Koenig aeha2005 short
-
Upload
society-for-heart-attack-prevention-and-eradication -
Category
Health & Medicine
-
view
20 -
download
0
Transcript of Koenig aeha2005 short
Emerging Atherosclerosis Drugs to Watch Emerging 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, FACCDept. of Internal Medicine II - CardiologyDept. of Internal Medicine II - Cardiology
University of Ulm Medical CenterUniversity of Ulm Medical CenterUlm, 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” SummitA 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
Cardiovascular Drugs To WatchCardiovascular Drugs To
WatchCardiovascular Drugs To WatchCardiovascular Drugs To
WatchCardiovascular Drugs To WatchCardiovascular Drugs To
WatchCardiovascular Drugs To WatchCardiovascular Drugs To
Watch
Cardiovascular Drugs To Watch
Direct and Indirect Effects Direct and Indirect Effects of PPAR Nuclear Receptorsof PPAR Nuclear Receptors
Plut
zky
J. S
cienc
e 20
03;3
02:4
06-4
07Pl
utzk
y J.
Scie
nce
2003
;302
:406
-407
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 0.0950.095Principal 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 study parallel-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 events Event 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 as Existing therapy continued with diet and glucose-lowering agents, as well as antihypertensives, lipid-altering agents, antithrombotic agents antihypertensives, lipid-altering agents, antithrombotic agents Patient management throughout study to be according to the 1999 International Patient management throughout study to be according to the 1999 International Diabetes Federation (Europe) Guidelines Diabetes Federation (Europe) Guidelines
*All-cause mortality, non-fatal MI and stroke*All-cause mortality, non-fatal MI and stroke
Pioglitazone Reduces Neointima Volume Pioglitazone Reduces Neointima Volume After Coronary Stent ImplantationAfter Coronary Stent Implantation
Day 1Day 1start of treatmentstart of treatmentstent implantationstent implantation
RandomizationRandomization
PlaceboPlacebo
PioglitazonPioglitazon30 mg OD30 mg OD
6 months6 monthsIVUSIVUS
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 distal 5 mm proximal and distal
of the stented segment of 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
00
11
22
33
44
55
PlaceboPlacebo
Neoi
ntim
al v
olum
eNe
oint
imal
vol
ume
(mm
³/mm
)(m
m³/m
m)
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
Tota
l Pla
que
Volu
me
Tota
l Pla
que
Volu
me
(mm
³/mm
)(m
m³/m
m)
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
Tota
l pla
que
volu
me
Tota
l pla
que
volu
me
(mm
³/mm
)(m
m³/m
m) **
proximalproximal
10.4±4.010.4±4.07.8±3.47.8±3.4
00
55
1010
1515
2020
PlaceboPlacebo PioglitazonePioglitazone
Tot
al p
laqu
evVo
lum
eTo
tal p
laqu
evVo
lum
e (m
m³/m
m)
(mm
³/mm
)**
distaldistal
8.1±4.38.1±4.36.0±3.06.0±3.0
Effect of Pioglitazone on Neointima and on Total Effect 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
Cardiovascular Drugs To Watch
CytokinesCytokinesPlaque Plaque
FormationFormation
Foam CellFoam Cell
MonocytesMonocytes
MacrophageMacrophage
LUMENLUMEN
MEDIAMEDIA
INTIMAINTIMA
Oxidized LDLOxidized LDL
Adhesion Adhesion MoleculesMolecules
Lyso-PCLyso-PCOxFAOxFA
Lp-PLALp-PLA22
Role of Lp-PLARole of Lp-PLA22 in Coronary Heart Disease in Coronary Heart Disease
Area
(mm
Area
(mm
22 ))Th
ickne
ss (m
m)
Thick
ness
(mm
)
Median LesionMedian LesionCross-sectional AreaCross-sectional Area
Median Lesion Median Lesion ThicknessThickness
In Pre-Clinical Studies, Inhibition of the Enzyme In 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
0.180.180.160.160.140.140.120.120.100.100.080.080.060.060.040.040.020.020.000.00
ControlControlSB-244323SB-244323
Benson et al. Atherosclerosis 2000;151:166Benson et al. Atherosclerosis 2000;151:166
-100-100
-80-80
-60-60
-40-40
-20-20
0040 mg40 mg 80 mg80 mg
N=103N=103% C
hang
e (L
p-PL
A%
Cha
nge
(Lp-
PLA 22))
Circulating Lp-PLACirculating Lp-PLA22::Healthy volunteers: selective Healthy volunteers: selective Lp-PLALp-PLA22 inhibitors produce inhibitors produce dose-dependent inhibition up dose-dependent inhibition up to to 95%95%Patients: dose-dependent Patients: dose-dependent inhibition up to 80% (14-28d)inhibition up to 80% (14-28d)
Plaque Lp-PLAPlaque Lp-PLA22
Dose-dependent enzyme Dose-dependent enzyme inhibition (14d) independent inhibition (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 undergoingcarotid endarterectomycarotid endarterectomy
Johnson et al. Johnson et al. Circulation 2004:110(suppl III):III-590Circulation 2004:110(suppl III):III-590
Lp-PLALp-PLA22: A More Specific Marker of : A More Specific Marker of Vascular Inflammation?Vascular Inflammation?
