Trial Outcomes & Findings for Promoting Adherence to Improve Effectiveness of Cardiovascular Disease Therapies (NCT NCT01251757)
NCT ID: NCT01251757
Last Updated: 2017-03-13
Results Overview
We used a modification of the Medication Possession Ratio (MPR) as our primary outcome measure. The MPR is computed as the number of days' supply of medication dispensed during a given time window divided by the time between the first dispensing in the window and the end of the window. Our modified MPR (mMPR) also accounted for medication that was on hand at the start of the window and ignored any days' supply that would extend beyond the end of the window. We used medication dispensing data from the Kaiser outpatient pharmacies to calculate a modified medication possession ratio (mMPR) for statins among the subset of randomized participants who were using these drugs. Nominally mMPR provides an estimate of the proportion of days during the follow-up period during which the participant was adherent to their prescribed medications.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
21752 participants
Primary outcome timeframe
12 months post randomization
Results posted on
2017-03-13
Participant Flow
Participant milestones
| Measure |
Usual Care (UC)
Participants in this arm had full access to all care they were normally entitled to as part of usual care
|
Interactive Voice Recognition (IVR)
In addition to their usual care, participants in the Interactive Voice Recognition (IVR) arm received automated phone calls, triggered by dispensing events in the electronic medical record (EMR), to educate patients about their medications and assist them in refilling their prescriptions.
The calls fell into two basic types: simple refill reminders and "tardy" calls for those who were overdue for a refill. Calls occured monthly and were triggered by dispensing information in the EMR. Call features included the ability to transfer individuals to Kaiser's automated prescription refill service as well as to care managers. Although the calls were triggered by and focused on use of ACE inhibitors, ARBs and statins, they also included reminders to use aspirin, which is known to also be effective for secondary prevention in this patient population.
|
Enhanced IVR (IVR+)
Participants in the IVR+ arm received all components of the IVR intervention and in addition were mailed educational materials bimonthly during the intervention. In addition, both IVR+ participants and their primary care providers received mailed notifications when they did not fill their medications in response to the automated calls.
The educational mailings included personalized health information such as the participant's cholesterol and blood pressure readings, as well as tools for improving adherence such as FAQs about their medications, a pocket-sized calendar for tracking refills with pertinent phone numbers and web site information and space for them to write their medical record number and prescription numbers.
|
|---|---|---|---|
|
Overall Study
STARTED
|
7255
|
7247
|
7250
|
|
Overall Study
COMPLETED
|
7255
|
7247
|
7250
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Promoting Adherence to Improve Effectiveness of Cardiovascular Disease Therapies
Baseline characteristics by cohort
| Measure |
Usual Care (UC)
n=7255 Participants
Participants in this arm had full access to all care they were normally entitled to as part of usual care
|
Interactive Voice Recognition (IVR)
n=7247 Participants
In addition to their usual care, participants in the Interactive Voice Recognition (IVR) arm received automated phone calls, triggered by dispensing events in the electronic medical record (EMR), to educate patients about their medications and assist them in refilling their prescriptions.
The calls fell into two basic types: simple refill reminders and "tardy" calls for those who were overdue for a refill. Calls occured monthly and were triggered by dispensing information in the EMR. Call features included the ability to transfer individuals to Kaiser's automated prescription refill service as well as to care managers. Although the calls were triggered by and focused on use of ACE inhibitors, ARBs and statins, they also included reminders to use aspirin, which is known to also be effective for secondary prevention in this patient population.
|
Enhanced IVR (IVR+)
n=7250 Participants
Participants in the IVR+ arm received all components of the IVR intervention and in addition were mailed educational materials bimonthly during the intervention. In addition, both IVR+ participants and their primary care providers received mailed notifications when they did not fill their medications in response to the automated calls.
The educational mailings included personalized health information such as the participant's cholesterol and blood pressure readings, as well as tools for improving adherence such as FAQs about their medications, a pocket-sized calendar for tracking refills with pertinent phone numbers and web site information and space for them to write their medical record number and prescription numbers.
