The impact of clinical pharmacists on adherence to acute myocardial infarction guidelines: A controlled before-after Interventional study

In this controlled before-and-after interventional study, the clinical pharmacist evaluated the application of performance measures (PMs) and quality measures (QMs) in the control group and the intervention group in Al-Gurayat General Hospital (GGH) in Saudi Arabia. The total number of PMs applied in the intervention group (n = 445) was significantly higher than that in the control group (n = 407) ( P-value =0.006). Considering individual PMs, only PM-4 (high-intensity statin prescription) was applied at a significantly higher frequency in the intervention group (n = 41, 82%) as compared to the control group (n = 29, 58%) ( P-value = 0.009). After acceptance of 60 out of the 75 recommendations made by the clinical pharmacist for the intervention group (80% acceptance rate), the number of treatment-related problems (TRPs) left on discharge of the intervention group was significantly reduced to 15 as compared to 61 TRPs left on discharge of the control group ( p <0.001). The clinical pharmacist-led interventions have a significant impact on ensuring adherence to PMs during the management of acute myocardial infarction (AMI) in GGH.


Introduction
Myocardial infarction (MI) is one of the most serious forms of heart disease, with significant short-and longterm morbidity and mortality.Patients with a suspicion or evidence of acute myocardial ischemia or infarction are referred to as having acute coronary syndrome (ACS) (Simons and Alpert 2020).The spectrum of ACS compris-deaths, ranking the country 34 th in the world (Ahmed et al. 2019).
Guideline-based acute management, secondary prevention, and treatment of post-MI patients is a critical part of the patient care process in order to improve patient outcomes (Sundararajan et al. 2020).According to the American College of Cardiology/American Heart Association (ACC/AHA) clinical performance and quality measures guideline for adults with STEMI and NSTEMI, the PMs and QMs in AMI management were created to evaluate the quality of care provided to patients with STEMI or NSTEMI in the inpatient setting (Jneid et al. 2017).Implementation of these measures by healthcare professionals and hospital systems will improve the quality of management and would likely improve outcomes for patients with STEMI and NSTEMI (O' Gara et al. 2013).This is especially important as a gap between guideline-recommended therapy and actual practice has been documented in the management of non-ST elevation acute coronary syndrome (NSTACS) (Engel et al. 2016).
Being the best source of information regarding medications, along with the available evidence of the role of pharmacists in improving outcomes in patients with cardiovascular diseases (Hassan et al. 2013;McNeely 2017), a clinical pharmacist is expected to provide an essential intervention in regards to MI management through the identification of adherence to quality measures among health care professionals.As the pharmacist is not a prescriber, most of the literature studies that assessed the role of pharmacist within the patient-care process focused on the identification of medication errors after prescription (Ashp and Guide 2010;Al Raiisi et al. 2019;Jabri et al. 2020).However, none of them assessed the leadership role of the pharmacist in ensuring adherence to quality performance measures as proposed by the American Society of Health-System Pharmacists (ASHP) (Ashp and Guide 2010).A previous report showed that counseling provided to patients by hospital pharmacists post-ACS was not associated with a significantly improved medication adherence or a reduction in hospital readmissions (Neville et al. 2021).However, more recent studies demonstrated that clinical pharmacist-led education of hospitalized ACS patients significantly improved medication adherence and reduced hospital readmission in post-ACS patients (El Hajj et al. 2023;Graham et al. 2024).To the best of our knowledge, there are no previous reports that assessed the role of clinical pharmacists in ensuring adherence to PMs and QMs for the management of acute MI patients.Therefore, the aim of the current study was to examine, for the first time, the impact of clinical pharmacy services on improving adherence to the ACC/AHA 2017 guidelines for performance and quality measures for adults with STEMI and NSTEMI (Jneid et al. 2017).This is critically important in GGH/Saudi Arabia, where clinical pharmacy service has not yet been established.In this study, the clinical pharmacist intervention included not only the identification of the actual/effective adherence to PMs and QMs for the management of patients with MI (STEMI and NSTEMI) in GGH but also the identification and prevention of other drug-related or treatment-related problems in these patients.Besides, this study aims to assess the acceptance of clinical pharmacists by physicians in GGH and would provide evidence to the decision-makers in GGH regarding the importance of establishing clinical pharmacy services there.

