Patient Education and Sacubitril/Valsartan: A Randomized Comparative Trial

Abstract

Objective: To compare video to pharmacist education for patients taking sacubitril/valsartan. Methods: We conducted a randomized controlled trial comparing video to pharmacist education with a second randomized intervention of education delivered through text or phone call at 14 days. The primary outcome compared the change in short term knowledge between groups and the secondary outcome was long term knowledge at 1 month. Results: Forty-three patients were included. Scores improved significantly (P < .05) in the pharmacist group from 54.1% to 85.9% and from 64.3% to 86.1% in the video education group, although there was no difference between groups (31.8% vs 22.9%, P = .13). At 30 days, scores were significantly higher than baseline (difference 16.5%, P < .05) although did decrease from the posttest (difference 7.4%, P < .05). There was no difference at 30 days between those that received text messages versus phone calls (−10% vs −5.5%, respectively; P = .36). Conclusion: We saw improvements in both short term and long term knowledge for patients receiving education through pharmacist or video education. Neither approach was more effective than the other. Clinicians can use either approach based on patient preference.

Introduction

Heart failure affected 6.5 million patients in the United States from 2011 to 2014 and is projected to increase 46% between 2012 and 2030. ¹ The mainstay of therapy for patients diagnosed with reduced ejection fraction heart failure (HFrEF) are medications which improve patient survival. For over 2 decades, angiotensin converting enzyme inhibitors (ACEI) have been a component of the gold standard of therapy, with angiotensin receptor blockers (ARBs) recommended as a substitute for patients who do not tolerate an ACEI.^2-4

Sacubitril/valsartan (Entresto^®) is an angiotensin receptor blocker and neprilysin inhibitor combination that was FDA approved for the treatment of HFrEF in 2015 after publication of the PARADIGM-HF trial. ⁵ This trial compared the use of sacubitril/valsartan versus an ACEI in patients with HFrEF and demonstrated that sacubitril/valsartan reduced cardiovascular mortality and heart failure hospitalizations. As a result, the American College of Cardiology/American Heart Association/Heart Failure Society of American (ACC/AHA/HFSA) guideline for the management of heart failure was updated in 2017 to recommend sacubitril/valsartan as a class I recommendation in patients with New York Heart Association (NYHA) Stage II-III HFrEF tolerating an ACEI or ARB to improve morbidity and mortality. ⁴ No studies have evaluated patient education strategies for patients started on sacubitril/valsartan.

Health care providers play a key role in educating patients on medications prior to discharge. However, providing education to all patients prior to discharge can be challenging. Having access to alternative delivery mechanisms for patient education can alleviate this burden. It is important that video education improves knowledge in a similar manner to direct instruction. Therefore, the purpose of this study was to compare video education to pharmacist counseling for patients taking sacubitril/valsartan.

Methods

We conducted a randomized controlled trial comparing patient education delivered through video or in-person counseling for patients receiving sacubitril/valsartan at Ascension St. John Hospital from January 2018 to August 2019. Patients were included in the study if they were 18 years of age or older, were to be discharged on sacubitril/valsartan for the treatment of HFrEF (EF <40%), were able to read and understand English, and had a phone enabled to receive text messages. Patients with Alzheimer’s or other types of dementia, patients who were pregnant, or those who were unable to execute the study procedures were excluded. Patients ability to execute study procedures was determined by a validated health literacy test. ⁶ Only the first patient admission during the study period was included. IRB approval was obtained prior to the start of the study.

The primary outcome compared the change in short term knowledge between those that received pharmacist versus video education. Short term knowledge was measured by the change in overall scores between a baseline test and an immediate recall test. The secondary outcome was long term retention measured by score on the post-test at 1 month.

Procedures

Patients receiving sacubitril/valsartan were identified via a real time medication surveillance system and then approached for consent by the study investigators. Once consent was obtained, baseline demographics were collected and the pre-test delivered to the patient (Figure 1). Patients were then randomized using REDCap, a secure encrypted web application, to either watch a sacubitril/valsartan educational video or receive standard pharmacist counseling by permuted block randomization with varying block sizes of 6 or 8. Following pharmacist counseling or video education, patients were given the immediate post-questionnaire.

