Managing CV risk in T2DM beyond glucose Richard Hobbs, Professor - PowerPoint PPT Presentation

Managing CV risk in T2DM beyond glucose Richard Hobbs, Professor and Head Nuffield Department of Primary Care Health Sciences University of Oxford, United Kingdom

Prevalence of diabetes in 2 0 3 0 2 0 1 0 2 0 3 0 Total number of people 285 million 438 million with diabetes (age 20-79) Prevalence of diabetes 6.6 % 7.8 % (age 20-79) IDF diabetes atlas, 4th edition, 2009

Diabetes doubles the risk of vascular disease Data from 102 prospective studies, 530,083 participants (adjusted for age sex, cohort, SBP, smoking, BMI) Outcome I 2 (95% CI) Number HR (95% CI) of cases Coronary heart disease 26 505 2.00 (1.83 - 2.19) 64 (54-71) Coronary death 11 556 2.31 (2.05 - 2.60) 41 (24-54) Non-fatal myocardial 14 741 1.82 (1.64 - 2.03) 37 (19-51) infarction Cerebrovascular disease 11 176 1.82 (1.65 - 2.01) 42 (25-55) Ischaemic stroke 3799 1 (0-20) 2.27 (1.95 - 2.65) Haemorrhagic stroke 1183 1.56 (1.19 - 2.05) 0 (0-26) Unclassified stroke 4973 1.84 (1.59 - 2.13) 33 (12-48) Other vascular deaths 3826 1.73 (1.51 - 1.98) 0 (0-26) 1 2 4 Hazard ratio (diabetes vs. no diabetes) Emerging Risk Factors Collab. Lancet. 2010 Jun 26;375(9733):2215-22

Type 2 diabetes increases CHD/CVD risk over time CHD equivalence threshold CHD risk ~10 years’ Diagnosis duration Age • CVD/CHD risk at or prior to diagnosis is determined by conventional CHD risk factors • Hyperglycaemia in the diabetic range increases CHD risk over time • After a diabetes duration of >10 years CHD risk equivalence is reached Sattar N. Diabetologia 2013;56:686-695 .

Managing CV risk beyond glucose control

Smoking Hazards & Cessation Benefits 113,752 w and 88,496 m aged ≥ 25y in US NHIS Jha N Engl J Med 2013; 368: 341-50

Lipid modification in diabetes

Statin vs control: Proportional effects on major vascular events per mmol/L LDL-C reduction (26 Trials, 170,000 Subjects) Relative risk (CI) per No. of events (% pa) Statin Control mmol/L LDL-C reduction 2310 (0.9%) 3213 (1.2%) 0.74 (0.69 - 0.78) Nonfatal MI 1242 (0.5%) 1587 (0.6%) 0.80 (0.73 - 0.86) CHD death Any major coronary event 3380 (1.3%) 4539 (1.7%) 0.76 (0.73 - 0.79) 816 (0.3%) 1126 (0.4%) 0.76 (0.69 - 0.83) CABG 601 (0.2%) 775 (0.3%) 0.78 (0.69 - 0.89) PTCA Unspecified 1686 (0.6%) 2165 (0.8%) 0.76 (0.70 - 0.83) Any coronary revascularisation 3103 (1.2%) 4066 (1.6%) 0.76 (0.73 - 0.80) 987 (0.4%) 1225 (0.5%) 0.80 (0.73 - 0.88) Ischaemic stroke Haemorrhagic stroke 188 (0.1%) 163 (0.1%) 1.10 (0.86 - 1.42) 555 (0.2%) 629 (0.2%) 0.88 (0.76 - 1.02) Unknown stroke Any stroke 1730 (0.7%) 2017 (0.8%) 0.85 (0.80 - 0.90) Any major vascular event 7136 (2.8%) 8934 (3.6%) 0.79 (0.77 - 0.81) 0.4 0.6 0.8 1 1.2 1.4 99% or 95% CI Statin better Control better CTT2. Lancet 2010;376:1670–81

