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Koenig aeha2005 short

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Koenig aeha2005 short

  1. 1. Emerging Atherosclerosis Drugs to WatchEmerging Atherosclerosis Drugs to Watch and Challenges and Promises of “PolyPill”and Challenges and Promises of “PolyPill” Wolfgang Koenig, MD, FRCP, FESC, FACCWolfgang Koenig, MD, FRCP, FESC, FACC Dept. of Internal Medicine II - CardiologyDept. of Internal Medicine II - Cardiology University of Ulm Medical CenterUniversity of Ulm Medical Center Ulm, GermanyUlm, Germany Association for Eradication of Heart AttackAssociation for Eradication of Heart Attack ““From Vulnerable Plaque to Vulnerable Patient” SummitFrom Vulnerable Plaque to Vulnerable Patient” Summit A satellite event during the annual scientific sessions of the AHAA satellite event during the annual scientific sessions of the AHA Saturday, November 12th, 2005,Dallas, TXSaturday, November 12th, 2005,Dallas, TX
  2. 2. Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch
  3. 3. Cardiovascular Drugs To Watch
  4. 4. Direct and Indirect EffectsDirect and Indirect Effects of PPAR Nuclear Receptorsof PPAR Nuclear Receptors PlutzkyJ.Science2003;302:406-407PlutzkyJ.Science2003;302:406-407
  5. 5. Dormandy et al. Lancet 2005;366:1279-1289Dormandy et al. Lancet 2005;366:1279-1289 3-Year Kaplan-Meier Estimate3-Year Kaplan-Meier Estimate Pioglitazone (%)Pioglitazone (%) Placebo (%)Placebo (%) RR (%)RR (%) PP Primary endpointPrimary endpoint 21.021.0 23.523.5 1010 0.0950.095 Principal secondary endpoint*Principal secondary endpoint* 12.312.3 14.414.4 1616 0.0270.027  Prospective, multi-centre, randomised, double-blind, placebo-controlled,Prospective, multi-centre, randomised, double-blind, placebo-controlled, parallel-group studyparallel-group study  Planned recruitment of 5000 patientsPlanned recruitment of 5000 patients  Minimum of 2.5 years exposure to treatmentMinimum of 2.5 years exposure to treatment  Event driven: >760 endpoint eventsEvent driven: >760 endpoint events • 90% power to detect a 20% reduction in the hazard rate90% power to detect a 20% reduction in the hazard rate  Existing therapy continued with diet and glucose-lowering agents, as well asExisting therapy continued with diet and glucose-lowering agents, as well as antihypertensives, lipid-altering agents, antithrombotic agentsantihypertensives, lipid-altering agents, antithrombotic agents  Patient management throughout study to be according to the 1999 InternationalPatient management throughout study to be according to the 1999 International Diabetes Federation (Europe) GuidelinesDiabetes Federation (Europe) Guidelines *All-cause mortality, non-fatal MI and stroke*All-cause mortality, non-fatal MI and stroke
  6. 6. Pioglitazone Reduces Neointima VolumePioglitazone Reduces Neointima Volume After Coronary Stent ImplantationAfter Coronary Stent Implantation Day 1Day 1 start of treatmentstart of treatment stent implantationstent implantation RandomizationRandomization PlaceboPlacebo PioglitazonPioglitazon 30 mg OD30 mg OD 6 months6 months IVUSIVUS Intravascular ultrasound (IVUS)Intravascular ultrasound (IVUS) •IVUS-catheter:IVUS-catheter: UltraCross™ 2.9F,UltraCross™ 2.9F, 30 mHz (Boston Scientific Scimed)30 mHz (Boston Scientific Scimed) • automated pullback at 0,5 mm/secautomated pullback at 0,5 mm/sec • computer-based contour detection programcomputer-based contour detection program (Medis Medical Imaging System)(Medis Medical Imaging System) • analysis:analysis: • stented segmentstented segment • 5 mm proximal and distal5 mm proximal and distal of the stented segmentof the stented segment Study designStudy design StentStent NeointimaNeointima Marx, Koenig et al. Circulation 2005;112:2792-2798Marx, Koenig et al. Circulation 2005;112:2792-2798
