To our knowledge, this is the first study to determine optimal medical therapy (OMT) prescription, clinical outcome, and associated factors among acute coronary syndrome (ACS) patients in Ethiopia. Based on this, we found that only 59.2% of patients received OMT at discharge. Age ≥ 65, atrial fibrillation, chronic kidney diseases, and cardiogenic shock were negative independent predictors of optimal medical therapy. On the other hand, male sex was independently associated with the use of optimal medical therapy.
In this study, the rate of OMT prescription was found to be 59.2% (95% CI = 54.4%, 64.0%). This finding was consistent with previous studies done in France (57.4%) [26, 29, 48]. But it was higher than those studies done in Sudan (45.2%), Thailand (42.6%), the Netherlands (43.2%, 43.7%), Iraq (53.5%), China (15.1%, 36%, 36.2%, 39.8%), and India (46%), respectively [25, 27, 30, 35, 46, 49,50,51,52,53]. This might be due to different reasons; first, in these studies, the definition of OMT is the use of five medications: aspirin, clopidogrel/P2Y12 inhibitors, beta-blockers, statins, and ACEIs/ARBs. Second, investigators from other low- and middle-income countries have also evaluated the use of optimal medical therapy in their registries. For example, the use of optimal medical therapy at discharge, defined by the concurrent use of aspirin, β-blockers, statin, and ACE-I/ARBs, was evaluated in the Clinical Pathways for ACS in China registries [54]. However, use of clopidogrel given its class I recommendation for all patients [33], which is not the case with ACE-I/ARBs, which requires concomitant heart failure, left ventricular systolic dysfunction, diabetes mellitus, or hypertension for a class I indication [24, 33]. The rate of OMT prescription in this study was lower than those studies done in Korea (63.2%, 75.71%), the Netherlands (69.1%), and Australia (65%), respectively [55,56,57,58]. The possible reason might be in OMT prescription at discharge in ACS patients among different studies: is local context, study time point, the severity of diagnosis, health coverage, and medication availability [27, 49, 53]. This suboptimal use of OMT leads to mortality and morbidity, as well as increased healthcare costs regarding hospital admission.
The current findings showed that elderly patients were less likely discharged with OMT than younger patients. This finding was in accord with studies done in Canada [29, 59], Korea [48], and the southern US [60]. This might be due to elderly patients exhibiting higher rates of comorbidities and having higher rates of adverse events [55, 59, 60]. Statins were found to be equally effective in lowering the risk of cardiovascular death, ACS, stroke, or coronary revascularization in patients 75 years of age or older, according to a recent meta-analysis [61]. The findings were also consistent across statin trials. Even with very low low-density lipoprotein levels, statins have no effect on patient-reported cognition [62], according to the most recent data, despite post-market studies raising concerns about cognitive damage, particularly in the aging population. However, recent emerging evidence showed no difference in efficacy and safety outcomes in relation to age [63,64,65]. Moreover, the existing evidence recommends OMT for all patients without considering age differences. Therefore, OMT should be considered for elderly patients with ACS with the exception of contraindications [23, 33, 40, 42, 66].
Regarding sex, our study indicated that male patients were more likely to be discharged with OMT than female patients. This outcome is consistent with research conducted in Australia [67,68,69], West China (17), Italy (54), Thailand [27], the Netherlands [67, 70], and Malaysia [71, 72]. Since females with ACS were less likely to present with chest pain and diaphoresis but more likely to present with shoulder pain or gastrointestinal symptoms. This could be explained by the fact that female patients are frequently older and more complex with multiple baseline adverse comorbidities [67,68,69,70, 73, 74]. Furthermore, females had higher rates of baseline renal dysfunction, which contributed to the lower rates of ACEI/ARB prescriptions. As a result, the advantages of OMT may be underestimated [70,71,72]. Despite the long-term benefits of ACEI/ARBs being well established, many physicians are still hesitant to prescribe them to patients with renal dysfunction. In addition, the lower rate of dual antiplatelet therapy (DAPT) prescriptions among females in this study is due to a fear of bleeding complications. However, studies have demonstrated there is no sex difference in major bleeding risk at 12 months with DAPT [67, 75].
This study found that CKD patients had a lower likelihood of receiving an OMT during discharge. The study findings concurred with research from Thailand and Canada [29]. This could be because using ACEI/ARBs increases the risk of side effects and may require precautions against hyperkalemia or acute renal injury [27]. Patients with chronic kidney disease (CKD) should typically have a renal function test in order to alter their dosage, as most secondary preventive drugs have different effects on the kidney. Nonetheless, this study brought to light concerning issues with ACEI/ARB usage in ACS patients. Only 50.5% of the study participants were discharged with an ACEI or ARBs; most of them had hypertension or diabetes. Moreover, even though statin use has been shown to lower mortality in patients with or at risk for ACS, patients with CKD who have ACS are less likely to receive this treatment [76,77,78]. Data from the National Registry of Myocardial Infarction 4 indicate that statin administration within the first 24 h of hospitalization for acute myocardial infarction significantly lowers the rate of early complications and in-hospital mortality, in addition to the long-term benefits of statin therapy in ACS patients [79]. In fact, statins seem to mitigate the effects of inflammation, endothelial dysfunction, and coagulation problems, which are all linked to acute myocardial infarction [80]. There is uncertainty regarding the causes of this under-use of OMT in ACS patients with CKD. Potential explanations include worry about harmful side effects and additional deterioration of renal function. Moreover, there is more co-morbidity in CKD patients, which increases their contraindications to these medications.
