Evaluation of Guideline-Directed Medical Therapy for Outpatients Living with Heart Failure with Reduced Ejection Fraction

Abstract

Background

Pharmacotherapy is the cornerstone of treatment for heart failure with reduced ejection fraction (HFrEF). The Canadian Cardiovascular Society and Canadian Heart Failure Society have defined guideline-directed medical therapy (GDMT) as 4 foundational medications. Despite strong recommendations for use of GDMT in HFrEF, current practice alignment with guidelines is unknown.

Objectives

The primary objectives were to determine the proportion of patients for whom optimized GDMT for HFrEF was prescribed, to describe the doses of foundational medications achieved, and to describe any documented rationale limiting the optimization of GDMT. The secondary objectives were to describe documented pharmacist activities outside of scheduled multidisciplinary appointments at the heart function clinic (HFC) and to describe heart failure–related hospital encounters in 2021.

Methods

A retrospective cohort study using medical records of patients with HFrEF who were receiving treatment at the Regina HFC as of December 31, 2021, was conducted.

Results

Of the 129 patients included in the study, 61 (47.3%) were prescribed optimized GDMT. Specifically, within the individual foundational medication classes, 82.2% (106/129), 80.6% (104/129), 79.1% (102/129), and 74.4% (96/129) of patients received optimized therapy with a renin–angiotensin system inhibitor, mineralocorticoid receptor antagonist, β-blocker, and sodium–glucose cotransporter 2 inhibitor, respectively. Documented rationale was not available in 35.8% (38/106) of instances of suboptimal utilization of GDMT and in 41.7% (60/144) of instances of suboptimal dosing of GDMT. The most common documented rationale for suboptimal utilization was intolerance to the medication (33.0% [35/106]), and the most common rationale for suboptimal dosing was intolerance to dose increases (57.6% [83/144]). Pharmacists documented a total of 553 patient care activities for 58.9% (76/129) of the patients, outside scheduled multidisciplinary appointments in the HFC. Sixteen patients (12.4%) had heart failure–related hospital encounters a total of 31 times in 2021.

Conclusions

Although many patients were receiving the benefits of multidisciplinary care at the Regina HFC, there remained a treatment gap in the use of GDMT for HFrEF. These findings will be used to inform strategies to improve clinic processes, including efficient identification of patients requiring optimization of GDMT, who would benefit the most from multidisciplinary care.

INTRODUCTION

Heart failure (HF) has reached epidemic proportions worldwide,¹ with an estimated 750 000 (3.6%) of Canadians ² and 26 000 (5%) of Saskatchewan residents 40 years or older currently living with HF.³

HF is categorized according to the left ventricular ejection fraction (LVEF) and includes HF with reduced ejection fraction (HFrEF), defined as LVEF less than or equal to 40%.^4,5 Pharmacotherapy is the cornerstone of treatment for HFrEF,^5–7 and the Canadian Cardiovascular Society (CCS) and the Canadian Heart Failure Society (CHFS) recommend 4 foundational therapies, referred to as guideline-directed medical therapy (GDMT).⁶ GDMT has been shown to decrease patient hospitalizations, mortality, and morbidity and to improve functional capacity and quality of life.⁷

Current GDMT for HFrEF includes these 4 foundational medications in combination: a renin–angiotensin system inhibitor (RASi), consisting of an angiotensin receptor/neprilysin inhibitor (ARNI), either as first-line therapy or switched from an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB); a β-blocker (BB); a mineralocorticoid receptor antagonist (MRA); and a sodium-glucose cotransporter 2 inhibitor (SGLT2i).⁷ Titration of all foundational therapies concurrently, to achieve doses proven beneficial in clinical trials or to maximally tolerated doses, should occur within 3 to 6 months.^7,8 Despite strong recommendations for the use of GDMT, implementation of recommendations into practice is inconsistent, with prevalent underutilization, underdosing, and clinical inertia.⁹

Heart function clinics (HFCs) offer a multidisciplinary approach to HF management, through collaboration of physicians and other allied health professionals.⁶ Studies have shown that patients with HFrEF receiving outpatient treatment in HFCs have better symptom control, fewer hospital admissions for HF, and lower mortality relative to those receiving usual care,^6,10 and patients with HF typically spend more than 90% of their time as outpatients.¹¹ Targeting improvements in the use of GDMT in the outpatient setting is necessary to improve patient outcomes and is especially important given that the standard of care has changed (e.g., the addition of SGLT2i to GDMT) and no prior quality control measures are available for benchmarking in this practice setting.

