Prevalence and predictors of polypharmacy and comorbidities among patients with chronic obstructive pulmonary disease: a cross-sectional retrospective study in a tertiary hospital in Saudi Arabia

Abstract

Objective

This study aimed to determine the prevalence of polypharmacy, comorbidities and to investigate factors associated with polypharmacy among adult patients with Chronic Obstructive Pulmonary Disease (COPD).

Methods

This was a retrospective single-centre cross-sectional study. Patients with a confirmed diagnosis of COPD according to the GOLD guidelines between 28 February 2020 and 1 March 2023 were included in this study. Patients were excluded if a pre-emptive diagnosis of COPD was made clinically without spirometry evidence of fixed airflow limitation. Population characteristics were presented as frequency for categorical variable. Logistic regression analysis was used to identify predictors of polypharmacy.

Results

The study sample included a total of 705 patients with COPD. Most of the study sample were males (60%). The mean age of the study population was 65 years old. The majority of the study population had comorbid diseases (68%), hypertension and diabetes were the most common co-existent diseases. Around 55% of the study sample had polypharmacy. Females were significantly less likely to be on polypharmacy compared to males (OR = 0.68, 95% CI = [0.50–0.92], P-value = 0.012)). On the other hand, older patients aged 65.4 or more (OR = 2.31, 95% CI = [1.71–3.14], P-value ≤ 0.001), those with high BMI (≥ 29.2) (OR = 1.42, 95% CI = [1.05–1.92], P-value = 0.024), current smokers (OR = 1.9, 95% CI = [1.39–2.62], P-value ≤ 0.001), those who are receiving home care (OR = 5.29, 95% CI = [2.46–11.37], P-value ≤ 0.001), those who have comorbidities (OR = 19.74, 95% CI = [12.70–30.68], P-value ≤ 0.001) were significantly more likely to be on polypharmacy (p ≤ 0.05).

Conclusions

Polypharmacy is common among patients with COPD. Patients with high BMI, previous ICU hospitalization and older age are more likely to have polypharmacy. Future analytical studies are warranted to investigate outcomes in patients with COPD and polypharmacy.

Background

COPD has emerged as one of the most common respiratory diseases worldwide [1]. COPD is considered as the fourth leading cause of morbidity and mortality [2]. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease caused by airway or alveolar abnormalities due to exposure to smoking and air pollutants. COPD is characterized by an irreversible airflow limitation and influenced by host factors [3].

Airway obstruction is a landmark in people with COPD [4]. However, it is mostly accompanied by other complex morbidities such as comorbidities disease [5]. Comorbidity is defined as when were more than two diseases are usually associated with patients [6], and this is common in COPD population [4]. The most common multiple morbidities associated with COPD includes cardiovascular diseases, lung neoplasms, obesity, gastroesophageal reflux disease [7], diabetes, obstructive sleep apnoea, and mental health conditions (40%) [8–10]. Cardiovascular disease (CVDs) and COPD co-existence are widely described in the literature [11]. It has been demonstrated that patients with COPD are at an increased risk of developing CVDs [12]. However, the distribution and the nature of other comorbidities appear to vary [12]. When considering clinical parameters such as survival, hospitalization, comorbidities, polypharmacy, and systemic inflammation, it has been reported that COPD is complex and includes several distinct phenotypes [13].

Comorbidity diagnosis and management are essential for the quality of life in COPD [14]. As a result, these comorbidities are taken into account by the COPD guidelines [15]. Bronchodilators, corticosteroids, long-term oxygen use, or pulmonary rehabilitation are all used treatments for COPD [16]. However, this will also be associated with polypharmacy (the concomitant use of more than 5 medications) and the use of other medications to treat the comorbidity [17]. Polypharmacy in general is associated with multiple health outcomes issues including adverse drug reactions, adherence, and hospitalizations, especially among the old age populations [4].

COPD-associated comorbidities, polypharmacy, exacerbation, and related hospitalization, have a detrimental effect on COPD patients' quality of life (HRQoL) [18, 19]. Both comorbidity and polypharmacy are associated with poorer quality of life and can be considered a major burden in the management of COPD which impact treatment outcomes [4, 20].

A previous study in Saudi Arabia found that the prevalence rate of COPD in 2019 has reached 2.05% [21]. The prevalence and extent of this coexistence of COPD and polypharmacy issue have not been described previously among the middle eastern population. Therefore, this study aims to determine the prevalence of polypharmacy, comorbidities and to investigate factors associated with polypharmacy among adult patients COPD.

