BACKGROUND/RATIONALE:
Anticoagulants and antiplatelets are commonly prescribed in combination to older veterans for secondary cardioprophylaxis (i.e. complex antithrombotic therapy, CAT). These agents are independently associated with clinically significant upper gastrointestinal events (UGIE), such as bleeding and perforation from ulcers of the stomach and duodenum, the magnitude of which remains unknown. Furthermore, little is known regarding preferences of elderly veterans for the risk-benefit of CAT strategies. To provide a basis for individualization of CAT strategies, we quantified national CAT-related bleeding events (i.e., UGIE, lower GI events [LGIE], transfusions and hospitalizations) and assessed preferences of elderly cardiac veterans when patient preference for risk aversion, cardiovascular benefit and medication benefit was explicitly considered. We then assessed how preference-elicitation influenced patient CAT adherence.

OBJECTIVE(S):
1- To quantify CAT-related UGIE, LGIE, transfusions, and hospitalizations among a large cohort of elderly cardiac veterans.
2- To elicit preferences for CAT strategies among older cardiovascular patients.
3- To explore how preference elicitation influenced 1-year medication adherence.


METHODS:
To quantify CAT-related bleeding events (i.e., UGIE, LGIE, transfusions and hospitalizations), we conducted a retrospective cohort study among elderly veterans prescribed a CAT strategy, using medical and pharmacy data from a merged VA-Medicare dataset from 10/01/02-09/30/08. A time-dependent analysis assessed the risks associated with CAT strategies.

Adaptive conjoint analysis (ACA) was used to define patient preferences for CAT strategies considering trade-offs for UGIE (as quantified in the first specific aim), cardiovascular benefits and medication strategy attributes (i.e., complexity of administration, need for follow-up, etc). Elderly multi-morbid cardiovascular patients from two VAMC sites (Houston and Connecticut) completed the interactive ACA computer survey. Previously obtained qualitative data regarding patient perceptions of CAT risks-benefits, burden of self-management and risk communication was used to create the ACA survey. VA pharmacy data, was used to assess each patient's adherence to their CAT strategy prior to and 1 year following preference elicitation. The post-ACA prescription strategy was categorized as concordant or discordant with the patient's elicited preferences and adherence assessed based on these strata.

FINDINGS/RESULTS:
Specific Aim #1: CAT-related bleeding events are a significant and clinically relevant risk. The incidence rates for UGIE, transfusions, and hospitalizations were greatest with triple therapy (TRIP; i.e. anticoagulant, antiplatelet and aspirin) at 27.6/1000 PY (95% CI: 24.8-30.6), 73.9/1000 PY (95% CI: 69.1-79.0), 118.3/1000 PY (95% CI: 112.1-124.8) and 800.8/1000 PY (95% CI: 773.3-829.1). Adjusted models revealed a 40-60% increased UGIE risk associated with CAT; a 30% increased LGIE risk with anticoagulant and antiplatelet dual therapy; a 3- to 6-fold increased risk in transfusions associated with CAT; and 30% increased risk of hospitalization associated with dual therapy and a 40% increase in risk with triple therapy.

Specific Aim #2: Participants (N=201) preferred to maximize cardiovascular benefit (reduced 5-year risk of MI and CVA) while minimizing potential CAT-related adverse events (intracranial hemorrhage and upper GI bleeding risk). There was little variation regarding dominant preferences after Monte-Carlo simulations. Alterations in lifestyle (i.e., changes in physical activity), nuisance side-effects (i.e., stomach discomfort) and complexity of CAT regimen (i.e., dual vs. triple CAT therapy with or without a gastroprotective agent) were important, but less so, than risk-benefit attributes. Rank order of the relative importances differed slightly by age. Among respondents 60-69 years, prevention of MI and CVA had greater relative importance than avoidance of neurologic (intracerebral hemorrhage [ICH} or CVA) or UGIE complications. Those aged 70-79 years valued CVA risk prevention more than MI risk prevention. The eldest respondents (80 years and older) showed increasing concern regarding neurologically induced incapacity with dominant preferences for reduction of CVA and ICH risk. Among all ages, prevention of UGIE was viewed as important, but its relative importance ranked after CV benefit and before the burden of medication self-management.