Within the Saskatchewan Health Authority (SHA), the Regina HFC serves patients living with HF who reside in Regina and southern Saskatchewan. Our aim was to evaluate whether changes to the GDMT standard for HFrEF had been incorporated into practice at the Regina HFC by collecting prescribing data and documented barriers to medication optimization. More specifically, the primary objectives were to determine the proportion of patients for whom GDMT for HFrEF was optimized, to describe the doses of GDMT achieved, and to describe documented rationales limiting the optimization of GDMT. The secondary objectives were to describe documented pharmacist interventions that occurred outside of multidisciplinary HFC appointments and to describe HF-related hospital encounters in 2021. This study contributes data that can be used to identify and improve care gaps at the Regina HFC and can serve as a template for gathering similar care metrics at other centres.

METHODS

This retrospective cohort study of outpatient medical records received ethics approval (REB 21-77) from the Regina Research Ethics Board and operational approval from the SHA. Given the retrospective nature of the data collection, a waiver for informed consent from patients was granted.

At the Regina HFC, a pharmacist (including O.B. at the time of the study) participates in the care of patients 3 days a week, including involvement with multidisciplinary clinics. The multidisciplinary clinics typically occur on 3 half-days a week, via telephone or in person, and incude cardiologists, nurses, a dietician, and a pharmacist.

A list was obtained of all living patients who were attending the Regina HFC in Regina, Saskatchewan, as of December 31, 2021. Data were extracted from 2 electronic medical record databases (Sunrise Clinical Manager and the Canadian Heart Failure Network), paper medical records, and Digital Health Analytics software (using ICD-10 [International Statistical Classification of Diseases and Related Health Problems, 10th revision] codes I50, I50.0, I50.1, and I50.9 for HF-related hospitalization and emergency department admission in 2021). Patients eligible for inclusion were those 18 years of age or older who had New York Heart Association (NYHA) Class I to IV HFrEF (most recent LVEF 40% or less) and had attended at least 2 multidisciplinary HFC appointments as of December 31, 2021. Excluded patients were those for whom we had no access to medical records within the HFC after December 31, 2021; those with no evidence of quantitative imaging of LVEF in the previous 3 years (after December 31, 2018); those with LVEF greater than 40% (including those whose HFrEF had improved); and those who were discharged from the HFC before December 31, 2021, or were not seen in clinic twice by the multidisciplinary team before the end of the study period.

Data were collected within the Research Electronic Data Capture (REDCap) platform,¹² hosted by the SHA. Patient characteristics, laboratory data, and documentation were gathered from the most recent multidisciplinary HFC visit before December 31, 2021.

For purposes of the primary objective, we defined optimized GDMT as the prescribing of 4 foundational therapies, taking into consideration contraindications and/or intolerances, at target or maximally tolerated doses. To determine optimized GDMT, we incorporated both utilization data and dosing data. Suboptimal utilization was defined as a patient not taking 1 or more of the 4 foundational medications appropriately, and the documented rationales that we captured for not utilizing a foundational medication included medication not indicated, medication contraindicated, medication not tolerated, patient unable to afford the medication, and patient preference or refusal of medication. For purposes of our definition of optimized therapy, we considered ACEI/ARB and ARNI as 1 group of medications, the RASi class, and did not assess for those specifically eligible for optimization on an ARNI. Patients were considered to have no indication for SGLT2i foundational therapy if they had NYHA Class I functional status.⁷ We did not assess patients for other disease states (e.g., type 2 diabetes mellitus or chronic kidney disease [CKD]) that have indications for SGLT2i. Finally, patients were considered to have no indications for a BB if they were in acute decompensated HF or had NYHA class IV symptoms.⁷