Methods

Study design and study settings

This was a retrospective single-centre cross-sectional descriptive study. Data were collected between 28 February 2020 and 1 March 2023 from Al-Noor Specialist in Mecca, Saudi Arabia [22]. Details of the data collection method and study settings were previously described [23]. We included inpatients with a confirmed diagnosis of COPD according to the GOLD 2023 guidelines. Only patients with a spirometry evidence of fixed airflow limitation were included in the study. Comorbid conditions were addressed by different teams led by qualified consultant.

Study variables

A standardized spreadsheet was used to collect data regarding the demographics including (Age, gender, smoking status, and body mass index). Comorbidities data were collected based on the Charlson comorbidity index. Medications used including (respiratory medication, oxygen therapy, and other medications used were reported at the latest recorded in the files or the medical record). Polypharmacy was defined as the use of 5 or more medications including COPD medications [24–26].

Statistical analysis

Data were analyzed using Statistical Package for Social Science (SPSS) software, version 27 (IBM Corp, Armonk, NY, USA). Population characteristics were presented as percentage for categorical variables and mean (SD) for continuous variables. Logistic regression analysis was used to identify predictors of polypharmacy. A confidence interval of 95% (P < 0.05) was applied to represent the statistical significance, and the level of significance was predetermined as 5%.

Ethical approval and consent to participate

This study was approved by the institutional ethics board at the Ministry of Health in Saudi Arabia (No. H-02-K-076–0523-951). Patients were informed that their clinical data will be used for clinical or research purposes with keeping all their personal information confidential. The need for written informed consent was waived by the ethics committee due to the retrospective nature of the study. All procedures were performed according to the Helsinki declaration.

Results

Patients’ baseline characteristics

The study sample included a total of 705 patients. The majority of the study sample were males (60%). More than 70% of the study sample were either smokers or ex-smokers. The mean age of the study were 65 years. Details of patients' baseline characteristics are listed in Table 1.

Table 1.

Patients' baseline characteristics (N = 705)

Variable	Frequency	Percentage
Gender
Males	425	60.3%
Mean age (Standard deviation (SD)) years	65.4 (25.3) years
Mean Body Mass Index (BMI) (Standard deviation (SD)) kg/cm2	29.2 (6.8) kg/cm2
Smoking status
Non-smoker	182	25.8%
Ex-smoker	258	36.5%
Current smoker	265	37.5%
Receive home care
Yes	55	7.8%
Percentage of Comorbidities among COPD
Yes	482	68.4%
Hypertension	287	40.3%
Diabetes mellitus	288	40.9%
Peptic ulcer	186	26.4%
Ischemic heart disease	135	19.1%
Obstructive sleep apnea (OSA)	92	13.0%
Heart failure	65	9.2%
Chronic kidney disease	40	5.7%
Cerebrovascular accident or stroke	38	5.4%
Tuberculosis	32	4.5%
Connective tissue diseases	23	3.3%
Tumour or malignancy	21	2.9%
Hemiplegia	16	2.3%
Peripheral vascular diseases	11	1.6%
Dementia	9	1.3%
Liver disease	4	0.6%
AIDS/HIV	2	0.3%
Rheumatological disease	1	0.1%
Hospital admission due to COPD exacerbations in the past two years
Yes	263	37.3%
ICU hospital admission due to COPD exacerbations in the past two years
Yes	84	12.4%

Comorbidity characteristics

The majority of the study population had comorbid diseases (68%). Diabetes was the highest co-morbid disease followed by hypertension, peptic ulcer diseases and ischemic heart diseases, respectively (40.9%, 40.3%, 26.4%, 19.1%). Details are listed in Table 1.

Medications use history

Around 55% of the study sample had polypharmacy. The most commonly prescribed respiratory medication was the Short acting beta agonist (SABA) 90% followed by the Long-acting muscarinic agonist (LAMA) 80%, Long-acting beta agonist (LABA) 60%, and Inhaled corticosteroid (ICS) 55%. Around 55% of the study population use 5 or more medications concomitantly. The highest concomitant medications used with COPD medications were antihypertensive medications, followed by antidiabetic medications 39%, proton pump inhibitors 27%, antihyperlipidemic 26%, and antiplatelet medications 21%, respectively. Details of medications history are listed in Table 2.

Table 2.

