Hybrid Effectiveness-Implementation Study to Improve Clopidogrel Adherence
Condition: Cardiovascular Disease; Acute Coronary Syndrome
MeSH terms: Cardiovascular Diseases; Acute Coronary Syndrome
Study type: Interventional

Summary: 
      Percutaneous coronary intervention (PCI) is a common invasive cardiovascular procedure
      performed in the VA with over 13,000 procedures in FY10. Clopidogrel is a critical adjuvant
      therapy following PCI with stent placement and is generally recommended for up to 1 year
      following the procedure. Despite the evidence supporting clopidogrel use, studies both
      outside and within the VA suggest that poor adherence to clopidogrel is common. However,
      prior interventions targeting non-adherence have not specifically focused on clopidogrel
      adherence among PCI patients.

      There are many potential reasons for early clopidogrel discontinuation that involve patient
      and healthcare system factors. Patients reported the following reasons for discontinuing
      clopidogrel within 1 month after drug-eluting stent (DES) implantation: 1) misunderstanding
      the intended treatment duration; 2) conflicting recommendations about intended duration; 3)
      cost of the medication; and 4) patients' own decision to stop. In contrast, patients who
      continued to take clopidogrel reported the following as helpful: 1) communication such as
      letters from their physician; and 2) receiving specific instructions on clopidogrel use.
      These findings suggest that there are specific interventions that can be implemented to
      improve clopidogrel adherence.

      Multi-modal interventions that incorporate frequent follow-up, especially with pharmacists
      and use interactive voice response (IVR) technology have improved medication adherence. IVR
      technology is a computer-based telephone system which initiates calls, receives calls,
      provides information, and collects data from users. IVR is currently a mainstay in the VA
      where patients frequently interact with these automated systems to get clinic appointments
      and/or refill prescriptions. IVR as part of multi-modal interventions have been well received
      by patients, increased adherence to medications (e.g., statins), and improved clinical
      outcomes (e.g., blood pressure, diabetes symptoms, health status). In addition, the
      investigators have successfully used IVR as part of a multi-modal, multi-site intervention
      including pharmacists to improve blood pressure levels among hypertensive patients.
      Accordingly, the investigators have designed the intervention to improve clopidogrel
      adherence that builds on the investigators' prior work and other successful adherence
      interventions from the literature.

      The investigators propose a hybrid effectiveness-implementation study of a multi-faceted
      intervention to improve clopidogrel adherence at VA PCI centers. The investigators will use
      the VA's Cardiovascular Assessment Reporting and Tracking (CART-CL), a uniform cath lab
      procedure reporting tool at all VA cath labs. The intervention consists of 4 components: a)
      an alert from CART-CL will be sent to an inpatient pharmacist prior to discharge that a
      patient has received a stent; b) a pharmacist will bring clopidogrel to the patient's bedside
      prior to hospital discharge as well as educate the patient on the importance of and adherence
      to clopidogrel following PCI; c) interactive voice response (IVR) calls will be made to
      patients prior to the time of clopidogrel refill to remind patients and to facilitate refills
      during follow-up; and d) a Patient Aligned Care Team (PACT) member will contact patients who
      delay filling clopidogrel.
    

Detailed description: 
      I. Hypotheses and Specific Aims

      The main objective is to conduct a type 1 hybrid effectiveness/implementation study to test
      the effectiveness of a successfully-piloted, evidence-based, multi-faceted intervention to
      improve patient adherence to clopidogrel following PCI. The proposed study will test the
      hypothesis that a successfully-piloted, evidence-based, multi-faceted intervention targeting
      Veterans following PCI procedure improves adherence to clopidogrel, reduces bleeding,
      myocardial infarction, stroke, and mortality among these patients, and is cost-effective. The
      proposed intervention will be based on the Chronic Care Model and will build on the
      investigators' pilot work as well as will leverage the VA's CART-CL, a uniform cath lab
      procedure reporting tool at all VA cath labs. The study will be evaluated using the REAIM
      framework consisting of the following components, reach, effectiveness, adoption,
      implementation and maintenance. The intervention will adapt elements of prior successful
      intervention, including patient education, collaboration between cath lab clinicians and
      impatient/outpatient pharmacy teams, and telemonitoring via interactive voice response (IVR)
      technology. This type I hybrid effectiveness/implementation study will be tested at 16 sites
      randomized to intervention with an average of 90 patients per site per 6 month period versus
      usual care.

      Specific Aims:

        1. To evaluate current practices at VA PCI facilities (n=20) to enhance adherence to
           clopidogrel, both at hospital discharge and during longitudinal follow-up.

        2. To implement the multi-faceted intervention at 16 total sites through 4 roll-out phases
           (4 sites during each roll-out) in a randomized stepped wedge trial design.

        3. To assess barriers and facilitators to intervention implementation during each roll-out
           phase through semi-structured interviews and incorporate lessons learned from each
           roll-out phase into subsequent roll-out phases.

        4. To determine the effectiveness of a successfully-piloted, evidence-based, multi-faceted
           intervention versus usual care for improving clopidogrel filling at hospital discharge
           and adherence to clopidogrel (primary outcomes).

        5. To determine the effectiveness of a successfully-piloted, evidence-based, multi-faceted
           intervention versus usual care for reducing the combined cardiovascular endpoints of
           bleeding, myocardial infarction, stroke, and mortality (secondary outcomes).

        6. To assess the incremental cost-effectiveness of the successfully-piloted,
           evidence-based, multi-faceted intervention compared with usual care.

