Value of the Clinical Pharmacist Interventions in the Application of the American College of Cardiology (ACC/AHA) 2018 Guideline for Cholesterol Management

Abstract

The study aims to examine the extent of implementing the ACC/AHA cholesterol guideline and its updates in practice as well as the role of clinical pharmacists in making such guidelines effective. A cross-sectional observational study was conducted on 272 adult patients who visited the hospital internal medicine clinic in the UAE and were candidates for statin therapy based on the 2018 ACC/AHA guidelines for cholesterol management. Clinical pharmacist interventions were determined. The chi-square test was used to compare compliance with the guidelines before and after clinical pharmacist interventions. Compliance with the recommendations for cholesterol management was significantly improved from 60.3% to 92.6% (X2=79.1, p=0.0001) after clinical pharmacist interventions. Among patients who were on statin therapy, the percentage of those who were on proper statin intensity increased significantly from 47.6% to 94.4% (X2=72.5, p=0.0001). The combination of statins with nonstatin therapies such as ezetimibe and PCSK9 inhibitors increased from 8.5% to 30.6% (X2=95, p<0.0001) and from 0.0% to 1.6% (X2=6, p=0.014), respectively. The use of other lipid-lowering agents was diminished from 14.6% to 3.2% (X2=19.2, p<0.0001). Collaboration between physicians and clinical pharmacists is a crucial strategy to achieve better health outcomes among patients suffering from dyslipidemia.

Introduction

Coronary heart disease (CHD) is considered one of the main causes of morbidity and mortality worldwide. One of the major risk factors that contributes to the development and progression of CHD is dyslipidemia (1). According to the World Health Organization (WHO), an estimated 17.9 million patients died in 2016 because of cardiovascular diseases, of which more than 80.0% of the deaths were due to stroke and myocardial infarction (2).

In the United Arab Emirates (UAE), ischemic heart diseases and stroke are among the top 3 leading causes of years of life lost (YLL) and mortality according to a global burden disease study in 2016 (3). Another recent study in UAE showed that the overall prevalence of dyslipidemia among adults was 72.5%, where the total cholesterol and LDL-C levels were high in 42.8% and 38.6% of the participants, respectively (4). In addition, a study including an expatriate population in the UAE reported a high prevalence of either overweight or obesity (75.3%) as well as known associated risk factors for developing both metabolic syndrome and dyslipidemia (5).

A large number of clinical trials have reported the benefits of lowering cholesterol levels, particularly LDL-C, in reducing the mortality rate among CHD patients (6). Based on that, the American College of Cardiology (ACC/AHA) published the 2013 blood cholesterol treatment guidelines to reduce atherosclerotic cardiovascular risk in adults. In this decade, this guideline has been updated several times since then (6). The latest update expands the role of LDL-C targets. It also specifies the importance of percentage reduction in LDL-C when prescribing high- or moderate-intensity statins as well as the medication’s adherence by LDL-C testing and the efficacy of statin therapy (7, 8). Furthermore, it highlights the importance of adding PCSK9 inhibitor therapy after receiving the maximum tolerated statin therapy and ezetimibe to achieve LDL-C < 70 mg/dl or non-HDL-C < 100 mg/dl for patients in each of the 4 statin benefit groups with atherosclerosis cardiovascular disease (ASCVD) with or without comorbidities (7, 8).

The present study aims to examine the extent to which the updated ACC/AHA cholesterol guideline (2018) is implemented in practice and to assess the value of the clinical pharmacist in implementing this guideline in UAE healthcare settings.

Results

Demographic and Clinical Characteristics of the Study Sample

The demographic and clinical characteristics of the study sample are shown in Table 1. The mean age of the studied patients was 52.6 ±10.5, and 71.3% (n= 194) of them were males. The majority of the patients (95.6%, n= 260) had previous illness or chronic disease. Out of these patients, 178 patients (65.4%) had hypertension, 150 patients (55.1%) had dyslipidemia, and 196 patients (72.1%) had diabetes mellitus. Nevertheless, 20 patients (7.4%) had LDL-C levels less than 70 mg/dl, 236 patients (86.8%) had LDL-C levels between 70-189 mg/dl, and 16 patients (5.9%) had LDL-C levels equal to or more than 190.

