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The American Journal of Managed Care December 2010
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Modes of Delivery for Interventions to Improve Cardiovascular Medication Adherence
Sarah L. Cutrona, MD, MPH; Niteesh K. Choudhry, MD, PhD; Michael A. Fischer, MD, MPH; Amber Servi, BA; Joshua N. Liberman, PhD; Troyen A. Brennan, MD, JD; and William H. Shrank, MD, MSHS
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Modes of Delivery for Interventions to Improve Cardiovascular Medication Adherence

Sarah L. Cutrona, MD, MPH; Niteesh K. Choudhry, MD, PhD; Michael A. Fischer, MD, MPH; Amber Servi, BA; Joshua N. Liberman, PhD; Troyen A. Brennan, MD, JD; and William H. Shrank, MD, MSHS

In this review of randomized controlled trials designed to improve adherence to cardiovascular medications, electronic interventions and in-person, pharmacy-based interventions showed the highest success rates.

Objective: To determine the optimal modes of delivery for interventions to improve adherence to cardiovascular medications.

Study Design: Systematic review.

Methods: We conducted systematic searches of English-language, peer-reviewed publications in MEDLINE and EMBASE, 1966 through December 31, 2008. We selected randomized controlled trials of interventions to improve adherence to medications for preventing or treating cardiovascular disease or diabetes. Articles were classified based on mode of delivery of the main intervention as (1) person-independent interventions (mailed, faxed, or hand distributed; or delivered via electronic interface) or (2) person-dependent interventions (nonautomated phone calls, in-person interventions).


Results: We identified 6550 articles. Of these, 168 were reviewed in full and 51 met inclusion criteria. Among person-independent interventions (56% successful), electronic interventions were most successful (67%). Among person-dependent interventions (52% successful), phone calls showed low success rates (38%). In-person interventions at hospital discharge were more effective (67%) than clinic interventions (47%). In-person pharmacist interventions were effective when held in a pharmacy (83% successful), but were less effective in clinics (38%).

Conclusions: Future medication adherence studies should explore new electronic approaches and in-person interventions at the site of medication distribution. Identifying times of increased patient receptivity to the adherence message such as hospital discharge also will be important.

(Am J Manag Care. 2010;16(12):929-942)

Interventions designed to improve adherence to cardiovascular medications may require a person to deliver them (in-person counseling, phone calls), or the delivery may be person independent (mailed information, electronic interface). The mode of delivery directly affects cost and long-term viability.


  • Among person-independent interventions, we found electronic approaches to be most effective at improving adherence.


  • For interventions delivered by a person, we found high success rates for in-person interventions delivered at a pharmacy or at the time of hospital discharge.
Nonadherence to essential chronic medication therapy for cardiovascular disease and diabetes is common, leading to substantial morbidity, mortality, and healthcare costs.1-3 Evidence- based efforts to improve adherence are needed. Previous studies have demonstrated the effectiveness of reduced dosing demands and complex, multifactorial interventions,4,5 but there is little evidence available comparing modes of delivery for adherence interventions.

Evidence-based information on modes of delivery would enhance the construction of adherence interventions in several domains: the communication channel (eg, written, electronic, phone, in person), the purveyor of information (eg, lay person, pharmacist, physician), and the optimal setting (hospital, home, pharmacy, clinic). The mode of delivery is  closely linked to an intervention’s cost and therefore to its long-term viability. Careful consideration of the comparative efficacy and intensity of different approaches is needed to develop evidence-based strategies.

We conducted a systematic review of interventions that sought to improve adherence to medications for cardiovascular disease and diabetes, a cardiovascular disease equivalent. We focused on the mechanism of information transfer to patients. By evaluating the effects of (1) the purveyor of information, (2) the channel of information, and (3) the setting of  transfer, we offer to payers, providers, and policy makers additional guidance on the development of adherence interventions.


We performed a systematic search of articles published in peer-reviewed, healthcare-related journals between 1966 and December 31, 2008. The search was performed using MEDLINE and EMBASE, with the help of a professional librarian. We limited our search to randomized controlled trials.

We used search terms related to the type of study (randomized controlled trial), adherence (ie, “adherence” OR “compliance” OR “medication adherence” or “treatment adherence”), prescription drugs (ie, “drug” OR “medication” OR “antihypertensive” OR “antihyperlipidemic” OR “hypoglycemic agents”), and cardiovascular disease and diabetes (myocardial infarction, coronary heart disease, heart failure; hypertension; hyperlipidemia; and diabetes). Articles with at least 1 search term in 3 of the main categories (study type AND adherence AND either drug OR disease) met criteria for the title/abstract review (see the eAppendix at

Search terms and parameters were adjusted for both databases while maintaining a common overall architecture. Search results from MEDLINE and EMBASE were combined and screened for duplicate entries.

Study Selection

Studies were included if they reported the results of randomized controlled trials that examined interventions to improve adherence to medications used for the prevention or treatment of cardiovascular disease or diabetes. Studies were limited to adult subjects (aged ≥18 years) in either the outpatient setting or at the inpatient/ outpatient transition. Data were gathered on outpatient adherence for all patients. Studies were excluded if they described an intervention characterized by regimen simplification (either unit-of-use packaging or changes in dose frequency or formulation), as they could not be placed into the study categorization, and previous studies have demonstrated their effectiveness.4 Studies were excluded if they were written in a language other than English. Those with a duration of less than 24 weeks were excluded because cardiovascular medications typically require long-term adherence.