The target dose of a medication was deemed to have been reached if the patient received at least 100% of the dose defined in the 2021 update of the CCS/CHFS guideline⁷ (see Appendix 1). Suboptimal dosing was defined as non-achievement of the CCS/CHFS–specified target dose for 1 or more of the 4 foundational therapies. The following documented rationales were captured for not achieving target doses: patient intolerance of dose increases (on the individual’s maximally tolerated dose), patient unable to afford medication, and patient preference/patient refusal.

Pharmacist activities of interest for our analysis encompassed activities that occurred outside the multidisciplinary clinic visits, all of which occurred virtually (by telephone or email). The following pharmacist activities were recorded: follow-up monitoring, patient counselling/education, changes to drug therapy, alternative activities focused on comorbidities, and drug coverage.

Statistical analyses were performed using Microsoft Excel (version 14.0, 2010), and SPSS Statistics software (version 22.0; IBM Corporation). Data are expressed as descriptive statistics.

RESULTS

A total of 270 patients were screened for study inclusion, with 129 (47.8%) meeting the inclusion criteria. Of the 141 patients excluded, 87 (61.7%) had LVEF greater than 40%, and 31 (22.0%) had not attended 2 multidisciplinary clinic appointments as of December 31, 2021 (Appendix 2).

Mean patient age was 70.1 years, and most study participants were men (72.1% [93/129]) (Table 1). The mean LVEF was 29.5%, and most patients had no or mild documented symptoms of HFrEF (34.9% [45/129] with NYHA Class I symptoms and 37.2% [48/129] with NYHA Class II symptoms). Diuretics were prescribed for 62.0% (80/129) of the patients. Mean blood pressure was 113/65 mm Hg, and mean heart rate was 68/min. Mean estimated creatinine clearance by the Cockcroft–Gault equation was 75.2 mL/min. The mean number of multidisciplinary HFC appointments during 2021 was approximately 2 per patient.

TABLE 1.

Patient Characteristics as of Most Recent Visit to Multidisciplinary Clinic

Characteristic	No. (%) of Patients or Mean ± SD (n = 129a)
Age (years)	70.1 ± 14.5
Sex, male	93 (72.1)
Weight (kg) (n = 128)	89.5 ± 23
Duration at heart function clinicb (years)	5.4 ± 3.7
Total no. of multidisciplinary clinic appointments in 2021	301
In person	217 (72.1)
Virtual	84 (27.9)
Average no. of appointments per patient	2.3 ± 2.1
Last measured left ventricular ejection fraction (%)	29.5 ± 7.8
NYHA Class I	45 (34.9)
NYHA Class II	48 (37.2)
NYHA Class III	22 (17.1)
NYHA Class IV	0
NYHA class not documented	14 (10.9)
Blood pressure (mm Hg) (n = 127)
Systolic	113 ± 19
Diastolic	65 ± 11
Heart rate (beats/min) (n = 125)	68 ± 11
SCr (μmol/L)	122.9 ± 61.3
Estimated CrClc (mL/min) (n = 15)	75.2 ± 45.7
Potassium (mmol/L)	4.6 ± 0.4
BNP (pg/mL) (n = 96)	939.4 ± 1118.8
NT-proBNP (pg/mL) (n = 3)	807.3 ± 1064.4
HbA1c (%)d (n = 49)	7.2 ± 1.2
Documented medical history and comorbidities
Coronary artery diseasee	83 (64.3)
Hypertension	67 (51.9)
Atrial fibrillation or flutter	59 (45.7)
Type 2 diabetes mellitus	49 (38.0)
Pulmonary diseasef	20 (15.5)
Cerebrovascular diseaseg	20 (15.5)
Chronic kidney diseaseh	13 (10.1)
Cardiac devices
Implantable cardioverter defibrillator	65 (50.4)
Cardiac resynchronization therapy	4 (3.1)
Pacemaker	3 (2.3)
Prescribed “personalized therapies”
Diuretics	80 (62.0)
Digoxin	15 (11.6)
Ivabradine	9 (7.0)
Nitrates	8 (6.2)
Hydralazine	4 (3.1)