|
Total
n=21752 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
63.6 years
STANDARD_DEVIATION 12.2 • n=99 Participants
|
63.6 years
STANDARD_DEVIATION 12.1 • n=107 Participants
|
63.5 years
STANDARD_DEVIATION 12.2 • n=206 Participants
|
63.6 years
STANDARD_DEVIATION 12.2 • n=7 Participants
|
|
Sex: Female, Male
Female
|
3432 Participants
n=99 Participants
|
3370 Participants
n=107 Participants
|
3415 Participants
n=206 Participants
|
10217 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
3823 Participants
n=99 Participants
|
3877 Participants
n=107 Participants
|
3835 Participants
n=206 Participants
|
11535 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
51 Participants
n=99 Participants
|
43 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
138 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
1270 Participants
n=99 Participants
|
1290 Participants
n=107 Participants
|
1254 Participants
n=206 Participants
|
3814 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
798 Participants
n=99 Participants
|
819 Participants
n=107 Participants
|
783 Participants
n=206 Participants
|
2400 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1168 Participants
n=99 Participants
|
1094 Participants
n=107 Participants
|
1109 Participants
n=206 Participants
|
3371 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
3403 Participants
n=99 Participants
|
3399 Participants
n=107 Participants
|
3408 Participants
n=206 Participants
|
10210 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
565 Participants
n=99 Participants
|
602 Participants
n=107 Participants
|
652 Participants
n=206 Participants
|
1819 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
7255 participants
n=99 Participants
|
7247 participants
n=107 Participants
|
7250 participants
n=206 Participants
|
21752 participants
n=7 Participants
|
|
ever smokers
yes
|
3482 participants
n=99 Participants
|
3537 participants
n=107 Participants
|
3560 participants
n=206 Participants
|
10579 participants
n=7 Participants
|
|
ever smokers
no
|
3773 participants
n=99 Participants
|
3710 participants
n=107 Participants
|
3690 participants
n=206 Participants
|
11173 participants
n=7 Participants
|
|
co-morbid diabetes mellitus
yes
|
5666 participants
n=99 Participants
|
5703 participants
n=107 Participants
|
5626 participants
n=206 Participants
|
16995 participants
n=7 Participants
|
|
co-morbid diabetes mellitus
no
|
1589 participants
n=99 Participants
|
1544 participants
n=107 Participants
|
1624 participants
n=206 Participants
|
4757 participants
n=7 Participants
|
|
co-morbid cardiovascular disease
yes
|
2626 participants
n=99 Participants
|
2616 participants
n=107 Participants
|
2661 participants
n=206 Participants
|
7903 participants
n=7 Participants
|
|
co-morbid cardiovascular disease
no
|
4629 participants
n=99 Participants
|
4631 participants
n=107 Participants
|
4589 participants
n=206 Participants
|
13849 participants
n=7 Participants
|
|
target medication use
statin only
|
2924 participants
n=99 Participants
|
2870 participants
n=107 Participants
|
2922 participants
n=206 Participants
|
8716 participants
n=7 Participants
|
|
target medication use
ACEI/ARB only
|
1770 participants
n=99 Participants
|
1790 participants
n=107 Participants
|
1820 participants
n=206 Participants
|
5380 participants
n=7 Participants
|
|
target medication use
statin and ACEI/ARB
|
2561 participants
n=99 Participants
|
2587 participants
n=107 Participants
|
2508 participants
n=206 Participants
|
7656 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 12 months post randomizationPopulation: All randomized participants who were taking statins at the time of randomization
We used a modification of the Medication Possession Ratio (MPR) as our primary outcome measure. The MPR is computed as the number of days' supply of medication dispensed during a given time window divided by the time between the first dispensing in the window and the end of the window. Our modified MPR (mMPR) also accounted for medication that was on hand at the start of the window and ignored any days' supply that would extend beyond the end of the window. We used medication dispensing data from the Kaiser outpatient pharmacies to calculate a modified medication possession ratio (mMPR) for statins among the subset of randomized participants who were using these drugs. Nominally mMPR provides an estimate of the proportion of days during the follow-up period during which the participant was adherent to their prescribed medications.
Outcome measures
| Measure |
Usual Care (UC)
n=5484 Participants
statin users in UC arm
|
Interactive Voice Recognition (IVR)
n=5453 Participants
statin users in IVR arm
|
Enhanced IVR (IVR+)
n=5429 Participants
statin users in IVR+ arm
|
|---|---|---|---|
|
Adherence to Statins
overall
|
0.55 mMPR as a fraction
Standard Deviation 0.35
|
0.57 mMPR as a fraction
Standard Deviation 0.34
|
0.58 mMPR as a fraction
Standard Deviation 0.34
|
|
Adherence to Statins
baseline adherence <= 0.40
|
0.38 mMPR as a fraction
Standard Deviation 0.37
|
0.41 mMPR as a fraction
Standard Deviation 0.36
|
0.41 mMPR as a fraction
Standard Deviation 0.36
|
|
Adherence to Statins
baseline adherence 0.4-0.75
|
0.61 mMPR as a fraction
Standard Deviation 0.31
|
0.63 mMPR as a fraction
Standard Deviation 0.31
|
0.65 mMPR as a fraction
Standard Deviation 0.30
|
|
Adherence to Statins
baseline adherence 0.75-0.90
|
0.75 mMPR as a fraction
Standard Deviation 0.27
|
0.77 mMPR as a fraction
Standard Deviation 0.27
|
0.75 mMPR as a fraction
Standard Deviation 0.29
|
PRIMARY outcome
Timeframe: 12 months post randomizationPopulation: All randomized participants who were taking an ACEI or an ARB at the time of randomization
We used medication dispensing data from the Kaiser outpatient pharmacies to calculate a modified medication possession ratio (mMPR) for the subset of randomized participants who were using ACEIs or ARBs. Nominally mMPR provides an estimate of the proportion of days during the follow-up period during which the participant was adherent to their prescribed medications.