Table 1

Demographic and clinical characteristics of the study sample
	Age Categories
	21 - <40	40 - 75	>75	Total
Total participants	36 (13.2%)	226 (83.1%)	10 (3.7%)	272 (100.0%)
Population characteristics
Gender:
Male	30 (11.0%)	160 (58.8%)	4 (1.5%)	194 (71.3%)
Female	6 (2.2%)	66 (24.3%)	6 (2.2%)	78 (28.7%)
Race:
White and others	28 (10.2%)	176 (64.7%)	4 (1.5%)	208 (76.5%)
Black	8 (2.9%)	50 (18.4%)	6 (2.2%)	64 (23.5%)
Smoking	22 (8.1%)	78 (28.7%)	2 (0.75%)	102 (37.5%)
Hypertensive patients	20 (7.4%)	150 (56.6%)	8 (2.9%)	178 (65.4%)
Total cholesterol	213±53.1	188±45.1	198±20.8	192±46.5
< 200mg/dl	14 (5.1%)	132 (48.5%)	2 (0.75%)	148 (54.4%)
200 – 239mg/dl	10 (3.7%)	58 (21.3%)	8 (2.9%)	76 (27.9%)
≥ 240mg/dl	12 (4.4%)	36 (13.2%)	0 (0%)	48 (17.6%)
HDL	37±5.6	39±8.6	46±6.3	39±8.3
< 40mg/dl	24 (8.8%)	132 (48.5%)	0 (0%)	156 (57.4%)
≥ 40mg/dl	12 (4.4%)	94 (34.6%)	10 (3.7%)	116 (42.6%)
LDL	128±44.2	120±37.3	135±5.1	121±38.1
< 70mg/dl	0 (0.0%)	20 (7.4%)	0 (0.0%)	20 (7.4%)
70 – 189mg/dl	32 (11.8%)	194 (71.3%)	10 (3.7%)	236 (86.8%)
≥ 190mg/dl	4 (1.5%)	12 (4.4%)	0 (0%)	16 (5.9%)
Dyslipidemia and on statin	18 (6.6%)	126 (46.3%)	6 (2.2%)	150 (55.1%)
Diabetes and on diabetic medications	26 (9.6%)	166 (61.1%)	4 (1.5%)	196 (72.1%)
eGFR:	99.3±22.8	87.1±22.3	69.6±27.8	88.3±22.9
BMI:	28.9±4.9	30.2±6.7	25.7±8.3	30±6.4
Mean of estimated 10 years risk of CVD*:	9.1±4.9	15.9±10.3	30.3±7.4	15.5±10.1
< 7.5%	6 (2.2%)	44 (16.2%)	0 (0%)	50 (18.4%)
≥ 7.5-<20%	22 (8%)	88 (32.4%)	4 (1.5%)	110 (40.5%)
≥20%	0 (0%)	50 (18.4%)	10 (3.7%)	60 (22.1%)
History of CVD	8 (2.9%)	44 (16.2%)	0 (0.0%)	52 (19.1%)
ASCVD not at very high risk	2 (0.75%)	12 (4.4%)	0 (0.0%)	14 (5.1%)
Very high risk ASCVD	6 (2.2%)	32 (11.8%)	0 (0.0%)	38 (14.0%)
*The estimated 10 years risk of CVD is measured using Pooled Cohort Risk Equation.
Mean risk is calculated among the participants without history of CVD.
eGFR = estimated glomerular filtration rate, HDL = high density lipoprotein, LDL = low density lipoprotein, BMI = body mass index, ASCVD = Atherosclerosis Cardiovascular Disease.