Most common prescribed respiratory medication (N = 705)

Variable	Frequency	Percentage
Patients on polypharmacy (defined as 5 or more medications including COPD medications)
Yes	389	55.2%
Short acting beta agonist (SABA)	640	90.8%
Long-acting muscarinic agonist (LAMA)	567	80.4%
Long-acting beta agonist (LABA)	418	59.3%
Inhaled corticosteroid (ICS)	390	55.3%
Systematic corticosteroids	139	19.7%
Home oxygen and BIPAP	55	7.8%
Home oxygen	37	5.2%
Oral antidiabetic agents or insulin	279	39.6%
Antiplatelet	151	21.4%
Anticoagulants	45	6.4%
Antihypertensive	288	40.9%
Anti HF	76	10.8%
Antihyperlipidemic	182	25.9%
Antipsychotic and antidepressants	54	7.7%
Proton pump inhibitors	190	27.0%
H2 blockers	8	1.1%
Osteoporosis drugs	51	7.2%
Oxygen	95	13.5%
BIPAP	61	8.7%

H2 blockers Histamine blockers, BIPAP Bilevel positive airway pressure

Predictors of polypharmacy

Females were significantly less likely to be on polypharmacy compared to males (OR = 0.68, 95% CI = [0.50–0.92], P-value = 0.012). On the other hand, older patients aged 65.4 or more (OR = 2.31, 95% CI = [1.71–3.14], P-value ≤ 0.001), those with high BMI (≥ 29.2) (OR = 1.42, 95% CI = [1.05–1.92], P-value = 0.024), current smokers (OR = 1.9, 95% CI = [1.39–2.62], P-value ≤ 0.001), those who are receiving home care (OR = 5.29, 95% CI = [2.46–11.37], P-value ≤ 0.001), those who have comorbidities (OR = 19.74, 95% CI = [12.70–30.68], P-value ≤ 0.001), and those who had hospital admission history(OR = 16.60, 95% CI = [4.58–9.49], P-value ≤ 0.001) or ICU admission history (OR = 27.44, 95% CI = [8.58–87.79], P-value ≤ 0.001) were significantly more likely to be on polypharmacy (p ≤ 0.05). Details of predictors of polypharmacy are listed in Table 3.

Table 3.

Binary logistic regression analysis (N = 705)

Variable	Odd ratio
Gender
Females (Reference category)	1.00
Males	0.68 (0.50–0.92)	0.012
Mean age (Standard deviation (SD)) years
Age ≤ 65.4 (25.3) years	1.00
Age ≥ 65.4 (25.3) years	2.31 (1.71–3.14)	≤ 0.001
Mean Body Mass Index (BMI) (Standard deviation (SD)) kg/cm2
BMI ≤ 29.2 (6.8) kg/cm2	1.00
BMI ≥ 29.2 (6.8) kg/cm2	1.42 (1.05–1.92)	0.024
Smoking status
Non-smoker (Reference category)	1.00
Ex-smoker	0.29 (0.21–0.40)	≤ 0.001
Current smoker	1.91 (1.39–2.62)	≤ 0.001
Receive home care
No (Reference category)	1.00
Yes	5.29 (2.46–11.37)	≤ 0.001
Comorbidities
No (Reference category)	1.00
Yes	19.74 (12.70–30.68)	≤ 0.001
Hospital admission due to COPD in the past two years
No (Reference category)	1.00
Yes	6.60 (4.58–9.49)	≤ 0.001
ICU hospital admission due to COPD in the past two years
No (Reference category)	1.00
Yes	27.44 (8.58–87.79)	≤ 0.001

Discussion

To the best of our knowledge, this study is the first to investigate the prevalence of polypharmacy and comorbidities among COPD patients in the population of the Middle East. Our study revealed that polypharmacy and comorbidities are common among COPD patients. Patients with advanced age, elevated BMI, current smokers, long-term oxygen therapy, multiple comorbidities, and frequent hospital or ICU admissions were more likely to be on polypharmacy.

In our study, we found that comorbid conditions were common among COPD patients, as 68.4% of 705 COPD patients reported having comorbid conditions, the majority of which were hypertension (40.7%), diabetes mellitus (30.9%), peptic ulcer disease (26.4%), and ischemic heart disease (19.1%). According to a previous systematic review of 29 studies from Europe and North America, patients with COPD had a two- to five-fold higher risk of developing major cardiovascular disease types such as ischemic heart disease, cardiac dysrhythmia, heart failure, diseases of the pulmonary circulation, and arterial diseases [12]. They also had a roughly one-third higher risk of developing hypertension and diabetes [12]. Comorbid diseases are frequently present in COPD patients, according to an observational, cross-sectional multicentre study conducted in Spain with 866 COPD patients involved [27]. The most prevalent comorbidities across all groups of COPD were systemic hypertension (57.1%), followed by hyperlipidaemia (33.3%) and diabetes mellitus (31.1%) [27]. In addition, patients with COPD have an increased risk of developing mental health issue, and the prevalence of anxiety and depression is high among patients with COPD. This was also highlighted in our study which showed that around (7.7%) were utilising antipsychotic and/or antidepressants medications, which may provide a reflection of the mental health profile of the study population. All studies support our findings that comorbidities are prevalent among COPD patients, with variations that could be attributed to the difference in sample size or the populations that each study included; while the other study included people from Europe, North America, and Spain, ours included people from the Middle East.

