Incorporating KT Concepts within Clinical Trials The RELY-ABLE Trial as an Example Stuart Connolly & Robby Nieuwlaat
Background - Dabigatran RE-LY Atrial fibrillation (AF) patients at high risk for stroke Randomized comparison 2 doses of dabigatran with warfarin 18,113 patients among 967 sites in 44 countries Study close-out December 2008 to March 2009 Many patients satisfied with taking dabigatran RELY-ABLE Offer patients on dabigatran to continue treatment Extended safety and efficacy data for 2 doses of dabigatran
Background - KT Total care for AF patients Most AF patients have 1 other cardiovascular problem Better management of AF and associated diseases can improve prognosis Multiple extensive guidelines difficult to integrate for care of complex patients RELY-ABLE High-risk AF patients Detailed patient data available Large number of centers: cluster randomization Large number of patients: test effect on outcomes
Aims of RELY-ABLE Dabigatran To collect extended safety and efficacy data for 2 doses of dabigatran for future clinical use Knowledge Translation To test whether a multifaceted KT intervention, that targets the total care of AF patients, can improve patient outcomes
Dabigatran etexilate 110mg bid RE-LY Documented AF Risk factor(s) for vascular events No exclusion criteria for RE-LY R Dabigatran etexilate 150mg bid Warfarin Mean follow-up 24 months End of RE-LY RELY-ABLE Patients who completed RE-LY on Dabigatran No exclusion criteria for RELY-ABLE RE-LY randomization maintained Dabigatran etexilate 110mg bid Dabigatran etexilate 150mg bid Clinical site randomization R Knowledge translation No Knowledge translation Mean follow-up for Dabigatran and Knowledge translation 24 months
KT Treatment Targets (1) Targets based on recent international guidelines (AHA, ACC, ADA, ESC, ESH) Hypertensives: average of last 3 SBP values <140 mmhg + Diabetes: <130 mmhg Diabetics: HbA1c <7% LDL-cholesterol: Smokers: <70 mg/dl (2.0 mmol/l) for high-risk <100 mg/dl (2.5 mmol/l) for moderate risk stop smoking
KT Treatment Targets (2) Rate control: heart rate <100 bpm in AF No CAD/stroke: stop ASA No SR in past year: stop AAD Systolic heart failure: prescribe ACEi/ARB + beta blocker Heart failure NYHA = 1: stop spironolactone
KT intervention Multifaceted KT intervention incorporating: 1. Patient-specific feedback letters to patient and physician in advance of each RELY-ABLE visit, to encourage interaction 2. Periodical feedback report cards on center performance, to encourage practice evaluation 3. Use of computer-assisted decision support to generate letters and report cards KT intervention targets management issues for which guideline recommendations are not met Opportunities to improve the total care for AF patients
Sample Patient Feedback Letter Page 1
Sample Patient Feedback Letter Page 2
RELY-ABLE Baseline Data
Number of centers Center Participation Total = 596
Number of patients Patient Participation Total = 5890
Number of patients Non-achievement of Targets - Prevention N=314 5% N=704 20% N=1214 50% N=560 47% N=434 32% N=83 44% SBP DM- SBP DM+ LDL High LDL moderate DM HbA1c Smoking
Non-achievement of Targets AF control Number of patients N=362 38% N=36 6% Rate control <100bpm AAD & no sinus rhythm in past year
Number of patients Non-achievement of Targets Drugs N=365 10% N=270 55% N=332 67% N=36 15% No CAD/stroke & no ASA HF & ACEi/ARB HF & BB HF NYHA=1 & no spironolactone
RELY-ABLE KT - Summary 5890 AF patients on dabigatran in 35 countries among 596 centers -> 301 centers randomized to KT Overall 4710 opportunities to improve total care of AF patients KT intervention: patient-specific audit & feedback to physician and patient, computer assistance and physician report cards Primary aim: improvement in patient outcomes KT intervention will enforce patients to get involved in their care and assist physicians to achieve targets for total AF care