1. How Do We Incorporate Patient Perspectives Into Clinical Trial Design?
Megan Coylewright, MD MPH
Interventional Cardiology
Associate Director of Structural Heart Disease Program
Heart and Vascular Center
Dartmouth-Hitchcock Medical Center

2. Disclosure Statement of Financial Interest
Megan Coylewright, MD MPH
Interventional Cardiology
Associate Director of Structural Heart Disease Program
Heart and Vascular Center
Dartmouth-Hitchcock Medical Center
I have spoken on shared decision making for Boston Scientific and Edwards LifeSciences.
Disclosure Statement of Financial Interest

4. 55 year old man, forester and downhill skier
PCI in 2009
Excessive nuisance bleeding on aspirin and apixaban
No longer taking aspirin
Advised not to ski
CHA2DS2VASc: 3, CHADS2: 2, HAS BLED: 1

7. Preference-sensitive
More than one reasonable option exists
Uncertainty exists in evidence
Patient preferences vary (i.e. geographically) or are distinct from healthcare professional preferences

8. “Persistence” is low
Prior studies: 20-50% discontinuation rates (ATRIA study, General Practice Research Database)
Orbit AF: 17% warfarin discontinuation
VA: NOACs better
At one year, 63% vs 39%
Prior studies: 20-50% discontinuation rates (ATRIA study, General Practice Research Database)
Orbit AF: prospective registry
At one year, warfarin 17% discontinuation rate
Physician preference 48%
Patient refusal 21%
VA study: warfarin vs dabigatran
At one year, 63% vs 39%
O’Brien, Peterson, et al. Am Heart J 2014; Zalesak et al. Circ Qual and Outcomes 2013

9. Even with NOACs, adherence low
More than half of patients on a NOAC missed their dose at least 20% of the time…and this predicts poor outcomes
Less than half of patients on a NOAC took their medication more than 80% of the time
BACKGROUND:
In comparison to warfarin, non-vitamin K antagonist oral anticoagulants (NOACs) have the advantages of ease of dosing, fewer drug interactions, and lack of need for ongoing monitoring. We sought to evaluate whether these advantages translate to improved adherence and whether adherence is associated with improved outcomes in patients with atrial fibrillation.
METHODS AND RESULTS:
We performed a retrospective cohort analysis by using a large US commercial insurance database to identify 64 661 patients with atrial fibrillation who initiated warfarin, dabigatran, rivaroxaban, or apixaban treatment between November 1, 2010, and December 31, During a median of 1.1 y of follow-up, 47.5% of NOAC patients had a proportion of days covered of ≥80%, compared with 40.2% in warfarin patients (P<0.001). Patients with CHA2DS2-VASc (risk based on the presence of congestive heart failure, hypertension age y, age ≥75 y, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, sex category) score ≥4 were at increased risk of stroke when they were not taking anticoagulation ≥1 month versus <1 week (1-3 months: hazard ratio [HR] 1.96, 3-6 months: HR 2.64, ≥6 months: HR 3.66; all P<0.001). Patients with CHA2DS2-VASc score 2 or 3 were at increased risk of stroke when they were not taking anticoagulation ≥6 months (HR 2.73, P<0.001). In these patients with CHA2DS2-VASc score ≥2, nonadherence was not associated with intracranial hemorrhage. Among patients with CHA2DS2-VASc score 0 or 1, time not taking anticoagulation was not associated with stroke, but not taking anticoagulation ≥3 months was associated with a significant reduction of bleeding.
CONCLUSIONS:
Adherence to anticoagulation is poor in practice and may be modestly improved with NOACs. Adherence to therapy appears to be most important in patients with CHA2DS2-VASc score ≥2, whereas the benefits of anticoagulation may not outweigh the harms in patients with CHA2DS2-VASc score 0 or 1.
Yao, Noseworthy, et al. J Am Heart Assoc 2016

11. FDA focuses on patient preferences
“Benefit/risk guidance”
Tolerance of risk and weighing of benefit
Premarket approval applications or de novo submissions
Patient preference information (PPI)
Recommendation, not requirement

12. Study design Prioritizing the question
Selecting primary and secondary endpoints
Defining clinically meaningful differences
Identifying subgroup analysis

13. …even if it did reduce stroke by 1-2%, this benefit would be balanced
by the 2-3% complication rate of implant.
Dr. John Mandrola

14. Controversy
Procedural complications
Disabling stroke

15. Holmes et al. JACC 2014

16. Reddy et al. Circ 2013

17. Controversy
Procedural complications
Disabling stroke

18. Groff AC et al. N Engl J Med 2016.

19. Groff AC et al. N Engl J Med 2016.
Days Spent at Home.
Mean Number of Days Spent at Home in the Last 6 Months of Life, by Hospital Referral Region, for Medicare Beneficiaries Who Died in 2012 or 2013. Sample sizes for regions shown in gray were below the Centers for Medicare and Medicaid Services minimum requirement for data reporting.
Groff AC et al. N Engl J Med 2016.

20. Disabling stroke or death.
Absolute risk reduction 2.3
per 100 patient-years
(RR reduction of 64%)
Reddy et al. Circ 2013

24. Preference-sensitive
More than one reasonable option exists
Uncertainty exists in evidence
Patient preferences vary (i.e. geographically) or are distinct from healthcare professional preferences

25. HealthDecision.org