Outcome measures
| Measure |
Usual Care (UC)
n=4330 Participants
statin users in UC arm
|
Interactive Voice Recognition (IVR)
n=4370 Participants
statin users in IVR arm
|
Enhanced IVR (IVR+)
n=4323 Participants
statin users in IVR+ arm
|
|---|---|---|---|
|
Adherence to Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs)
baseline adherence 0.50-0.75
|
0.69 mMPR expressed as a fraction
Standard Deviation 0.30
|
0.70 mMPR expressed as a fraction
Standard Deviation 0.29
|
0.71 mMPR expressed as a fraction
Standard Deviation 0.29
|
|
Adherence to Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs)
overall
|
0.57 mMPR expressed as a fraction
Standard Deviation 0.36
|
0.59 mMPR expressed as a fraction
Standard Deviation 0.35
|
0.61 mMPR expressed as a fraction
Standard Deviation 0.34
|
|
Adherence to Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs)
baseline adherence <=0.50
|
0.45 mMPR expressed as a fraction
Standard Deviation 0.37
|
0.47 mMPR expressed as a fraction
Standard Deviation 0.37
|
0.50 mMPR expressed as a fraction
Standard Deviation 0.36
|
|
Adherence to Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs)
baseline adherence 0.75-0.90
|
0.76 mMPR expressed as a fraction
Standard Deviation 0.26
|
0.76 mMPR expressed as a fraction
Standard Deviation 0.28
|
0.77 mMPR expressed as a fraction
Standard Deviation 0.29
|
SECONDARY outcome
Timeframe: 12 months post randomizationPopulation: All randomized participants who were taking statins at the time of randomization.
Binary indicator of good statin adherence, defined as an mMPR\>0.80. 1=yes, 0=no.
Outcome measures
| Measure |
Usual Care (UC)
n=5484 Participants
statin users in UC arm
|
Interactive Voice Recognition (IVR)
n=5453 Participants
statin users in IVR arm
|
Enhanced IVR (IVR+)
n=5429 Participants
statin users in IVR+ arm
|
|---|---|---|---|
|
Percentage With Good (>80%) Statin Adherence
Overall
|
32.9 percent with good adherence
|
35.9 percent with good adherence
|
35.8 percent with good adherence
|
|
Percentage With Good (>80%) Statin Adherence
baseline adherence <=0.40
|
21.5 percent with good adherence
|
22.6 percent with good adherence
|
21.8 percent with good adherence
|
|
Percentage With Good (>80%) Statin Adherence
baseline adherence 0.4-0.75
|
36.2 percent with good adherence
|
39.4 percent with good adherence
|
40.1 percent with good adherence
|
|
Percentage With Good (>80%) Statin Adherence
baseline adherence 0.75-0.90
|
58.1 percent with good adherence
|
63.5 percent with good adherence
|
62.6 percent with good adherence
|
SECONDARY outcome
Timeframe: 12 months post randomizationPopulation: All randomized participants who were taking an ACEI or an ARB at the time of randomization
Binary indicator of good ACEI/ARB adherence, defined as an mMPR\>0.80. 1=yes, 0=no.