Additionally, 52 patients (19.1%) had a history of clinical ASCVD. Of these, 38 patients (14.0%) were at very high risk of recurrent CVD. Out of all participants without a history of clinical ASCVD, 50 patients (18.4%) had an estimated 10-year CVD risk less than 7.5%, 110 patients (40.5%) had an estimated 10-year CVD risk greater than or equal to 7.5% but less than 20.0%, and 60 patients (22.1%) had an estimated 10-year CVD risk equal to or greater than 20.0%.

The Adherence with the 2018 ACC/AHA Guideline Recommendations for the Management of Cholesterol in Adults before Clinical Pharmacist Interventions

Compliance with the 2018 ACC/AHA guideline recommendations for the management of cholesterol in adults is shown in Table 2. Based on the inclusion criteria, all the patients who were enrolled (100.0%, n = 272) were identified as statin benefit groups according to the 2018 ACC/AHA guideline recommendations. Of these patients, 60.3% (n= 164) were initiated on statin therapy.

Table 2

The compliance with the 2018 ACC/AHA guideline recommendations for the management of cholesterol in adults before clinical pharmacist intervention.
LDL-C level	History of ASCVD			DM	ASCVD risk score*			Total “n”	Use of statins		Statin intensity level
	Not at very high risk		Very high risk⸙		<7.5%	≥7.5<20%	≥20%		Adherence	Non-adherence	Low	Moderate	High	Adherence	Ezetimibe		PCSK9 Inhibitors		Other lipid lowering agents
	≤75	>75
															Required	Initiated	Required	Initiated	Initiated	Drug used
< 70 mg/dl			√					8	6	2	0	4	2	2	2	2	0	0	0
				√	√			4	2	2	2	0	0	0	0	0	0	0	0
				√		√		4	4	0	2	0	2	2	0	0	0	0	0
				√			√	2	2	0	0	2	0	0	0	0	0	0	2	Fenofibrate 145mg
						√		2	0	2	0	0	0	0	0	0	0	0	0
70–189 mg/dl			√					20	14	6	0	8	6	6	8	0	0	0	2	Fenofibrate 300mg
	√							20	14	6	0	11	3	3	7	2	0	0	0
				√	√			40	24	16	2	14	8	22	10	2	0	0	0
				√		√		70	42	28	4	23	15	15	19	4	0	0	16	Fenofibrate 145mg
				√			√	46	30	16	6	10	14	14	14	0	0	0	2	Fenofibrate 145mg
						√		28	6	22		2	4	6	4	0	0	0	0
							√	12	8	4		4	4	4	4	0	0	0	0
≥ 190 mg/dl			√					2	2	0	0	0	2	2	2	2	2	0	0
	√							2	2	0	0	2	0	0	2	2	2	0	0
				√	√			2	2	0	0	2	0	0	2	0	0	0	0
				√		√		2	2	0	0	0	2	2	2	0	2	0	2	Gemifibrozil 600mg
					√			4	2	2	0	2	0	0	4	0	0	0	0
						√		4	2	2	0	2	0	0	4	0	0	0	0
Total =								272	164 (60.3%)	108 (39.7%)	16 (9.8%)	86 (52.4%)	62 (37.8%)	78 (47.6%)	84 (51.2%)	14 (8.5%)	6 (3.7%)	0 (0%)	24 (14.6%)
Compliance with guideline									60.3%		47.6%				16.7%		0%
ASCVD = Atherosclerosis Cardiovascular Disease, DM = Diabetes Mellitus, n = number of patients.
*The estimated 10 years risk of CVD is measured using Pooled Cohort Risk Equation. Risk is calculated among the participants without history of CVD.
⸙Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions according to the guideline.

