Clinical trial NCT02694185: Secondary Event Prevention Using Population Risk Management After PCI and for Anti-Rheumatic Medications
Official title: Secondary Event Prevention Using Population Risk Management After PCI
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Myocardial Ischemia
Rheumatic Diseases
Keywords: Medication Adherence
Randomized Controlled Trial
Veterans
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2016-02-29
Enrollment: 5269
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Ischemic heart disease (IHD) and its treatment carry profound public health and economic implications. Among Veterans, IHD represents one of the most common causes of death and disability, with over 500,000 affected individuals' annually. Rheumatic disease, though far less common than IHD can affect multiple organ systems and requires therapies costing in excess of $50,000 a year. Optimal treatment of Veterans with IHD and rheumatic disease requires a number of medications to maintain or improve health. Not taking medications as prescribed, however, is common and increases the risk of subsequent adverse events (cardiac death and myocardial infarction \[MI\]).

To improve medication adherence rates and the cardiac health of Veterans with IHD, the investigators propose to test a medication adherence intervention. Known as VA SEPPRMACI-ARM (Secondary Event Prevention using Population Risk Management After PCI and for Anti-Rheumatic Medications), this intervention will consist of: proactive real-time adherence monitoring of patients and targeting of individuals if they have not refilled their medication a given number of days after it was due for refill. The intervention will employ a tailored, escalating-intensity approach which begins with some combination of personalized short messaging service (SMS) text messages and interactive voice response (IVR) telephone technology, depending on patient preference. Patients not completing SMS and then IVR by not refilling their medication (or declining SMS and not completing IVR) escalate to a trained research interventionalist. The interventionalist will contact the patient and address adherence barriers based on the dimensions outlined by the World Health Organization (WHO) that are specific to each patient. The investigators will test the intervention on IHD patients who have recently undergone PCI-a cardiac procedure commonly used among IHD patients to improve the heart's blood flow and in patients starting anti-rheumatic medication. The investigators will test the intervention at four VA Cardiac Catheterization Laboratories (CCLs) and have 12 sites serving as usual care controls.

Detailed description: Ischemic heart disease (IHD) and rheumatic diseases are both pervasive, expensive, and results in grave health consequences. IHD affects an estimated 15.4 million Americans 20 years of age-representing 6.4% of the adult population. The direct and indirect cost of IHD has been estimated at $195.2 billion, with a doubling of cost projected by 2030.5 Similarly, the direct cost to the U.S. workforce for rheumatoid arthritis alone approaches $5.8 billion yearly.

Widely-accepted national evidence-based guidelines support the use of cardio-protective medications to reduce the risk of adverse consequences resulting from IHD and disease modifying anti-rheumatic medications (DMARDs) to reduce the risk of adverse consequence in rheumatic diseases. For example, numerous rigorously conducted randomized trials show that statins improve outcomes and reduce mortality in patients with established cardiovascular disease (i.e., secondary prevention), including those undergoing percutaneous coronary interventions (PCI). The use of statins and beta-blockers have been repeatedly demonstrated to be cost-effective in lowering cardiovascular event (CVE) rates, in part by their effects on cholesterol, and blood pressure, respectively. Accordingly, the most recent VA performance measures and American Heart Association guidelines encourage the use of statins in patients with atherosclerotic disease; beta-blockers in subjects with left ventricular systolic dysfunction (ejection fraction less than 40%), prior MI, or blood pressure of 140/90 or greater; and clopidogrel following any acute coronary syndrome (ACS) or PCI with stent. The rheumatology literature provides similar evidence for the benefit of DMARDs in rheumatic diseases, and guidelines strongly endorse their use.

Unfortunately, non-adherence to medications is common, and increases the risk of poor outcomes. The investigators' 2011 national preliminary data from VA cardiac catheterization laboratories (CCLs) demonstrate that over 6300 patients experienced at least one refill gap of \>= 7 days for statins in the year following PCI. The mean proportion of days covered (PDC) for these patients was only 75%-below the PDC threshold of 80% that typical defines adherent patients, based on the empiric evidence for effectiveness of medications at this cut-point. Non-adherent patients were present at all CCLs without substantial variation in mean PDC by center, suggesting a global problem.

Systematic problems underlie and contribute to non-adherence to medications. Usual care of IHD and rheumatic disease patients is encumbered by systematic deficiencies including: passive monitoring (contact with patients only when initiated by the patient) and inefficiency (time-consuming patient-by-patient approach, rather than through population management). The proposed intervention addresses both the complex patient-specific factors (emphasizing forgetfulness and carelessness) and the systematic inadequacies using a multi-modal, escalating approach.

Objectives

1. To assess the effectiveness of a multi-faceted patient-centered intervention versus usual care in improving medication adherence as measured by proportion of days covered (PDC, primary outcome). This will be tested among IHD patients for statins, beta-blockers and clopidogrel in the year after PCI and among rheumatology clinic patients chronically prescribed DMARDs. Hypothesis: The PDC for patients in the intervention arm will exceed the PDC for the usual care arm by a 10% absolute difference.
2. (Secondary outcome): To determine the effectiveness of a multi-faceted patient-centered intervention versus usual care in reducing secondary CVEs (myocardial infarction \[MI\], repeat revascularization \[PCI or coronary bypass graft\], and all-cause mortality) among IHD patients at 18 months post-PCI and progressive erosive disease demonstrated on plain film radiographs in patients with rheumatic diseases (i.e. "radiographic progression"). Hypothesis: The rate of CVEs and radiographic progression will be 5% relatively lower for patients in the intervention arm compared with usual care.
3. (Secondary outcome): To establish the cost to implement and maintain the intervention, above the cost of usual care, as well as the incremental cost effectiveness (ICE; e.g. cost to achieve at 10% improvement in PDC; cost per CVE prevented). Hypothesis: This aim does not posit a hypothesis as the objective is descriptive. The available funding for this project limits this outcome to IHD patients (no rheumatic disease patients will be analyzed according to cost).