Outcome measures
| Measure |
Usual Care (UC)
n=4330 Participants
statin users in UC arm
|
Interactive Voice Recognition (IVR)
n=4370 Participants
statin users in IVR arm
|
Enhanced IVR (IVR+)
n=4323 Participants
statin users in IVR+ arm
|
|---|---|---|---|
|
Percentage With Good (>80%) ACEI/ARB Adherence
Overall
|
37.4 Percent with good adherence
|
40.3 Percent with good adherence
|
41.6 Percent with good adherence
|
|
Percentage With Good (>80%) ACEI/ARB Adherence
Baseline adherence <=0.50
|
24.5 Percent with good adherence
|
27.0 Percent with good adherence
|
28.2 Percent with good adherence
|
|
Percentage With Good (>80%) ACEI/ARB Adherence
Baseline adherence 0.50-0.75
|
48.4 Percent with good adherence
|
51.1 Percent with good adherence
|
52.0 Percent with good adherence
|
|
Percentage With Good (>80%) ACEI/ARB Adherence
Baseline adherence 0.75-0-.90
|
59.7 Percent with good adherence
|
62.0 Percent with good adherence
|
66.8 Percent with good adherence
|
SECONDARY outcome
Timeframe: 12-months post randomizationPopulation: The analysis sample was restricted to ACEI/ARB users with at least one post intervention SBP measurement recorded in the EMR. We did not impute any missing data.
Mean of last 5 SBP measurements captured in the electronic medical record for the 12 months post randomization.
Outcome measures
| Measure |
Usual Care (UC)
n=3980 Participants
statin users in UC arm
|
Interactive Voice Recognition (IVR)
n=3980 Participants
statin users in IVR arm
|
Enhanced IVR (IVR+)
n=3971 Participants
statin users in IVR+ arm
|
|---|---|---|---|
|
Systolic Blood Pressure (SBP)
Overall
|
129.2 mm Hg
Standard Deviation 13.1
|
128.6 mm Hg
Standard Deviation 13.2
|
129.0 mm Hg
Standard Deviation 13.2
|
|
Systolic Blood Pressure (SBP)
Baseline SBP<=130mmHg
|
123.5 mm Hg
Standard Deviation 10.7
|
122.8 mm Hg
Standard Deviation 11.1
|
123.4 mm Hg
Standard Deviation 11.1
|
|
Systolic Blood Pressure (SBP)
Baseline SBP 130-140mmHg
|
132.8 mm Hg
Standard Deviation 10.7
|
132.2 mm Hg
Standard Deviation 10.1
|
132.7 mm Hg
Standard Deviation 10.1
|
|
Systolic Blood Pressure (SBP)
Baseline SBP>140mmHg
|
140.6 mm Hg
Standard Deviation 13.3
|
140.4 mm Hg
Standard Deviation 13.2
|
140.9 mm Hg
Standard Deviation 13.2
|
SECONDARY outcome
Timeframe: 12 months post randomizationPopulation: All randomized participants who were taking an ACEI or an ARB at the time of randomization and who had at least one post randomization BP recorded in the EMR. Missing data were not imputed.
Using the mean of last 5 available blood pressure measurements post randomization, we defined BP control as a means systolic BP \<140 mmHg and a mean diastolic BP \< 90 mmHg.
Outcome measures
| Measure |
Usual Care (UC)
n=3980 Participants
statin users in UC arm
|
Interactive Voice Recognition (IVR)
n=3980 Participants
statin users in IVR arm
|
Enhanced IVR (IVR+)
n=3971 Participants
statin users in IVR+ arm
|
|---|---|---|---|
|
Percentage With Good (<140/90 mmHg) Blood Pressure Control
Overall
|
81.1 percentage of subjects with good control
|
82.1 percentage of subjects with good control
|
81.3 percentage of subjects with good control
|
|
Percentage With Good (<140/90 mmHg) Blood Pressure Control
Baseline SBP<=130 mmHg
|
93.7 percentage of subjects with good control
|
94.0 percentage of subjects with good control
|
92.9 percentage of subjects with good control
|
|
Percentage With Good (<140/90 mmHg) Blood Pressure Control
Baseline SBP 130-140 mmHg
|
78.4 percentage of subjects with good control
|
78.4 percentage of subjects with good control
|
78.3 percentage of subjects with good control
|
|
Percentage With Good (<140/90 mmHg) Blood Pressure Control
Baseline SBP>140 mmHg
|
49.2 percentage of subjects with good control
|
52.4 percentage of subjects with good control
|
50.2 percentage of subjects with good control
|
SECONDARY outcome
Timeframe: 12 months post randomizationPopulation: All randomized participants who were taking statin at the time of randomization and who had at least one post randomization LDL measurement recorded in the EMR. Missing data were not imputed.
We used the latest LDL (fasting or nonfasting) available during 12 months post randomization. no missing data were imputed.