Statin vs control: Proportional effects on vascular events per mmol/L LDL-C reduction, by baseline LDL No. of events (% pa) Relative risk (CI) per Statin/more Control/less mmol/L LDL-C reduction More vs less statin <2.0 704 (17.9%) 795 (20.2%) 0.71 (0.52 - 0.98) ³2,<2.5 1189 (18.4%) 1317 (20.8%) 0.77 (0.64 - 0.94) ³2.5,<3.0 1065 (20.1%) 1203 (22.2%) 0.81 (0.67 - 0.97) ³3,<3.5 517 (20.4%) 633 (25.8%) 0.61 (0.46 - 0.81) ³3.5 303 (23.9%) 398 (31.2%) 0.64 (0.47 - 0.86) 3837 (19.4%) 4416 (22.3%) 0.72 (0.66 - 0.78) Total Statin vs control 206 (9.0%) 217 (9.7%) 0.87 (0.60 - 1.28) <2.0 ³2,<2.5 339 (7.7%) 412 (9.1%) 0.77 (0.62 - 0.97) ³2.5,<3.0 801 (8.2%) 1022 (10.5%) 0.76 (0.67 - 0.86) ³3,<3.5 1490 (10.8%) 1821 (13.3%) 0.77 (0.71 - 0.84) 4205 (12.6%) 5338 (15.9%) 0.80 (0.77 - 0.84) ³3.5 7136 (11.0%) 8934 (13.8%) 0.79 (0.77 - 0.81) Total All trials 910 (14.7%) 1012 (16.4%) 0.78 (0.61 - 0.99) <2.0 ³2,<2.5 1528 (14.0%) 1729 (15.9%) 0.77 (0.67 - 0.89) ³2.5,<3.0 1866 (12.4%) 2225 (14.7%) 0.77 (0.70 - 0.85) ³3,<3.5 2007 (12.3%) 2454 (15.2%) 0.76 (0.70 - 0.82) 4508 (13.0%) 5736 (16.5%) 0.80 (0.76 - 0.83) ³3.5 10973 (13.0%) 13350 (15.8%) 0.78 (0.76 - 0.80) Total 99% or 95% CI 0.5 0.75 1 1.25 1.5 Statin/more better Control/less better CTT2. Lancet 2010;376:1670–81

Statin vs control: Proportional effects on cause- specific mortality per mmol/L LDL-C reduction No. of deaths(% pa) Relative risk (CI) per Statin/more Control/less mmol/L LDL-C reduction Vascular causes CHD 1887 (0.5%) 2281 (0.6%) 0.80 (0.74 - 0.87) 1446 (0.4%) 1603 (0.4%) 0.89 (0.81 - 0.98) Other cardiac 3333 (0.9%) 3884 (1.1%) 0.84 (0.80 - 0.88) All cardiac 153 (0.0%) 139 (0.0%) 1.04 (0.77 - 1.41) Ischaemic stroke Haemorrhagic stroke 102 (0.0%) 89 (0.0%) 1.12 (0.77 - 1.62) 228 (0.1%) 273 (0.1%) 0.85 (0.66 - 1.08) Unknown stroke Stroke 483 (0.1%) 501 (0.1%) 0.96 (0.84 - 1.09) 404 (0.1%) 409 (0.1%) 0.98 (0.81 - 1.18) Other vascular Any vascular 4220 (1.2%) 4794 (1.3%) 0.86 (0.82 - 0.90) Non-vascular 1781 (0.5%) 1798 (0.5%) 0.99 (0.91 - 1.09) Cancer Respiratory 224 (0.1%) 237 (0.1%) 0.88 (0.70 - 1.11) 127 (0.0%) 127 (0.0%) 0.98 (0.70 - 1.38) Trauma 811 (0.2%) 832 (0.2%) 0.96 (0.83 - 1.10) Other non-vascular Any non-vascular 2943 (0.8%) 2994 (0.8%) 0.97 (0.92 - 1.03) 479 (0.1%) 539 (0.1%) 0.87 (0.76 - 0.99) Unknown death Any death 7642 (2.1%) 8327 (2.3%) 0.90 (0.87 - 0.93) 99% or 95% CI 0.4 0.6 0.8 1 1.2 1.4 Statin/more better Control/less better CTT2. Lancet 2010;376:1670–81

Statin vs control: Proportional effects on site specific cancer per mmol/L LDL-C reduction No. of first cancers (% pa) Relative risk (CI) per mmol/L LDL-C reduction Statin/more Control/less 1166 (0.3%) 1194 (0.3%) 0.97 (0.87 – 1.09) Gastrointestinal 1596 (0.5%) 1645 (0.5%) 0.97 (0.88 – 1.06) Genitourinary 813 (0.2%) 814 (0.2%) 1.00 (0.88 – 1.15) Respiratory 267 (0.3%) 241 (0.3%) 1.07 (0.84 – 1.38) Female breast 305 (0.1%) 291 (0.1%) 1.04 (0.84 – 1.30) Haematological Melanoma 159 (0.0%) 142 (0.0%) 1.14 (0.83 – 1.56) Other/unknown 754 (0.2%) 737 (0.2%) 1.04 (0.89 – 1.21) Any 5060 (1.4%) 5064 (1.4%) 1.00 (0.96 – 1.04) 99% or 95% CI 0.4 0.6 0.8 1 1.2 1.4 Statin/more Control/less better better CTT2. Lancet 2010;376:1670–81