BNP = brain natriuretic peptide, CrCl = creatinine clearance, HbA1c = hemoglobin A1c, NT-proBNP = N-terminal prohormone of brain natriuretic peptide, NYHA = New York Heart Association, SCr = serum creatinine, SD = standard deviation.

^aExcept where indicated otherwise.

^bTime at clinic is defined as the period from first multidisciplinary clinic visit until December 31, 2021.

^cCrCl estimated from Cockcroft–Gault equation using actual body weight (in kilograms), as follows: CrCl for males (mL/min) = [(140 – age in years) × weight/SCr (μmol/L)] × 1.23; CrCl for females (mL/min) = [(140 – age in years) × weight/SCr (μmol/L)] × 1.04.

^dData for HbA1c collected only for participants with documented type 2 diabetes mellitus.

^eCoronary artery disease was defined as stable angina, unstable angina, or history of acute coronary syndrome.

^FPulmonary disease was defined as asthma or chronic obstructive pulmonary disease.

^gCerebrovascular disease was defined as stroke or transient ischemic attack.

^hChronic kidney disease was defined as SCr > 220 μmol/L or CrCl < 30 mL/min.

The prescribing patterns for the 4 foundational medications, irrespective of doses, indications, or contraindications, were as follows: 96.9% (125/129) of the patients received a BB, 96.1% (124/129) received a RASi, 76.0% (98/129) received an MRA, and 48.8% (63/129) received an SGLT2i. Overall, 35.7% (46/129) of the patients were simultaneously receiving the 4 foundational medication classes (Appendix 3). Importantly, the assessment of whether a patient is receiving GDMT is based on more than prescription of all 4 foundational therapies. For example, an individual may be on GDMT without receiving all 4 foundational therapies, once patients’ individual indication, stage of disease, and contraindications are taken into consideration. Similarly, an individual may be taking the 4 foundational therapies, but not at target doses, and thus would not be considered as receiving GDMT.

The most commonly prescribed medication within each class of the foundational therapies was sacubitril/valsartan within the RASi class (49.2% [61/124]), carvedilol within the BB class (61.6% [77/125]), spironolactone within the MRA class (77.6% [76/98]), and dapagliflozin within the SGLT2i class (54.0% [34/63]) (Appendix 4).

The target dose was achieved by 69.4% (68/98) of patients receiving an MRA, 57.3% (71/124) of those receiving a RASi, and 51.2% (64/125) of those receiving a BB (Figure 1). For SGLT2i, the mean dose achieved was 16.4 (standard deviation [SD] 7.4) mg for empagliflozin and 9.7 (SD 1.2) mg for dapagliflozin (Appendix 4).

FIGURE 1.

Doses achieved for foundational medications. ACEI = angiotensin-converting enzyme inhibitor, ARB = angiotensin receptor blocker, ARNI = angiotensin receptor/neprilysin inhibitor, BB = ß-blocker, MRA = mineralocorticoid receptor antagonist, RASi = renin–angiotensin system inhibitor.

There were 106 instances of non-utilization of a foundational medication: 4 instances of BB non-use, 5 instances of RASi non-use, 31 instances of MRA non-use, and 66 instances of SGLT2i non-use (Appendix 5). No documented rationale was available in 35.8% (38/106) of these instances of presumed suboptimal utilization. For the other 64.2% (68/106) of instances, the rationale was documented, the most common rationales being intolerance to the medication class (33.0% [35/106]), no indication (13.2% [14/106]), or contraindication (9.4% [10/106]) (Figure 2).

FIGURE 2.

