Population models of health impact of combination polypharmacy
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1 Population models of health impact of combination polypharmacy Global Summit on Combination Polypharmacy for CVD, 25 th September 2012 Dr Mark Huffman Northwestern University, Chicago Charity No: Particular thanks to: Simon Capewell, Don Lloyd-Jones, Earl Ford, Martin O Flaherty, Darwin Labarthe, Julia Critchley, Iain Buchan et al, Katie Huffman
2 This talk Recent US CHD/CVD mortality trends Looking for explanations Building a CHD policy model- IMPACT Using the model to explain past trends Exploring potential polypharmacy contributions Implications for future CVD strategies
3 US Trends in age-adjusted CHD mortality rates: men & women aged 35 years Ford & Capewell JACC Per 100,000 population Women Men Year
4 International mortality trends men, coronary heart disease [CHD] Source:BHF Heartstats (WHO statistics Men aged 35-74, Standardised)
5 International mortality trends men, coronary heart disease [CHD] Why have CHD mortality rates halved? Source:BHF Heartstats (WHO statistics Men aged 35-74, Standardised)
6 Aim Our IMPACT CHD Model To explain falls in CHD mortality in recent decades in USA & elsewhere Ford et al NEJM
7 What is modelling?
8 What is modelling? a simplification of reality
9 What is modelling? a simplification of reality Visit Australia!
10 Data INPUT Logic OUTPUT
11 IMPACT Model is comprehensive Main Components F RISK FACTORS Cholesterol Blood Pressure Smoking Blood Pressure BMI & Diabetes Physical Activity Patient Groups Age & Sex AMI Angina Heart Failure 2' Prevention 50 TREATMENTS CABG/PTCA Medical Therapy surgery OUTCOMES Death Survival Ford et al NEJM
12 Large evidence base for CHD treatments: RCTs & meta-analyses Acute Myocardial Infarction (AMI) Secondary Prevention Chronic Angina & Unstable Angina CABG surgery & Angioplasty (PTCA) Hypertension Heart Failure Hyperlipidaemia Smoking cessation Ford et al NEJM
13 Evidence base: Meta-analyses & RCTs Example: Initial treatments for AMI TREATMENT Relative Risk Reduction (95% CI) First author (year) Thrombolysis 26% (15-37) Primary angioplasty Aspirin 32% (5-50) 15% (11-19) Beta-blockers 4% (-8, 15) ACE-I 7% (2-11) Estess et al 2002, FTT 1997 Cucherat et al 2003 Antithrombotic Trialists Collaboration 2002 Freemantle et al 1999 Latini et al 1998 Ford NEJM 2007; 356: 2388.
14 Treating individual CHD patients - impact on population CHD mortality: US example AMI: Aspirin, Men years Patients Treatment Relative 30d Case Deaths prevented eligible uptake risk Fatality or postponed (DPP) reduction a x b x c x d = a x b x c x d 102,000 X 84% x 0.15 x 0.05 = 640 SOURCES NHDS Paper ATC Medicare MEPS audits Meta-analyses Ford et al NEJM 2007
15 Sensitivity analyses Brigg s Analysis of Extremes method (using minimum & maximum plausible values) US example AMI Aspirin Men years Patients Treatment Relative Case Deaths prevented eligible uptake risk Fatality or postponed reduction (DPP) a x b x c x d = a x b x c x d Best Estimate 102,000 X 84% x 0.15 x 0.05 = 640 Minimum 90,000 X 75% x 0.11 x 0.03 = 230 Maximum 110,000 X 95% x 0.19 x 0.07 = 1390 Ford et al NEJM 2007
16 Explaining the fall in CHD deaths in USA CHD deaths NEJM 2007; 356: , 745 fewer deaths in
17 Explaining the fall in CHD deaths in USA : RESULTS CHD deaths NEJM 2007; 356: 2388 Risk Factors worse + 1 7% Risk Factors better - 61 % 341, 745 fewer deaths in Treatments - 47%
18 Explaining the fall in CHD deaths in USA : RESULTS NEJM 2007; 356: CHD deaths 341, 745 fewer deaths in Risk Factors worse + 1 7% Obesity (increase) + 7% Diabetes (increase) + 1 0% Risk Factors better - 61 % Population BP fall - 20% Smoking - 1 2% Cholesterol (diet) - 24% Physical activity - 5% Treatments - 47% AMI treatments - 1 0% Secondary prevention - 11% Heart failure - 9% Angina: CABG & PTCA - 5% Hypertension therapies - 7% Statins (primary prevention) - 5% Unexplained - 9%
19 What if more patients were treated with combination therapy? US treatment rates, 2000 AMI 2 prevention after MI 2 prevention after revasc. Chronic stable angina Primary prevention Aspirin, % B-blocker, % ACE-I, % Statin, % Deaths prevented or postponed if 1980 CHD trends persisted 8,870 17,740 5,330 2,040 16,580 Am J Cardiol 2007; 356: 2388.