Outcome measures
| Measure |
Usual Care (UC)
n=4621 Participants
statin users in UC arm
|
Interactive Voice Recognition (IVR)
n=4610 Participants
statin users in IVR arm
|
Enhanced IVR (IVR+)
n=4545 Participants
statin users in IVR+ arm
|
|---|---|---|---|
|
Post Intervention Low Density Lipoprotein (LDL) Level
Overall
|
92.4 mg/dL
Standard Deviation 35.3
|
91.8 mg/dL
Standard Deviation 34.0
|
91.3 mg/dL
Standard Deviation 33.3
|
|
Post Intervention Low Density Lipoprotein (LDL) Level
Baseline LDL <=80 mg/dL
|
75.5 mg/dL
Standard Deviation 26.1
|
75.5 mg/dL
Standard Deviation 25.7
|
75.6 mg/dL
Standard Deviation 26.1
|
|
Post Intervention Low Density Lipoprotein (LDL) Level
Baseline LDL 80-100 mg/dL
|
92.0 mg/dL
Standard Deviation 27.8
|
91.5 mg/dL
Standard Deviation 25.9
|
90.7 mg/dL
Standard Deviation 24.9
|
|
Post Intervention Low Density Lipoprotein (LDL) Level
Baseline LDL>100 mg/dL
|
114.9 mg/dL
Standard Deviation 37.9
|
113.0 mg/dL
Standard Deviation 37.9
|
111.4 mg/dL
Standard Deviation 36.6
|
SECONDARY outcome
Timeframe: 12 months post randomizationPopulation: All randomized participants who were taking a statin at the time of randomization and who had at least one post randomization LDL measurement recorded in the EMR. Missing data were not imputed.
Using the last LDL measurement (fasting or nonfasting) available in the EMR post randomization, we defined good control as an LDL level \<= 100 mg/dL.
Outcome measures
| Measure |
Usual Care (UC)
n=4621 Participants
statin users in UC arm
|
Interactive Voice Recognition (IVR)
n=4610 Participants
statin users in IVR arm
|
Enhanced IVR (IVR+)
n=4545 Participants
statin users in IVR+ arm
|
|---|---|---|---|
|
Percentage With Good (<=100mg/dL) Low Density Lipoprotein (LDL) Control
Baseline LDL 80-100 mg/dL
|
73.7 percentage with controlled LDL
|
74.0 percentage with controlled LDL
|
74.9 percentage with controlled LDL
|
|
Percentage With Good (<=100mg/dL) Low Density Lipoprotein (LDL) Control
Overall
|
69.1 percentage with controlled LDL
|
69.8 percentage with controlled LDL
|
70.4 percentage with controlled LDL
|
|
Percentage With Good (<=100mg/dL) Low Density Lipoprotein (LDL) Control
Baseline LDL <=80 mg/dL
|
88.4 percentage with controlled LDL
|
88.0 percentage with controlled LDL
|
88.1 percentage with controlled LDL
|
|
Percentage With Good (<=100mg/dL) Low Density Lipoprotein (LDL) Control
Baseline LDL > 100 mg/dL
|
39.9 percentage with controlled LDL
|
43.5 percentage with controlled LDL
|
44.1 percentage with controlled LDL
|
Adverse Events
Usual Care (UC)
Serious events: 25 serious events
Other events: 0 other events
Deaths: 141 deaths
Interactive Voice Recognition (IVR)
Serious events: 21 serious events
Other events: 0 other events
Deaths: 146 deaths
Enhanced IVR (IVR+)
Serious events: 22 serious events
Other events: 0 other events
Deaths: 140 deaths
Serious adverse events
| Measure |
Usual Care (UC)
n=7255 participants at risk
usual medical care
|
Interactive Voice Recognition (IVR)
n=7247 participants at risk
usual care plus automated phone calls
|
Enhanced IVR (IVR+)
n=7250 participants at risk
usual care plus automated phone calls plus educational mailings and mail follow-up for persistent nonadherence
|
|---|---|---|---|
|
Vascular disorders
potential ACEI/ARB related hospitalization
|
0.55%
24/4330 • Number of events 24 • 12 months post randomization
|
0.43%
19/4370 • Number of events 19 • 12 months post randomization
|
0.46%
20/4323 • Number of events 20 • 12 months post randomization
|
|
Hepatobiliary disorders
potential statin related hospitalization
|
0.03%
1/3980 • Number of events 1 • 12 months post randomization
|
0.05%
2/3980 • Number of events 2 • 12 months post randomization
|
0.05%
2/3971 • Number of events 2 • 12 months post randomization
|
Other adverse events
Adverse event data not reported
Additional Information
William M Vollmer, PhD
Kaiser Permanente Center for Health Research
Phone: 503-335-2400
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place