Ethics approval

This study received ethical approval from the College of Pharmacy at the University of Mustansiriyah. In addition, the hospital gave approval for patient-level data to be collected from medical records. All patient-level data were anonymised prior to analysis to ensure patient confidentiality.

Study design and setting

This study used an observational retrospective cross-sectional design, applied to routinely collected patient-level data. The study was conducted within a major teaching hospital in Baghdad, Iraq’s largest city, which provides free state-funded health care and delivers ACS care to approximately 700 patients per year.

Participant identification and data collection

Patients were eligible for this study if they were admitted to the study site and survived an ACS event from May 2016 to January 2017. For the purposes of the study an ACS event was defined as incident STEMI, NSTEMI, or unstable angina recorded in the medical notes of an admitted patient, plus clinical signs/symptoms of chest pain associated with electrocardiography changes and/or troponin level elevation. Patients were excluded from the study if they left against medical advice, died or were transferred to another hospital. If patients were admitted twice during the study, only their first admission was included. Given the descriptive nature of the study, resource constrains and the incidence rate of ACS within the site, a sample size of 200 patients was deemed appropriate. These patients were identified via convenience sampling by hospital administrative staff who screened medical records for incident ACS until 200 patients were included. The sampling methodology was not random and did not include consecutive patients.

Following identification, retrospective patient-level data were collected from written medical records, from October 2016 to February 2017, by one experienced clinical pharmacist using a standardised data collection form. Data included: age, gender, primary diagnosis, past medical history, blood pressure at discharge, heart rate at discharge, and prescribed drugs and doses on the day of discharge. The hospital inpatient prescription on the day of discharge was used to confirm the discharge medication, as the formal discharge prescription is not permanently stored in the patient’s records, but given to the patient at discharge.

Measurement of outcomes

The primary endpoint was the number of patients prescribed appropriate secondary prevention medications at discharge. For the purpose of the study, appropriate secondary prevention medications were defined as being prescribed dual antiplatelet therapy, statin, ACEI/ARB and beta-blocker at discharge in accordance with AHA/ACC guidance. When patients had a clinical contraindication, in accordance with AHA/ACC guidance, precluding the use of one or more medications this was also counted as appropriate secondary prevention therapy.¹³,¹⁴

Secondary endpoints were the number of patients receiving optimal doses of ACEI/ARBs, beta-blockers, and high-intensity statins at discharge.¹³,¹⁴ The following daily target doses were used: beta-blockers (metoprolol 200 mg; atenolol 100 mg; carvedilol 50 mg; and bisoprolol 10 mg) ACEI/ARBs (captopril 150 mg; enalapril 20 mg; lisinopril 10 mg; ramipril 10 mg; valsartan 320 mg; losartan 150 mg; and candesartan 32 mg) and high-intensity statins (atorvastatin 80 mg or rosuvastatin 20 mg or 40 mg).¹⁵,¹⁶,¹⁸ A dose intensity ranking was then used to define optimal doses as low (<50% of target dose), medium (50-74%) and high (≥75%).¹¹ Systolic blood pressure and heart rate were evaluated for patients to determine whether low systolic blood pressure prevented dose optimization in low dose users of ACEI/ARBs and beta-blockers.

Statistical analysis

Descriptive statistics were used to describe patient demographics, the proportion and percentage of patients receiving secondary prevention medications, and target doses at discharge. Pearson’s chi-squared test, Fisher’s exact test (categorical variables) and the independent t-test (continuous variables) were used as appropriate, depending on the data, to test for associations between demographic characteristics and the use of medications at discharge. Based on the results of the above tests, variables with statistical significance associated with receiving all five medications at discharge were also subjected to binary logistic regression in order to determine independent predictors associated with receiving all five medications at discharge. Data were analysed using SPSS version 26.0 (INM Corp, Chicago, IL) and two-tailed p- values less than 0.05 were used to indicate statistical significance.

Prescription of secondary prevention medications

During the study period, 522 patients were admitted with ACS. Of these, 439 (84.1%) were eligible for the study, and 45.6% (200/439) were included. Of the 83 (15.9 %) ineligible patients, 39 left against medical advice, 31 died, and 13 transferred to another hospital.