Eligibility criteria: Inclusion Criteria:

Patients will qualify for inclusion if they:

1. Undergo PCI or are prescribed a DMARD.
2. Are prescribed any of the following medications:

   \[for the IHD intervention\]
   * Statin
   * Beta-blocker
   * Thienopyridines (dual platelet inhibitors)

   \[for the DMARD intervention\]
   * Oral methotrexate
   * Sulfasalazine
   * Azathioprine
   * Leflunomide
   * Tofacitinib
   * Hydroxychloroquine \[Note: as a study focused on adherence, the investigators will NOT address the appropriateness of prescribed medications, which is an important, but separate issue\]
3. Receive their care from the VA. This is defined by the presence of a VA-assigned-PCP in the year prior to PCI or in the year following PCI (IHD intervention) or in the year prior to or following index DMARD prescription (rheumatic disease intervention).

Exclusion Criteria:

Patients will be excluded under the following circumstances:

* Undergoing only diagnostic (non-interventional) catheterization
* Receive their index medicines (listed in item above) from a non-VA source
* Discharge to nursing home or skilled nursing facility
* Individuals with impaired decision making capacity
* Prisoners
* Pregnant women
* The terminally ill

Primary outcomes:
measure: Proportion of Days Covered (PDC)
timeFrame: 1 year
Secondary outcomes:
measure: Cardiovascular Events (CVE)
timeFrame: 1 year
measure: Incremental Cost Effectiveness (ICE)
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco VA Medical Center, San Francisco, CA
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center, Aurora, CO
state: Colorado
city: Baltimore
country: United States
facility: Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
state: Maryland
city: Durham
country: United States
facility: Durham VA Medical Center, Durham, NC
state: North Carolina
city: San Juan
country: Puerto Rico
facility: VA Caribbean Healthcare System, San Juan, PR
Study officials:
affiliation: Rocky Mountain Regional VA Medical Center, Aurora, CO
name: Liron Caplan, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Raghavan S, Liu WG, Michael Ho P, Plomondon ME, Baron AE, Caplan L, Joynt Maddox KE, Magid D, Saxon DR, Voils CI, Bradley SM, Maddox TM. Coronary artery disease severity modifies associations between glycemic control and both mortality and myocardial infarction. J Diabetes Complications. 2018 May;32(5):480-487. doi: 10.1016/j.jdiacomp.2018.01.010. Epub 2018 Jan 31.
citation: Baker JF, Sauer B, Teng CC, George M, Cannon GW, Ibrahim S, Cannella A, England BR, Michaud K, Caplan L, Davis LA, O'Dell J, Mikuls TR. Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis Is Associated With Changes in Blood Pressure. J Clin Rheumatol. 2018 Jun;24(4):203-209. doi: 10.1097/RHU.0000000000000736.
citation: Yazdany J, Caplan L, Fitzgerald J, Schmajuk G. Editorial: The Evolving Art and Science of American College of Rheumatology Guidelines. Arthritis Rheumatol. 2019 Jan;71(1):2-4. doi: 10.1002/art.40725. Epub 2018 Nov 30. No abstract available.
citation: McCulley CB, Barton JL, Cannon GW, Sauer BC, Teng CC, George MD, Caplan L, England BR, Mikuls TR, Baker JF. Body mass index and persistence of conventional DMARDs and TNF inhibitors in rheumatoid arthritis. Clin Exp Rheumatol. 2019 May-Jun;37(3):422-428. Epub 2018 Nov 7.
citation: Hirsh J, Wood P, Keniston A, Boyle D, Quinzanos I, Caplan L, Davis L. Universal Health Literacy Precautions Are Associated With a Significant Increase in Medication Adherence in Vulnerable Rheumatology Patients. ACR Open Rheumatol. 2020 Feb;2(2):110-118. doi: 10.1002/acr2.11108. Epub 2020 Jan 19.
citation: Raghavan S, Liu WG, Berkowitz SA, Baron AE, Plomondon ME, Maddox TM, Reusch JEB, Ho PM, Caplan L. Association of Glycemic Control Trajectory with Short-Term Mortality in Diabetes Patients with High Cardiovascular Risk: a Joint Latent Class Modeling Study. J Gen Intern Med. 2020 Aug;35(8):2266-2273. doi: 10.1007/s11606-020-05848-5. Epub 2020 Apr 24.
citation: Daniel CM, Davila L, Makris UE, Mayo H, Caplan L, Davis L, Solow EB. Ethnic Disparities in Atherosclerotic Cardiovascular Disease Incidence and Prevalence Among Rheumatoid Arthritis Patients in the United States: a Systematic Review. ACR Open Rheumatol. 2020 Sep;2(9):525-532. doi: 10.1002/acr2.11170. Epub 2020 Sep 1.