Documented rationale for suboptimal utilization and dosing of all foundational medications.

There were 144 instances of patients not achieving the target dose of a foundational medication: 30 instances involving an MRA, 53 instances involving a RASi, and 61 instances involving a BB. No rationale was documented in 41.7% (60/144) of these instances of presumed suboptimal dosing (Figure 2). The rationale was documented for the remaining 58.3% (84/144) of instances, the most common being intolerance to dose increases (57.6% [83/144]). Specifically, dose increases were not tolerated in 62.3% (33/53) of cases of suboptimal dosing for RASi therapy, 59.0% (36/61) for BBs, and 46.7% (14/30) for MRAs. The rationale for use of less than 10 mg of dapagliflozin (1 instance) was not captured.

After integration of the above data, it was determined that optimized GDMT was prescribed for 61 of 129 patients (47.3%). Within the individual foundational medication classes that make up GDMT, 82.2% (106/129) of patients received optimal RASi therapy, 80.6% (104/129) received optimal MRA therapy, 79.1% (102/129) received optimal BB therapy, and 74.4% (96/129) received optimal SGLT2i therapy (Figure 3).

FIGURE 3.

Achievement of guideline-directed medical therapy (GDMT) by class of foundational medications. BB = ß-blocker, MRA = mineralocorticoid receptor antagonist, RASI = renin–angiotensin system inhibitor, SGLT2i = sodium–glucose cotransporter 2 inhibitor.

A total of 553 pharmacist activities were documented outside of the multidisciplinary HFC appointments from January 1 to December 31, 2021, involving 58.9% (76/129) of the HFC patients. The most common types of pharmacist activities completed virtually (by telephone or email) were follow-up monitoring (32.4% [179/553]), patient education (21.0% [116/553]), and changes to drug therapy (18.4% [102/553]).

From January 1 to December 31, 2021, 16 (12.4%) of the 129 patients had hospital encounters, for a total of 31 HFrEF-related visits.

DISCUSSION

The aim of this study was to evaluate whether changes to the GDMT standard for HFrEF were incorporated into practice. The results indicate alignment of practice with guidelines in under half (47.3%) of eligible patients attending the Regina HFC, with consideration of contraindications and/or intolerances, at target or maximally tolerated doses. Specifically, approximately 20% of patients were not receiving optimal RASi, BB, or MRA therapy, and 25% were not receiving optimal SGLT2i therapy.

There is a paucity of published literature assessing the use of 4 foundational medications as GDMT in the outpatient HFC setting.⁷ Available published literature for the outpatient setting comes largely from US and global registry data assessing 3 foundational medications, as defined in the 2017 comprehensive update of the CCS guidelines for the management of HF.⁶ The population seen at the Regina HFC aligns with existing literature^9,13 in terms of both sex and cardiac function; notably, however, our population was older, had fewer symptoms, and had different proportions of comorbidities, with more acute coronary syndrome [ACS] and atrial fibrillation and less CKD.

Medications in the BB, RASi, and MRA classes, irrespective of dose, were prescribed in 96.9%, 96.1%, and 76.0% of patients, respectively, at the Regina HFC, proportions substantially higher than those reported from the CHAMP-HF registry.⁹ One possible explanation is that patients in the CHAMP-HF registry received usual outpatient care, whereas our study population received care from a cardiologist-led multidisciplinary HFC. Previous work has shown that care in multidisciplinary HFCs leads to better symptom control, fewer hospitalizations, and lower mortality, primarily through optimization of pharmacotherapy.^6,14 Higher prescribing patterns for BBs and MRAs in our population could also be related to differences in comorbidities (higher prevalence of ACS and atrial fibrillation and lower prevalence of CKD) relative to previous studies.^9,13

