acid (listed by 151 countries), furosemide (listed by 148 countries), and spironolactone (listed by 147 countries).

Ischemic heart disease

For ischemic heart disease, the range of medicine coverage scores spanned from 3 (Romania) to 83 (Greece), with a median of 34 (IQR: 27.25–42). Variables included the ischemic coverage score, health expenditure per capita (U$S), and population size. The unadjusted regression model showed listing ischemic heart disease medicines accounted for roughly 1.90% of the variation in amenable mortality and that the association between coverage and amenable mortality did not reach statistical significance (p = 0.084). The model including adjustments for population size and health expenditure explained 10.51% of the variation in amendable mortality. In this adjusted model, medicine coverage was not associated with amenable mortality (p = 0.182) compared to health expenditure, which was associated with the amenable mortality (p < 0.0001) (Table 2; Fig. 1).

Table 2 ¹Ischemic heart disease: regression results

Fig. 1

Ischemic death rates by coverage score

Cerebrovascular disease

For cerebrovascular disease, the medicine coverage scores ranged from 1 (Japan, Panama, Romania) to 70 (Greece), with a median of 25 (IQR: 19–33). Variables included the stroke coverage score, health expenditure per capita (U$S), and population size. The unadjusted regression model explained only 2.29% of the variation in amenable mortality and adjusting for population and health expenditure increased the amount of variation explained to just 3.55%. In the initial unadjusted regression, there was no association between medicine coverage score and HAQ score for cerebrovascular disease (p = 0.058). This was also the case in the adjusted model (p = 0.111). Population (p = 0.305) and health expenditure (p = 0.298) were also not associated with amenable mortality (Table 3; Fig. 2).

Fig. 2

Stroke death rates by coverage score

Table 3 ¹Cerebrovascular disease: regression results

Hypertensive heart disease

For hypertensive heart disease, the medicine coverage scores range from 0 (Japan, Panama, Romania) to 61 (Greece), with a median of 20.5 (IQR: 16.25–28). Variables included the hypertensive coverage score, health expenditure per capita (U$S), and population size. The unadjusted model accounted for little variation in the amenable mortality (5.89%), compared to the adjusted model (18.87%). There was an association between medicine coverage score and amenable mortality in the unadjusted (p = 0.002) and adjusted (p = 0.015) models. Health expenditure (p = 0.000) was also associated with amenable mortality, compared to population (p = 0.268), which was not (Table 4; Fig. 3). Examples of countries with lower HAQ scores include Central African Republic, Somalia, and Chad, and have hypertensive medicine coverage scores of 18, 16, and 24 respectively. These three countries did not list 55 hypertensive medicines such as carvedilol, diltiazem, lercanidipine, nitroprusside, prazosin, and rosuvastatin that are all medicines commonly listed by other countries.

Fig. 3

Hypertensive death rates by coverage score

Table 4 ¹Hypertensive heart disease: regression results

Discussion

Listing of cardiovascular disease treatment is associated with amenable mortality from hypertensive heart disease, but not for ischemic or cerebrovascular disease. Health expenditure per capita was associated with amendable ischemic and hypertensive mortality.

Given that expenses for cardiovascular disease treatment surpass the per capita health expenditure in many low to middle-income countries [19], prioritized access to cardiovascular disease treatments alongside improvements in care may be beneficial in many countries [20]. The benefits of prioritized access to cardiovascular disease treatments may be greatest in low- and middle-income countries [21].

Of course, medicine access is only one important aspect of the care pathways; a cross-sectional study in 44 low and middle-income countries highlighted the need for designing and implementing health policies for hypertension in health systems where their performance tend to be poor, with less than 50% of people with hypertension being diagnosed and less than a third receiving pharmacological treatment [22].

Strengths and limitations

This is the largest study of cardiovascular disease essential medicines as far as we know. Causation should not be inferred from a cross-sectional study. Mortality-related data is estimate. The scoring system does not consider therapeutically interchangeable medicines within a class; theoretically, the presence of just one medicine in a class might suffice, rendering others redundant. There might also exist other potentially relevant covariates, such as population insurance coverage, lifestyle factors, or healthcare infrastructure. The presence of a medicine in the EML does not mean its accessibility and affordability, as some countries have public and private health sectors coexisting. Despite the limitations associated with developing a medicine coverage score, our methodology enabled the derivation of an overarching score for cross-country comparisons. Our study employed data used to estimate the HAQ score for countries and that dataset has limitation [11].

Conclusions

In conclusion, these findings suggest that the listing of cardiovascular disease treatments appears to specifically impact mortality rates amenable to hypertensive heart disease treatment, while not significantly influencing outcomes related to ischemic or cerebrovascular disease. Additionally, higher health expenditure per capita is associated with reduced amenable mortality for both ischemic and hypertensive heart diseases. These results emphasize the importance of targeted health investments and the potential for improved outcomes in specific cardiovascular conditions, highlighting the nuanced role of essential medicines for cardiovascular disease and healthcare allocation in reducing disease-specific mortality rates.

Future work should delineate the contributions of types of medicines or specific medicines in addressing cardiovascular mortality.