Study settings
This study was conducted during the period from July 2021 through January 2022 in the cardiology center of GGH in AlGurayat, which is a small city residing in the north of Saudi Arabia with a population size of 167,080 as of 2022.GGH is a 220-bed hospital.The cardiology center was established in May 2018.A catheterization laboratory is available, while clinical pharmacy service has not yet been established.
This study included patients aged ≥18 years who were admitted to GGH with an acute presentation of MI during the study period.Patients who died after admission for acute MI were excluded.

Study protocol and study design
In this interventional study, we assessed the impact of the clinical pharmacist services on the primary outcome measure of adherence to the clinical PMs and QMs for adults with STEMI and NSTEMI according to the 2017 ACC/AHA report (Jneid et al. 2017).Besides, the role of the clinical pharmacist in the secondary outcome measure of the identification and prevention of other TRPs in the study population was also assessed.The acceptance rate of clinical pharmacist recommendations by the physicians was also assessed.The study protocol was approved by the local research ethics committee in AlGurayat Health Affairs (IRB no.076/2021), and the study was performed in accordance with relevant guidelines and regulations.The data obtained was considered confidential, and patients' names were not collected.
The minimum required sample size for this study was estimated to be 20 using power calculations as previously described (Charan and Biswas 2013).The following equation was used: where N is the sample size; Z α/2 = 1.96 at type 1 error of 5%; Z β = 0.842 at 80% power; p1−p2 = difference in proportion of events in two groups; P = pooled prevalence = [prevalence in case group (p1) + prevalence in control group (p2)]/2.The values of p1 and p2 were estimated based on the results of a previous report, which demon-strated that clinical pharmacist intervention significantly increased the optimal prescribing of five guideline-direct medical therapies in patients with ACS from 35% (p2) of the patients in the observation phase into 80% (p1) of the patients in the intervention phase (Jabri et al. 2020).The target sample size was inflated to 50 in each cohort to account for any possible dropouts.
The researcher who collected the data was a clinical pharmacist who holds a Master's degree in clinical pharmacy and has obtained training on the field of critical care, including the coronary care unit.The data was collected from the patient records through the hospital information system and from the patients or their caregivers after obtaining informed consent.In addition, the relevant physician was also consulted throughout the process of data collection in cases of discrepancies and to ensure the reliability and completeness of the obtained data.The data collection process was continuously monitored and verified for accuracy by members of our research team.
A four-part data collection sheet was structured based on previous reports (AbuRuz et al. 2006;Jneid et al. 2017) and was face-validated by several colleagues in the field of clinical pharmacy.Piloting was also conducted, and the data obtained were not included in the final analysis.The first two parts of the collection sheet included patients' demographics and medical histories.The third part included the 17 PMs and the 6 QMs as described in the 2017 ACC/ AHA report (Jneid et al. 2017).The PMs and QMs were selected based on their applicability within the hospital setting and healthcare system in GGH.Therefore, of the 17 PMs, PM-10 and PM-11 could not be assessed due to the difficulty in assessing the relevant time intervals that are related to first medical contact (FMC) for patients referred from non-percutaneous coronary intervention (PCI)-capable facilities into GGH.In addition, QM-6 could not be assessed as prasugrel was not available in GGH during the study interval.The last part included a modified TRP assessment tool (AbuRuz et al. 2006) for the identification of treatment and drug therapy problems related to unnecessary drug therapy, untreated conditions, drug efficacy, drug safety, miscellaneous, and treatment-related problems on discharge medications.
This study is a controlled before-and-after quasi-experimental interventional study (Fig. 1).Two cohorts of patients were included: the historical retrospective (control) and the prospective (intervention) cohorts.This study design is justifiable when there are ethical concerns in recruiting patients for the control arm in life-threatening diseases such as AMI (Harris et al. 2006;Ghadessi et al. 2020).In addition, this study design ensures the blindness of physicians and the avoidance of any reflective interference from the intervention group on the control group.The historical control group included the eligible patients who had been admitted to the hospital from August 2020 to June 2021 and received standard-of-care treatment.For the intervention cohort, eligible patients who were admitted during the period of July 2021 to January 2022 were included.The medical records of patients in both groups were reviewed by the researcher clinical pharmacist and assessed for adherence to the 2017 ACC/AHA clinical performance and quality measures and for the presence of other TRPs.However, the management plan of the patients in the intervention cohort-but not the control cohort-was then discussed with the relevant cardiologist before setting recommendations.Physicians' acceptance rate of clinical pharmacist recommendations was recorded.
The proportion of patients whose management plan included the application of the different individual PMs or QMs was calculated and compared between the two cohorts.The total frequencies of the PMs or the QMs applied in either group were determined and compared.The total number of TRPs identified during hospitalization was calculated for each group.The total number of TRPs left without resolution at discharge was calculated and compared between the two groups.