  7. 7. 00 11 22 33 44 55 PlaceboPlacebo NeointimalvolumeNeointimalvolume (mm³/mm)(mm³/mm) PioglitazonePioglitazone ** 3.1±1.63.1±1.6 2.3±1.12.3±1.1 * P<0.05 for comparison* P<0.05 for comparison of parameters between groupsof parameters between groups TotalPlaqueVolumeTotalPlaqueVolume (mm³/mm)(mm³/mm) 00 55 1010 1515 2020 PlaceboPlacebo PioglitazonePioglitazone ** 13.2±4.213.2±4.2 11.2±3.211.2±3.2 * P<0.05 for comparison* P<0.05 for comparison of parameters between groupsof parameters between groups StentStent 00 55 1010 1515 2020 PlaceboPlacebo PioglitazonePioglitazone TotalplaquevolumeTotalplaquevolume (mm³/mm)(mm³/mm) ** proximalproximal 10.4±4.010.4±4.0 7.8±3.47.8±3.4 00 55 1010 1515 2020 PlaceboPlacebo PioglitazonePioglitazone TotalplaquevVolumeTotalplaquevVolume (mm³/mm)(mm³/mm) ** distaldistal 8.1±4.38.1±4.3 6.0±3.06.0±3.0 Effect of Pioglitazone on Neointima and on TotalEffect of Pioglitazone on Neointima and on Total Plaque Volume Formation After 6 monthsPlaque Volume Formation After 6 months Marx, Koenig et al. Circulation 2005;112:2792-2798Marx, Koenig et al. Circulation 2005;112:2792-2798
  8. 8. Cardiovascular Drugs To Watch
  9. 9. CytokinesCytokines PlaquePlaque FormationFormation Foam CellFoam Cell MonocytesMonocytes MacrophageMacrophage LUMENLUMEN MEDIAMEDIA INTIMAINTIMA Oxidized LDLOxidized LDL AdhesionAdhesion MoleculesMolecules Lyso-PCLyso-PC OxFAOxFA Lp-PLALp-PLA22 Role of Lp-PLARole of Lp-PLA22 in Coronary Heart Diseasein Coronary Heart Disease
  10. 10. Area(mmArea(mm22 )) Thickness(mm)Thickness(mm) Median LesionMedian Lesion Cross-sectional AreaCross-sectional Area Median LesionMedian Lesion ThicknessThickness In Pre-Clinical Studies, Inhibition of the EnzymeIn Pre-Clinical Studies, Inhibition of the Enzyme Slows Atherosclerotic Disease ProgressionSlows Atherosclerotic Disease Progression Effect of SB-244323 (10mg/kg/day) on aortic lesions in WHHL rabbitsEffect of SB-244323 (10mg/kg/day) on aortic lesions in WHHL rabbits ** ** *p<0.03*p<0.03 0.180.18 0.160.16 0.140.14 0.120.12 0.100.10 0.080.08 0.060.06 0.040.04 0.020.02 0.000.00 ControlControl SB-244323SB-244323 Benson et al. Atherosclerosis 2000;151:166Benson et al. Atherosclerosis 2000;151:166
  11. 11. -100-100 -80-80 -60-60 -40-40 -20-20 00 40 mg40 mg 80 mg80 mg N=103N=103 %Change(Lp-PLA%Change(Lp-PLA22)) Circulating Lp-PLACirculating Lp-PLA22:: Healthy volunteers: selectiveHealthy volunteers: selective Lp-PLALp-PLA22 inhibitors produceinhibitors produce dose-dependent inhibition updose-dependent inhibition up toto ≥≥95%95% Patients: dose-dependentPatients: dose-dependent inhibition up to 80% (14-28d)inhibition up to 80% (14-28d) Plaque Lp-PLAPlaque Lp-PLA22 Dose-dependent enzymeDose-dependent enzyme inhibition (14d) independentinhibition (14d) independent of concomitant statin therapyof concomitant statin therapy Clinical Experience with Lp-PLAClinical Experience with Lp-PLA22 Inhibitors:Inhibitors: SB-480848 Decreases Plasma and Plaque ActivitySB-480848 Decreases Plasma and Plaque Activity Plasma ActivityPlasma Activity Plaque ActivityPlaque Activity Pre-surgical dosing in patients undergoingPre-surgical dosing in patients undergoing carotid endarterectomycarotid endarterectomy Johnson et al.Johnson et al. Circulation 2004:110(suppl III):III-590Circulation 2004:110(suppl III):III-590