The largest care gap identified in our assessment of the foundational medications was that 25% of patients with symptomatic HFrEF were not receiving an SGLT2i; however, this finding was unsurprising, given that the guideline update specifying use of SGLT2i as part of GDMT was released only 8 months before the end of the study period.^7,15 Our study was not designed to capture indications for SGLT2i beyond symptomatic HFrEF, so we may have underestimated the proportion of patients for whom an SGLT2i would be recommended by the 2021 CCS/CHFS guideline update,⁷ given that 14 of the patients had no documented HFrEF indication, with only NYHA class I symptoms. The second-largest care gap occurred within the RASi class, where only 49.2% (61/124) of patients were receiving an ARNI. This group of drugs is recommended as first-line therapy, before ACEI/ARB, for patients who remain symptomatic despite treatment with appropriate doses of GDMT, those with recent hospitalization for decompensated heart failure, and those admitted to hospital with a new diagnosis of HFrEF, in the absence of contraindications.⁷ For purposes of our definition of optimized therapy, we considered ACEI/ARB and ARNI as equivalent within the RASi class; as such, we do not have data for the number of patients with optimal ARNI therapy as part of GDMT. The limiting factor for prescription of an ARNI in Saskatchewan is the restrictive accessibility criteria for publicly funded treatment, which include undergoing testing for brain natriuretic peptide (BNP) or N-terminal prohormone of BNP. Drug plan criteria do not always align with the most recent guideline recommendations. Investigating the optimization of ARNI therapy as part of GDMT would be a valuable topic for future research.

Compared with existing literature assessing the dosing of GDMT, we observed greater proportions of patients with achievement of target doses of the foundational medications,⁶ approximately 2 to 3 times higher for ACEIs, BBs, and ARBs,¹³ whereas proportions with achievement of target doses of MRAs were similar.¹³ Given that only a single dose of SGLT2i was evaluated in HFrEF clinical trials,^16,17 it was not possible to determine the dose-ranging effects of SGLT2i.⁴ Receiving care at a specialty HFC likely explains higher achievement of the target dose in our study. When documented, the most common rationale limiting dose titration was intolerance to dose increases, which highlights that maximally tolerated doses are acceptable⁶ and also emphasizes the importance of individualized approaches to patient dosing and documentation of any rationale for limiting dose titration.¹³ Recording and stratifying the specific intolerances reported by patients for each foundational medication (e.g., asymptomatic low blood pressure or hyperkalemia) were outside the scope of this manuscript.

No rationale was documented for suboptimal utilization in 35.8% of instances, a proportion that fell in the middle of the range for documentation of rationale in the QUALIFY HF survey.¹³ One factor that may contribute to poor documentation is the current limitations of electronic health records (EHRs) and clinic processes, which do not efficiently facilitate identification of patients eligible for GDMT optimization.

Nearly 60% of the HFC patients had documentation of pharmacist activities outside of multidisciplinary HFC appointments in 2021; however, for the remaining 40% of patients, the pharmacists were not able to complete activities outside the HFC. Existing literature illustrates that collaborative models of care involving pharmacists, nurses, and physicians have been associated with improved uptake and optimization of foundational medications.¹⁸ The types of activities that pharmacists completed at the Regina HFC aligned with the literature, including follow-up monitoring, adjusting medication therapy, answering drug information questions, encouraging adherence, promoting self-advocacy, and providing education^5,18 Continued evolution of the pharmacist’s role, including collaborative prescribing and ordering laboratory tests, could ensure efficient care.⁶

Only 16 patients (12.4%) experienced HF exacerbation requiring additional support from a medical facility over the course of 1 year, lower than the 34% observed in the QUALIFY HF registry.¹³ This finding indicates that the population at the Regina HFC was more stable. Given the limited capacity of the specialist clinic, discharge may be appropriate for some current patients, which would allow the HFC to serve a less stable and higher-risk outpatient population with HFrEF.⁷