Out of those who were on statin therapy, 9.8% (n= 16) were on low intensity statin (e.g., simvastatin 10 mg and pitavastatin 1 mg), 52.4% (n = 86) were on moderate intensity statin (e.g., simvastatin 40 mg, rosuvastatin 10 mg, atorvastatin 20 mg, pitavastatin 2 mg and 4 mg) and 37.8% (n = 62) were on high intensity statin (e.g., atorvastatin 40 mg and 80 mg and rosuvastatin 20 mg and 40 mg). Of these patients, 47.6% (n = 78) complied with the recommendations regarding the level of statin intensity used.

The addition of nonstatin therapies to achieve LDL-C goals was also assessed, and ezetimibe was required for 51.2% (n = 84) of those who were on statin therapy. While it was initiated for 8.5% (n = 14). PCSK9 inhibitors were required for 3.7% (n = 6) of those who were on statin and ezetimibe therapies. However, such treatment was not initiated.

Other lipid-lowering agents, such as fibric acid derivatives (fenofibrate 145 mg and 300 mg and gemfibrozil 600 mg), were initiated on 14.6% (n = 24) of those who were on statin therapy.

The Value of the Clinical Pharmacist Interventions on Applying the 2018 ACC/AHA Guideline Recommendations

The impact of the clinical pharmacist interventions on applying the 2018 ACC/AHA guideline recommendations is shown in Table 3. In patients with LDL-C<70 mg/dl, 18 recommendations were made, ranging from adding moderate- or high-intensity statins for those who were not initiated on statins (need additional therapy – class I and IIa recommendations), changing to moderate- or high-intensity statin agents for those who were on lower-intensity statin agents and stopping other lipid-lowering agents that may not help in achieving LDL-C goals (dose adjustment/stop unnecessary medications - class I and IIa recommendations). However, the physicians’ acceptance of the aforementioned recommendations was 22.2%.

Table 3

The value of the clinical pharmacist interventions on applying the 2018 ACC/AHA guideline recommendations
LDL group	Recommendations		Interventions		Physicians response
	No.	Type	Type	Rational	%	Reasons for rejecting
Patients with LDL-C<70mg/dl	4	Adding high intensity statin	Need additional therapy	Class I recommendation Class IIa recommendation	50%	Low LDL-C level, concerns about side effect and the additional cost
	2	Adding moderate intensity statin	Need additional therapy	Class I recommendation	100%
	2	Change to high intensity statin	Change drug	Class IIa recommendation	0%	Low LDL-C level, concerns about side effect and the additional cost
	4	Change to high intensity statin	Dose adjustment	Class I recommendation	0%	Low LDL-C level, concerns about side effect and the additional cost
	4	Change to high intensity statin/stop fenofibrate	Dose adjustment/ Unnecessary medication	Class IIa recommendation	0%	Patients can’t tolerate the higher dose
	2	Change to moderate intensity statin	Dose adjustment	Class I recommendation	0%	Low LDL-C level, concerns about side effect and the additional cost
Total =	18				22.2%
Patients with LDL-C between 70-189mg/dl	50	Adding ezetimibe	Need additional therapy	Class I recommendation Class IIa recommendation	90%	Low LDL-C level (72), concerns about side effect and the additional cost
	8	Adding ezetimibe/stop fenofibrate	Need additional therapy/unnecessary medication	Class IIa recommendation	100%
	82	Adding high intensity statin	Need additional therapy	Class I recommendation Class IIa recommendation	80.5%	Low LDL-C level (70-87), concerns about side effect and the additional cost
	16	Adding moderate intensity statin	Need additional therapy	Class I recommendation	87.5%	Low LDL-C level (79), concerns about side effect and the additional cost
	6	Change to high intensity statin	Change drug	Class I recommendation	100%
	60	Change to high intensity statin	Dose adjustment	Class I recommendation Class IIa recommendation	71.7%	18.3% Patients can’t tolerate the higher dose. 10% Low LDL-C level (70-76), concerns about side effect and the additional cost
	4	Change to high intensity statin/stop fenofibrate	Change drug/ unnecessary medication	Class I recommendation	0%	Patients can’t tolerate the higher dose
	24	Change to high intensity statin/stop fenofibrate	Dose adjustment/unnecessary medication	Class I recommendation Class IIa recommendation	83.4%	Patients can’t tolerate the higher dose.
	12	Change to high intensity statin/stop fenofibrate/add ezitimibe	Dose adjustment/unnecessary medication/need additional therapy	Class I recommendation	50%	Patients can’t tolerate the higher dose.
Total =	262				79.4%
Patient with LDL-C ≥190mg/dl	6	Adding ezetimibe/adding PCSK9/stop gemfibrozil	Need additional therapies/unnecessary medication	Class I recommendation/very high LDL-C level	66%	The decision for adding PCSK9 inhibitors has been delayed for the next follow-up
	8	Adding high intensity statin/ Adding ezetimibe	Need additional therapy	Class I recommendation/very high LDL-C level	100%
	4	Adding PCSK9	Need additional therapy	Class I recommendation/very high LDL-C level	100%	50% not tolerating moderate or high intensity statin
	12	Change to high intensity statin/adding ezitimibe	Dose adjustment/need additional therapy	Class I recommendation/very high LDL-C level	100%
Total =	30				93.2%