  12. 12. Lp-PLALp-PLA22: A More Specific Marker of: A More Specific Marker of Vascular Inflammation?Vascular Inflammation?  Mechanistic studiesMechanistic studies - role in formation of human atheroma- role in formation of human atheroma - impact of Lp-PLA- impact of Lp-PLA22 inhibition in relevant tissuesinhibition in relevant tissues  Clinical index of risk (surrogate endpoints)Clinical index of risk (surrogate endpoints) - plaque imaging: structural vs compositional- plaque imaging: structural vs compositional - plasma biomarkers & global approach…omics- plasma biomarkers & global approach…omics  Outcome studies: closing therapeutic gap in „post HPS/PROVE-IT era“:Outcome studies: closing therapeutic gap in „post HPS/PROVE-IT era“: - high risk populations: post ACS, metS/diabetes, renal impairment…- high risk populations: post ACS, metS/diabetes, renal impairment… May represent a link between lipid metabolismMay represent a link between lipid metabolism and inflammationand inflammation Observational studies (clinical endpoints) inObservational studies (clinical endpoints) in diverse populations with varying absolute riskdiverse populations with varying absolute risk
  13. 13. Cardiovascular Drugs To Watch
  14. 14. Rimonabant – a Selective Type 1Rimonabant – a Selective Type 1 Cannabinoid-Receptor-AntagonistCannabinoid-Receptor-Antagonist RimonabantRimonabant Effects on central nervousEffects on central nervous systemsystem Metabolic effectsMetabolic effects Nutrient intakeNutrient intake AdiponectinAdiponectinSmokingSmoking Body weightBody weight Waist girthWaist girth Oxidation of fattyOxidation of fatty acids and -excretionacids and -excretion Insulin sensitivityInsulin sensitivity HDLHDL CRPCRP TriglyceridesTriglycerides Spieker et al. Kardiovaskuläre Medizin 2005;8:18–22Spieker et al. Kardiovaskuläre Medizin 2005;8:18–22
  15. 15. ITT LOCF 5 mg vs placebo:nsITT LOCF 5 mg vs placebo:ns 20 mg vs placebo: p=0.00320 mg vs placebo: p=0.003 BaselineBaseline 1 Year1 Year CompletersCompleters ∆∆ - 0.7- 0.7 ±± 0.30.3 p=0.005p=0.005 2.42.4 2.62.6 2.82.8 3.03.0 3.23.2 HOMA(%)HOMA(%) 2.82.8 3.13.1 3.13.1 3.03.0 3.13.1 2.62.6 PlaceboPlacebo RimonabantRimonabant 20 mg20 mg RimonabantRimonabant 5 mg5 mg Van Gaal et al. Lancet 2005;365:1389-1397Van Gaal et al. Lancet 2005;365:1389-1397 Rimonabant:Rimonabant: Effect on HOMA-derivedEffect on HOMA-derived Insulin Resistance (Insulin Resistance (RIO Europe)RIO Europe)
  16. 16. - 60- 60 - 50- 50 - 40- 40 - 30- 30 - 20- 20 - 10- 10 00 - 21%- 21% - 53%- 53% p<0.001p<0.001 - 21%- 21% - 51%- 51% p<0.001p<0.001 - 39%- 39% p<0.001p<0.001 - 8%- 8% Rimonabant: Reduction in MetabolicRimonabant: Reduction in Metabolic Syndrome (ITT, 1 Year)Syndrome (ITT, 1 Year) PlaceboPlacebo Rimonabant 20 mgRimonabant 20 mg Reduction(%)Reduction(%) Van Gaal et al. Lancet 2005;365:1389-1397Van Gaal et al. Lancet 2005;365:1389-1397
