Prevalence of Drug-Related Problems in Patients with Acute Heart Failure Admitted to the Intensive Critical Care Unit

Heart Failure (HF) is defined universally as a clinical condition characterized by symptoms and signs resulting from a cardiac abnormality, either structural or functional, supported by elevated natriuretic peptide levels and/or objective indications of pulmonary or systemic congestion.¹ “Congestive Heart Failure” refers to evidence of peripheral and lung congestion.² Acute Heart Failure (AHF) is characterized by the sudden or gradual onset of symptoms and/or severe signs of heart failure that require immediate medical attention. It is a leading cause of hospitalization in those over 65 and has high rates of rehospitalization and mortality.³ Drug-Related Problems (DRPs) refer to any undesirable events associated with drug therapy that interferes with treatment goals. Like other medical issues, DRPs require prompt identification and resolution.⁴ Studies have revealed that polypharmacy and comorbidities are significant risk factors for DRPs, particularly among heart failure outpatients.^5,6 CVD-hospitalized patients also showed a higher frequency of drug-related problems compared to outpatients.⁷ The significance of this study emerges from the intricate challenges posed by comorbidity and polypharmacy in heart failure care, which escalates the susceptibility to Drug Therapy Problems (DTPs). Polypharmacy, prevalent in heart failure, exacerbates risks such as drug interactions and non-adherence.^8,9 Notably, studies have reported alarmingly high rates of DTPs, reaching up to 83.5% of heart failure cases.¹⁰

A Spanish study found prevalent issues among heart failure outpatients, such as ineffective treatment and inappropriate dosing regimens.¹¹ Polypharmacy leads to recurrent hospitalizations, adverse drug events and patient non-compliance.^12,13 Pharmacists’ participation in the therapeutic hospital team can increase awareness of DRPs.¹⁴

Collaborative interventions by clinical pharmacists and physicians have effectively mitigated drug-related problems among ambulatory heart failure patients.^15,16

The findings of Shareef et al. underscore the significance of a pharmacist’s role within a multidisciplinary healthcare team. Their research emphasizes the necessity of pharmacists’ regular drug therapy reviews to identify and address drug-related problems, ultimately leading to enhanced therapeutic outcomes and improved patient care.¹⁷ Thus, this study aims to assess DTP frequency, ascertain prevalence and identify risk factors in heart failure patients. The findings will aid pharmacists in proactively identifying, resolving and preventing these issues.

The prospective cross-sectional study took place at a Tertiary Care Hospital, lasting six months, with prior approval from the hospital’s review board (VH/IEC/Pharm D/003-2023). Participants aged 45-85 diagnosed with heart failure as per ACC/ AHA guidelines and admitted to the ICCU were included after informed consent. Exclusion criteria covered incomplete records, liver disorders, active malignancy, critical illness, stroke, cognitive impairment, pregnancy, or non-compliance. A study by Tigabu et al. reported a 73.5% prevalence of Drug-Related Problems (DRPs),¹⁸ guiding our aim for a similar rate within a 95% CI and 10% precision. One hundred sixty-eight patients were initially recruited for the study, which was later narrowed down to 150, as shown in Figure 1. No dropouts were reported during the study, ensuring the data set’s integrity and completeness.

The study analyzed drug interactions and adverse reactions using Drugs.com’s database and Clinirex Software. Cipolle’s classification assessed DRPs. Upon confirmation of DRPs, treatment regimens were modified based on clinical insights and evidence-based practices. Despite its observational nature, confirmed DRPs were communicated to healthcare professionals, prompting necessary drug therapy adjustments. Documentation of detailed decision rationale, considering clinical stability, patient preferences and therapeutic efficacy. This approach underscored clinical adaptability to evolving patient needs and therapeutic goals.

The data collected was entered into Microsoft Excel and analysed using SPSS version 28.1.1. Pearson chi-square tests were conducted to calculate p-values to determine statistical significance. A p-value of >0.05 was considered statistically significant.

