1 / 58

Lowering sugars in diabetes – a cardiovascular waste of time?

Lowering sugars in diabetes – a cardiovascular waste of time?. Hamish Courtney Regional Endocrine Centre Royal Victoria Hospital Belfast. OASIS Study: Total Mortality. Diabetes/CVD (n = 1148). RR=2.88 (2.37–3.49). Diabetes/No CVD (n = 569). No Diabetes/CVD (n = 3503).

knoton
Télécharger la présentation

Lowering sugars in diabetes – a cardiovascular waste of time?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lowering sugars in diabetes – a cardiovascular waste of time? Hamish Courtney Regional Endocrine Centre Royal Victoria Hospital Belfast

  2. OASIS Study: Total Mortality Diabetes/CVD (n = 1148) RR=2.88 (2.37–3.49) Diabetes/No CVD (n = 569) No Diabetes/CVD (n = 3503) No Diabetes/No CVD (n = 2796) RR=1.99 (1.52–2.60) Event Rate RR=1.71 (1.44–2.04) RR=1.00 3 6 9 12 15 18 21 24 Months Malmberg K et al. Circulation 2000;102:1014-1019.

  3. Estimates of Diabetes Prevalence in World Regions Estimated prevalence (millions) 2000 1995 2025 Africa Americas EasternMediterranean Europe SoutheastAsia WesternPacific WHO Report 1997. World Health Organization. Geneva;1997.

  4. How low can you go.....safely?

  5. UKPDS United Kingdom Prospective Diabetes Study

  6. Main Randomisationn=4209 (82%) 342 allocated to metformin 3867 Conventional Policy30% (n=1138) Intensive Policy70% (n=2729) Insulinn=1156 Sulphonylurean=1573 UKPDS

  7. HbA1c

  8. UKPDS Microvascular Endpoints

  9. OASIS Study: Total Mortality Diabetes/CVD (n = 1148) RR=2.88 (2.37–3.49) Diabetes/No CVD (n = 569) No Diabetes/CVD (n = 3503) No Diabetes/No CVD (n = 2796) RR=1.99 (1.52–2.60) Event Rate RR=1.71 (1.44–2.04) RR=1.00 3 6 9 12 15 18 21 24 Months Malmberg K et al. Circulation 2000;102:1014-1019.

  10. 5 p<0.0001 Hazard ratio 1 14% change per 1% change in HbA1c 0 . 5 0 5 6 7 8 9 1 0 1 1 Updated mean HbA1c UKPDS 35. BMJ 2000; 321: 405-12 Fatal and Non-Fatal Myocardial Infarction

  11. 30 20 10 0 UKPDS and myocardial infarction Conventional Intensive p=0.06 % of patients with MI Risk reduction 16% (CI 95%: 0-29%) 0 3 6 9 12 15 Years after randomisation UKPDS 33 Lancet. 1998;352:837-853

  12. 0 UKPDS and myocardial infarction 40 Conventional (896) Chlorpropamide (619) Glibenclamide (615) 30 Insulin (911) % of patients with MI 20 10 CvGv IP =0.66 15 0 3 6 9 12 Years after randomisation

  13. Myocardial Infarction Mv Cp=0.010 Mv Ip=0.12

  14. University Group Diabetes Program (UGDP) North-American multicentre study Duration: 8 years (1961-1969) 1027 patients randomised into 5 groups Placebo - diet Tolbutamide - fixed dosage 1.5 g/d Phenformin - fixed dosage 100 mg/d Insulin - fixed dosage Insulin - adjusted dosage Klimt et al. Diabetes. 1970;19(suppl 2):747-783

  15. UGDP Meinert et al. Diabetes. 1970;19(suppl 2):789-830

  16. Intensive glycaemic control Does intensive glycaemic control reduce cardiovascular outcomes in T2DM? - ACCORD - ADVANCE - VADT - UKPDS follow up

  17. ACCORD Glycaemic intervention Intensive (HbA1c <6%) vs Standard (HbA1c 7.0-7.9%) Primary end point nonfatal MI, stroke or cardiovascular death

  18. Glycaemic Control N Engl J Med 2008;358:2545-2559

  19. ACCORD: Glucose-lowering drugs Patients (%) Intensive therapy(n = 5128) Standard therapy(n = 5123) Metformin 94.7 86.9 SU 86.6 73.8 Thiazolidinedione 91.7 58.3 α-Glucosidase inhibitor 23.2 5.1 Incretin 17.8 4.9 Insulin 77.3 55.4 N Engl J Med 2008;358:2545-2559