  17. 17. Weightchange(kg)Weightchange(kg)Weight Change at 1 Year is Consistent Across All TrialsWeight Change at 1 Year is Consistent Across All Trials The Plateau is a Physiological Phenomenon!The Plateau is a Physiological Phenomenon! CompletersCompleters PlaceboPlacebo Rimonabant 20 mgRimonabant 20 mg -10-10 -8-8 -6-6 -4-4 -2-2 00 00 1616 3232 4848 WeeksWeeks PlaceboPlacebo Rimonabant 20 mgRimonabant 20 mg PlaceboPlacebo Rimonabant 20 mgRimonabant 20 mg
  18. 18. 36.2%36.2% 20.2%20.2% 20.6%20.6% 0%0% 20%20% 40%40%27.6%27.6% 15.6%15.6% 16.0%16.0% 0%0% 10%10% 20%20% 30%30% STRATUS-US TrialSTRATUS-US Trial Smoking abstinence at 7-10 weeksSmoking abstinence at 7-10 weeks Smoking abstinence at end of studySmoking abstinence at end of study Rimonabant 20 mgRimonabant 20 mg Rimonabant 5 mgRimonabant 5 mg PlaceboPlacebo p < 0.001 for high-dose vs placebop < 0.001 for high-dose vs placebo p = NS for low-dose vs placebop = NS for low-dose vs placebo p < 0.001 for high-dose vs placebop < 0.001 for high-dose vs placebo p = NS for low-dose vs placebop = NS for low-dose vs placebo ACC 2004ACC 2004
  19. 19. Cardiovascular Drugs To Watch
  20. 20. Cardiovascular Drugs To Watch
  21. 21. Cardiovascular Drugs To Watch
  22. 22. Cardiovascular Drugs To Watch
  23. 23. DeCaterina&Zampolli.NEnglJMed2004;350:4-7DeCaterina&Zampolli.NEnglJMed2004;350:4-7 Inhibitors of Membrane BoundInhibitors of Membrane Bound 5-Lipoxygenase Activating Protein (FLAP)5-Lipoxygenase Activating Protein (FLAP) FLAPFLAP
  24. 24. Hakonarson et al. JAMA 2005;293:2245-2256Hakonarson et al. JAMA 2005;293:2245-2256 Estimation of Effects of DG-031 on Pts Who ReceivedEstimation of Effects of DG-031 on Pts Who Received the 2 Higher Doses of DG-031 During the First Rx Periodthe 2 Higher Doses of DG-031 During the First Rx Period Error bars indicate SDs.Error bars indicate SDs. CarryoverCarryover EffectEffect CarryoverCarryover EffectEffect C-reactive ProteinC-reactive Protein Serum Amyloid ASerum Amyloid A 2 3 4 5 6 72 3 4 5 6 7 2 3 4 5 6 72 3 4 5 6 7 VisitVisit VisitVisit EffectEffect 0.20.2 00 -0.2-0.2 -0.4-0.4 -0.6-0.6 -0.8-0.8 -1.0-1.0 EffectEffect 0.20.2 00 -0.2-0.2 -0.4-0.4 -0.6-0.6 -0.8-0.8 -1.0-1.0
  25. 25. Cardiovascular Drugs To Watch
  26. 26. CART-1: Lumen Volume ChangeCART-1: Lumen Volume Change -Reference Segments-Reference Segments ∆∆Lumenvolume(mmLumenvolume(mm33 )) IVUS - Non-PCI siteIVUS - Non-PCI site p = 0.05p = 0.05 AGI 140 mg vs placeboAGI 140 mg vs placebo p = 0.09p = 0.09 AGI 280 mg vs placeboAGI 280 mg vs placebo p = 0.077 AGI dose-responsep = 0.077 AGI dose-response EnlargementEnlargementNarrowingNarrowing Tardif et al. Circulation 2003; 107:552-558Tardif et al. Circulation 2003; 107:552-558 -6-6 -5-5 -4-4 -3-3 -2-2 -1-1 00 11 22 33 44 -5.3-5.3±18.3±18.3 -0.2-0.2±16.9±16.9 -2.4-2.4±17.7±17.7 3.53.5±21.4±21.4 1.81.8±21.3±21.3 PlaceboPlacebo ProbucolProbucol AGI-1067AGI-1067 70 mg70 mg AGI-1067AGI-1067 140 mg140 mg AGI-1067AGI-1067 280 mg280 mg (n = 42)(n = 42) (n = 48)(n = 48) (n = 41)(n = 41) (n = 38)(n = 38) (n = 42)(n = 42)
  27. 27. The ARISE Trial:The ARISE Trial: AAggressiveggressive RReduction ofeduction of IInflammationnflammation SStopstops EEventsvents  Patients withPatients with CHD as evidencedCHD as evidenced by recent MI/UAby recent MI/UA  > 7 days < 270 days> 7 days < 270 days Patient populationPatient population (N =(N = 66000)000)  DeathDeath  Non fatal MINon fatal MI  Non fatal StrokeNon fatal Stroke  RevascularizationRevascularization  Admission for UAAdmission for UA Primary efficacyPrimary efficacy end point:end point: PlaceboPlacebo TreatmentTreatment (12-24 months)(12-24 months) AGI-1067 300 mgAGI-1067 300 mg Steering committee co-chairs: JC Tardif, M PfefferSteering committee co-chairs: JC Tardif, M Pfeffer