Mechanistic studies Mechanistic studies - role in formation of human atheroma- role in formation of human atheroma - impact of Lp-PLA- impact of Lp-PLA22 inhibition in relevant tissues inhibition 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
Cardiovascular Drugs To Watch
Rimonabant – a Selective Type 1 Rimonabant – a Selective Type 1 Cannabinoid-Receptor-AntagonistCannabinoid-Receptor-Antagonist
RimonabantRimonabant
Effects on central nervous Effects on central nervous system system
Metabolic effectsMetabolic effects
Nutrient intakeNutrient intake AdiponectinAdiponectinSmokingSmoking
Body weightBody weightWaist girthWaist girth
Oxidation of fatty Oxidation 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
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 0.3 0.3p=0.005p=0.005
2.42.4
2.62.6
2.82.8
3.03.0
3.23.2
HOM
A (%
)HO
MA
(%)
2.82.8
3.13.1 3.13.13.03.0
3.13.1
2.62.6
PlaceboPlacebo Rimonabant Rimonabant 20 mg 20 mg
Rimonabant Rimonabant 5 mg 5 mg
Van Gaal et al. Lancet 2005;365:1389-1397Van Gaal et al. Lancet 2005;365:1389-1397
Rimonabant:Rimonabant: Effect on HOMA-derived Effect on HOMA-derived Insulin Resistance (Insulin Resistance (RIO Europe)RIO Europe)
- 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 Metabolic Rimonabant: Reduction in Metabolic Syndrome (ITT, 1 Year)Syndrome (ITT, 1 Year)
PlaceboPlacebo Rimonabant 20 mgRimonabant 20 mg
Redu
ctio
n (%
)Re
duct
ion
(%)
Van Gaal et al. Lancet 2005;365:1389-1397Van Gaal et al. Lancet 2005;365:1389-1397
Wei
ght c
hang
e (k
g)W
eigh
t cha
nge
(kg)
Weight Change at 1 Year is Consistent Across All TrialsWeight Change at 1 Year is Consistent Across All TrialsThe Plateau is a Physiological Phenomenon!The Plateau is a Physiological Phenomenon!
CompletersCompleters
PlaceboPlaceboRimonabant 20 mgRimonabant 20 mg
-10-10
-8-8
-6-6
-4-4
-2-2
00
00 1616 3232 4848
WeeksWeeks
PlaceboPlaceboRimonabant 20 mgRimonabant 20 mg
PlaceboPlaceboRimonabant 20 mgRimonabant 20 mg
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 TrialSmoking abstinence at 7-10 weeksSmoking abstinence at 7-10 weeks Smoking abstinence at end of study Smoking abstinence at end of study
Rimonabant 20 mgRimonabant 20 mgRimonabant 5 mgRimonabant 5 mgPlaceboPlacebo
p < 0.001 for high-dose vs placebop < 0.001 for high-dose vs placebop = 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 placebop = NS for low-dose vs placebop = NS for low-dose vs placebo
ACC 2004ACC 2004
Cardiovascular Drugs To Watch
Cardiovascular Drugs To Watch
Cardiovascular Drugs To Watch
Cardiovascular Drugs To Watch
De C
ater
ina
& Za
mpo
lli. N
Eng
l J M
ed 2
004;
350:
4-7
De C
ater
ina
& Za
mpo
lli. N
Eng
l J M
ed 2
004;
350:
4-7
Inhibitors of Membrane Bound Inhibitors of Membrane Bound 5-Lipoxygenase Activating Protein (FLAP)5-Lipoxygenase Activating Protein (FLAP)
FLAPFLAP
Hakonarson et al. JAMA 2005;293:2245-2256Hakonarson et al. JAMA 2005;293:2245-2256
Estimation of Effects of DG-031 on Pts Who Received Estimation 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.