Statistical analysis
Statistical analysis was performed using SPSS version 26.0 (SPSS Inc., Chicago, IL).Descriptive statistics of frequencies and percentages were used to describe the categorical variables, while mean and SD were used to describe continuous variables.Bivariate analyses were used to find between-group differences.Normality testing was performed using the Kolmogorov-Smilnorv and Shapiro-Wilk tests.An independent sample t-test was used to compare the means of normally distributed continuous variables.For non-normally distributed continuous variables, the Mann-Whitney U test was employed.For categorical variables, the chi-square test was applied.Fisher's exact test replaced the Chi-square test when counts were less than 5. Valid percentages were used to account for missing data.A P value < 0.05 was considered statistically significant.

General characteristics of participants
One hundred eligible patients with symptoms of STEMI and NSTEMI were included in this study, with 50 cases in each of the control and intervention groups.As presented in Table 1, there were no statistically significant differences between the control and the intervention groups in terms of age, gender, smoking, or the presence of previous comorbidities.This indicates that the population in both groups was homogenous.Both groups showed similarities in the proportion of comorbidities presented at the time of admission.Sixty percent of the control group and 76% of the intervention group had at least one comorbidity documented in the medical file.The most commonly encountered medical conditions were diabetes mellitus, hypertension, heart failure, and ischemic heart disease.However, the specific type of ACS (STEMI, NSTEMI, or unstable angina) was not clearly documented in the patient's medical file.

Performance measures studied
Of the 17 PMs described by the 2017 ACC/AHA report, PMs 1-6, 8, 9, 13, and 16 were applicable and could be evaluated (Table 2).Analysis of the application of the individual PMs revealed that of the 9 PMs evaluated, only PM-4 was applied at a significantly higher frequency in the intervention group as compared to the control group.High-intensity statin prescription at discharge was significantly higher in the intervention group (n= 41, 82%) as compared to the control group (n=29, 58%) (P-value = 0.009).Interestingly, the total number of PMs applied to all patients in the intervention group was significantly higher than that in the control group (P-value = 0.006).
The measures were generally applied at an overall higher frequency in the intervention group as compared to the control group, with the measures PM-1, PM-2, and PM-16 being applied to 100% of the patients in that group.PM-3, 4, 5, and 6 were not applied to some of the patients in the intervention group due to physician opinion or the presence of contraindications.PM-8 was applied to only 60% of the patients in the intervention group, which means GGH should develop an emergency protocol to handle ACS cases in a timely manner.PM-9 was applied to 92% (n = 46) of the intervention group, where PCI was performed on all patients with a presentation of ACS admitted to GGH regardless of being STEMI or NSTEMI, while the remaining patients (n = 4; 8%) were transferred to another hospital for coronary artery bypass grafting (CABG).PM-13 was applied to all patients in the intervention group with the exception of one, as the patient was transferred to another hospital to pursue his management.PM-7, PM-10, PM-11, PM-12, PM-14, PM-15, and PM-17 were not collected in this study due to the reasons presented in Table 3.None of the patients in this study received fibrinolytic therapy, and therefore PM-7 was not evaluated.Among the patients referred from other hospitals, there was not an accurate approach to determining neither the door-in-door-out time (PM-10) nor the FMC to PCI time (PM-11) in a PCI-capable hospital.Cardiac rehabilitation services are not available in GGH; therefore, none of the patients were transferred to such services prior to discharge (PM-12).None of the patients were resuscitated out of the hospital, so PM-14 could not be evaluated for this group of patients.PM-15 could not be addressed as all the patients were managed with invasive angiography rather than a conservative strategy.Regarding PM-17, the GGH does not participate in the national registry for AMI.