The study involved 150 heart failure patients admitted to the intensive critical care unit, with 62% male and 38% female (Table 1). The age distribution showed 44.66% between 45 and 60 years, 26% between 61 and 69 years, 21.33% between 70 and 79 years and 8% over 80 years (Table 2), with no significant age-DRP association (p-value: 0.895). Comorbidities were prevalent, with hypertension (74%) and diabetes mellitus (56.6%) being the most common (Figure 2). Smoking (10%) and alcohol consumption (18.6%) were reported, while 70% had no social habits. Various types of heart failure were observed, with ADHF being predominant (72%). During the study, 27 patients had a hospital stay of less than three days, accounting for 18% of all cases. For 62 patients (41.33%), hospitalization lasted four to six days, while 35 (23.33%) required seven to nine days. Twenty-six patients (17.34%) had a hospital stay exceeding ten days (Table 2). Hospitalization duration did not correlate significantly with DRPs (p-value: 0.37).

Among the 150 patients studied, 15 (10%) were prescribed ten or fewer drugs, 84 (56%) received between 11 and 20 drugs and 51 (34%) were prescribed 21 or more drugs (Table 3). A total of 2,748 drugs were prescribed during the hospital stay, with diuretics being the most frequently used class for heart failure (5.45%) (Figure 3). Among the patients, 92% experienced Drug-Related Problems (DRPs), with the most common type being Adverse Drug Reactions at 50%. Other kinds of DRPs included Unnecessary Drug Therapy (23.8%), Needs Additional Drug Product and Different Drug Products (8.4%) and non-compliance (5.5%) (Table 3). Polypharmacy significantly correlated with DRPs (p-value: 0.018) (Table 4).

The drug analysis (Figure 4) revealed notable contributors to drug-related issues, with antiplatelets, antidiabetics and diuretics being significant. Adverse reactions, accessed via the Naranjo scale (Figure 5), showed varying severities: 3.7% definite, 25.3% probable, 54.7% possible and 16.1% unlikely. Drug interactions (Figure 6) were identified, with 6.25% minor, 79.16% moderate and 14.59% major cases. Major interactions included Spironolactone and Alprazolam, Furosemide and Amiodarone and Diltiazem and Bisoprolol. Statins exhibited a noteworthy association with comorbidities contributing to DRPs.

Figure 1:
Enrolment, Allocation of Heart Failure Patients.

Figure 2:
Comorbid Conditions of the Study Participants. The chart depicts comorbidity prevalence among patients. Hypertension is most common (74%), followed by Diabetes Mellitus (56.5%). Other comorbidities include thyroid disorders (12%), renal diseases (23.3%), respiratory disorders (10.6%), psychiatric disorders (0.66%) and other cardiovascular diseases (49.3%). Only 4% of patients had no comorbidities. (Reproduction size: full page width).

Our study provides insights into the prevalence, types and underlying causes of Drug-Related Problems (DRPs) in Cardiovascular Disease (CVD) patients, particularly those with heart failure; understanding these issues is crucial for improving patient care and reducing adverse outcomes and healthcare costs associated with managing CVDs (Niriayo et al.,2024).¹⁹

Among the 150 heart failure patients included in our study, we observed a male predominance of 62%, aligning with previous research indicating males’ heightened susceptibility to CVDs (Amankwa Harrison et al., 2022).²⁰ Our study found that heart failure mainly affects older individuals, consistent with previous research by Sefera et al., 2022.²¹ The study found no significant age-related association with Drug-Related Problems (DRPs) in Cardiovascular Disease (CVD) patients, consistent with Tsige AW et al., 2021.²² Drug therapy problems were more common in older people, according to Niriayo YL et al.¹⁹

Figure 3:
Classes of Drugs Prescribed. ARB: Angiotensin receptor Blocker, ACEI: Angiotensin-converting enzyme inhibitors, B-blockers: Beta Blockers, ARNI: Angiotensin receptor/neprilysin inhibitor, If Channel Blockers: funny current blockers, PPI: Proton pump inhibitors. The bar chart displays medication utilization among participants, primarily cardiovascular drugs. Out of 2748 prescriptions, diuretics comprise 5.45%, the highest among prescribed medications. Antiplatelets (8.22%), antidiabetic agents (7.86%), bronchodilators (6.84%) and anticoagulants (5.53%) follow in utilization. Other medication classes were also prescribed, contributing to the participants’ comprehensive treatment. (Reproduction size: at full page width).