To influence change, study results have been communicated to stakeholders and the multidisciplinary team at the Regina HFC. Four opportunities for quality improvement have been identified. The first of these involves increasing capabilities of the EHR. We hypothesize that standardizing the GDMT documentation template for the EHR and automating notifications (including identifying patients for whom GDMT has not been optimized, those due for diagnostic tests or blood work, and those at higher risk because of comorbidities and frequent hospital encounters) would standardize the approach to care and increase the achievement of GDMT.¹⁹ Also, ensuring EHR capacity to generate routine electronic reports and audits, not currently in place, should be completed so the effectiveness of measures taken to improve patient outcomes can be assessed. Second, criteria to identify low-risk patients for discharge from the HFC should be established, to allow prioritization of high-risk patients for care. Third, alignment between skills and tasks should be optimized, and the roles of collaborative team members, including pharmacists, outside multidisciplinary HFC appointments should be defined and standardized, to ensure that clinic resources are focused toward priority patients or interventions associated with reductions in morbidity and mortality. Fourth, care should be transitioned to more virtual follow-ups, the feasibility of which was demonstrated during the COVID-19 pandemic.²⁰ Further research should focus on assessing the timeline for achievement of GDMT before and during HFC care, as well as wait times from referral to first multidisciplinary HFC appointments.

This study provides valuable information for quality improvement and adds contemporary information about the use of SGLT2i and ARNI as part of the 4 foundational HFrEF therapies. Our study was limited by its small sample size and its retrospective design, with interpretation of data being dependent on documentation in the medical records. Documentation was presumed to be accurate, with no further patient assessments completed by the investigators. We were unable to quantify the time required to achieve GDMT or wait times to access the multidisciplinary team after referral to the clinic. Our data represent the situation at one point in time (as of December 31, 2021), but we were unable to represent patients undergoing active titration or to quantify those with recovery of LVEF with medical therapy; also, the study did not include an assessment of adherence. There was a lack of standardized approach in the HFC to measuring functional capacity (NYHA class), which may have led to an overestimate of asymptomatic NYHA class I patients, and generalizability may be limited. At the Regina HFC, all of the prescribers were cardiologists, so our data do not reflect adherence to guidelines by other providers. Finally, we did not collect data on the doses of personalized therapies, such as diuretics, only the proportion of patients using them; these medications could affect optimization of GDMT.

CONCLUSION

Although many patients are receiving the benefits of multidisciplinary care at the Regina HFC, there remains a treatment gap in the utilization of GDMT for HFrEF. These findings can inform strategies to improve clinic processes, including efficient identification of patients requiring optimization of GDMT, who would benefit the most from multidisciplinary care.

APPENDIX 1: Target doses of the 4 foundational medications for guideline-directed medical therapy.^a

Drug	Target Dose
Angiotensin-converting enzyme inhibitors
Captoprilb	50 mg TID
Enalaprilc	10 mg BID (or 20 mg BID if NYHA Class IV)
Lisinoprilc	20–35 mg daily
Perindoprilc	4–8 mg daily
Ramiprilc	5 mg BID
Trandolaprilc	4 mg daily
Angiotensin receptor blockers
Candesartanc	32 mg daily
Losartanb	50 mg daily
Valsartanc	160 mg BID
Angiotensin receptor/neprilysin inhibitor
Sacubitril/valsartanc	97/103 mg BID
β-Blockers
Bisoprololc	10 mg daily
Carvedilolc	If body weight ≤ 85 kg, 25 mg BID If body weight > 85 kg, 50 mg BID
Metoprolol succinate (CR/XL)c	200 mg total daily dose
Metoprolol tartrate (IR/SR)c	200 mg total daily dose
Mineralocorticoid receptor antagonists
Spironolactonec	25–50 mg daily
Eplerenoneb	50 mg daily
SGLT2id
Dapagliflozinc	10 mg daily
Empagliflozinc	10 mg daily

NYHA = New York Heart Association, SGLT2i = sodium–glucose cotransporter 2 inhibitor.

^aPatients were considered to be receiving the target dose if they were taking at least the minimum dose of a range. Target doses set out by the Canadian Cardiovascular Society (CCS) and the Canadian Heart Failure Society (CHFS) were used when available; for agents not included in the CCS/CHFS guidelines, the recommendations of the American Heart Association (AHA) were used. Where a dosing range exists, the target dose was assumed to have been reached if the minimal value of the range was met.