Quality measures studied
Of the seven quality measures provided in the 2017 ACC/ AHA report, only QM-4 was applicable and evaluated in the current study (Table 4).About 60% (n = 8) of those patients who are eligible for aldosterone antagonist treatment in the control group and 28.5% (n = 4) of those eligible in the intervention group had actually received aldosterone antagonist treatment.This difference was not statistically significant (P-value = 0.222).
None of the patients included in this study was eligible for QM-1, QM-2, QM-3, QM-5, QM-6, or QM-7.For QM-1 and QM-2, all the patients went to immediate and early invasive strategies, and no risk stratification score (TIMI or GRACE scores) was calculated.For QM-3, none of the patients in either group was comatose with out-of-hospital cardiac arrest.For QM-5, none of the patients in either of the groups were prescribed NSAIDs during hospitalization.Prasugrel was not prescribed during the study period to any of the patients as this drug was not available in GGH (QM-6).Finally, the inappropriate prescription of a high-dose aspirin (>100 mg) with Ticagrelor at discharge was not assessed due to the unavailability of a high-dose aspirin dosage in GGH, where all patients were prescribed 81 mg of aspirin at discharge (QM-7).

Treatment-related problems identified and left on discharge
As presented in Table 5, the clinical pharmacist identified 136 TRPs in both groups.Sixty-one TRPs were identified in the control group, while 75 TRPs were identified in the intervention group.A total of 82 TRPs were related to QMs and PMs in both groups.There was no statistically significant difference between the groups in terms of the number of TRPs identified, neither individual TRP classes nor the overall number of TRPs (Table 5).However, the clinical pharmacist provided recommendations in relation to all TRPs in the intervention group, and 60 out of the 75 recommendations were accepted and implemented by a physician.Consequently, the number of TRPs in the intervention group was reduced to 15 TRPs on discharge.This was significantly lower than the number of TRPs left on discharge for the patients in the control group (61 TRPs) (p < 0.001).Therefore, the clinical pharmacist service significantly reduced the number of TRPs on discharge of the patients in the intervention group as compared to the control group, with an acceptance rate of 80%.

Discussion
The primary objective of this study was to evaluate, for the first time, the role of clinical pharmacists in improving health care providers' adherence to the myocardial infarction management guideline through the PMs and QMs defined in the ACC/AHA 2017 guidelines for adults with STEMI and NSTEMI (Jneid et al. 2017).The main role of the clinical pharmacist-led intervention in this study was auditing and providing feedback and recommendations to health-care teams to encourage adherence to PMs and QMs in patients with AMI in GGH.In this study, patients who were in either of the control or intervention groups had similar baseline clinical characteristics.Therefore, differences in the number of PMs applied or TRPs identified between the control and intervention groups are attributed to casual associations with the interventions provided by clinical pharmacist recommendations.
The results of this study proved that the clinical pharmacist significantly improved adherence to the quality measures evaluated in this study in GGH.Clinical pharmacists  significantly increased the overall number of PMs met in the interventional group as compared to the control group.
In terms of individual PMs, the prescription of high-intensity statin at discharge was the only measure applied at a significantly higher frequency in the intervention group as compared to the control group.These results are in parallel with other previous reports that indicated that the presence of a pharmacist in cardiology units resulted in a higher use of beta-blockers, aspirin, and statins at discharge of patients with ACS for secondary prevention (Hassan et al. 2013;Jabri et al. 2020) or increased statin prescription in patients with diabetes (Anderson et al. 2020).Moreover, this finding is consistent with the conclusion of previous studies that pharmacist-led programs appear to be the most effective intervention for increasing statin use in eligible patients (Anderson et al. 2020;Elkomos et al. 2022).
In this study, the clinical pharmacist was able to evaluate 10 PMs while the other 7 measures were not applicable (PM-7, PM-10, PM-11, PM-12, PM-14, PM-15, and PM-17) for the reasons described in Table 3.
The present study used treatment-related problem classification tools to improve the identification, resolution, and prevention of treatment-related problems.The clinical pharmacist identified 136 TRPs among the 100 patients.TRPs in the control group were documented for study purposes without providing recommendations.Sixty-one TRPs were identified in the control group, while 75 TRPs were identified in the intervention group.The number of TRPs left without correction for the patients in the intervention group was reduced to 15, which is significantly lower than the control group (61).The most common classes of TRPs in this study were related to untreated medical conditions, efficacy, and miscellaneous.Of the encountered examples of untreated condition-related TRPs, diabetic patients were discharged without diabetic medications or without endocrinologists' evaluation.Efficacy-related TRPs were mostly about the need for additional drugs, efficacy dosage regimen issues, or the availability of more effective drugs (ex: the need for ACEI or ARBs, high-intensity statin, or heparin dosage regimen issues).The need for additional diagnostic tests or more frequent monitoring (ex: the need for performance of Echo, HbA1c, troponin, or kidney function tests) or the need for consultation (ex: a nephrologist) had a higher frequency in the miscellaneous TRPs.
Interestingly, the acceptance rate for clinical pharmacist recommendations was 80%; this indicates a positive attitude of physicians towards clinical pharmacy services in GGH.This acceptance rate mostly matches another study conducted in Saudi Arabia at Jazan General Hospital, where 78% of pharmacists recommendations regarding drug-related problems were accepted by physicians, and the patient's therapy was changed accordingly (Babelghaith et al. 2020).In a similar regional study, 692 interventions were recommended by the pharmacists in the outpatient pharmacy department of Khoula Hospital in Muscat, Oman, of which 98.2% were accepted by the prescribers (Adusumilli and Adepu 2014).Another study conducted in Iraq by Jabri et al. (2020) indicated that clinical pharmacists had made crucial interventions, 88% of which were related to adding necessary medications, followed by dose optimization (10% of the interventions) and removing medication duplication (2%).In that study, 74% of the provided recommendations were accepted by the cardiologists (Jabri et al. 2020).