Our study revealed that patients with atrial fibrillation (AF) were less likely to be discharged with OMT as compared to patients without AF. This result is consistent with studies done in Thailand [27] and Serbia [81]. Compared to patients without AF, those with AF had a lower likelihood of receiving beta-blockers, according to the GISSI-3 data [82]. In this study, digoxin and antiarrhythmic medications were used more frequently to treat AF patients. Another investigation revealed that patients with AF who had never been diagnosed before had a lower chance of receiving clopidogrel [83]. AHA/ACC and ESC guidelines recommend the use of triple therapy for patients with atrial fibrillation, consisting of DAPT and warfarin or a non-vitamin K anticoagulant (NOAC) or dual therapy (P2Y12 inhibitors plus warfarin or NOACs) to prevent stroke in patients who are more likely to experience thromboembolism-related problems [41, 81, 84, 85]. However, double therapy may be used in place of DAPT, which has an impact on the percentage of DAPT prescriptions in this study.
Our study also suggested that patients who experienced cardiogenic shock had a lower likelihood of being discharged with OMT. The finding was similar to the study done in six Middle Eastern countries [32]. The possible reason might be due to the presence of patients who are comparatively contraindicated. These patients may have started off hemodynamically unstable but later improved and became candidates for starting B-blockers. Therefore, the commencement of beta-blockers, which may have begun at a low dose and increased based on the patient’s state, was overlooked for these individuals when their hemodynamic stability and progress were seen. Another possible cause is a disruption in the medicine delivery [10]. Additionally, because this study was retrospective, there was a risk that the number of real contraindications may not have been recorded in the patient files, lowering the actual secondary prevention.
In terms of clinical outcomes, over a 5-year period, approximately 16.6%, 95% CI (13.2%, 20.5%), of ACS patients died, and 30.8%, 95% CI (26.4–35.5%), had MACE, which included 11.4% of CHF cases, 14.2% of stroke cases, and 5.2% of re-infarction cases. Overall, OMT prescription at discharge was associated with a reduction in 5-year mortality (AHR = 0.431; 95%CI: 0.222–0.835; P = 0.013).
Regarding to all-cause mortality, our finding is in accord with studies done in Israel (15.8%) [86], Netherlands (16.7%) [87], and Australia (16.8%) [88]. The results were higher than studies done in China (6.8%) [35], and Japan (7.1%, 6.3%) [89, 90]. On one hand, it might be due to sample size variation; in this study, only 422 patients were included, whereas the sample size in China, Australia, and Japan was larger. The other possible reasons might be due to the non-availability of thrombolytic drugs, non-adherence to the recommended guidelines, lifestyle issues, non-availability of CABG (coronary artery bypass graft), PCI (percutaneous coronary interventions) procedures, and P2Y12 inhibitors (ticagrelor, prasugrel) in the study area, which could all be the possible reasons.
Overall, our study revealed that patients who were discharged from the hospital with an optimal medical therapy (OMT) regimen consisting of four medications—aspirin, clopidogrel/P2y12 inhibitors, beta-blockers, statins, or the use of ACEI/ARBs on the top of the above medications if the patient had comorbidities like diabetes or hypertension—had a lower all-cause mortality rate. The present findings align with previous studies that have demonstrated improved outcomes for patients receiving OMT at the time of discharge [25, 26, 29, 35, 36, 48, 91, 92]. Optimal medical therapy (OMT) had been associated with lower MACE, according to a study conducted in Italy [92]. However, in this study, there was no statistically significant difference in MACE between the OMT and non-OMT groups. This study supports the use of OMT with all four drugs in combinations, as OMT was associated with a 56.9% reduced risk of all-cause mortality in patients with ACS.
Study strength and limitations
It is important to emphasize this study’s advantages. This is the first study that assessed secondary prevention medication after ACS for a five-year period in Ethiopia. Because the research is based on actual data, it offers a reliable representation of the therapeutic advantages of OMT regimens. The assessment of the causal link between OMT prescriptions and therapeutic benefit on mortality yielded reliable findings with strong statistical power.
This study has some limitations. Due to the retrospective nature of the study design, it was not possible to capture important data from the patient charts, such as contraindications and pertinent laboratory values. Second, the study was conducted at a single center, which may limit its external validity and scientific rigor in justifying broad practice modifications. It is unclear if the patients took the prescribed drugs, as many had multiple comorbidities and were taking various medications that are associated with poor adherence. However, a retrospective analysis found no significant difference in medication adherence rates at 3 months and 1 year after discharge for patients with acute myocardial infarction [93].
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