In the present study, 55.2% of 705 COPD patients reported being on polypharmacy (≥ 5 medications). A previous observational, cross-sectional, and multicentre study conducted in Spain and included 398 patients showed a total of 224 (56.3%) patients presented polypharmacy and 22 (5.5%) excessive polypharmacy (≥ 10 medications) [28]. Another observational, cross-sectional, and multicentre study conducted in England, Scotland, and Wales and included 8317 self-reported COPD patients found that more than half (52%) reported polypharmacy and 15% reported excessive polypharmacy [4].

Our study revealed that short-acting beta-agonists (SABA) account for 90% of all medications taken, followed by long-acting muscarinic agonists (LAMA) at 80%, long-acting beta agonists (LABA) at 60%, inhaled corticosteroids (ICS) at 55%, antihypertensive drugs at 40.9%, oral diabetes medications at 39.6%, proton pump inhibitors at 27%, anti-hyperlipidemia at 25%, and antiplatelet at 21.4%, respectively, and they are compatible with the results of common comorbidities.

In our study, we discovered that individuals who were older had a higher BMI, and were current smokers had a higher likelihood of being on multiple medications. This conclusion could be explained by the fact that older individuals [4, 29, 30], obese or high BMI individuals [31–37], and current smokers [38–42] typically have other concomitant illnesses, and patients with comorbidity are more likely to get multi-drug therapy [28, 43–45]. Moreover, we found that polypharmacy is more prevalent in patients who have a history of hospitalization or ICU admission which could be explained by the fact that they are regularly admitted due to a severe illness course or the presence of concomitant conditions. A prior study found that patients with acute COPD exacerbations who were hospitalized received a mean of five prescription medicines prior to admission, and that number increased after discharge. [28] Comorbidities, particularly heart failure, and poor lung function are the conditions linked to higher pharmaceutical use [28].

COPD is associated with deteriorating health outcomes and a poorer quality of life [46]. Furthermore, comorbidity worsens COPD prognosis since a higher number of comorbidities is associated with a higher risk of mortality [47]. Polypharmacy or Complex pharmacotherapy is a major factor in nonadherence [48–50], increased risk of drug- to-drug and drug- to-disease interactions [4, 51–58], poor disease control [59], and significant cost of illness [60]. Yet, there are no clear guidelines for the optimum approach for treating individuals with comorbidity, which poses a problem for healthcare systems [61]. As a result, clinicians have little information or evidence on how to integrate care decisions for patients with various chronic illnesses. [61, 62].

There hasn't been a prior study in the Middle East that examines the prevalence of polypharmacy and comorbidities among COPD patients. In addition, we collected data on comorbidities using the Charlson Comorbidity Index. On the other hand, it is important to take into account some of our study's limitations. First, the patients whose data were gathered were admitted to internal medicine departments. Patients with COPD in these departments tend to be older and have more concomitant conditions. This might prevent our findings from being generalized outside of this setting. Second, the study had a limited sample size and was conducted in a single institution. Third, due to the nature of retrospective cross-sectional study design, a causal relationship cannot be determined from the study's findings. In addition, we were unable to investigate the quality of life, medications adherence, and drug-drug interactions of patients with COPD, and we urge for future research to address these important outcomes. Fourth, we did not investigate the prevalence of each comorbid conditions based on the GOLD-COPD severity scale, and if there is any association between the COPD severity and behaviour of each disease prevalence separately. Lastly, our study population had less prevalent psychiatric diseases compared to the published data likely attributed to our method utilized for data collection, namely Charlson Comorbidity Index.

Conclusion

Polypharmacy is common among patients with COPD. Patients with high BMI, previous ICU hospitalization and older age are more likely to have polypharmacy. Future analytical studies are warranted to investigate outcomes in patients with COPD and polypharmacy.

Authors’ contributions

Conceptualization, HA Data curation, AYN, OB and HA Formal analysis, AYN and HA; Investigation, AYN and HA; Methodology, HA; Project administration, OB and HA; Resources, OB and HA; Supervision, HA; Validation, AYN and HA; Writing original draft, AYN, DA, SA, JS, SA, AA and HA; Writing – review & editing, All authors.

Funding

NA.

Availability of data and materials

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

The ethics committee of the Ministry of Health in Saudi Arabia approved the study and waived informed consent due to the retrospective nature of the study (approval No. H-02-K-076–0523-951). All procedures were performed according to the Helsinki declaration.

Consent for publication

NA.

Competing interests

The authors declare no competing interests.