Lifetime clinical and economic benefits of statin-based LDL lowering in the 20-year Followup of the West of Scotland Coronary Prevention Study

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1 Lifetime clinical and economic benefits of statin-based LDL lowering in the 20-year Followup of the West of Scotland Coronary Prevention Study Harvey White Green Lane Cardiovascular Service and Cardiovascular Research Unit Auckland City Hospital, Auckland, New Zealand

2 20-year Followup of the West of Scotland Coronary Prevention Study Most of the statin trials have an average duration that is fairly short to study the long-term effects and safety of drugs that should be taken lifelong Longer followup of patients is important; need 20 year followup for development of solid tumors

3 20-year Followup of the West of Scotland Coronary Prevention Study After 5 years of treatment the findings are remarkable 27% reduction in CHD mortality 13% reduction in all-cause mortality 19% reduction in CABG or PCI 31% reduction in heart failure admissions 21% reduction in length of stay, and cost saving No effect on stroke No decrease in non-cvd death No increase in cancer Gain of 5 event free years for primary endpoint of CHD death or MI; no age interaction

4 20-year Followup of the West of Scotland Coronary Prevention Study Questions Which statins were used, what doses, what was the adherence, what were the LDLs What was the % of follow-up Was the follow-up the same in both arms Other costs besides hospital stay What do we know about subgroups eg smokers 44% at randomization, patients with diabetes or hypertension What were the causes of death; cancer or from infections

5 Long term follow up in statin studies WOSCOPS experience CHD mortality All-cause mortality

6 20-year Followup of the West of Scotland Coronary Prevention Study Legacy Effect Ongoing carry-over effect related to a slowing of the progression of the disease and/or stabilization of existing coronary artery plaque Mechanism is unknown:? Pleiotropic effects e.g. gene regulation 1 1. Schroder A et al. Bioinformatics. 2011;27:2473

7 20-year Followup of the West of Scotland Coronary Prevention Study Legacy Effect: why might this have occurred and not in other studies Different populations Primary prevention Lower use of statins (31%), less effective statin (pravastatin) Younger patients (55years) than in other trials and plaques may not be calcified and more able to be modified and stabilized Earlier treatment

8 Long-term followup of statin trials Study Populations Age (yrs) Baseline lipids Followup lipids Followup years On statins KM curves and treatment benefit 4S MI or angina (51% 60) cholesterol 4.9 mmol/l, 190 mg/dl cholesterol 5.1 mmol/l, 196 mg/dl 10 84% Maintained for mortality LIPID MI or angina Median 62 LDL 3.9 mmol/l, 150 mg/dl LDL 3.9 mmol/l, 150 mg/dl 16 85% Maintained for CHD mortality HPS CAD, occlusive arterial disease, diabetes (27% 60) LDL 3.4 mmol/l, 132 mg/dl LDL 2.6 mmol/l, 100 mg/dl % Diverged 14% first year, then parallel for major vascular events ASCOT Primary prevention, hypertension Mean 63 LDL 4.4 mmol/l, 169 mg/dl % Diverged for mortality and non CV mortality PROSPER Vascular disease or risk Mean mmol/l 147 mg/dl Maintained for CHD mortality WOSCOPS Primary prevention, males Mean 55 LDL 4.9 mmol/l, 190 mg/dl % Diverged for CHD mortality

9 Comparative CHD risk reduction with earlier and later LDL-C lowering Ference BA et al. J Am Coll Cardiol. 2012;60:2631

10 Long term followup of statin trials: Cancer incidence

11 20-year Followup of the West of Scotland Coronary Prevention Study Conclusions Important study showing the value of linkage of data sets and research Legacy effect with reduced mortality and gain in 5 event free years over 20 years attributable to 5 year treatment allocation No increase in cancer The investigators should be congratulated for performing 20 year follow-up of a landmark study

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