Dpm mesa cardia v14 nov2012

• 1. Politics and Polypills: Strategies forImproving Global Cardiovascular Health Mark Huffman, MD, MPHNorthwestern University Feinberg School of Medicine 16 November 20121

2. Outline Political economy of NCDs WHO 25 by 25 Polypills Kerala ACS Registry and ACS QUIK2 3. POLITICAL ECONOMYOF NCDs3 4. Are NCDs neglected? Fuster V, Voute J. Lancet 2005; 366:1512 Horton R. Lancet 2005; 366:1514 5. Calls to action publishedin medical journals: 19662007Ebrahim S. Int. J. Epidemiol. 2008;37:225-230 6. Potential reasons why NCDsmight be neglected1. Apathy NCDs are difficult/complex to tackle Arent NCDs part of normal aging? Myth that risk factors only account for 50% of deaths2. Inadequate funding Development aid for health (DAH) has risen from$5.6B (1990) to $22B (2007), but how much for NCDs?3. NCDs are invisible Scandal of ignorance as described by Setel et al. (lack of vital registration systems) Stuckler D, et al. in Sick Societies. Eds. Stuckler and Siegel. Oxford, 2011. 7. Whos in charge of NCDs? World Health Organization United Nations development agenciesInternational financial institutions (World Bank, IMF)National development agenciesMinistries of health Academic institutions Private donors (for-profit and not-for-profit groups)Stuckler D, et al. in Sick Societies. Eds. Stuckler and Siegel. Oxford, 2011. 8. Whos in charge of NCDs? World Health Organization United Nations development agenciesInternational financial institutions (World Bank, IMF)National development agenciesMinistries of health Academic institutions Private donors (for-profit and not-for-profit groups)3 indicators to assess the power/influence of these institutions:1) Where does the money come from? How much? Where does it go?2) Who sits on the board and whose interests do they serve?3) Who wins conflicts? Stuckler D, et al. in Sick Societies. Eds. Stuckler and Siegel. Oxford, 2011. 9. Where does the money come from?DAH commitments (2007): $22B PRIVATE MONEY Ravishankar N, et al. Lancet 2009; 363:2113. 10. Where does the money come from?DAH commitments (2007): $22Bbut only ~2/3 ($15B) can be accounted for(and do not represent disbursements) Ravishankar N, et al. Lancet 2009; 363:2113. 11. But little funding for NCDs ($ millions)2500020000 Chronic diseases15000 Infectious diseases10000(HIV, TB, malaria) Total health aid 5000 02001 2002 2003 200420052006200711Nugent R, Feigl A. Center for Global Development WP 228, 2011. 12. But little funding for NCDs ($ millions)2500020000 Chronic diseases15000 Infectious diseases10000(HIV, TB, malaria) Total health aid 5000 02001 2002 2003 2004200520062007NCDs:$0.78/DALY ID:$23.9/DALY Total: $16.4/DALY12Nugent R, Feigl A. Center for Global Development WP 228, 2011. 13. Who are the NCD funders?FunderPurpose5 year total (2004-2008)WHO (incl. PAHO) General NCDs$873MWellcome Trust General NCDs$458MBloomberg + Gates Tobacco, cervical cancer $250MWorld Bank General NCDs$183MNovo NordiskDiabetes $58MGE FoundationGeneral NCDs$41MNIHTobacco, cancer, CVD$27MInterAmerican Development Bank General NCDs$21MInternational Diabetes Federation Diabetes $18MHilton FoundationSense organ diseases$12MNugent R, Feigl A. Center for Global Development WP 228, 2011. 