Statin vs more statin: Proportional effects on major vascular events per extra 1 mmol/L LDL reduction (5 more vs . less statin trials, 39,612 subjects) No. of events (% pa) Relative risk (CI) More statin Less statin 1175 (1.3%) 1380 (1.5%) 0.85 (0.76 - 0.94) Nonfatal MI 645 (0.7%) 694 (0.7%) 0.93 (0.81 - 1.07) CHD death Any major coronary event 1725 (1.9%) 1973 (2.2%) 0.87 (0.81 - 0.93) 637 (0.7%) 731 (0.9%) 0.86 (0.75 - 0.99) CABG 1166 (1.3%) 1508 (1.8%) 0.76 (0.69 - 0.84) PTCA Unspecified 447 (0.5%) 502 (0.6%) 0.87 (0.74 - 1.03) Any coronary revascularisation 2250 (2.6%) 2741 (3.2%) 0.81 (0.76 - 0.85) 440 (0.5%) 526 (0.6%) 0.84 (0.71 - 0.99) Ischaemic stroke Haemorrhagic stroke 69 (0.1%) 57 (0.1%) 1.21 (0.76 - 1.91) 63 (0.1%) 80 (0.1%) 0.79 (0.51 - 1.21) Unknown stroke Any stroke 572 (0.6%) 663 (0.7%) 0.86 (0.77 - 0.96) Any major vascular event 3837 (4.5%) 4416 (5.3%) 0.85 (0.82 - 0.89) 0.4 0.6 0.8 1 1.2 1.4 More statin better Less statin better 99% or 95% CI CTT2. Lancet 2010;376:1670–81

Effects on major vascular events per mmol/L LDL-C reduction by years of treatment Events (%) RR & CI Rate Ratio Year Treatment Control (Treatment : Control) (CI) 0-1 year 1747 (3·9) 1951 (4·3) 0·90 (0.85 – 0·96) 1-2 years 1231 (2·9) 1603 (3·8) 0·78 (0·73 – 0·83) 2-3 years 1151 (2·8) 1543 (3·9) 0·74 (0·69 – 0·79) 3-4 years 946 (2·6) 1306 (3·8) 0·72 (0·67 – 0·78) 4-5 years 811 (2·9) 993 (3·7) 0·79 (0·74 – 0·86) 5+ years 468 (2·8) 598 (3·8) 0·74 (0·67 – 0·82) Overall 6354 (14·1) 7994 (17·8) 0·79 (0·77 – 0·81) p < 0·00001 Test for trend: c 2 = 13·9; p = 0·0002 0·5 1·0 1·5 Treatment Control better better Cholesterol Trialists Collaboration, Lancet 2005

Statins – similar reductions in CV events in diabetes versus non diabetes (per 1 mmol/L or 39mg/dl lower LDL-C) CTT Lancet 2 0 0 8 , 3 7 1 , 1 1 7 -2 5

Efficacy of fibrates in CV risk reduction Lee M, Efficacy of fibrates for CV risk reduction: a meta-analysis. Atherosclerosis, 2011 a

Fibrates and CVD risk reduction in those with atherogenic dyslipidemia TG>1.7mmol/L & HDL <1mmol/L Sacks et al NEJM 2010

IMPROVE-IT: Reduction in endpoints driven by reductions in MI and ischemic stroke Ezetimibe did not significantly reduce all-cause death, CV death, or CHD death Ezetimibe Placebo 20 HR 0.99 HR 0.87 RRR 1% RRR 13% p=0.782 p=0.002 15,4 15,3 14,8 15 13,1 Patients (%) HR 1.00 RRR 0% HR 0.96 10 p=0.997 RRR 4% HR 0.86 HR 0.79 p=0.499 RRR 14% 6,9 6,8 RRR 21% p=0.052 5,8 5,7 p=0.008 4,8 5 4,2 4,2 3,4 0 All-cause CV death CHD death MI Stroke Ischemic death stroke *CV death, MI, hospital admission for UA, revascularization, or stroke; † Death due to any cause, major coronary event, or nonfatal stroke; ‡ CHD death, nonfatal MI, or urgent coronary revascularization; § CV death, nonfatal MI, hospital admission for UA, revascularization, and nonfatal stroke Cannon C. AHA, Chicago, IL, November 17 2014; LBCT.02