Polypill in the Management of Secondary Preven6on in La6n America: A Look at the Future

Transcription

1 Polypill in the Management of Secondary Preven6on in La6n America: A Look at the Future Alvaro Sosa Liprandi MD, MTSAC, FACC Head of Cardiology. Sanatorio Güemes, Buenos Aires. Argentina Director. Lezica Cardiovascular Institute, San Isidro. Argentina Director. Instituto Cardiovascular Austral, Ushuaia Director. Idea Médica, Research & Education Director. Post Graduated Medical School in Cardiology. Buenos Aires University

2 No drugs One drug Two drugs 3-4 drugs TOTAL 0 High Medium Low Very Low PURE study, N= ; 17 countries; IHD= 5650 Yusuf et al, Lancet 2011

3 The care gap Secondary Prevention

4 Time to Major cardiac Event by Adherence Levels Bansilal S et al. JACC 2016; 68:

5 Medica6on Non-Adherence America s another drug problem 13% of the total US healthcare expenditure! 45% of US popula6on

6 Factors Reported to Affect Adherence Social and economic Health care system Condition related Patient Related Therapy related Social and economic Health care system Condi6on related Educa6on level Social Support Living condi6ons Insurance Medica6on cost Access Cost Co-payments Poor Access Long wait 6mes Discon6nuity of care Chronic condi6on Lack of symptoms Depression Psychological disorders

7 Factors Reported to Affect Adherence Pa6ents related Therapy related Physical factors (cogni6ve level) Phycological factors Informa6on Mo6va6on Alcohol/Substances abuse Complexity of medica6ons (N and techniques) Dura6on Changes in regimen Side effects No percep6on of benefit

8 Improving medica6on adherence. Simplifica6on of treatment: Polypill

9 Improving medica6on adherence. Simplifica6on of treatment: Polypill Wald NJ, Law MR BMJ 2003

10 Improving medica6on adherence. Simplifica6on of treatment: Polypill The Indian Polycap Study (TIPS) Lancet, 2009

11 Improving medica6on adherence. Simplifica6on of treatment: Polypill The Indian Polycap Study (TIPS) Lancet, 2009

12 Improving medica6on adherence. Simplifica6on of treatment: Polypill The Indian Polycap Study (TIPS) Lancet, 2009

13 Space Program: Results RCTs USING A POLYPILL TO STUDY THE EFFECT ON ADHERENCE Kanyini GAP IMPACT UMPIRE Control Polypill 0 Control Polypill 0 Control Polypill Median Follow Up: 18 months n=623 Primary + Secondary Self reported no. of days medica6on was taken in the preceding week Patel et al. European Journal of Preven1ve Cardiology, 2014 Median Follow Up: 12 months n=497 Primary Self Reported names and dosages of all prescrip6on and OCD currently being taken. Selak et al. BMJ (Published 27 May 2014) Median Follow Up: 15 months n=2004 Primary + Secondary Self reported no. of days medica6on was taken in the preceding week Thom S, et al. JAMA 2013;310:

14 SPACE Program: Results Primary Endpoints Adherence awer 1 Year UMPIRE: n= 2002, India & Europe Kanyini-GAP: n=623 Australia IMPACT: n=513 en New Zealand Control Polypill Risk Ra6o (95% CI) P value Kanyini-GAP (1) 96/249 (38.6%) 196/249 (78.7%) 2.04 (1.72,2.42) <0.01 IMPACT (2) 106/218 (48.6%) 172/233 (73.8%) 1.52 (1.30,1.78) <0.01 UMPIRE (3) 602/925 (65.1%) 827/935 (88.4%) 1.36 (1.29, 1.43) <0.01 Overall 1.58 (1.32, 1.90) <0.01 1/4 Control 1 Polypill 4 Beber Beber 1. Patel et al. European Journal of Preven1ve Cardiology, Selak et al. BMJ (Published 27 May 2014) 3. Thom S, et al. JAMA 2013;310:

15 Fixed-dOse Combina6on DrUg for Secondary Cardiovascular Preven6on. Phase II Study Study Sites 64 Clinical Sites in Spain, Italy, Argentina, Brazil and Paraguay (outpatients clinics and hospital-based clinic sites)