A 15% increase in medication adherence was observed in patients prescribed a preference-concordant CAT strategy and a 6% increase in adherence was observed in patients prescribed a preference-discordant strategy. Qualitative analysis of exit interviews (n=56) suggested preference elicitation contributed to enhanced cognitive engagement, awareness and activation of patients to discuss CAT preferences with their physicians.


IMPACT:
This project fills three fundamental gaps in our knowledge: 1) quantification of the real-life risk of CAT-associated events (i.e., UGIE, LGIE, hospitalization and transfusion) among elderly veterans; 2) quantification of how patients trade-off between the potential cardioprotective benefit of CAT and the risk of UGIE; and most importantly, 3) how preferences influence medication adherence in a longitudinal fashion.
Our results reveal CAT-related bleeding events, including UGIE, LGIE, transfusions and hospitalizations, are a clinically relevant risk. VA providers should be cognizant of the magnitude of bleeding risk and counsel elderly veterans accordingly. The preference data suggested there was little variation among elderly veterans' dominant preferences- lowering CV risk was valued more strongly than UGIE bleeding aversion. However, the oldest elderly patients focus more on preserving function over survival.
Pharmacoepidemiology data demonstrated a 20% improvement in CAT adherence among patients prescribed a preference-concordant strategy, and a 6% improvement among the preference-discordant group. We hypothesize preference elicitation served as an "educational moment" for patients; by working through trade-offs, patients actively engaged in clarifying their preferences, explicitly learning about risks and benefits and the burden of CAT self-management. We further hypothesize the ACA task improved adherence through behavioral and perceptual mediators, including 1) enhanced patient cognitive engagement and activation, 2) patient reassurance with prescribed goals of therapy, and 3) enhanced "buy-in" regarding the prescription decision that exceeded their pre-survey perception.
The promotion of shared-decision making and patient-centered care is fundamental to the Department of Veterans Affairs. We have shown preference-elicitation, active patient engagement in decision-making, improvement of patient education regarding risks-benefits and veteran empowerment to voice concerns and desires regarding CAT-related outcomes positively impacts subsequent CAT medication adherence. We plan to use our results to develop educational and behavioral tools to educate and support patients in the process of making medication decisions in the ambulatory care setting.

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External Links for this Project

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PUBLICATIONS:

Journal Articles

1. Makris UE, Kohler MJ, Fraenkel L. Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. The Journal of rheumatology. 2010 Jun 1; 37(6):1236-43. [view]
2. Abraham NS, Naik AD, Street RL, Castillo DL, Deswal A, Richardson PA, Hartman CM, Shelton G, Fraenkel L. Complex antithrombotic therapy: determinants of patient preference and impact on medication adherence. Patient preference and adherence. 2015 Nov 19; 9(1):1657-68. [view]
3. Fraenkel L. Feasibility of Using Modified Adaptive Conjoint Analysis Importance Questions. The patient. 2010 Jan 1; 3(4):209-215. [view]
4. Naik AD, Street RL, Castillo D, Abraham NS. Health literacy and decision making styles for complex antithrombotic therapy among older multimorbid adults. Patient education and counseling. 2011 Dec 1; 85(3):499-504. [view]
5. Abraham NS. Prescribing proton pump inhibitor and clopidogrel together: current state of recommendations. Current Opinion in Gastroenterology. 2011 Oct 1; 27(6):558-64. [view]
6. Abraham NS. Proton pump inhibitors: potential adverse effects. Current Opinion in Gastroenterology. 2012 Nov 1; 28(6):615-20. [view]
7. Abraham NS, Naik AD, Street RL. Shared decision making in GI clinic to improve patient adherence. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2012 Aug 1; 10(8):825-7. [view]
8. Andreas DC, Abraham NS, Naik AD, Street RL, Sharf BF. Understanding risk communication through patient narratives about complex antithrombotic therapies. Qualitative Health Research. 2010 Aug 1; 20(8):1155-65. [view]
9. Constantinescu F, Goucher S, Weinstein A, Smith W, Fraenkel L. Understanding why rheumatoid arthritis patient treatment preferences differ by race. Arthritis Rheum. 2009 Apr 15; 61(4):413-8. [view]