Figure 4:
Drug Class Causing Drug-Related Problem. ARB’s: Angiotensin receptor Blockers, ACEI’s: Angiotensin-converting enzyme inhibitors, B-blockers: Beta Blockers, ARNI: Angiotensin receptor/neprilysin inhibitor, If Channel Blockers: Funny current blockers, PPI: Proton pump inhibitors. The graph depicts drug classes contributing to Drug-Related Problems, including diuretics (9.32%), antiplatelets (11.18%), antidiabetic agents (9.42%) and others (12.3%). Notably, β blockers (6.68%), proton pump inhibitors and H2 receptor antagonists (9.21%) and statins (6.57%) are also prominent. Less frequent contributors include antibiotics (3.17%) and bronchodilators (7.23%). (Reproduction size: full page width).

Figure 5:
Severity of Adverse Drug Reactions. The Figure illustrates the severity of adverse drug reactions based on corresponding scores in 453 cases. Adverse reactions were categorised as Definite (3.7%, 17 cases), Probable (25.3%, 115 cases), Possible (54.7%, 248 cases) and Unlikely (16.1%, 73 cases). (Reproduction size: at full page width).

Figure 6:
Severity of Drug Interactions. The Figure depicts the severity distribution of Drug Interactions. Out of 240 identified Drug-Drug Interactions, 15 were minor (6.25%), 190 were moderate (79.16%) and 35 were major (14.59%). (Reproduction size: at full page width).

Despite the prevalent comorbidities, including hypertension and diabetes mellitus, among our sample population, we found no conclusive relationship between hospitalization duration and DRPs in heart failure patients (Seid et al., 2022). This underscores the multifactorial nature of DRP occurrence, warranting further investigation into contributing factors (Seid et al., 2022).²³

Polypharmacy, characterized by the concurrent use of multiple medications, was prevalent in our study population and correlated significantly with increased DRPs, consistent with previous research highlighting the association between polypharmacy and medication-related harm (Yirga et al., 2018; Mohan et al.,2018).^10,24

Out of 150 patients, 138 (92%) experienced Drug-Related Problems (DRPs), aligning closely with a study by Wendie and Angamo findings., 2020 (91.3%).²⁵ Consistent results across studies show the persistent nature of DRPs in clinical practice. Vigilant monitoring and comprehensive management of medication therapy are critical for patients with CHF due to the high prevalence of DRPs.

Notably, half of the identified DRPs were attributed to Adverse Drug Reactions (ADRs), differing from previous findings where additional drug therapy predominated (Gelchu and Abdela, 2019; Gokcekus et al., 2016).^26,27 The significant contribution of diuretics, beta-blockers, antiplatelet medications and anticoagulants to drug-related issues underscores the importance of tailored interventions and vigilant monitoring in managing medication regimens for heart failure patients (Yirga et al., 2018).¹⁰

Our research identified 256 adverse reactions using the Naranjo scale, with most reactions being either possible or probable. A study by Sharma et al. reported similar results with probable and possible adverse reactions.²⁸ Systematic assessment and comparison of adverse reaction findings can enhance patient safety measures. Our study also evaluated adverse reactions and Drug-Drug Interactions (DDIs), revealing variations in severity compared to previous research by Haq et al., 2020 and Straubhaar et al., 2006.^29,30 While our study reported a substantial proportion of moderate DDIs, tailored interventions and proactive management strategies are imperative to optimize medication safety and mitigate patient risks in clinical practice. Understanding these variations can inform targeted approaches for effective DDI management in CVD patients, ultimately improving patient outcomes and healthcare delivery.

In conclusion, our study sheds light on the complexity of Drug-Related Problems (DRPs) in Cardiovascular Disease (CVD) patients, particularly those with heart failure. Through thoroughly examining 150 patients, we identified prevalent patterns and underlying causes of DRPs, emphasizing the need for tailored interventions to optimize medication management and improve patient outcomes.

Our findings underscore the importance of a holistic approach to patient care, considering individual characteristics, comorbidities and medication regimens. Vigilant monitoring and proactive management strategies are crucial in mitigating risks associated with DRPs, such as adverse drug reactions and drug-drug interactions. Moving forward, collaborative efforts and continued research are vital to develop effective strategies for identifying, preventing and addressing DRPs in heart failure patients, ultimately enhancing the quality of care for this vulnerable population.

We extend our heartfelt appreciation to all those who contributed to the successful completion of this research. We are grateful for the guidance, mentorship and collaboration of colleagues and research participants.