In patients with LDL-C between 70-189 mg/dl, 262 recommendations were carried out ranged from adding ezetimibe and stopping other ineffective LDL-C lowering agents for those who were in maximum tolerated dose of statin (need additional therapy/stop the unnecessary medication – class I and IIa recommendations), adding moderate or high intensity statin for those with who were not initiated on statin (need additional therapy – class I and IIa recommendations) and changing to high intensity statin dose or drug for those who were on lower intensity statin agents and stopping other ineffective LDL-C lowering agents (dose adjustment/change drug/stop the unnecessary medications - class I and IIa recommendations). Importantly, the physicians’ responses against these recommendations were 79.4%.

In patients with LDL-C ≥190 mg/dl, 30 recommendations were accomplished, ranging from adding ezetimibe, PCSK9 inhibitor and stopping gemfibrozil for those with very high LDL-C results and requiring a more than 25.0% reduction in LDL-C levels despite the use of high-intensity statins (requiring additional therapy – class I recommendation), adding high-intensity statins together with ezetimibe for those who were not on statins (requiring additional therapies – class I recommendation), adding PCSK9 inhibitors for those with high LDL-C levels, although they were on high-intensity statins together with ezetimibes (requiring additional therapy – class I recommendation) and changing to high-intensity statins and adding ezetimibe for those on moderate-intensity statins even though the LDL-C level was more than or equal to 190 mg/dl (dose adjustment/requiring additional therapy – class I recommendation). Interestingly, the physicians’ responses to these recommendations reached 93.2%.

Figures 1 and 2 summarize the number of recommendations and type of interventions performed by the clinical pharmacist to achieve the desired outcomes and the physicians’ responses against the aforementioned recommendations.

The Differences in Adherence with the 2018 ACC/AHA Guideline before and After Clinical Pharmacist Interventions

Compliance with the 2018 ACC/AHA guideline for the management of cholesterol in adults after clinical pharmacist interventions is shown in Table 4. Accordingly, the number of patients who were initiated on statin therapy increased significantly up to 92.6% (n = 252) after the clinical pharmacist interventions were implemented (X² (df = 1, n = 272) = 79.1, p = 0.0001).

