Clinical Pharmacy Medication Therapy Management and Patient Follow-up to Improve
Real-world Adherence to Novel Oral Anticoagulants: a Single-center Prospective Study
Maher Abdel-Sattar, PharmD ; Farzad Daneshvar, PharmD ; Nicole Nielsen, PharmD ; Huang-Chia Chang, PharmD candidate ;
Melissa McCart, PharmD, MS1; Paulo Guillinta, MD2; Robert Schoenhaus, PharmD2
1
2
2
3
Xcenda, Palm Harbor, FL; 2Sharp Rees-Stealy, San Diego, CA; 3The Ohio State University College of Pharmacy, Columbus, OH
1
BACKGROUND
Table 1: Patient Demographics
• The 2016 CHEST guidelines on antithrombotic therapy for venous thromboembolism (VTE)
recommend the use of novel oral anticoagulants (NOACs) over vitamin K antagonist therapy
(warfarin) for the long-term treatment of VTE patients without cancer.1
t
<60
Age
60 to 79
≥80
Male
Gender
Female
1 to 5
Number of
6 to 10
Drugs
Over 10
English
Language
Spanish
Atrial fibrillation
Paroxysmal atrial
fibrillation
Atrial flutter
• However, patients prescribed XARELTO (rivaroxaban), ELIQUIS (apixaban), PRADAXA
(dabigatran), or SAVAYSA® (edoxaban) for chronic use are not frequently monitored by
anticoagulation teams, as is traditionally done for patients taking warfarin for similar indications.
®
®
®
• In 2013, the Pharmacy Quality Alliance (PQA) endorsed a new adherence measure for
NOACs to identify the percentage of patients 18 years and older who meet the proportion of
days covered (PDC) threshold of 80%.2
• Retrospective analyses of health insurance claims in the Humana database from June 2012 to
December 2013 (N=9,948) and from July 2013 and December 2014 (N=21,175) reported that
only 67.2% to 75.4% of NOAC patients met the PDC threshold of the PQA measure.3,4
• Suboptimal adherence to NOACs puts patients at higher risk of thromboembolic events
associated with the development of stroke or myocardial infarction and leading to increases
in morbidity and mortality, healthcare resource utilization, and direct and indirect costs.5
DVT
Indication*
PE
Prevention of
recurrent VTE
CVA
• To better manage patient adherence to NOACs, it is important to understand the reasons
behind non-adherence and evaluate the impact of routine patient follow-up.
Other
OBJECTIVE
• To assess real-world adherence and barriers to adherence for patients chronically taking
NOACs, and to review the benefits of pharmacy medication therapy management and regular
monitoring of NOAC patients.
PRADAXA
(dabigatran)
n=3 (2.8%)
All Patients
N=107 (100%)
N
21
35
12
33
35
20
30
17
66
2
28
%
30.9%
51.5%
17.6%
48.5%
51.5%
29.4%
44.1%
25.0%
97.1%
2.9%
41.2%
N
2
21
13
16
20
1
20
15
35
1
27
%
5.6%
58.3%
36.1%
44.4%
55.6%
2.8%
55.6%
41.7%
97.2%
2.8%
75.0%
N
0
3
0
3
0
0
1
2
3
0
2
%
0%
100%
0%
100%
0%
0%
33.3%
66.7%
100%
0%
66.7%
N
23
59
25
52
55
21
51
34
104
3
57
%
21.5%
55.1%
23.4%
48.6%
51.4%
19.6%
47.7%
31.8%
97.2%
2.8%
53.3%
8
11.8%
8
22.2%
0
0%
16
15.0%
2
2.9%
1
2.8%
0
0%
3
2.8%
20
8
29.4%
11.8%
0
0
0%
0%
1
0
33.3%
0%
21
8
19.6%
7.5%
4
5.9%
0
0%
0
0%
4
3.7%
1
1.5%
0
0%
0
0%
1
0.9%
1
1.5%
1
2.8%
0
0%
2
1.9%
Table 2: Results From Initial Phone Calls
XARELTO
(rivaroxaban)
n=68 (63.6%)
METHODS
Appropriate
Dosing
STUDY DESIGN
• Single-center, single-arm, prospective database study
Duplicate
Anticoagulant
DATA SOURCE
• Sharp Rees-Stealy registry data gathered from electronic medical records were used to identify
patients who initiated chronic NOAC therapy between January 26 and September 25, 2015.
