1. MANAGEMENT OF HYPPERTENSION IN T2DM TRIALS, TRIBULATIONS, GUIDELINES AND GOALS Dr.Dr. RajeevRajeev AgarwalaAgarwala Jaswant Rai Speciality Hospital Meerut.Jaswant Rai Speciality Hospital Meerut. Email : rajeev_jrsh@yahoo.co.inEmail : rajeev_jrsh@yahoo.co.in

2. Rev. Stephen Hales (1677-1761) BP = 8 feet 3 inches of water 3. April 12, 1945 4. PROFILE OF THE DISEASE 5. How Common is this Duo? HTN is twice as common in DMHTN is twice as common in DM New onset DM is 2.5 times in HTN 20 to 40% of IGT pts have HTN20 to 40% of IGT pts have HTN 40 to 50% of Type 2 DM have HTN40 to 50% of Type 2 DM have HTN Only 1/4 of HTN in DM is controlledOnly 1/4 of HTN in DM is controlled DM + HTN CV Risk 3 foldDM + HTN CV Risk 3 fold 6. Relative Risk of DM + HTN Diabetes + HTN versus Diabetes Neuropathy 1.6 Nephropathy 2.0 Retinopathy 2.0 Stroke 4.0 CHD 3.0 Mortality 2.0 7. MRFIT: Association of Systolic BP and Cardiovascular Death in Type 2 Diabetes 250 225 200 175 150 125 100 75 50 0 25 < 120 120 139 140159 160179 180199 200 Systolic blood pressure (mm Hg) Cardiovascular mortality rate/10,000 person-yr Nondiabetic Diabetic Stamler J et al. Diabetes Care. 1993;16:434-444./ hypertensiononline.org 8. Meta-analysis of 61 prospective, observational studies One million adults, 12.7 million person-years 2 mmHg decrease in mean SBP 10% reduction in risk of stroke mortality 7% reduction in risk of ischaemic heart disease mortality Lowering BP reduces cardiovascular risk Lewington et al. Lancet. 2002;360:19031913 Small SBP reductions yield significant benefit Lesson learned Community based approach & Individual Approach 9. UKPDS: Tight blood control and risk of macrovascular and microvascular complications in T2DM 1148 patients randomized to right control or less tight control Tight control defined as < 150/85 mm Hg Less tight control defined as < 180/105 mm Hg Half of tight control to ACE inhibitors (captopril) and half to beta blockers (atenolol) Mean follow-up of 8.4 years Part of larger UKPDS with follow-up every 3-4 months 10. UKPDS 38: tight control had a greater effect on blood pressure Bloodpressure(mmHg) Baseline 9 years 0 140 145 150 155 160 165 Tight Less tight Systolic BP 0 78 80 82 84 86 88 90 92 94 96 Baseline 9 years Diastolic BP UKPDS 38: BMJ 1998;317:70313 11. UKPDS: Results Mean blood pressure during follow-up Tight control: 144/82 mm Hg Less tight control: 154/87 mm Hg 1/3 patients in tight control group required 3 or more medications 24% decrease in diabetes-related endpoints 32% decrease in deaths related to diabetes 37% decrease in microvascular endpoints Mostly related to reduced risk of laser treatment 44% decrease in strokes BMJ 317: 703, 1998 12. UKPDS 38: relative risk reduction with tight blood pressure control -60 -50 -40 -30 -20 -10 0 Relativeriskreductiontightvs lesstightBPcontrol(%) M icrovascular endpoint D iabetes death M I All-cause m ortality Stroke Peripheralvascular disease Any diabetes endpoint ** * p < 0.05 ** p < 0.01 ** * * UKPDS 38: BMJ 1998;317:70313 13. Risk reduction (%) in the UKPDS Participants: Initial results & 10-years follow-up UKPDS 38: BMJ 1998;317:70313 NEJM 2008;359:1565-76 14. UKPDS 38: Antihypertensive requirements for tight BP control UKPDS Study Group. BMJ. 1998;317:703-13. 0 20 40 60 80 100 % of patients Number of antihypertensive agents 3 2 1 0 Mean BP in tight control group: 144/82 mm Hg 1 2 3 4 5 6 7 8 Years from randomization 15. HOT: Hypertension Optimal Treatment 18,790 patients from 26 countries, age 50 -80, and diastolic blood pressure 100-115 mm Hg were recruited Patients were randomized to 3 groups based on diastolic pressure goal (< 90, < 85, and < 80 mm Hg) Primary endpoint was composite macrovascular outcome of non-fatal MI, non-fatal stroke, or CV death Major finding was that patients with diabetes had a 51% reduction in primary endpoint No increase in side effects. Hansson et al. Lancet 351:1755, 1998 16. HOT Trial: Effect of targeted DBP on CV events over 4 years 17. Clinical Trials of Blood Pressure Lowering in Diabetic Patients: Systolic (SBP) Trial N Mean SBP, less intense Mean SBP, more intense CVD Risk Reduction SHEP 583 155* 146* 22-56% Syst-Eur 492 162 153 62-69% HOT 1,501 148 144 30-67% UKPDS 1,148 154 144 32-44% ABCD 470 138 132 No CVD reduction Cushman, et al. Am J Cardiol 2007;99:44i- 55i 18. ADVANCE 215 centers in 20 countries with 11,140 patients with type 2 diabetes randomized to fixed combination of perindopril and indapamide or matching placebo, Primary endpoints were composites of major macro- and microvascular events Death from CV disease, non-fatal stroke or non-fatal MI New or worsening renal or diabetic eye disease 19. ADVANCE: a factorial randomised trial of blood pressure lowering and intensive glucose control in 11,140 patients with type 2 diabetes Effects of a fixed combination of the ACE inhibitor, perindopril, and the diuretic, indapamide on major vascular events Lancet 2007 Sept 8;370:829-40 Presented at European society of Cardiology, Vienna, 9/2/07 20. ADVANCE RESULTS 4.3 years of follow-up Compared to placebo, there was a drop in pressure of 5.6/2.2 mm Hg There was not a significant decrease in macrovasular (p = 0.16) events or microvascular events (p = 0.16) separately There was a 9% decrease in combination(p=0.04) There was a decrease in CV death (p = 0.03) and death from any cause (p = 0.03) Lancet 370:829, 2007 21. ADVANCE: BLOOD PRESSURE REDUCTION 2.2 mmHg (95% CI 2.0-2.4); p