João V. Vitola, MD, PhD

Transcription

1 Pharmacologic Stress using A2a Agonist João V. Vitola, MD, PhD Cardiologist and Nuclear Medicine Physician Quanta Diagnostico Nuclear Curitiba - Brazil DISCLOSURES Honorarium Research and Conferences in Nuclear Cardiology BMS, CVT, Astellas International Atomic Energy Agency Royalties Publications in Nuclear Cardiology Springer-Verlag Verlag-Nuclear Cardiology and Correlative Imaging: a teaching file, NY, 2004 Lippincott Williams & Wilkins, - Nuclear Medicine teaching File,, 2009

2 N = 784 J Nucl Cardiol 2007; 14: Regadenoson FDA approved in April 2008

3 Phase 3 Studies: ADVANCE MPI 1 and 2 ADenoscan Versus RegAdenosoN Comparative Evaluation for Myocardial Perfusion Imaging Two phase 3, randomized, double-blind blind studies in patients undergoing stress MPI N=2015 with known or suspected CAD indicated for pharmacologic stress MPI Cerqueira M et al, for the ADVANCE MPI Investigators. JACC: Cardiovasc Imaging

4 WHAT DO WE KNOW IN 2009? REGADENOSON = ADENOSINE IDENTIFY INDIVIDUALS WITH ISCHEMIA QUALITY OF IMAGES SOME POTENTIAL ADVANTAGES TO BE DISCUSSED

5 New Perspectives Bolus administration

6 Regadenoson-induced Blood Flow Time to 2.4-fold above baseline: 33 sec Duration at 2.5-fold above baseline: 2.3 min 3.5 Window for Tracer Uptake mcg regadenoson APV ratio Time (min) Lieu HD, et al. J Nucl Cardiol. 2007;14(4):

7 Bolus Administration Time to 2.4-fold above baseline: 33 sec Speeds Stress Potential for a 2-3 min Stress Test Easier than adenosine pump *** ***

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9 How do patients feel compared to adenosine?

10 84% equal or better

11 New Perspectives Bolus administration Standard dose

12 Standard dose 400 ug independent of body weight Rational Receptor binding = First pass phenomenon Initial experience - works regardless of body weight further evaluation desirable

13 New Perspectives Bolus administration Standard dose Selectivity and low to moderate receptor binding affinity

14 Selectivity Xu Circ 2000

15 ADVANCE MPI Change in Systolic BP from Baseline SBP Change from Baseline, mmhg Decrease by 3 mmhg Decrease by 7 mmhg Time post Dosing* (min) Adenosine Regadenoson * Post-infusion for adenosine and post-bolus for regadenoson Courtesy Dr. Manuel Cerqueira, Cleveland

16 Selectivity A 1 A 2B A 3 A 2A Undesirable effects (eg, AV block) Undesirable effects (eg, bronchospasm) Increase coronary blood flow

17 Selectivity Gao Journal of Pharm Exp Ther 2001

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19 Selectivity A 1 A 2B A 3 A 2A Undesirable effects (eg, AV block) Undesirable effects (eg, bronchospasm) Increase coronary blood flow

20 Perspective to apply in COPD Various types of COPD patients Limited data still needs caution Further studies, larger experience is needed What is the literature showing?

21 Regadenoson in Asthma Randomized, double-blind, blind, crossover trial of 24 mild asthmatics & 24 moderate asthmatics All with a positive response to nebulized adenosine monophosphate (AMP), a validated marker of airway inflammation. Regadenoson was well tolerated Leaker B et al. JNC, 2008