Study limitations
Although the current study provides interesting findings regarding the need for and the vital role of clinical pharmacists in the cardiology center in GGH, it still has several limitations.The current study was conducted in only one hospital in Saudi Arabia, and that limits the generalizability of our findings.In addition, exact differentiation in the diagnosis of either STEMI or NSTEMI was not clearly identified where all patients with angina pain were treated with PCI.This study used a historical retrospective control rather than a concurrent control group.This is attributed to ethical concerns, as it is not ethical to deny patients in the control group the proper quality of care provided by the clinical pharmacist.Furthermore, the use of a historical control guarantees the blindness of physicians and the avoidance of applying the recommendations provided by clinical pharmacists regarding the intervention group to the control groups if both groups were run concurrently.This allowed a valid comparison of PMs and QMs applied before and after clinical pharmacist intervention.

Conclusions
The clinical pharmacist interventions have a significant impact on improving overall adherence to PMs in GGH in regards to the management and secondary prevention of AMI.The physicians in GGH showed a positive attitude towards clinical pharmacists, as reflected in the high acceptance rate of clinical pharmacist recommendations.
The decision-makers in GGH are advised to accelerate the establishment of the clinical pharmacy service in GGH in order to improve the quality of health services and enhance adherence to disease-specific management guidelines.

Figure 1 .
Figure 1.Workflow for the study.

Table 1 .
General characteristics of the study population.
ParameterControl group n (%) d Intervention group n (%) e P-value* a Independent sample t-test; b Chi-square test; c Fisher's exact test; d percent from the control group (N = 50); e percent from the Intervention group (N = 50); *Significant at P-value <0.05.

Table 2 .
The proportion of patients who met the performance measures.

Control group a n (%) Interventional group b n (%) P-value PM-1
e Independent sample T-test; f These measures apply only to patients with STEMI; g These measures apply only to patients with NSTEMI; *A p-value < 0.05 was considered statistically significant.

Table 4 .
The proportion of patients who met the quality measures.
ACE: angiotensin-converting enzyme; AMI: acute myocardial infarction; LVEF: left ventricular ejection fraction; NSTEMI: non-ST segment elevation myocardial infarction; QM: quality measure.a valid percent from the eligible control group (n = 13); b valid percent from the eligible intervention group (n =14); c chi-square test; A p-value < 0.05 was considered statistically significant.

Table 3 .
Excluded performance measures.Time to Fibrinolytic Therapy ≤30 min.None of the patients in this study received fibrinolytic therapy PM-10 Time From ED Arrival at STEMI Referral Facility to ED Discharge From STEMI Referral Facility in Patients Transferred for Primary PCI is ≤30 min Lack of an accurate approach for the determination of the exact time of arrival and discharge for the patients who were initially seen at non-PCI capable hospitals.Non-invasive Stress Testing Before Discharge in Conservatively Treated Patients All patients received invasive coronary angiography.

Table 5 .
Frequencies of TRPs among control and intervention groups.