Figure 1.

Process of patient enrollment, randomization, and outcome ascertainment.

Note. Day 0: Patients were screened, inclusion/exclusion criteria were checked, baseline questionnaire performed, and patients were randomized to pharmacist or video education. After education the immediate post questionnaire was administered.

Day 14: Patients received either education via text or phone call.

Day 30: Knowledge questionnaire administered for final time.

After the questionnaire was complete, the investigators answered any additional questions related to sacubitril/valsartan. If the patient was deficient in any area of education (evident by the post-test or patient questions), the investigators reeducated the patient on deficient points. Patients in both groups were instructed that one of the investigators would either text them a link for the educational video or call them to provide follow-up education in 14 days. At this point, patients were randomized to receive a text message or phone call by permuted block randomization of sizes 6 to 8 after the immediate post-test. Text messages and phone calls were manually performed up to 3 times until patient contact was confirmed. Lastly, they were informed that one of the investigators would call to administer the questionnaire 30 days after study enrollment. This questionnaire was the same questionnaire that had been administered previously. If the patient was not reached after 3 attempts, they were recorded as lost to follow up.

Tool Development

Prior to conduction of this study, a sacubitril/valsartan educational video and counseling script was developed by the investigators, along with the questionnaire (Table 1) to assess knowledge. The video, counseling script, and questionnaires addressed 5 main constructs: purpose of the medication, how to take the medication, management of missed doses, identifying adverse events, and when to seek emergency treatment. Two dummy questions unrelated to the study were included to observe if scores improved after repeated testing. Content validation of the questionnaire and video was performed by 3 specialists with expertise in heart failure and the videos were pilot tested in 5 associates with no prior medical training. The pre-questionnaire and post-questionnaire were composed of identical questions. The video is hosted on YouTube and can be viewed at the following link https://youtu.be/utniZ7IXtT8. The questionnaire has a sixth-grade reading level according to Flesch-Kincaid analysis.

Table 1.

Sacubitril/Valsartan Knowledge Questionnaire.

Construct	Question 1	Question 2
Medication purpose	Which disease is Entresto® (sacubitril/valsartan) used to treat?	What type of medication is Entresto® (sacubitril/valsartan)?
	(a) Heart failure	(a) Lowers blood pressure
	(b) High cholesterol	(b) Diabetes medication
	(c) Diabetes	(c) Lowers cholesterol
	(d) Blood clots	(d) Blood thinner
Identify adverse effects	What is a side effect of Entresto® (sacubitril/valsartan)?	Which of the following is a sign of low blood pressure?
	(a) High blood pressure	(a) Cough
	(b) High potassium level	(b) Dizziness
	(c) High cholesterol level	(c) Swelling of tongue, lips, or throat
	(d) High sugar level	(d) Leg cramping
How to take the medication	How should you take Entresto® (sacubitril/valsartan)?	When can Entresto® (sacubitril/valsartan) be stopped safely?
	(a) With food	(a) When you run out of prescription refills
	(b) Without food	(b) When you start eating healthy
	(c) It doesn’t matter (with or without food)	(c) When the doctor tells you to stop
	(d) Without water	(d) When you feel better
Missed doses	How often will you take Entresto® (sacubitril/valsartan)?	What should you do if you miss a dose of Entresto® (sacubitril/valsartan) and remember when you’re about to take your next dose?
	(a) Once daily	(a) Take two pills
	(b) Once weekly	(b) Skip the dose
	(c) Three times a day	(c) Call your pharmacist
	(d) Twice a day	(d) Seek medical attention
When to seek emergency attention	When should you seek emergency attention while taking Entresto® (sacubitril/valsartan)?	Which of the following is a sign of angioedema?
	(a) 1 lb. weight gain	(a) Cough
	(b) Swelling of legs	(b) Swelling of lips, tongue, or throat
	(c) Difficulty breathing	(c) Bruising
	(d) Out of medication	(d) Headache
Screen questions	What is the fifth closest planet to the sun?	What color do you get when you mix blue and yellow?
	(a) Mars	(a) Purple
	(b) Saturn	(b) Green
	(c) Venus	(c) Orange
	(d) Jupiter	(d) Brown

Statistical Analysis

Estimates for sample size were calculated using a previous study evaluating an apixaban educational video which showed an average difference between groups of 19.7% and a standard deviation of 5.2% (between the pre- and immediate post-test). ⁷ We estimated we would require 15 subjects per group, although we decided to target 30 in each group to account for possible non normally distributed data and patient drop out.

