This study aimed to assess the patterns of utilization and drug optimization and associated factors of guideline directed medical therapy in heart failure with reduced ejection fraction patients attending selected hospitals in Addis Ababa, Ethiopia. The results demonstrated that only one-tenth (11.4%) patients were on appropriate GDMT (quadruple therapy), with certain factors such as age older than 65 years, history of previous hospitalization and lesser number of medications being associated with GDMT underutilization.
In this study, only one-tenth (11.4%) of the studied patients were taking all classes of GDMT. This is low compared to the CHAMP-HF study, where 22.1% of the patients were simultaneously prescribed some dose of ACEI/ARB/ARNI, beta-blocker, and MRA therapy among patients eligible for all classes of medication (20).
In particular, 52.5% of HFrEF patients were receiving either ACEIs or ARBs. This finding is in agreement with the Egyptian study that documented that 51.4% of cardiac patients were on the same group of medications (21). However, the present proportion of patients using RAS inhibitors was lower than that of the multinational study from the ASIAN-HF registry and the Korean study, which documented that RAS inhibitors were utilized among 77% and 75.3% of the cardiac patients, respectively (19, 22). The relatively lower utilization of ACEIs or ARBs in the current study as compared with the studies done in developed nations may explained by clinical inertia due to lack of frequent renal function and electrolyte monitoring as to the standard, which might be partly due to financial reasons..
The current finding differs from previous research in the United States, Taiwan, and Italy, where RAS inhibitors were used in 81.4%, 73%, and 62% of HFrEF cases, respectively (20, 23, 24). In Italy, 68.2% of cardiac patients received RAS inhibitors (25). This percentage is lower than the 74.7% reported in Ethiopia (18). Moreover, 77.7% of patients in the present study were on beta-blockers, similar to the ASIAN-HF registry's multinational study (79%) (19). This is comparable to Demissie et al.'s findings (79%) (26). However, it exceeds rates in the CHAMP-HF study, Southwest Ethiopia, and Korea (67%, 67%, and 54.9%, respectively) (17, 20, 22). In contrast, it falls below the US and Italy rates (93.4–94.4%) for beta-blocker usage.(23, 25).
In this study, 27% of the studied patients were on SGLT2 inhibitors. This is comparatively higher than the previous Ethiopian and Spanish studies, where only 5% and 6.7% of patients with HFrEF were on SGLT2 inhibitors, respectively (26, 27). This can be due to the better availability of the medications in urban areas. On the contrary, the present finding was much lower than the pattern observed in the nation-wide German study, in which more than half (54.8%) of cardiac patients were on SGLT2 inhibitors (28). Furthermore, this study found 58.9% on MRAs, similar to Ethiopia (58.7%) and Egypt (54.9%) (26, 29). On the contrary, lower rates were seen in southwest Ethiopia (32.5%) and Italy (17.4%), while Oman had higher usage (77%) (17, 25, 30). Generally, the underutilization of SGLT2 inhibitors in the current study is most likely due to low availability of these drugs in the market and financial constraints.
In aggregate, this study showed that most of the patients were not in quadruple therapy, with no apparent justification for not initiating the medications recorded upon review of the health record or discussion with the patient. Such low level of GDMT implementation in our setup might be due to lack of compelling local guidelines, perceived fear of intolerance, absence of frequent laboratoy monitoring for drug adverse effects, lack of access to prescribed medications (especially SGLT2is) and differences in the practice of multidisciplinary care, with suboptimal medical practitioners’ expertise and high clinical inertia in resource-poor countries. It could be also pointed out resource-poor settings such as ours do not widely use technology to enhance adherence to GDMT, as opposed to developed ones (31).
Apart from this, the proportion (11.4%) of patients on appropriate GDMT (quadruple therapy) obtained in this study is low given the recent evidence, such as the STRONG-HF trial, that demonstrated that rapid drug implementation and up-titration in the absence of absolute contraindications is superior to the traditional and more gradual step-by-step approach in which valuable time is wasted to up-titration (32–34).
In this study, age older than or equal to 65 years was negatively associated with use of GDMT among the studied patients. This is in agreement with the previous Egyptian and Ethiopian studies, which independently found that younger age was associated with better GDMT utilization (18, 29, 35). Among others, this can be explained by the probability that older patients are likely to be dependent on others to take their medications appropriately and they are also more likely to have coexisting medical conditions such as renal dysfunction and orthostatic hypotension, which may prohibit their eligibility for morbidity- and mortality-reducing therapies, such as ACEi, ARB, ARNI, BBs or MRA.
Patients with history of hospitalization in the preceding one year were more likely to have underutilized the novel GDMT compared to those with no previous hospitalization. This is consistent with the report of Niriayo et al., who found that previous hospitalization for heart failure was associated with poor GDMT utilization(18). This is, in fact, can be an indicator of the fact that lack of adherence to the evidence-based quadruple therapy (GDMT) results in increased morbidity among cardiac patients, which would likely result in frequent hospitalization for inpatient care (26, 36, 37).
Patients on polypharmacy were more likely to utilize GDMT than those on lesser number of medications. Although there is limited previous literature regarding this finding, this apparent association can be justified by the fact that the those patients who are on polypharmacy are probably more sicker more counseled by health care providers and their family members, that might increase their utilization of GDMT. Moreover, patients with multi-morbidity (and as a consequence, on polypharmacy) are likely to be subjected to subspecialist consultations, which may in turn lead to a meticulous clinical decision regarding GMDT therapy.
This study is among the leading studies to be done in Ethiopian setting, particularly after the endorsement of the latest guideline (2022 AHA/ACC/HFSA). However, its cross-sectional design limits causal inferences and alternative interpretations. The study did not include exhaustive list of physician and pharmacy related variables that would influence the GDMT utilization and optimization.