14. Who are the NCD funders?FunderPurpose5 year total (2004-2008)WHO (incl. PAHO) General NCDs$873MWellcome Trust General NCDs$458MBloomberg + Gates Tobacco, cervical cancer $250MWorld Bank General NCDs$183MNovo NordiskDiabetes $58MGE FoundationGeneral NCDs$41MNIHTobacco, cancer, CVD$27MInterAmerican Development Bank General NCDs$21MInternational Diabetes Federation Diabetes $18MHilton FoundationSense organ diseases$12MNugent R, Feigl A. Center for Global Development WP 228, 2011. 15. Who are the NCD funders?FunderPurpose5 year total (2004-2008)WHO (incl. PAHO) General NCDs$873MWellcome Trust General NCDs$458MBloomberg + Gates Tobacco, cervical cancer $250MWorld Bank General NCDs$183MNovo NordiskDiabetes $58MGE FoundationGeneral NCDs$41MNIHTobacco, cancer, CVD$27MInterAmerican Development Bank General NCDs$21MInternational Diabetes Federation Diabetes $18MHilton FoundationSense organ diseases$12MWhose interests are being served? What ties to these organizations have tofood/beverage, agriculture, and pharmaceutical industries?Nugent R, Feigl A. Center for Global Development WP 228, 2011. 16. MAPPER16 17. BMGF Stock PortfolioHoldingPortfolio Rank $USD (B)Berkshire Hathaway 1 $5.9BMcDonalds 2 $0.6BCoca-Cola4 $0.5BWaste Management 5 $0.5BWalmart7 $0.4BCoca-Cola FEMSA9 $0.4BCostco 10 $0.3BMonsanto>20 $0.02BTotal $11.9BStuckler D, et al. PLoS Med 2011; 8:e1001020. 18. BMGF Stock PortfolioHoldingPortfolio Rank $USD (B)Berkshire Hathaway 1 $5.9BMcDonalds 2 $0.6BCoca-Cola4 $0.5BWaste Management 5 $0.5BWalmart7 $0.4BCoca-Cola FEMSA9 $0.4BCostco 10 $0.3BMonsanto>20 $0.02BTotal $11.9BStuckler D, et al. PLoS Med 2011; 8:e1001020. 19. WHO Budget, 2000-2013 projected2007: ~12% of WHO budget directed to NCDs Nugent R, Feigl A. Center for Global Development WP 228, 2011. 20. Where does the WHO get its money?Nugent R, Feigl A. Center for Global Development WP 228, 2011. 21. Where does the WHO get its money? Gates annual operating budget: $3.8B Gates WHO contribution: $150M (14% of VC)Nugent R, Feigl A. Center for Global Development WP 228, 2011. 22. Public/global health and politicsResearch!America respondentsGBD Siegel KR, et al. Global Health Action 2011; 4:6339. 23. Public/global health and politics5 types of political incentives:1. Political: squeaky wheel2. Economic: private companies seek to shift priorities3. Organizational: sustaining (or growing) the status quo4. Symbolic: MDGs5. Scientific: technical arguments (weakest) Political economy of NCDs will likely remain weak without paying attention to these incentives Stuckler D, et al. in Sick Societies. Eds. Stuckler and Siegel. Oxford, 2011. 24. WHO 25 BY 2524 25. 25 http://daccess- ods.un.org/TMP/3950904.30974 26. 26 http://daccess- ods.un.org/TMP/3950904.30974 27. 27 http://daccess- ods.un.org/TMP/3950904.30974 28. 65th World Health Assembly:May 26, 201228 who.int 29. WHO Draft Framework: Oct 31, 2012 Premature = policiesDose titration, side effectsLower margins 37. Polypill, or Fixed Dose Combination, Origins Goals: 4 drugs in 1 (ASA, BB, ACE, statin) Improve adherence Lower cost Richard Peto 38. Research Requirements for Polypill1) Stability testing2) Bioavailability testing3) Assessment of short-term effects on BP, LDL cholesterol, and platelet aggregation4) Assessment of safety and short-term symptomatic side effects5) Study of interactions and effects on combination of drugs on physiologic mechanisms6) Studies on adherence to treatmentMultiple polypills (at least 2 doses per drug) envisionedWHO/Wellcome Trust were charged with partnering withindustry for testing, including cost-effectiveness via RCTs orcommunity demonstration projects (5-year timeline!) 