20 What if more patients were treated with combination therapy? 60%+ uptake AMI 2 prevention after MI 2 prevention after revasc. Chronic stable angina Primary prevention Aspirin, % B-blocker, % ACE-I, % Statin, % Deaths prevented or postponed if 1980 CHD trends persisted 11,790 (33%) 43,615 (146%) 9,605 (80%) 2,630 (29%) 35,890 (116%) Am J Cardiol 2007; 356: 2388.
21 What if treatment rates were increased to 60%? Am J Cardiol 2007; 356: 2388.
22 What if treatment rates were increased to 60%? Am J Cardiol 2007; 356: 2388.
23 CHD Deaths Prevented or Postponed: Trends vs. Treatment in 1 and 2 Prev. Am J Prev Med 2010; 39:228.
24 IMPACT MODEL LIMITATIONS Assumes that RCT efficacy = effectiveness Data patchy ~ especially women & elderly Model explains 91% fall (9% not explained) Therefore Sensitivity Analyses & Validation are key NEJM 2007; 356: 2388.
25 Explaining CHD mortality fall USA Sensitivity Analysis: % contributions to mortality reduction
26 Comparisons with other studies % CHD mortality falls attributed to: NEJM updated
27 US IMPACT Model Fit in specific age groups (Columns = Observed fall in deaths ; Diamonds = Best Estimates, Bars = minimum and maximum estimates,) Deaths prevented or postponed Men Women NEJM 2007; 356: 2388.
28 IMPACT: Explaining past trends Large CHD mortality falls in Western countries Reductions in major risk factors often played a bigger role than medical therapies Increased treatment coverage has substantial potential for CHD prevention Comprehensive CHD strategy important: active promotion of primary prevention particularly diet & tobacco control also maximise effective treatments & secondary prevention in eligible patients
29 Quantifying the fall in CHD mortality due to aspirin treatment. Using the IMPACT Model in USA & beyond Conclusions 1 CHD mortality: big falls in USA, UK & elsewhere 50%-75% due to risk factor reductions 25%-50% due to evidence-based therapies Gains from therapies could double if treatment uptake reached 60%
30 Quantifying the fall in CHD mortality due to aspirin treatment. Using the IMPACT Model in USA & beyond Conclusions 2?? CHD mortality: big falls in USA, UK & elsewhere 50%-75% due to risk factor reductions 25%-50% due to evidence-based therapies Gains from therapies could double if treatment uptake reached 60% small reductions in risk factors could halve CHD deaths in US, UK & elsewhere
31 Population models of health impact of combination polypharmacy Global Summit on Combination Polypharmacy for CVD, 25 th September 2012 Dr Mark Huffman Northwestern University, Chicago Charity No: Particular thanks to: Simon Capewell, Don Lloyd-Jones, Earl Ford, Martin O Flaherty, Darwin Labarthe, Julia Critchley, Iain Buchan et al, Katie Huffman
32 Fall in CHD Mortality: 1 vs. 2 Prevention Risk factor Absolute decline in population risk In healthy individuals (1 prevention) Cholesterol 0.32 mmol/l 107,300 (67, ,575) In CHD patients (2 prevention) 22,210 (11,780-33,330) Totals 129,510 34% 7% Systolic blood pressure 4.86 mmhg 97,555 (64, ,285) 34,330 (18,290-40,360) 131,885 31% 11% Am J Prev Med 2010; 39:228.
33 IMPACT vs. Wald/Law: Differences in relative decreases for CHD death Aspirin 15% IMPACT Wald/Law Notes (ATC) Statin 23% BP lowering drugs (CTT) 13% to 29% (Law, 2003) 32% (23%-40%) 61% (51%-71%) per (1.8 mmol/l reduction) One drug: 19% (17-21%) Two drugs: 34% (29-40%) Three drugs: 46% (39-54%) with SBP by ~9.1mmHg, DBP by ~5.5 mmhg 2003 meta-analysis Based on differences at age years using cohort data Based on differences at age years using cohort data
34 β Coefficients = % fall in CHD mortality per unit decrease in risk factors (from meta-analyses & cohorts, Ford et al, NEJM : 2388 Cholesterol lowering PSC 2007 Reduction in CHD deaths 5mg/dl mean pop cholesterol 5% Blood pressure PSC Lancet mmhg Systolic BP 5% Obesity Bogers, Kg/M 2 BMI 2.5% Smoking InterHEART, % Smoking prevalence 1% Diabetes InterHEART, % diabetic population 2% Physical Activity InterHEART, % inactive population 0.3% Ford et al NEJM 2007
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