Table 4

The compliance with the 2018 ACC/AHA guideline for the management of cholesterol in adults after the clinical pharmacist interventions.
LDL-C level	History of ASCVD			DM	ASCVD risk score			Total “n”	Use of statins		Statin intensity level				Adding of non-statin therapy to achieve LDL-C goals
	Not at very high risk		Very high risk⸙		<7.5%	≥7.5-<20%	≥20%		Adherence	Non-adherence	Low	Moderate	High	Adherence		Ezetimibe			PCSK9 Inhibitors		Other lipid lowering agents
	≤75	>75
																Required	Initiated		Required	Initiated	Initiated	Drug used
< 70 mg/dl			√					8	6	2	0	4	2	2		2	2		0	0	0
				√	√			4	4	0	2	2	0	2		0	0		0	0	0
				√		√		4	4	0	2	0	2	2		0	0		0	0	0
				√			√	2	2	0	0	2	0	0		0	0		0	0	2	Fenofibrate 145mg
						√		2	2	0	0	0	2	2		0	0		0	0	0
70–189 mg/dl			√					20	18	2	0	2	16	16		8	6		0	0	2	Fenofibrate 300mg
	√							20	18	2	0	4	14	18		7	7		0	0	0
				√	√			40	38	2	0	18	20	38		10	10		0	0	0
				√		√		70	62	8	0	7	55	62		19	18		0	0	2	Fenofibrate 145mg
				√			√	46	44	2	2	2	40	42		14	12		0	0	2	Fenofibrate 145mg
						√		28	26	2	0	2	24	26		4	2		0	0	0
							√	12	12	0	0	0	12	12		4	4		0	0	0
≥ 190 mg/dl			√					2	2	0	0	0	2	2		2	2		2	2	0
	√							2	2	0	0	2	0	2		2	2		2	2	0
				√	√			2	2	0	0	0	2	2		2	2		0	0	0
				√		√		2	2	0	0	0	2	2		2	2		2	0	0
					√			4	4	0	0	0	4	4		4	4		0	0	0
						√		4	4	0	0	0	4	4		4	4		0	0	0
Total =								272	252 (92.6%)	20 (7.4%)	6 (2.4%)	45 (17.9%)	201 (79.8%)	238 (94.4%)		84 (33.3%)	77 (30.6%)		6 (2.4%)	4 (1.6%)	8 (3.2%)
Compliance with guideline									92.6%		94.4%				91.7%			66.7%
ASCVD = Atherosclerosis Cardiovascular Disease, DM = Diabetes Mellitus, n = number of patients.
*The estimated 10 years risk of CVD is measured using Pooled Cohort Risk Equation. Risk is calculated among the participants without history of CVD.
⸙Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions according to the guideline.
List of Figures:

Consequently, the number of patients who were on low- or moderate-intensity statins decreased dramatically to 2.4% (n = 6) and 17.9% (n = 45), respectively. However, the number of patients who were on high-intensity statins potentially increased to almost 79.8% (n = 201). Based on that, compliance with the recommendations regarding the level of statin intensity used was significantly improved to 94.4% (n = 238) after the clinical pharmacist interventions (X²(df = 1, n = 252) = 72.5, p = 0.0001).

The use of ezetimibe as an add-on nonstatin therapy was encouraged and effectively added to the treatment plan to achieve LDL-C goals. The number of patients who were initiated ezetimibe increased significantly to 91.7% (n = 77) after the clinical pharmacist interventions (X² (df = 1, n = 84) = 95, p < 0.0001).

Interestingly, for those who were on statin and ezetimibe therapies and required PCSK9 inhibitors to achieve LDL-C goals, compliance with the recommendations was effectively improved to 66.7% (n = 4); (X² (df = 1, n = 6) = 6, p = 0.014). The use of other lipid-lowering agents, such as fibrates, was markedly reduced to 3.2% (n = 8) for those who were on statin therapy after the clinical pharmacist interventions (X²(df = 1, n = 208) = 19.2, p < 0.0001).

Figure 3 shows the summary of the comparison of compliance with the 2018 ACC/AHA guideline recommendations for the management of cholesterol before and after clinical pharmacist interventions regarding the initiation of statins, the proper use of moderate- or high-intensity statins, evidence-based addition of ezetimibe and PCSK9 inhibitors and minimization of other lipid-lowering agent abuse.