39. Was 80% RiskReduction Realistic? Reduction IHD event riskStroke riskRisk factorAgentin risk factorreduction (%) reduction (%)LDL cholesterolStatin 70 mg/dl61 (51 to 71)17 (9 to 25)3 classes of drug at11 mmHgBlood pressure46 (39 to 53) 63 (55 to 70)half standard dose (DBP)SerumFolic acid (0.8 mg/d) 3 mol/L16 (11 to 20) 24 (15 to 33)homocysteine NotPlatelet functionAspirin (75 mg/d)32 (23 to 40)16 (7 to 25) quantifiedCombined effectAll88 (84 to 90) 80 (71 to 87) Wald and Law. BMJ, 2003. 40. Stability Testing and Costs:Unanticipated Hurdles theheart.org 41. The Indian Polycap Study (TIPS)2,053 patients with 1 major risk factor included; 12 week trial in India (2007-2008)Polycap: ASA 100 mg, simvastatin 20 mg, atenolol 50 mg, ramipril 5 mg, HCTZ 12.5 mgManufactured by Cadila Pharmaceuticals, Ltd.Yusuf S, et al. Lancet, 2009;373:1341. 42. Polycaps Short-Term Effects Blood pressure= 5.7 mmHg fall Platelet aggregationLDL = 31 mg/dl fallProjected Risk ReductionIHDStroke Wald/Law88%80% Polycap 62%48% Yusuf S, et al. Lancet, 2009;373:1341. 43. Adherence to Polycap at 12 Weeks OverallPolycap N=2,053 N=412Drugs permanently stopped303 (14.8%)66 (16.0%)Drug-specific reasons 77 (3.8%)14 (3.4%)Cough 9 (0.4%)1 (0.2%)Dizziness/hypotension 46 (2.2%)10 (2.4%)Gastritis/dyspepsia 15 (0.7%) 1 (0.2%)Hyperkalemia3 (0.1%)1 (0.2%)Bradycardia 4 (0.2%)1 (0.2%)Other reasons 69 (3.4%)20 (4.9%)Social reasons/refused treatment 201 (9.8%)40 (9.7%) Yusuf S, et al. Lancet, 2009;373:1341. 44. Low Secondary Prevention Rx Rate: PURE CHD Stroke153,996 participants across 628 urban/rural communities in 17 countries (2003-2009)Yusuf S, et al. Lancet, 2011; 378:1231. 45. Polypill: But For Whom?45 theheart.org 46. (Potential) Limitations of PolypillHow will I be able to evaluate my patients side effectsof the individual medications? Possibly overstated given distinctions across drugs-Bleeding vs. mylagias vs. orthostasis vs. coughI need to titrate the doses of my patients drugs. Limited role dose escalation/de-escalation for most patients-Low dose aspirin and high-dose statin preferred for 2o prev. Likely does not require cardiologist, nor even physicianWhat about clopidogrel for my post-MI patients? 47. Estimated Costsof 5 Priority InterventionsCost per personInterventionsper year ChinaIndia RussiaTobaccoFCTC0.14 0.16 0.49Mass-media, voluntary actionDietary salt0.05 0.06 0.16by food industry Mass-media, food taxes,Obesity, unhealthy dietsubsidies, labeling and 0.43 0.35 1.18and physical inactivitymarketing restriction Tax, advertising bans,Harmful alcohol intake0.07 0.05 0.52 restricted accessCardiovascular risk Combination of drugs,1.020.9 1.73reduction polypharmacyTotal cost per person 1.72 1.52 4.08 Beaglehole R, et al. Lancet 2011; 377:1438. 48. Cost-effectiveness of Polypillfor CVD in India (per 1M/10yrs)> 35%> 25%> 15% Costs and EffectsNo PolypillRisk Risk Risk Total cost (millions)$23.5$34.5 $51.4 $92.2 MI averted-- 10,200 14,400 21,300 Deaths from CHD averted -- 10,500 13,500 19,600 Cost per DALY averted --$300 $990$1,500Note: Each strategy is compared with no polypill.Disease Control Priorities in Developing Countries, 2nd edition, 2006, Table 45.6 49. Polypill 2o Prevention TrialsSample PrimaryTitleManufacturer SponsorSizeOutcomeUMPIREDr. Reddys Lab European Comm.2,000 AdherenceIMPACTDr. Reddys Lab Health Research600Adherence Council (NZ)Kayini GAPDr. Reddys LabNational Health and1,000 AdherenceResearch Council(Australia)SPACE Dr. Reddys LabHospital do2,000 AdherenceCoracaoFOCUS* FerrerCINI/Ferrer4,000 AdherenceTIPS-K*Cadila Cadila 500Adherence*Only two true 2o prevention trials; others include high CV risk (>15% over 5 years) 49Prabhakaran D, et al. Clin Invest 2012; in press. 