      II. Background and Significance:

      The investigators have successfully piloted the intervention to improve clopidogrel adherence
      following PCI. The investigators developed a software application integrated within CART-CL
      that assessed whether patients fill their clopidogrel prescription at hospital discharge. If
      clopidogrel was not filled, patients were contacted to identify barriers to medication
      filling. During follow-up, automated telephone calls were sent to patients to educate them
      about the importance of medication adherence and to remind them to refill clopidogrel prior
      to the refill due date. The software application successfully identified all 15 patients
      enrolled in the pilot who underwent PCI and whether they filled clopidogrel at hospital
      discharge at 2 VAMCs. In qualitative interviews about the automated calls, all patients
      indicated that the refill reminder messages were helpful. A majority of participants
      indicated that they felt the education/support from the messages or participation in the
      study was helpful or would be helpful to others. A few patients shared that the messages also
      supported refilling other medications and reminding them to ask clarifying questions about
      other medications. Following the successful pilot, the investigators' next step is to test
      the effectiveness of the intervention and study the implementation process across a range of
      VA facilities.

      Building on the prior work and evidence from the literature, the investigators have developed
      the intervention informed by the Chronic Care Model (CCM) which is a framework that uses
      clinical information systems to facilitate evidence-based quality improvement. The
      investigators will leverage CART-CL, IVR technology, patient self-management, and team-based
      care to foster efficient, productive interactions between activated patients and proactive
      clinical teams to improve clopidogrel adherence. Further the components of the intervention
      directly address many of the reasons that patients have highlighted as leading to early
      clopidogrel discontinuation.

      This study will refine the current state of knowledge on improving medication adherence in
      multiple ways. First, it combines multiple interventions that have been separately shown to
      be effective in improving medication adherence and addresses causes of clopidogrel
      non-adherence identified by patients. Second, the intervention focuses on a novel setting
      (i.e., patients discharged following PCI and transitioning to outpatient care) in contrast to
      prior adherence interventions that have focused only on patients with stable chronic diseases
      (e.g., hypertension). Prior work by the investigators' group and others suggest that the
      immediate post-ACS period, and more generally transitions from the inpatient to the
      outpatient setting, are particularly 'vulnerable periods' for medication adherence. Yet prior
      interventions have not specifically targeted this setting. Third, the targeted medication in
      this study has demonstrated short-term benefits and where non-adherence can have immediate
      adverse outcomes (e.g., stent thrombosis). Prior studies have focused on medications (e.g.,
      hypertension medications) where non-adherence leads to problems longer term rather than the
      short term. Fourth, the study utilizes existing resources (i.e., cardiac data systems
      integrated with the VA electronic health record, VA pharmacists and patient-aligned care
      teams) to implement the intervention, improving the feasibility of broader implementation.
      Prior adherence interventions have generally required significant additional resources and
      the majority of quality improvement interventions are not continued following the end of the
      research project. This proposal will extend the current state of knowledge on medication
      adherence by demonstrating that a successful intervention will need multiple evidence-based
      components, and designed with plans for implementation in mind. Finally, this study is being
      conducted as a type I hybrid implementation study and therefore includes extensive study of
      the implementation process, which will yield both contributions to implementation science and
      facilitate wider dissemination if the intervention is found to be effective.

      Furthermore, the study will make two important contributions to implementation science.
      First, the investigators will integrate a structured survey, the organizational readiness to
      change assessment (ORCA), for use in the formative and summative evaluations (described
      further in the evaluation plan). The ORCA has previously been psychometrically validated and
      found to predict implementation effectiveness. However, it has not been previously tested as
      a tool to support implementation. Findings from this study will help us understand if and how
      the ORCA can be used to support other implementation projects, and will contribute to users'
      materials for the survey. Second, the investigators are using an innovative study design, a
      randomized stepped wedge design, and building-in iterative formative evaluation to guide
      implementation of the intervention at sites in subsequent cohorts. As far as the
      investigators know, this kind of iterative rollout design with planned formative evaluation
      has not been used in an effectiveness/implementation hybrid study. If it works as planned,
      and provides useful formative evaluation findings from early cohorts, it may represent an
      important adaptation of the hybrid design.

      In terms of VA patient care, if the intervention is successful, it will increase adherence to
      clopidogrel by helping patients take their anti-platelet medication routinely as prescribed,
      the quality of cardiovascular care for Veterans since adherence to clopidogrel has been
      associated with reductions in cardiovascular morbidity and mortality following PCI, and the
      efficiency of care by using telephone calls and telemonitoring for communication with
      patients rather than clinic visits. This study will leverage the automated pharmacy system
      and tele-monitoring technology for which the VA is a nationally recognized leader. Further,
      the study will address an important gap in knowledge (i.e., how to improve adherence to
      clopidogrel medications following PCI) and the findings can inform future interventions to
      improve adherence to other chronic cardiovascular medications. Finally, since the study is
      designed to be implemented using existing personnel/staff and current national platforms
      (i.e., CART-CL and PACT teamlets), it will be generalizable to other VA Medical Centers and
      Veterans.
    

Intervention name(s): Multifaceted Intervention with pharmacist and IVR
Intervention type(s): Other
Intervention description(s): An alerted inpatient pharmacists will bring the clopidogrel medication to the patient who has received a stent. The patient will return home and receive IVR messages about the importance of their medication as well as a refill reminder call.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research
Keywords: Acute Coronary Syndrome; adherence