Center Products

1. Abraham NS. How to manage antiplatelet therapy in the peri-endoscopic period. ACG Education Universe Annual Postgraduate Course [Online PowerPoint slide presentation]. 2011 Oct 29. [view]

VA Cyberseminars

1. Abraham NS. Management of PPIs and antiplatelet agents. ACG Education Universe. [Cyberseminar]. 2012 Oct 20. [view]

Conference Presentations

1. Abraham NS. Antiplatelet therapy and the endoscopist. Paper presented at: Digestive Disease Week Annual Meeting; 2012 May 20; San Diego, CA. [view]
2. Abraham NS. Antiplatelets, ASA and anticoagulants: Balancing risks and benefits. Paper presented at: Digestive Disease Week Combined Clinical Annual Symposia; 2010 May 5; New Orleans, LA. [view]
3. Abraham NS, Naik AD, Richardson PA, Hartman C. Complex antithrombotic therapy (CAT) and national risk of upper gastrointestinal bleeding (UGIB), lower gastrointestinal bleeding (LGIB), transfusions and hospitalizations. Poster session presented at: Digestive Disease Week Annual Meeting; 2012 May 19; San Diego, CA. [view]
4. Abraham NS, Naik AD, Richardson P, Hartman C. Complex Antithrombotic Therapy (CAT) and the Risk of Upper Gastrointestinal Events (UGIE) among vulnerable elders. Poster session presented at: Digestive Disease Week Annual Meeting; 2009 May 30; Chicago, IL. [view]
5. Abraham NS. How to manage antiplatelet therapy in the peri-endoscopic period. Presented at: American College of Gastroenterology Annual Meeting; 2011 Oct 29; Washington, DC. [view]
6. Abraham NS. Management of PPIs and antiplatelet agents. Presented at: American College of Gastroenterology Annual Meeting; 2012 Oct 20; Las Vegas, NV. [view]
7. Abraham NS. Managing antiplatelets and anticoagulants in the peri-endoscopic period. Presented at: American College of Gastroenterology Midwest Regional Meeting; 2012 Aug 15; Indianapolis, IN. [view]
8. Abraham NS. Reducing the gastrointestinal risks of combined antiplatelet and NSAID agents. Paper presented at: North Carolina Society of Gastroenterology Annual Meeting; 2010 Feb 26; Pinehurst, NC. [view]
9. Abraham NS. Shared decision making for cardioprotective drug prescription among older adults. Poster session presented at: United European Gastroenterology Week Medical Congress; 2010 Oct 24; Barcelona, Spain. [view]
10. Abraham NS. State of the Art Lecture: PPI and clopidogrel interaction-fact or fiction? and, Controversies in GI Bleeding. Paper presented at: Post-Digestive Disease Week / GI Society Conference; 2010 Jul 24; Dana Point, CA. [view]
11. Abraham NS. The management of patients on an antithrombotic who requires endoscopy. Presented at: Digestive Disease Week / American Gastroenterological Association Annual Conference; 2011 May 8; Chicago, IL. [view]

DRA: Aging, Older Veterans' Health and Care, Health Systems, Cardiovascular Disease
DRE: Treatment - Observational
Keywords: Chronic disease (other & unspecified), Outcomes, Patient preferences
MeSH Terms: none