Descriptive statistics were used to characterize demographic and clinical factors. Continuous variables were described using the mean and standard deviation and categorical variables were described using frequencies and proportions. The difference between the pre- and immediate post-scores in each group were assessed using the paired t-test. The change in scores between video and pharmacist groups or text and phone call groups were compared using the Student’s t-test. If differences between education groups existed linear regression was performed. A subgroup analysis was performed on patients’ educational level, prior sacubitril/valsartan use, and newly diagnosed heart failure. The secondary outcome, score improvement on post-test from the pre-test at 1 month was assessed using the paired t-test. All data was analyzed using SPSS V 26.0 and a P-value of .05 or less was used to indicate statistical significance.

Results

Eight-nine patients were screened for the study and 43 patients were included. Reasons for exclusion included consent denial (21), lack of a cell phone with texting capacity (13), dementia (6), and failure of the health literacy test (6). Baseline characteristics are listed in Table 2. Twenty-three patients completed the 30 day follow-up. Patients lost to follow-up were similar in terms of age (62.7 ± 11 vs 61.7 ± 13.5, P = .79) and previous treatment with sacubitril/valsartan (80% vs 65.2%, P = .33).

Table 2.

Baseline Characteristics.

Variable a	Pharmacist (N = 22)	Video (N = 21)	P value
Age	61 (13)	64 (11)	.49
Female	10 (45.5)	5 (23.8)	.13
Race
African American	17 (77.3)	11 (52.4)	.09
Caucasian	5 (22.7)	10 (47.6)
Education level
High school or less	18 (81.8)	14 (66.7)	.25
Some college	4 (18.2)	7 (33.3)
Prior sacubitril/valsartan	8 (36.4)	4 (19)	.21
Newly diagnosed HFrEF	6 (27.3)	0 (0)	.02
Medication insurance
Private	10 (45.5)	9 (42.9)	.86
Medicaid	12 (54.5)	12 (57.1)

^aValues described as N (%) or mean (SD).

Patient scores improved from the pretest to the posttest by 27.4% (95% Confidence Interval (CI): 21.5%-33.3%). Scores improved significantly (P < .05) in the pharmacist group from 54.1% to 85.9% and from 64.3% to 86.1% in the video education group. There was no significant difference in the change in score from pretest to posttest between pharmacist versus video education (22.9% vs 31.8%, P = .13). Controlling for new heart failure diagnosis did not change the observed effect between groups compared to the unadjusted analysis (7.8% vs 8.9%). Improvement in score did not depend on prior use of sacubitril/valsartan, new heart failure diagnosis, or education level (Figure 2, P > .05 for all comparisons). Individual questions and constructs are displayed in Table 3. Improvements were seen in each construct including medication purpose, identifying adverse effects, how to take the medication, what to do with missed doses, and when to seek emergency attention. No change was seen in the percent correct of the dummy questions (57.1% vs 57.1% and 38.1% vs 38.1%).

Figure 2.

Knowledge change does not depend on education level, prior heart failure diagnosis, or prior sacubitril/valsartan use.

Table 3.

Number and Percent Correct on Pretest and Immediate Posttest for Individual Questions in the Pharmacist and Video Groups.