Carryover Carryover EffectEffect
Carryover Carryover EffectEffect
C-reactive ProteinC-reactive Protein Serum Amyloid ASerum Amyloid A
2 3 4 5 6 7 2 3 4 5 6 7 2 3 4 5 6 7 2 3 4 5 6 7 VisitVisit VisitVisit
Effe
ctEf
fect
0.20.2
00
-0.2-0.2
-0.4-0.4
-0.6-0.6
-0.8-0.8
-1.0-1.0Ef
fect
Effe
ct
0.20.2
00
-0.2-0.2
-0.4-0.4
-0.6-0.6
-0.8-0.8
-1.0-1.0
Cardiovascular Drugs To Watch
CART-1: Lumen Volume ChangeCART-1: Lumen Volume Change-Reference Segments-Reference Segments
Lum
en v
olum
e (m
mLu
men
vol
ume
(mm
33 ))IVUS - Non-PCI siteIVUS - Non-PCI site
p = 0.05p = 0.05 AGI 140 mg vs placeboAGI 140 mg vs placebop = 0.09p = 0.09 AGI 280 mg vs placeboAGI 280 mg vs placebop = 0.077 AGI dose-responsep = 0.077 AGI dose-response
Enla
rgem
ent
Enla
rgem
ent
Narro
wing
Narro
wing
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-106770 mg70 mg
AGI-1067AGI-1067140 mg140 mg
AGI-1067AGI-1067280 mg280 mg
(n = 42)(n = 42) (n = 48)(n = 48) (n = 41)(n = 41) (n = 38)(n = 38) (n = 42)(n = 42)
The ARISE Trial: The ARISE Trial: AAggressive ggressive RReduction of eduction of IInflammation nflammation SStops tops EEvents vents
Patients with Patients with CHD as evidenced CHD as evidenced by recent MI/UAby recent MI/UA
> 7 days < 270 days> 7 days < 270 days
Patient population Patient population (N = (N = 66000)000)
DeathDeath Non fatal MINon fatal MI Non fatal StrokeNon fatal Stroke RevascularizationRevascularization Admission for UAAdmission for UA
Primary efficacy Primary efficacy end point:end point:
PlaceboPlacebo
Treatment Treatment (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
Polyphenols: The Case of ResveratrolPolyphenols: The Case of Resveratrol
Resveratrol has been found to exert a Resveratrol has been found to exert a number of potentially cardioprotective number of potentially cardioprotective effects in vitro including:effects in vitro including:
Inhibition of platelet aggregationInhibition of platelet aggregation Promotion of vasodilation by Promotion of vasodilation by enhancing the production of NOenhancing the production of NO Inhibition of inflammatory enzymesInhibition of inflammatory enzymes
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®® dosages dosages••Chow diet with the anti-inflammatory fenofibrateChow diet with the anti-inflammatory fenofibrate
AIM: Assess anti-inflammatory potency of Vasovin AIM: Assess anti-inflammatory potency of Vasovin ®®by measurement of CRP, Fibrinogen, other inflammatory markersby measurement of CRP, Fibrinogen, other inflammatory markers
Effect of Vasovin Effect of Vasovin on Basal Plasma Fibrinogen Levelson Basal Plasma Fibrinogen Levels
Fibr
inog
en (µ
g/m
L)Fi
brin
ogen
(µg/
mL)
*P<0.05*P<0.05two-sidedtwo-sidedpaired t-testpaired t-test
Con 0.045% 0.15% 0.45% FFCon 0.045% 0.15% 0.45% FF
Plasma FbgnPlasma Fbgnat 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
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:
Effect of Effect of „Polypill“„Polypill“ on CHD- and Stroke Risk on 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 CHD CHD StrokeStroke
LDL-cholesterolLDL-cholesterol Statin †Statin † 1.8 mmol/l 1.8 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 0.5 3 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) 3 3 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 evening LDL=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.
How Much Interest in Polypills?How Much Interest in Polypills?
Increasing interest in preventive medicine and multiple / global Increasing interest in preventive medicine and multiple / global RF assessment / treatment – vs. tailored therapy based on RF 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 heart each 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?
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 for Reduced need for MD contact and follow up; reduced need for
screening and confirmatory tests; new care locations (health club, screening and confirmatory tests; new care locations (health club, Pharmacist, self Rx)Pharmacist, self Rx)
CostCost• US and EU pharmacy cost-containment US and EU pharmacy cost-containment • Developing CountriesDeveloping Countries
Potential for improved outcomes. Actual …?Potential for improved outcomes. Actual …? NewsworthinessNewsworthiness
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, 1 Perm 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, a 1 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
Designing a PolypillDesigning a Polypill Commercially viable clinical indicationCommercially viable clinical indication Existing components with known characteristics Existing components with known characteristics Pharmaceutically stable when compoundedPharmaceutically stable when compounded PalatablePalatable Same dosing / comparable and compatible kinetics Same 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 ~exponentially Predictable interactions: probability ~exponentially
related to # of drugsrelated to # of drugs Predictable AE profilePredictable AE profile
ChallengesChallenges Primum non nocere Primum 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 (blockbuster Limited pharma interest – competition, low margin (blockbuster
unlikely), erratic use, poaching existing Rx market. So who will unlikely), erratic use, poaching existing Rx market. So who will develop, market, regulate? develop, market, regulate?
Importation, counterfeiting, internet sales – FDA already can’t Importation, counterfeiting, internet sales – FDA already can’t effectively regulate. Could further compromise US prescription and effectively regulate. Could further compromise US prescription and OTC markets.OTC markets.
Who will regulate the explosion of DTC advertising, and false claims Who will regulate the explosion of DTC advertising, and false claims (esp. for OTCs?)(esp. for OTCs?)
Who will conduct and report outcomes and pharmacoeconomic Who 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 Polypill Will future studies be obliged to include a Polypill du jourdu jour as active as active control?control?
Cardiovascular Drugs To WatchCardiovascular Drugs To
WatchCardiovascular Drugs To WatchCardiovascular Drugs To
WatchCardiovascular Drugs To WatchCardiovascular Drugs To
WatchCardiovascular Drugs To WatchCardiovascular Drugs To
Watch