50. UMPIRE 1o ResultsFixed-dose combinationUsual careTreatment effectOutcome(n=1002)(n=1002) (95% CI)1.33Adherence (%) 8665 (1.26 to 1.41)Systolic blood -2.6129.2 131.7pressure (mm Hg)(-4.0 to -1.1)LDL cholesterol,-0.112.18 (84.3) 2.29 (88.5)mmol/L (mg/dL) (-0.17 to -0.05) "If we could address the shortfall in adherence, we would do more [for CVD prevention] than generating another blockbuster drug for a single risk factor. -Simon Thom, November 6, 201250theheart.org 51. SeptemberDecember January March April8-month timeline of events 51 52. Kerala ACS Registry/ACS QUIK52 53. Kerala ACS Registry25,748 ACS Admissions 2007-2009Mohanan P, et al. Eur Heart J 2012; Sept 7 [Epub ahead of print] 54. Kerala ACS Registry:Baseline Characteristics STEMI Non-STEMIUnstable Angina N (%) 9,5969 (37)7,857 (31) 8,322 (32) Demographics Male, N (%) 7,400 (77.3)5,932 (75.5) 6,591 (79.2) Age, years (SD) 60.4 (12.1) 60.5 (11.9) 60.5 (12.1) No education, N (%) 1,187 (22.5)1,015 (25.9) 579 (11.8) Key risk factors History of diabetes, N (%)3,314 (34.6)2,981 (37.9) 3,388 (40.7) History of hypertension, N (%)5,315 (55.5)3,788 (48.2) 3,365 (40.4) History of smoking, N (%) 3,376 (35.3)2,980 (37.9)2,511 (30.2) History of MI, N (%)1,257 (13.1)1,212 (15.4) 1,186 (14.3) History of stroke, N (%) 212 (2.2) 170 (2.2) 264 (3.2) History of PCI/CABG, N (%)8 (0.1) 10 (0.1)55 (0.7)54Mohanan P, et al. Eur Heart J 2012; Sept 7 [Epub ahead of print] 55. Kerala ACS Registry: Baseline CharacteristicsSTEMI Non-STEMIUnstable AnginaN (%) 9,5969 (37)7,857 (31) 8,322 (32)Clinical features on presentationSymptom to presentation >6 hrs, N3,915 (41.2)2,809 (36.1)3,213 (39.0)(%)Door-to-needle 1, N (%) 1,048 (20.8) 828 (19.1) 1,120 (25.5)Fasting blood glucose, mg/dl (IQR) 115 (94, 156) 112 (91, 152) 116 (93, 158)55Mohanan P, et al. Eur Heart J 2012; Sept 7 [Epub ahead of print] 56. In-hospital Diagnostics/Treatments STEMI Non-STEMI 100 Unstable Angina80% 604020 056Mohanan P, et al. Eur Heart J 2012; Sept 7 [Epub ahead of print] 57. In-hospital Event Rates(p6 hrs vs. 30 min vs. 1 vs. 1 (ref)(0.50, 0.63)(0.59, 0.75)1.171.71NSTEMI vs. unstable angina (ref)(0.95, 1.45)(1.35, 2.16)0.511.39STEMI vs. unstable angina (ref)(0.42, 0.62)(1.15, 1.68)2.140.74Enzyme positive vs. negative (ref)(1.75, 2.62)(0.60, 0.90)1.030.97Creatinine (per mg/dl)(0.97, 1.10)(0.90, 1.04)Optimal in-hospital medical therapy vs.10.4860--non optimal (ref)(9.37, 11.72) 61. ACS Quality Improvement in Kerala(ACS QUIK): 2012-2017Cluster-randomized, stepped wedge clinical trialAim to develop, implement, and evaluate quality improvement toolkit on 30 day MACE (9.3%7.3%)Focus group discussions (Nov 2012) with help from Drs. David Victorson and Shifalika Goenka to build toolkitsAudit/feedback, standardized clinical pathways, checklists (likely including Polycap or other avail. FDC)2o outcomes: process of care, hrQOL, microeconomic impact61 62. Take Home PointsPoliticsEvidence is necessary but insufficient for political change;private forces dominate NCD landscape of weak political econ.WHO 25 by 25Premature focus on individuals