	Q1 pretest	Q1 posttest	P value	Q2 pretest	Q2 posttest	P value
	N (%)	N (%)		N (%)	N (%)
Video (N = 21)
Medication purpose	20 (95.2)	21 (100)	1.0	10 (47.6)	19 (90.5)	<.01
Identify adverse effects	8 (38.1)	12 (57.1)	.125	14 (66.7)	19 (90.5)	.13
How to take the medication	9 (42.9)	16 (76.2)	.039	21 (100)	21 (100)	NA
Missed doses	15 (71.4)	21 (100)	.031	17 (81)	21 (100)	.13
When to seek emergency attention	16 (76.2)	18 (85.7)	.5	13 (61.9)	15 (71.4)	.013
Pharmacist (N = 22)
Medication purpose	21 (95.5)	21 (95.5)	1.0	12 (54.5)	20 (90.9)	<.01
Identify adverse effects	4 (18.2)	15 (68.2)	<.01	13 (59.1)	18 (81.8)	.13
How to take the medication	10 (45.5)	17 (77.3)	.016	18 (81.8)	21 (95.5)	.25
Missed doses	10 (45.5)	20 (20.9)	<.01	13 (59.1)	22 (100)	<.01
When to seek emergency attention	10 (45.5)	16 (72.7)	.07	8 (36.4)	19 (86.4)	<.01

At 30 days, scores were significantly higher than baseline (81.3% vs 64.8%; difference 16.5%, 95% CI: 7.8%-25.2%) although did decrease from the posttest (81.3% vs 88.7%; difference 7.4%, 95% CI: 0.01%-13.4%). There was no difference in change in score from posttest to 30 days between those that received text messages versus phone calls (−10% vs −5.5%, respectively; P = .36). No interactions were observed between initial group allocation (pharmacist vs video) and secondary group allocation (text vs phone call).

Discussion and Conclusion

Discussion

No studies have evaluated the effectiveness of any type of patient education for patients taking sacubitril/valsartan. We found that a short three-minute video or pharmacist education was effective in improving short and long term knowledge, although neither strategy was superior to the other. This was impressive given that 74% of our patient population had a high school education or less. We did not observe differences between subgroups such as prior sacubitril/valsartan use, newly diagnosed heart failure, or education level. This demonstrates that either strategy would be effective for patient education. We also did not observe an effect with follow-up text or phone call, and importantly no interaction with initial group assignment. This again shows either strategy can be effective and could be based on patient preference. Alternatively, in a resource-thin pharmacy setting the primary method at 14 days could be automatic text as this would use less time and personnel resources.

Our study shows similarities and differences to prior research. One key similarity is that the largest gains in knowledge are seen immediately, and knowledge gains tend to decrease over time. In a study that evaluated knowledge on rivaroxaban after 7 days, patients retained about 75% of the initial knowledge gained. ⁸ However a study that evaluated apixaban knowledge after 30 days showed no long term knowledge retention. ⁷ To address knowledge loss after 30 days we added a 2 week patient education point in an attempt to further prevent knowledge loss. This approach resulted in an average 60% knowledge retention at 30 days. We believe further research could aim to further improve this number. We hypothesize improvements may be seen if patient preferences for education were matched with the delivery of educational materials.

This study offers options for patient education on sacubitril/valsartan. It is critical that patients have access to validated educational material. We made the video freely available after patient recruitment had been completed. To replicate knowledge retention we observed at 30 days, it is important to advocate for watching the video at a later point, so knowledge will not decrease over time. However, we do not know the optimal number of reeducation sessions and timing, but this likely varies from patient to patient. This issue can be addressed by providing patients with easy to access educational materials which will allow patients to use this information at their own pace.

This research had some strengths and limitations. First, we randomized patients to two sets of separate interventions. This allowed us to evaluate both interventions, as there was no interaction present between the two allocations. Randomization did not produce equal groups for all characteristics due to the small sample size, however controlling for these factors did not change the results observed. Our 30-day follow up numbers did have loss to follow-up, but this is a reflective of what occurs in practice. Notably, patients that did not follow-up were not systematically different from those that did. Lastly, while we did have diverse patient enrollment, our study results may not be applicable to those with the lowest health literacy, patients without a phone, or those who do not speak English, as these patients were excluded.

Conclusion

We saw improvements in both short term and long term knowledge for patients receiving pharmacist or video education. While these approaches were effective, neither approach was more effective than the other. Clinicians can use either approach based on patient preference.