^bTarget dose recommended in AHA guidelines, update 2021.¹

^cTarget dose recommended in CCS/CHFS guidelines, update 2021.²

^dDrugs in the SGLT2i class do not have target doses. These medications are initiated and continued at 10 mg daily.

References

¹Writing Committee; Maddox TM, Lanuzzi JL Jr, Allen LA, Breathett K, Butler J, Davis LL, et al. 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;77(6):772–810.

²McDonald M, Virani S, Chan M, Ducharme A, Ezekowitz JA, Giannetti N, et al. CCS/CHFS heart failure guidelines update: defining a new pharmacologic standard of care for heart failure with reduced ejection fraction. Can J Cardiol. 2021;37(4):531–46.

APPENDIX 2: Screening and patient enrolment

LVEF = left ventricular ejection fraction.

APPENDIX 3: Utilization of foundational medications for guideline-directed medical therapy, irrespective of dose

ACEI = angiotensin-converting enzyme inhibitor, ARB = angiotensin receptor blocker, ARNI = angiotensin receptor/neprilysin inhibitor, BB = ß-blocker, MRA = mineralocorticoid receptor antagonist, SGLT2i = sodium–glucose cotransporter 2 inhibitor.

APPENDIX 4: Rate of use and doses achieved within each of the 4 classes of foundational medications for guideline-directed medical therapy (n = 129)

Medication	No. of Patients Using	Dose (mg/day) (mean ± SD)	Dose Relative to Target; No. (%) of Patients
			< 50%	50%–99%	> 100%
RASi (n = 124)			23 (18.5)	30 (24.2)	71 (57.3)
ARNI (n = 61)			10 (16.4)	23 (37.7)	28 (45.9)
Sacubitril/valsartan	61	280.8 ± 121.1	10	23	28
ACEI (n = 45)			2 (4.4)	3 (6.7)	40 (88.9)
Lisinopril	1	20 ± 0	0	0	1
Perindopril	18	7.3 ± 1.7	0	1	17
Ramipril	24	10.1 ± 4.7	2	2	20
Trandolapril	2	4 ± 0	0	0	2
ARB (n = 18)			11 (61.1)	4 (22.2)	3 (16.7)
Candesartan	13	11.4 ± 8.1	8	4	1
Losartan	2	28.1 ± 30.9	1	0	1
Valsartan	3	160.0 ± 138.6	2	0	1
BB (n = 125)			26 (20.8)	35 (28.0)	64 (51.2)
Bisoprolol	30	7.6 ± 3.02	5	8	17
Carvedilol	77	58.9 ± 31.6	17	21	39
Metoprolol (tartrate)	18	133.3 ± 65.9	4	6	8
MRA (n = 98)			3 (3.1)	27 (27.6)	68 (69.4)
Spironolactone	76	25.4 ± 11.0	1	14	61
Eplerenone	22	34.1 ± 19.4	2	13	7
SGLT2i (n = 63)
Dapagliflozin	34	9.7 ± 1.2	No target dose; 32 patients received 10 mg daily, 2 patients received 5 mg daily
Empagliflozin	29	16.4 ± 7.4	No target dose; 14 patients received 10 mg daily; 3 patients received 12.5 mg daily, 12 patients received 25 mg daily

ACEI = angiotensin-converting enzyme inhibitor, ARB = angiotensin receptor blocker, ARNI = angiotensin receptor/neprilysin inhibitor, BB = ß-blocker, MRA = mineralocorticoid receptor antagonist, RASi = renin–angiotensin system inhibitor, SGLT2i = sodium–glucose cotransporter 2 inhibitor.

APPENDIX 5: Documented rationale for suboptimal utilization of individual foundational medications

BB = ß-blocker, MRA = mineralocorticoid receptor antagonist, RASi = renin–angiotensin system inhibitor, SGLT2i = sodium–glucose cotransporter 2 inhibitor.