  28. 28. Polyphenols: The Case of ResveratrolPolyphenols: The Case of Resveratrol Resveratrol has been found to exert aResveratrol has been found to exert a number of potentially cardioprotectivenumber of potentially cardioprotective effects in vitro including:effects in vitro including:  Inhibition of platelet aggregationInhibition of platelet aggregation  Promotion of vasodilation byPromotion of vasodilation by enhancing the production of NOenhancing the production of NO  Inhibition of inflammatory enzymesInhibition of inflammatory enzymes
  29. 29. Effect of VASOVIN on Human CRP LevelsEffect of VASOVIN on Human CRP Levels in a h-CRP-transgenic mouse model under basal and interleukin-in a h-CRP-transgenic mouse model under basal and interleukin-66 stimulated conditionsstimulated conditions 40 male mice, 5 groups, 5 weeks.40 male mice, 5 groups, 5 weeks. ••Chow diet onlyChow diet only ••Chow diet with 3 increasing VasovinChow diet with 3 increasing Vasovin®® dosagesdosages ••Chow diet with the anti-inflammatory fenofibrateChow diet with the anti-inflammatory fenofibrate AIM: Assess anti-inflammatory potency of VasovinAIM: Assess anti-inflammatory potency of Vasovin ®® by measurement of CRP, Fibrinogen, other inflammatory markersby measurement of CRP, Fibrinogen, other inflammatory markers
  30. 30. Effect of VasovinEffect of Vasovin on Basal Plasma Fibrinogen Levelson Basal Plasma Fibrinogen Levels Fibrinogen(µg/mL)Fibrinogen(µg/mL) *P<0.05*P<0.05 two-sidedtwo-sided paired t-testpaired t-test Con 0.045% 0.15% 0.45% FFCon 0.045% 0.15% 0.45% FF Plasma FbgnPlasma Fbgn at t=0, 2, 4 wat t=0, 2, 4 w ** ** ** ** ** ** 0.00.0 0.50.5 1.01.0 1.51.5 2.02.0 2.52.5 3.03.0 3.53.5
  31. 31. A Pill to Prevent 80% of Heart AttacksA Pill to Prevent 80% of Heart Attacks BMJ 28-06-03BMJ 28-06-03 The Polypill:The Polypill:
  32. 32. Effect ofEffect of „Polypill“„Polypill“ on CHD- and Stroke Riskon CHD- and Stroke Risk After 2 Years of Therapy (Age 55-64 Years)After 2 Years of Therapy (Age 55-64 Years) Wald & Law. BMJ 2003;326:1419-1425Wald & Law. BMJ 2003;326:1419-1425 % Risk Reduction (95% CI)*% Risk Reduction (95% CI)* Risk FactorRisk Factor CompoundCompound Red. of RFRed. of RF CHDCHD StrokeStroke LDL-cholesterolLDL-cholesterol Statin †Statin † 1.8 mmol/l1.8 mmol/l (70mg/dl) LDL-C(70mg/dl) LDL-C 61 (51 to 71)61 (51 to 71) 17 (9 to 25)17 (9 to 25) Blood pressureBlood pressure 3 compunds with 0.53 compunds with 0.5 standard dosestandard dose 11 mm Hg DBP11 mm Hg DBP 46 (39 to 53)46 (39 to 53) 63 (55 to 70)63 (55 to 70) HomocysteineHomocysteine Folic acid (0.8 mg/d)Folic acid (0.8 mg/d) 33 μμmol/lmol/l 16 (11 to 20)16 (11 to 20) 24 (15 to 33)24 (15 to 33) Platelet functionPlatelet function Aspirin (75 mg/day)Aspirin (75 mg/day) NANA 32 (23 to 40)32 (23 to 40) 16 (7 to 25)16 (7 to 25) Combined EffectCombined Effect AllAll 88 (84 to 91)88 (84 to 91) 80 (71 to 87)80 (71 to 87) LDL=low density lipoprotein. †Atorvastatin 10 mg/die, or simvastatin or lovastatin 40 mg/day in the eveningLDL=low density lipoprotein. †Atorvastatin 10 mg/die, or simvastatin or lovastatin 40 mg/day in the evening or 80 mg/day in the morning.or 80 mg/day in the morning.