Medication
On-hand
Understanding of
Indication
INCLUSION CRITERIA
• Age 18 years or older
• English and/or Spanish speakers
• Prescribed a NOAC for at least 3 months
• Initiated NOAC treatment between January 26 and September 25, 2015
• Received care by the Sharp Rees-Stealy Medical Group in San Diego, California
• Enrolled in a fully delegated health maintenance organization insurance plan
• Verbally consented to participate in this study and received an initial call and 1 or more
follow-up calls
INITIAL PHONE CALLS
• Prior to the initial call, pharmacists performed a comprehensive medication review for each
patient and checked for appropriateness of NOAC dosing, drug-drug interactions (DDIs), and
potential therapeutic duplications.
• Initial calls were conducted by registered clinical pharmacists within the first month of NOAC
treatment initiation.
• Each patient’s understanding of the treatment indication, directions of use, adverse drug
reactions (ADRs), missed-dose management, and importance of adherence were assessed
during the initial call.
• Pharmacists also documented medication possession by asking patients if they had their
NOACs on-hand during the initial call and by contacting their respective pharmacies to verify
that their NOAC prescription was successfully filled.
ELIQUIS
(apixaban)
n=36 (33.6%)
* The sum of percentages exceeds 100% because some patients had multiple indications for chronic NOAC therapy.
Key: CVA – cerebral vascular accident; DVT – deep vein thrombosis; PE – pulmonary embolism; VTE – venous thromboembolism.
t
EXCLUSION CRITERIA
• Patients diagnosed with Alzheimer’s disease, dementia, schizophrenia, or cognitive deficit due
to stroke, and/or placement in hospice care for a documented terminal illness
• Patients who switched NOAC agents or discontinued NOAC treatment due to adverse effects
or other reasons before completing at least 3 months of therapy
XARELTO
(rivaroxaban)
n=68 (63.6%)
Understanding of
Rx Directions
Understanding
of Adverse Drug
Reactions
Understanding
of Missed-dose
Management
Understanding
the Importance of
Adherence
References
1. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.
Chest. 2016;149(2):315-352.
2. Pharmacy Quality Alliance (PQA). PQA performance measures – adherence to non-warfarin oral anticoagulants. http://www.
pqaalliance.org/measures. Accessed March 25, 2016.
3. McHorney CA, Crivera C, Laliberté F, et al. Adherence to non-vitamin-K-antagonist oral anticoagulant medications based on the Pharmacy Quality Alliance measure. Curr Med Res Opin. 2015;31(12):2167-2173.
4. Crivera C, Nelson WW, Bookhart B, et al. Pharmacy quality alliance measure: adherence to non-warfarin oral anticoagulant medications. Curr Med Res Opin. 2015;31(10):1889-1895.
5. Shore S, Carey EP, Turakhia MP, et al. Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the Veterans Health Administration. Am Heart J. 2014;167(6):810-817.
All Patients
N=107 (100%)
N
%
N
%
N
%
N
%
Yes
67
98.5%
34
94.4%
3
100%
104
97.2%
No
1
1.5%
2
5.6%
0
0%
3
2.8%
Yes
10
14.7%
1
2.8%
1
33.3%
12
11.2%
No
58
85.3%
35
97.2%
2
66.7%
95
88.8%
Yes
66
97.1%
35
97.2%
3
100%
104
97.2%
No
2
2.9%
1
2.8%
0
0%
3
2.8%
Yes
65
95.6%
33
91.7%
3
100%
101
94.4%
No
3
4.4%
3
8.3%
0
0%
6
5.6%
Yes
67
98.5%
35
97.2%
3
100%
105
98.1%
No
1
1.5%
1
2.8%
0
0%
2
1.9%
Yes
33
48.5%
15
41.7%
2
66.7%
50
46.7%
No
35
51.5%
21
58.3%
1
33.3%
57
53.3%
Yes
20
29.4%
11
30.6%
2
66.7%
33
30.8%
No
48
70.6%
25
69.4%
1
33.3%
74
69.2%
Yes
64
94.1%
34
94.4%
3
100%
101
94.4%
No
4
5.9%
2
5.6%
0
0%
6
5.6%
XARELTO
(rivaroxaban)
n=68 (63.6%)
t
ELIQUIS
(apixaban)
n=36 (33.6%)
PRADAXA
(dabigatran)
n=3 (2.8%)
All Patients
N=107 (100%)
N
%
N
%
N
%
N
%
Yes
66
97.1%
36
100%
3
100%
105
98.1%
No
2
2.9%
0
0%
0
0%
2
1.9%
Yes
11
16.2%
7
19.4%
0
0%
18
16.8%
No
57
83.8%
29
80.6%
3
100%
89
83.2%
Yes
Missed 1 or More
Doses in Past Month No
20
29.4%
13
36.1%
1
33.3%
34
31.8%
48
70.6%
23
63.9%
2
66.7%
73
68.2%
Medication
On-hand
Missed 1 or More
Doses in Past Week
Figure 1: Patient-reported Barriers to Adherence (n=23)
34.8%
43.5%
Forgetfulness
Cost
Adverse Drug Reactions
RESULTS
Sponsorship
This unsolicited, independent research effort was a collaboration between Sharp Healthcare and Xcenda/AmerisourceBergen
Corporation, without external funding.