22 Regadenoson in Asthma Leaker B et al. JNC, 2008

23 Pilot Study in COPD patients (n=49) Thomas G et al. JNC 2008

24 Thomas G et al. JNC 2008

25 Thomas G et al. JNC 2008

26 Thomas G et al. JNC 2008

27 Experience in Patients With Bronchoconstrictive Disease Two randomized, double-blind, blind, placebo-controlled, controlled, crossover studies in patients with COPD (N=49) or asthma (N=47) No change in measures of respiratory function up to 2 hours post-dosing No SAEs or termination due to AEs Dyspnea was the most commonly reported AE but was not associated with respiratory deterioration Very promissing but caution needed

28 New Perspectives Bolus administration Standard dose Selectivity and low to moderate receptor binding Special issues Potential to combine with exercise

29 Regadenoson + low level exercise DipEx since 1998 Vitola J et al, J Nucl Cardiol 2001, 8 (6):652-9

30 % of Vasodilator Stress Studies Performed with Exercise (US) 20% 17% 15% 10% 5% 5% 7% 0% G Thomas Adapted from imv Nuclear Medicine Census Market Summary Reports 11-02, 12-03, 7-06

31 Exercise Favored as a Stress Modality Tipo de exame Exercício 70% Dobutamina 1% Combinado 11% Dipiridamol 18% 37.3% of Pharmacologic Stress are combined Stress Exercício cio Dipiridamol Combinado Dobutamina Freqüência Percentual 70,0% 17,8% 11,2% 0,9% Total ,0% Vitola JV et al. Quanta database Curitiba - Brazil

32 Tc-99m-sestamibi Ad-Ex Ad Rest Short Axis Horizontal Long Axis Vertical Long Axis Ad-Ex Ad Rest EK Samady H et al, JNC,;9:

33 The RegEx Trial A Multi-center, Randomized, Double Blind, Placebo- and Active-controlled Trial of the Safety & Effect on Image Quality and Detection of Perfusion Defects in Patients Undergoing Regadenoson Submaximal Exercise Testing vs. Adenosine Supine Exercise Testing, Gregory S. Thomas, Randall C. Thompson, Mahesh P. Shah Michael I. Miyamoto, Tze K. Ip, M Crager, Vandana S. Mathur 1. Thomas et al.. J Nucl Cardiol. May/June 2008 on line 2. Thomas GS, et al. J Nucl Cardiol 2007:14:S109

34 Study Design Double blind, randomized, placebo and active control RegEx AdenoSup Adenosine SPECT MPI Supine position 6 min protocol Regadenoson SPECT MPI Low level exercise n = 39 PlcEx Placebo Low level exercise n = 21

35 Hemodynamics: Heart Rate 120 AdenoSup HR RegEx HR PlcEx HR HR (bpm) Minute AdoSup: mean ± SE; RegEx, PlcEx: LS Mean ± SE

36 Hemodynamics: Systolic BP 160 AdenoSup SBP RegEx SBP PlcEx SBP 150 SBP (mm Hg) Minute AdoSup: mean ± SE; RegEx, PlcEx: LS Mean ± SE

37 Patient Questionnaire Q: How does this compare to the test in which you were lying down? 50 49% Percentage of Patients (%) % 21% ~70% Pts felt better w/ RegEx much better somewhat better about the same 11% somewhat worse 0% much worse

38 Conclusions of the RegEx Trial This pilot trial suggest that it is feasible to add low level exercise to Regadenoson Compared to AdenoSup, RegEx appears to have Greater increase in heart rate Better patient tolerability Fewer adverse effects Improved target to background ratio Improved image quality Trend toward more pts with reversible defects

39 Cortes Tomográficos-Referência Potential for on the fly protocol Eixo Curto Eixo Longo Vertical 30 secs from peak hyperemia Pts on meds Depressed chronotropic response Effects of Max Hyperemia on MPI Sensitivity? Eixo Longo Horizontal

40 Conclusions Regadenoson is similar to adenosine to detect ischemia Regadenoson has the advantage of bolus administration and less side effects than adenosine Potential for utilization in patients with bronchospasm Potential for combination with exercise FDA approved in 2008 Will cost allow wide spread utilization?

41 Thank you