Included patients varied in age from 25 to 90 years old (mean 57.8) and 78.0% (n=156) were male, with 84.5% (n=169) having a primary diagnosis of myocardial infarction and 15.5% (n=31) having unstable angina. Baseline cardiac risk factors included; 58.5% (n=117) hypertension; 38.5% (n=77) diabetes and 31.5% (n=63) with a previous history of ischemic heart disease. The median duration of hospital stay was 4 days, (range 1 to 29 days); see Table 1.

In total, 53.5% (n=107) of patients were prescribed all five medications, see Table 2. Thirteen additional patients had contraindications for one or more secondary prevention medications. Therefore, when valid contraindications were accounted for, 60.0% (n=120) of patients were assessed against guidelines to be prescribed appropriate secondary prevention therapy. Most commonly prescribed medications were: clopidogrel 98.0% (n=196), statins 94.5% (n=189) (52.4% atorvastatin, 47.6% rosuvastatin), aspirin 93.5% (n=187), dual antiplatelet therapy 92.5% (n=185) (aspirin and clopidogrel in all cases), beta-blockers 87.0% (n=174) (78.2% metoprolol, 14.4% carvedilol, 5.7% bisoprolol and 1.7% atenolol) and ACEI/ARBs 69.5% (n=139) (82.7% captopril, 5.0% enalapril, 2.2% lisinopril, 0.7% ramipril, 5.8 % candesartan, 2.2% valsartan and 1.4% losartan). No patients were co-prescribed ACEI and ARB. There was statistically significant association between the use of all five medications and mean diastolic blood pressure. In addition, there was a significant association between ACE/ARBs prescribing and hypertension, diabetes mellitus and being discharged on oral nitrate, see Table 3.

Binary logistic regression indicated that comorbidities such as hypertension (odd ratio=2.05, 95%CI 1.11 to 3.79; p=0.022) and diabetes mellitus (odd ratio=0.42, 95%CI 0.23 to 0.78; p=0.006) as well as oral nitrate prescription (odd ratio=2.95 95%CI 1.22 to 7.12; p=0.016) were associated with receiving all five medications at discharge.

Dosing of secondary prevention medications

Regarding optimal dosing, all patients prescribed antiplatelets received optimal doses: aspirin 100 mg and/or clopidogrel 75 mg daily. Of the 94.5% of patients (n=189) who received a statin, 80.9% (n=153) were prescribed a high-intensity statin. Of the 69.5% of patients (n=139) that received ACEI/ARBs, 12.2% (n=17) were prescribed a dose in the high target range. Of the 87.0% of patients (n=174) that received a beta-blocker, 9.2% (n=16) were prescribed a dose in the high target range. (Table 2). Of the 53.5% of patients (n=107) prescribed all five medication classes, only 1.9% patients (n=2) were prescribed all five medication classes within the high target dose range.

The number of patients who remained on low or moderate dose of beta-blockers (n=158) and were affected by marginal hemodynamics was low; 4.4% (7/158) had a heart rate >60 beats per minutes (bpm) and were therefore not candidates for titration to target dose whereas 83.5% (132/158) had a heart rate of ≥70 bpm. Only 20.9 % (33/158) had a systolic blood pressure reading >110 mmHg, 24.1% (38/158) had blood pressure level between 110-119 mmHg and 55.1% (87/158) had blood pressure ≥120mmHg.

Of the patients who remained on low or moderate doses of ACEI/ARBs (n=122), only 17.2% (21/122) had blood pressure >110 mmHg and were not considered for dose up-titration whereas 18.9% (23/122) had blood pressure reading between 110-119 mmHg with the majority 63.9% (78/122) had blood pressure over 120 mmHg.