  33. 33. How Much Interest in Polypills?How Much Interest in Polypills?  Increasing interest in preventive medicine and multiple / globalIncreasing interest in preventive medicine and multiple / global RF assessment / treatment – vs. tailored therapy based onRF assessment / treatment – vs. tailored therapy based on genetic profilegenetic profile  Wald and Law: One in three people would directly benefit,Wald and Law: One in three people would directly benefit, each on average gaining 11-12 years of life without hearteach on average gaining 11-12 years of life without heart attack or stroke.attack or stroke.  CNN web poll (based on the above): 95% would take a polypillCNN web poll (based on the above): 95% would take a polypill  Google search: poly pill(s) + polypill (s) > 55,000 hitsGoogle search: poly pill(s) + polypill (s) > 55,000 hits  Patents: 130?Patents: 130?
  34. 34. In Favor of PolypillsIn Favor of Polypills  AdherenceAdherence  Pharma and IP holders – new product, market expansion,Pharma and IP holders – new product, market expansion, commercial advantage over competitors for same indication(s)commercial advantage over competitors for same indication(s)  Reduced need for MD contact and follow up; reduced need forReduced need for MD contact and follow up; reduced need for screening and confirmatory tests; new care locations (healthscreening and confirmatory tests; new care locations (health club, Pharmacist, self Rx)club, Pharmacist, self Rx)  CostCost • US and EU pharmacy cost-containmentUS and EU pharmacy cost-containment • Developing CountriesDeveloping Countries  Potential for improved outcomes. Actual …?Potential for improved outcomes. Actual …?  NewsworthinessNewsworthiness
  35. 35. Against - How Many Polypills Could There Be?Against - How Many Polypills Could There Be?  By US pharmacopeia, for CHD prevention alone:By US pharmacopeia, for CHD prevention alone:  Perm any combination of 1 of 6 statins, 1 of 10 ACEis, 1Perm any combination of 1 of 6 statins, 1 of 10 ACEis, 1 of 7 thiazides, 1 of 9 beta-blockersof 7 thiazides, 1 of 9 beta-blockers • = 3780 combinations= 3780 combinations  1 of 7 ARBs, 1 of 10 CCBs, 1 of 10 other BP meds, a1 of 7 ARBs, 1 of 10 CCBs, 1 of 10 other BP meds, a folic acid, an ASA.folic acid, an ASA.  Dose ranges for some componentsDose ranges for some components  ? Add others e.g fibrate, niacin, CETPi, TZD, COX-2 or? Add others e.g fibrate, niacin, CETPi, TZD, COX-2 or other anti-inflammatory, cpds in developmentother anti-inflammatory, cpds in development  ? Add OTC / other ‘natural’ products? Add OTC / other ‘natural’ products
  36. 36. Designing a PolypillDesigning a Polypill  Commercially viable clinical indicationCommercially viable clinical indication  Existing components with known characteristicsExisting components with known characteristics  Pharmaceutically stable when compoundedPharmaceutically stable when compounded  PalatablePalatable  Same dosing / comparable and compatible kineticsSame dosing / comparable and compatible kinetics (e.g. qd vs bid, qam vs qhs, food effects, etc)(e.g. qd vs bid, qam vs qhs, food effects, etc)  Predictable interactions: probability ~exponentiallyPredictable interactions: probability ~exponentially related to # of drugsrelated to # of drugs  Predictable AE profilePredictable AE profile
  37. 37. ChallengesChallenges  Primum non nocerePrimum non nocere – e.g. Lovastatin 10mg (EC), ½ strength BP meds– e.g. Lovastatin 10mg (EC), ½ strength BP meds – overlap with same OTC argument– overlap with same OTC argument  Who will educate pts and monitor, evaluate, report AEs?Who will educate pts and monitor, evaluate, report AEs?  Limited pharma interest – competition, low margin (blockbusterLimited pharma interest – competition, low margin (blockbuster unlikely), erratic use, poaching existing Rx market. So who willunlikely), erratic use, poaching existing Rx market. So who will develop, market, regulate?develop, market, regulate?  Importation, counterfeiting, internet sales – FDA already can’tImportation, counterfeiting, internet sales – FDA already can’t effectively regulate. Could further compromise US prescription andeffectively regulate. Could further compromise US prescription and OTC markets.OTC markets.  Who will regulate the explosion of DTC advertising, and false claimsWho will regulate the explosion of DTC advertising, and false claims (esp. for OTCs?)(esp. for OTCs?)  Who will conduct and report outcomes and pharmacoeconomicWho will conduct and report outcomes and pharmacoeconomic studies? Will they be done?studies? Will they be done?  Will future studies be obliged to include a PolypillWill future studies be obliged to include a Polypill du jourdu jour as activeas active control?control?
  38. 38. Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch Cardiovascular Drugs To Watch

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