PRADAXA
(dabigatran)
n=3 (2.8%)
Table 3: Results From Follow-up Calls
FOLLOW-UP PHONE CALLS
• Patients received follow-up phone calls by registered clinical pharmacists on a monthly basis.
• Pharmacists provided patient education, and documented NOAC possession and timeliness
of refills, the patient-reported number of missed doses, and each patient’s main reasons for
lapses in adherence.
• Prescribers were notified if patients had consistently poor persistence to NOAC therapy based
on the number of missed doses and/or not refilling NOAC prescriptions in a timely manner.
• 107 patients received an initial call and at least 1 follow-up call, including 68 (63.6%) patients
on rivaroxaban, 36 (33.6%) on apixaban, 3 (2.8%) on dabigatran, and 0 (0%) on edoxaban
(Table 1).
• Included patients were 51.4% female, had a mean age of 68.7 years, and reported taking 8.9
prescription and over-the-counter medications on average (Table 1).
• By conducting a comprehensive medication review prior to the initial call, pharmacists identified
12 duplications in anticoagulation therapy, 3 instances of inappropriate NOAC dosing, and 21
patients with potential DDIs.
• 104 (97.2%) patients had filled their NOAC prescription by the initial call and 106 (99.1%)
reported having the medication on-hand during the follow-up calls (Table 2 and Table 3).
• Only 50 (46.7%) patients were aware of the potential ADRs of NOACs and only 33 (30.8%)
knew how to manage missed doses (Table 2).
• 18 (16.8%) patients reported missing at least 1 dose in the past week and 34 (31.8%) reported
missing at least 1 dose in the past month during follow-up calls (Table 3).
• Based on 23 responses, the most prevalent barriers to adherence were forgetfulness (43.5%),
cost (34.8%), and ADRs (17.4%) (Figure 1).
• On average, initial and follow-up calls lasted 11.6 and 4.6 minutes, respectively.
ELIQUIS
(apixaban)
n=36 (33.6%)
4.3%
Complexity of Regimen
17.4%
CONCLUSIONS
• Approximately one-third of patients missed at least 1 NOAC dose per month due to
forgetfulness, cost, ADRs, or the complexity of their regimen.
• Given that most NOAC patients have a relatively high pill burden, a comprehensive medication
review by a pharmacist at the initiation of NOAC therapy may be essential in identifying
potential DDIs, accidental duplications in therapy, and/or inappropriate NOAC dosing.
• Limited patient understanding of NOAC ADRs and proper missed-dose management
identifies an opportunity for pharmacists to fill knowledge gaps and improve adherence through
regular patient follow-up.
LIMITATIONS
• Data collected during phone calls were patient-reported and subjective in nature.
• Patients who selected to participate in this study may be more involved in their healthcare
management, and may therefore have better persistence to treatment in comparison to patients
who refused to participate.
• Most of the patients enrolled in the study were on either rivaroxaban or apixaban; therefore,
the results may not be generalizable to dabigatran or edoxaban due to the lack of data.
Presented at AMCP’s Managed Care & Specialty Pharmacy Annual Meeting • April 19-22, 2016 • San Francisco, CA