Discussion

Based on this study, compliance with the 2018 ACC/AHA guideline recommendation for the management of cholesterol in adult patients before clinical pharmacist interventions was 60.3% for the initiation of statins and 47.6% for adherence to proper intensity statin therapy. Accordingly, the initiation of statins, particularly high-intensity statins, is prescribed to far fewer patients than recommended. Consequently, the use of nonstatin therapies such as ezetimibe and PCSK9 inhibitors was nearly diminished, taking into consideration that several studies highlighted the importance of pharmacist intervention on cholesterol risk management and revealed the treatment gap between research evidence and clinical practice (9–12).

According to our findings, the clinical pharmacist plays a crucial role in the management of cholesterol levels by recommending new therapies, adjusting or increasing drug doses and stopping or changing medications. Furthermore, systematic reviews and meta-analyses of randomized trials conducted by Machado M et al. (2008) and Santschi V et al. (2011) emphasized the importance of pharmaceutical care interventions in the management of CVDs (13, 14). Pharmacist interventions achieved greater reductions in systolic and diastolic blood pressure (BP), total cholesterol (TC), and LDL-C and in the risk of smoking compared with the usual care group (13, 15, 16).

In this study, compliance with the 2018 ACC/AHA guideline to achieve the required LDL-C goals was significantly improved after clinical pharmacist interventions and the implementation of the appropriate recommendations. Consistently, Bozovich M et al. (2000) and Tahaineh L et al. (2011) showed significant improvement in achieving LDL-C goals when clinical pharmacists managed lipid clinics or through clinical pharmacy services under the supervision of cardiologists (17, 18). The same was achieved by Tsuyuki RT et al. (2016) (19).

In the current study, physicians’ acceptance of the recommendation provided by the clinical pharmacist according to the guidelines was variable based on patients’ LDL-C levels. For instance, physcians’ acceptance of clinical pharmacist interventions was low among patients with LDL-C<70 mg/dl. Interestingly, there was a high rate of physician agreement with clinical pharmacists among patients with LDL-C levels ≥70 mg/dl. Subsequently, this resulted in greater amelioration of LDL-C levels and improvement in health outcomes. Likewise, recent studies reported that primary healthcare physicians significantly relied on clinical pharmacists in assessing and improving patients’ adherence to their medications as well as in educating and counseling the patients to avoid clinical malpractice (20, 21).

Several studies presented the major explanations for statin refractoriness reported by healthcare practitioners, and patients were concerns about adverse events (9, 22–27). Rosenson, R. S (2016) stated that evaluation of potential adverse events requires validated tools to differentiate between statin-associated adverse events versus nonspecific complaints. Additionally, treatment options for statin-intolerant patients include the use of different statins, often at a lower dose or frequency. To lower LDL cholesterol, lower doses of statins may be combined with ezetimibe or bile acid sequestrants (28). Newer treatment options for patients with statin-associated muscle symptoms may include proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors (9).

There are many reasons that contribute to downcompliance with the guidelines. In this study, the reasons beyond the untoward were mostly related to the extracautions about the side effects that could lead to patients’ discomfort and complete discontinuation of therapy or the claiming reports of patients’ intolerability of such medications. Other reasons were the low LDL-C level and high cost of certain medications. Nevertheless, various clinical trials have illustrated great benefits of statin use, such as pleiotropic effects, which could be beneficial for the treatment and management of several comorbidities (29–31).

In clinical trials, statin-associated adverse events showed no differences between participants assigned to statins or placebo (9, 22). However, it is important to know that these trials select patients with better tolerability and lower risk for myopathy based on their ages, absence of musculoskeletal complaints, normal renal function and less concomitant medications that may alter the pharmacokinetic pathways (9, 23).

However, one of the solutions to overcome the problem is to switch to the fully human monoclonal antibodies proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab and evolocumab) that caused fewer muscle symptoms based on clinical trials and were no more often than when ezetimibe was used (24–26). However, the cost of such treatment is still one of the main barriers.