16 PROJECT OVERVIEW Phase 1 Phase R Phase 1: Observa6onal ü To determine the propor6on of post-mi pa6ents receiving appropriate secondary preven6on ü To es6mate the level of pa6ent adherence ü To iden6fy factors that contribute to poor adherence. ü Morisky Green: Assessment of adherence * Fuster-Sanz 3 drugs separately 9 months CNIC-FS*-FERRER TRINOMIA Aspirin 100 Ramipril 2, Simvasta6n 40 Adherence- Visit+ MG + Pill Count Phase 2: Prospec6ve RCT ü To compare adherence to treatment in post MI pa6ents receiving a FDC vs. those with conven6onal treatment (3 drugs provided separately) ü Primary Endpoint: Adherence measured by Morisky-Green and Pill Count combined ü To evaluate the effect of TRINOMIA on BP and LDL-C ü Safety and tolerability of TRINOMIA

17 FOCUS Phase 1 Results MORISKY GREEN: EVALUATION OF ADHERENCE (N=2118) Paraguay Brazil Argenhna America 17,7 30,1 36,4 40 Spain Italy Europe 49,3 50,3 49,8 Global 45, % adherent (Original Morisky-Green = 20)

18 FOCUS Phase 1 Results FACTORS THAT INFLUENCE ADHERENCE Pahent characterishcs Clinical: ü AMI date** ü AMI locahon ü History of CHF ü History of angina ü > 10 Pills* ü Complexity of treatment* Sociodemographic: ü Age** ü Sex ü Socioeconomic status ü Illiteracy* ü Educahonal level ü Occupahonal history ü Distance from medical centre** Risk factors: ü Diabetes ü BMI* ü Hypertension ü Lipid levels ü Smoking** ü Sedentary** ü Family history Psychosocial factors: ü Depression** (PHQ-9) ü Social support** *p<0.05 **p<0.001

19 FOCUS Phase 2 Results POLYPILL VS. CONTROL AFTER 9 MONTHS EFFECT ON ADHERENCE 80 MORISKY (20) + PILL COUNT (80-110) MORISKY GREEN (20) p=0.049 Percentage ,7 p= ,8 55,7 p=0.364 Visit 1 (1m) Visit 3 (9m) Control Polypill percentage Control 68 Polypill

20 INTENTION TO TREAT Control Polypill p value SBP (mmhg) 0.88 (-0.76;2.53) (-2.02;1.38) 0.32 DBP (mmhg) 0.38 (-0.69;1.46) -0.11(-1.13;0.90) 0.51 LDL-chol (mg/dl) 2.17 (-0.96;5.29) 5.27(-0.31;10.86) 0.34 PER PROTOCOL FOCUS Phase 2 Results There were no differences between groups in BP or LDL-cholesterol SBP (mmhg) 0.63 (-1.47;2.74) -0.97(-3.15;1.21) 0.30 DBP (mmhg) 0.49 (-0.86;1.85) -0.58(-1.91;0.74) 0.27 LDL-chol (mg/dl) 2.90 (-1.15;6.95) 5.13 (-2.97;13.24) 0.64

21 FOCUS Phase 2 Results Adverse Effects Control (n=345) n (%) Polypill (n=350) n (%) AE 112 (32,5) 124 (35,4) SAE 23 (6,6) 21 (6,0) Patients 13 (3,7) 14 (4,0) interrupting Rx Death* 1 (0,3) 1 (0,3) Re-infarction 2 (0,6) 2 (0,6) Hospitalization 23 (6,7) 21 (6,0) Hematological AE 6 (1,7) 5 (1,4) Other Cardiac AE # 4 (1,1) 10 (2,8) Musculoskeletal AE 10 (3,8) 5 (1,4) Cough 6 (1,7) 5 (1,4) Dizziness 2 (0,6) 2 (0,6) Hypotension 7 (0,2) 0 (0,0) *Control (cancer); Polypill (traffic accident) # Other cardiac AE included for eg.- Non-specific angina

22 Position paper: Pollypill as a strategy to improve adherence in primary and secondary prevention. A Latin American Perspective Consensus expert panel UCLA / DELPHI methods - Kick-off project, Bibliographic review 1ª round Questionnaire Fieldwork, Analysis 2ª round Questionnaire Fieldwork, Analysis Results Presentations Publications Q 2 / 2016 Q 3 / 2016 Q 4 / 2016 Q1 / 2017 Timelines

23 Conclusions Ø Improving adherence to treatments should be a primary goal in an abempt to reduce cardiovascular mortality. Ø The loss of adherence to essenhal medicines is a mulh-causal phenomenon, in which the complexity of the treatment is only one part of the problem. Ø The simplificahon of the treatment through the polypill has proven to be safe and effechve to improve the adherence of our pahents. Ø The implementahon of this simple strategy will be parhcularly useful in terms of public health, especially in low- and moderate-income countries

24 Thank you Álvaro Sosa Liprandi