  20. ACCORD Primary Outcome N Engl J Med 2008;358:2545-2559

  21. ADVANCE Glycaemic intervention Intensive using gliclazide (HbA1c <6.5%) vs Standard (HbA1c to local guidelines) Primary end point composite macrovascular and microvascular events

  22. ADVANCE: Glucose-lowering drugs • ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-72.

  23. ADVANCE: primary macrovascular outcome CV death, MI, stroke 25 20 HR 0.94 (0.84-1.06)P = 0.32 Standard control 15 Cumulative incidence (%) 10 Intensive control 5 0 0 6 12 18 24 30 36 42 48 54 60 66 Follow-up (months) • ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-72.

  24. ADVANCE: all-cause mortality 25 20 HR 0.93 (0.83-1.06)P = 0.28 Standard control 15 Cumulative incidence (%) 10 Intensive control 5 0 0 6 12 18 24 30 36 42 54 60 66 48 Follow-up (months) • ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-72.

  25. ADVANCE: primary microvascular outcome New/worsening nephropathy, retinopathy 25 20 HR 0.86 (0.77-0.97)P = 0.01 Standard control 15 Cumulative incidence (%) 10 Intensive control 5 0 0 6 12 18 24 30 36 42 48 54 60 66 Follow-up (months) • ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-72.

  26. VADT Glycaemic intervention Intensive (HbA1c <6.0%) vs Standard (HbA1c to local guidelines) Primary end point composite macrovascular event

  27. VADT Duckworth W et al. N Engl J Med 2009;360:129-139

  28. VADT Duckworth W et al. N Engl J Med 2009;360:129-139

  29. Reasons? Drugs used?

  30. ACCORD: Glucose-lowering drugs Patients (%) Intensive therapy(n = 5128) Standard therapy(n = 5123) Metformin 94.7 86.9 SU 86.6 73.8 Thiazolidinedione 91.7 58.3 α-Glucosidase inhibitor 23.2 5.1 Incretin 17.8 4.9 Insulin 77.3 55.4 N Engl J Med 2008;358:2545-2559

  31. Reasons? Drugs used? Increase in hypoglycaemia? Increase in weight? Too rapid reduction in HbA1c?

  32. Glycaemic Control N Engl J Med 2008;358:2545-2559

  33. Reasons? Drugs used? Increase in hypoglycaemia? Increase in weight? Too rapid reduction in HbA1c? Chance?

  34. 30 20 10 0 UKPDS and myocardial infarction Conventional Intensive p=0.06 % of patients with MI Risk reduction 16% (CI 95%: 0-29%) 0 3 6 9 12 15 Years after randomisation UKPDS 33 Lancet. 1998;352:837-853

  35. UKPDS resultspresented Post-Trial Changes in HbA1c Mean (95%CI)

  36. Intervention TrialMedian follow-up 10.0 years Intervention Trial + Post-trial monitoringMedian follow-up 16.8 years RR=0.88 (0.79-0.99) P=0.029 Conventional Sulfonylurea/Insulin Conventional Sulfonylurea/Insulin Any Diabetes-related Endpoint

  37. (fatal or non-fatal myocardial infarction or sudden death) Intensive (SU/Ins) vs. Conventional glucose control HR (95%CI) Myocardial Infarction Hazard Ratio

  38. Intensive (SU/Ins) vs. Conventional glucose control HR (95%CI) All-cause Mortality Hazard Ratio

  39. Aggregate Endpoint19972007 Any diabetes related endpoint RRR: 12% 9% P: 0.029 0.040 Microvascular disease RRR: 25% 24% P:0.0099 0.001 Myocardial infarction RRR: 16% 15% P:0.052 0.014 All-cause mortality RRR: 6% 13% P:0.44 0.007 RRR = Relative Risk Reduction, P = Log Rank Legacy Effect of Earlier Glucose Control

  40. ACCORD/ADVANCE 25 20 N Engl J Med 2008;358:2545-2559 Standard control 15 Cumulative incidence (%) 10 Intensive control 5 0 0 6 12 18 24 30 36 42 48 54 60 66 Follow-up (months) • N Engl J Med. 2008;358:2560-72.

More Related