Strengths

This is the first study to evaluate the in-depth prescribing of secondary prevention medications, including dose, after ACS in Iraq. The cohort represents nearly half of the eligible patients admitted during the study period and hence should be representative of hospital admissions. The data were collected by one experienced clinical pharmacist, thus limiting inter-researcher variation. Utilizing routine medical records overcomes coding issues associated with electronic databases and thus, represents a more accurate method for data collection.⁹,²⁰ Moreover, measuring guideline adherence for prescribing optimal doses of secondary prevention medications overcomes the limitation of previous studies.⁸,²⁰

Limitations

As a retrospective study using routinely collected patient-level data, the study was limited by data accuracy due to record-keeping errors, such as undocumented contraindications or medication intolerance. However, the clinical pharmacist who collected the data was aware of such potential issues and took time to identify contraindications and drug allergies during data collection. The sampling methodology was not random and did not include consecutive patients, which may introduce bias; however, the final cohort constituted 45.6% of eligible patients during the study period. The presence of full echocardiogram and angiography results, incorporating post-infarct left ventricular function and the presence and burden of residual coronary heart disease, was also unavailable. These results may have influenced physician decisions around ACE/ARB and beta-blocker prescribing. As this study was conducted in a single hospital, it may not reflect wider Iraqi practice. Finally, given the cross-sectional nature of the study data on post-discharge mortality rates, new hospitalizations and disease recurrence were not available and would require further research.

Policy, practice and research implications

This study concentrated on the short-term prescription of secondary prevention medications during the discharge phase of ACS hospital care. To date, there is no published literature on the post-discharge phase of Iraqi ACS care. Standard Iraqi post-discharge care, usually involves a patient visiting a cardiologist either in a state-funded or in a private primary care facility. In such settings, the prescriber is expected to optimise ACEI/ARB and beta-blocker doses to achieve the target dose based on the patient’s tolerance and hemodynamics. The cost of medication and certain aspects of healthcare is however a potential barrier to the long-term persistence with therapy. In addition, the quality of care in the public sector is suboptimal due to the heavy workload experienced by physicians.²⁶ Thus, every attempt should be made to titrate the doses during hospital admission, whenever possible.¹³,¹⁷

The exact individual reasons for 40.0% of patients not being treated according to guidelines are unknown. The regression analysis showed that patients with hypertension or those using oral nitrates were more likely to be treated in accordance with guidelines. Both of these cohorts represent ‘higher’ risk cohorts and that may have influenced clinician behaviour. It is uncertain why diabetic patients, another high risk cohort, were less likely to be treated in accordance with guidelines.

Quality improvement strategies such as continued education, integrated care, and pre-discharge checklists have been shown to enhance compliance with evidence-based guidelines.⁸,²⁷,²⁸ Addressing the issue of suboptimal ACEI/ARB and beta-blocker prescribing, which is also common in Europe, North America, and the Middle East, seems key.⁵,¹¹,¹⁵,¹⁶ In other countries, pharmacists working in primary and secondary care have been shown to be effective in improving the prescribing rates and dosing of secondary prevention cardiac medications.²⁹,³⁰ In Iraq, clinical pharmacists are not usually involved in the coronary care unit, as their role is limited to dispensing medications.³¹ Thus, the incorporation of pharmacists into the multidisciplinary team to improve the prescribing and dosing of secondary prevention medications may improve the quality of care for these patients.²⁹,³⁰ In addition, pharmacists can educate patients and caregivers as per the guidelines recommendations about drug therapy, discussing indications, possible side effects, drug-drug or food-drug interactions, and monitoring.¹³,¹⁴,³²

Iraq has a workforce of over 11,000 practicing pharmacists, most of whom work in state-funded primary and secondary care or privately owned community pharmacies, where services centre on traditional dispensing and distribution of medicines.³¹ The opportunities for Iraqi pharmacists to assume clinical roles have grown over the last 20 years.³¹ Specialisation, involving post-graduate qualifications and board certification, is becoming commonplace.³¹ A future opportunity, therefore, exists to develop extended roles in specialities such as cardiology, as seen in the US and the UK.³²,³³ Government funding models and legislation changes many ultimately be required to facilitate this.³¹ Future studies in Iraq should assess barriers and variations to optimal prescribing of ACEI/ARBs and beta-blockers in clinical practice using quantitative and qualitative methods. These studies should also consider assessing and evaluating clinical pharmacist interventions in optimising patient care to support future professional and service developments.