The current analysis had several strengths; the study was conducted after the implementation of the 2018 ACC/AHA guideline, where compliance with this guideline could be evaluated. This highlights the importance of clinical pharmacist roles that make a significant improvement in patients’ health outcomes.

The clinical pharmacist has a key role in the management of cholesterol levels by recommending new therapies, adjusting or increasing drug doses and stopping or changing medications. Furthermore, compliance with the latest updated guideline recommendations to achieve the desired treatment goals was notably enhanced after the clinical pharmacist interventions and the implementation of the appropriate recommendations. Last but foremost, the clinical pharmacist needs to engage in educating and cooperating with other healthcare providers to achieve proper patient care and avoid clinical malpractice, hence improving health outcomes.

Methods

Subjects and Settings

A cross-sectional observational study was conducted in adult patients who visited the hospital internal medicine clinic in AlAin city, UAE from Jan to April 2019 (n = 647). Patient’s information was collected through the Hospital Information System (HIS). The collected data did not include any personal or sensitive information such as patients’ identity or file numbers. Patients who aged ≥ 21 years old, whom managed in the hospital and were candidate for statin therapy based on the four statin benefit groups; were included in this study (n = 272, 42%). Individuals who did not meet the criteria were excluded (n = 375). Cardiovascular disease (CVD) risk was calculated using the pooled cohort risk equation (32). This study was approved by the Research Ethics Committee of the hospital – Mediclinic Middle East/MCME Research and Ethical Committee (ref. CR/2018/40). All methods were performed in accordance with the relevant guidelines and regulations.

Study Outcomes

The following outcomes were investigated in this study:

1. Compliance with the 2018 ACC/AHA guideline recommendations was measured by determining the following:

A. The number and percentage of patients who were identified as statin benefit groups

B. The number and percentage of patients who were initiated on statin therapy

C. The type of statin therapy used.

D. The need for additional nonstatin therapy.

2. The impact of the clinical pharmacist interventions on applying guideline recommendations was determined by measuring the following:

A. Number and type of recommendations attained by the clinical pharmacist

B. The type and rationale of clinical pharmacist interventions

C. Physicians’ response and the reasons for rejecting recommendations

3. Comparing the differences in compliance with the 2018 ACC/AHA guidelines before and after the clinical pharmacist interventions.

Statistical Analysis

All data were entered and analyzed using Statistical Package for the Social Sciences (SPSS) version 22 (IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp.). Descriptive statistics were used to measure the frequencies and percentages. The chi-square test was used to compare compliance with the guidelines before and after clinical pharmacist interventions. A p-value of 0.05 was considered statistically significant, using a 95.0% confidence interval of differences.

Declarations

Acknowledgments: We would like to thank the hospital team, particularly the clinical pharmacist, for their assistance in this study.

Authors' contributions: MMA wrote the manuscript and collected and analyzed the data. KA carried out some of the research responsibilities and participated in collecting and analyzing the data. SZ and AS made substantial contributions to the work and analyzed or interpreted the data for the work. IA made substantial contributions to the conception or design of the work and the acquisition, analysis, or interpretation of data for the work. SA made substantial contributions to the conception or design of the work editing the manuscript and overseeing the study overall.

Ethics declaration and consent to participate: This study was approved by the Research Ethics Committee of the hospital – Mediclinic Middle East/MCME Research and Ethical Committee (ref. CR/2018/40). All methods were performed in accordance with the relevant guidelines and regulations. The collected data did not include any personal or sensitive information such as patients’ identity or file numbers. Therefore, the consent was waived by the Ethical Committee - MCME Research and Ethical Committee (ref. CR/2018/40).

Consent for publication: All authors are aware of and have approved the submission to be published in the Implementation Science journal. All authors are aware and have agreed to post the submission as a preprint if a preprint of the paper has been uploaded to a preprint server.

Availability of data and materials: The data that support the findings of this study are available on request from the first author and the corresponding author.

Competing interests: The authors declare that there are no conflicts of interest in this study.

Funding: There are no funding sources for this research.

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