After exclusions, 51 articles (Figure) were classified by the mode of delivery of the intervention. Person-independent interventions included (1) mailed, faxed, or hand-distributed interventions and (2) interventions delivered via electronic system. Person-dependent interventions included (1) interventions delivered via nonautomated phone calls and (2) in-person interventions (classified based on site of delivery, ie, home, work site, pharmacy, clinic, or hospital). Persondependent interventions were further classified based on the level of training required of the person administering the intervention: (1) trained lay person, (2) nurse, (3) pharmacist, (4) physician, or (5) not specified.

For those studies that incorporated 2 or more modes of intervention, we assigned categories based on what appeared to be the main mode of intervention. Where categories appeared to be equivalent, we assigned priority in the following order: person dependent (in person, followed by phone) and person independent (electronic system, followed by mailed, faxed, or hand distributed).

Data Extraction

Data were extracted by 2 investigators (SLC, WHS) with disagreements resolved by consensus. We assessed a number of variables related to the organization and outcome of studies, including the study design, setting, characteristics of population studied, the number of participants, characteristics of intervention, methods used to measure medication adherence, clinical outcomes, and medication adherence outcomes. We report confidence intervals (CIs) when available and P values when no CIs were available.


Our search retrieved a total of 6550 articles. Of these articles, 168 were reviewed in full and 51 met inclusion criteria6-56 (Figure, Table 1, Table 2). The majority (55%) of interventions were aimed at subjects with hypertension. Other patient populations studied included those with diabetes (8%), coronary artery disease (8%), congestive heart failure (14%), and dyslipidemia (10%); 6% of the studies evaluated patients with a mix of cardiovascular and noncardiovascular diseases.

Person-Independent Interventions: Mailed, Faxed, or Hand-Distributed Material

There were 3 studies6-8 in which the main intervention was delivered via mail, fax, or hand distribution of paper or video information; 1 was successful.6 Smith et al followed 907 patients after discharge from a hospital stay for myocardial infarction; 2 letters sent to patients and to primary care providers describing the importance of beta-blocker use yielded improved adherence as measured by pharmacy claims data. Patients receiving mailings were 17% more likely to have 80% of days covered (relative risk = 1.17; 95% CI = 1.02, 1.29). The 2 unsuccessful studies described direct patient mailings of written information on hypertension7 or video information on 1 of 4 medications (2 blood pressure agents, an antihyperlidemic, and transdermal estrogen).8 Takala defined adherent patients as those still under treatment after 2 years,7 and Powell and Edgren studied mean medication possession ratios.8

Person-Independent Interventions: Electronic Systems

There were 6 studies9-14 that examined a range of electronic interventions, including use of electronic pillboxes with programmable reminders, automated phone calls with interactive components, computer-generated individualized interventions, and home automatic blood pressure monitoring. Overall, this group included more positive studies than the mailed/faxed/hand-delivered group (4 out of 6 showed improved adherence).

Rosen et al14 studied 33 people with diabetes whose baseline adherence was less than 80%. This study tested use of electronic pill caps with a time display and programmable beeper compared with electronic pill caps alone. Participants with programmable beeper pill caps showed improved adherence (80% intervention vs 60% control; P = .017).

Friedman et al10 and Piette et al13 studied the effect of automated phone calls. Friedman and colleagues followed 299 hypertensive patients, randomizing patients to an interactive computer-based home telemonitoring system versus usual care. Patients called in weekly, shared information by phone regarding automated blood pressure readings and adherence, and received targeted education and motivational counseling (all automated), with responses forwarded to doctors. Adherence, measured by pill count, was not  significantly different between groups in unadjusted analysis; adjustment for age, sex, and baseline adherence yielded significant differences (17.7% adherence in intervention group vs 11.7% in control group; P = .03). Piette et al randomized 280 patients to biweekly automated interactive phone calls with structured messages that were adjusted based on patient responses, followed by targeted nurse calls versus usual care. Differences from Friedman et al’s intervention include outgoing calls to patients (Friedman et al required patients to call in) and limited nonautomated phone follow-up. Piette and colleagues found that intervention patients were “substantially less likely to report adherence problems” (based on self-report using modified Morisky scale) (P = .003, no adherence percentages given) but did not provide baseline adherence (56% reported “any medication problem” at baseline).

Johnson et al11 followed 404 adults, describing the impact of a computer program designed to mimic the reasoning and problem-solving of humans based on an integrative model of behavioral change (the transtheoretical model) and incorporating an individualized computer-generated report mailed to patients. They found an improvement in adherence at 18 months (odds ratio = 2.86, P <.05). Emmett et al9 studied 217 patients newly diagnosed with hypertension who were randomized in a factorial manner to a computerized decision analysis intervention, mailed video and leaflet, both, or neither. Neither the decision analysis nor the mailed video and leaflet resulted in significant improvement. Marquez-Contreras et al12 examined use of home automatic blood pressure monitoring (along with a phone call with instructions on use) in 250 patients with uncontrolled or newly diagnosed hypertension. At the end of 6 months, 92% of the intervention group had adherence greater than 80% (assessed using electronic pillboxes) compared with 74% of the control group (P <.05).

Person-Dependent Interventions: Nonautomated Phone Calls

Eight studies described the use of nonautomated phone calls to improve adherence. Calls were made by trained lay people,15,16 nurses,17 pharmacists,18,19 or a nonspecified caller.20-22 Overall, 5 of these studies showed a nonsignificant improvement in adherence, a single study20 showed significant improvement but did not clearly define its adherence outcome measure, and 2 showed significant improvement with clearly defined outcomes.

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