1. UKHDS (UKPDS): UK Hypertension in Diabetes Study Purpose To determine whether tight control of blood pressure (aiming for BP <150/85 mmHg) reduces/prevents complications and reduces mortality in hypertensive patients with type 2 diabetes Reference UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703 – 13.

2. UKHDS (UKPDS): UK Hypertension in Diabetes Study - TRIAL DESIGN - Design Randomized, open, controlled trial Patients 1148 hypertensive patients with type 2 diabetes, mean age 56 years, mean BP at entry 160/94 mmHg Follow up and primary endpoint Mean follow up 8.4 years. Primary endpoints morbidity and mortality related to diabetes and all-cause mortality Treatment Tight control of BP with ACE inhibitor (captopril) or beta-blocker (atenolol) aiming for BP <150/85 mmHg, or less tight control aiming for BP <180/105 mmHg. Other agents added if control criteria not met (frusemide, nifedipine, methyldopa and prazosin)

3. UKHDS (UKPDS): UK Hypertension in Diabetes Study - RESULTS: BP Control and side effects - Mean BP during follow up maintained at significantly lower level in group assigned to tight control (144/82 mmHg) than in group assigned to less tight control (154/87 mmHg) 29% of patients in group assigned to tight control required three or more antihypertensive treatments to maintain BP at target levels No significant difference in cumulative incidence of hypoglycemia in groups assigned to tight (6.1%) and less tight (4.4%) BP control Mean weight gain similar in both groups (1.3 and 2.0 kg, respectively, P=0.13)

4. UKHDS (UKPDS): UK Hypertension in Diabetes Study - RESULTS: BP Control and side effects - Mean systolic and diastolic BP Years from randomization 0 80 321456789 100 140 160Blood pressure (mmHg) Less tight control (n=156) Tight control (n=297) UK Prospective Diabetes Study Group. BMJ 1998;317:703–13.

5. UKHDS (UKPDS): UK Hypertension in Diabetes Study - RESULTS: Morbidity and mortality - Group assigned tight BP control had significant reduction in: —All diabetes-related endpoints combined —Death related to diabetes —Stroke (fatal or non-fatal) —Microvascular end points combined (predominantly due to significantly reduced risk of retinal photocoagulation) —Heart failure Less deterioration of retinopathy and visual acuity in group assigned tight BP control Trends towards reduction in MI, PVD, amputation, fatal/non-fatal renal failure and all-cause mortality were not significant

6. UKHDS (UKPDS): UK Hypertension in Diabetes Study - RESULTS: : Morbidity and mortality - Tight control (n=758) P Clinical events per 1000 patient years UK Prospective Diabetes Study Group.BMJ 1998;317:703–13. Less tight control (n=390) Relative risk for tight control (95% CI) Clinical end point a Any diabetes-related endpoint50.967.40.76 (0.62–0.92)0.0046 b Death related to diabetes13.720.30.68 (0.49–0.94)0.019 All-cause mortality22.427.20.82 (0.63–1.08)0.17 c Myocardial infarction18.623.50.79 (0.59–1.07)0.13 Stroke (fatal and non-fatal)6.511.60.56 (0.35–0.89)0.013 Peripheral vascular disease1.42.70.51 (0.19–1.37)0.17 Microvascular disease12.019.20.63 (0.44–0.89)0.0092 Retinal photocoagulation10.216.60.65 (0.39–1.06)0.023 Heart failure3.68.10.44 (0.20–0.94)0.0043 a Sudden death, death from hyper/hypoglycemia, fatal/non-fatal MI, angina, heart failure, stroke, renal failure, amputation, vitreous hemorrhage, retinal photocoagulation, blindness in one eye or cataract extraction b Death due to MI, sudden death, stroke, peripheral vascular disease, renal disease, hyper/hypoglycemia c Fatal/non-fatal MI, or sudden death

7. UKHDS (UKPDS): UK Hypertension in Diabetes Study - RESULTS: : Morbidity and mortality - Tight control (%) P Progression of retinopathy and deterioration in vision UK Prospective Diabetes Study Group. BMJ 1998;317:703–13. Less tight control (%) Relative risk for tight control (95% Cl) Progression of retinopathy by > 2 steps Median 1.5 years Median 4.5 years Median 7.5 years Deterioration in vision by > 3 ETDRS lines a Median 1.5 years Median 4.5 years Median 7.5 years 20.2 27.5 34.0 5.4 7.5 10.2 23.1 36.7 51.3 6.8 8.9 19.4 0.88 (0.60–1.29) 0.75 (0.55–1.02) 0.66 (0.50–0.89) 0.79 (0.39–1.62) 0.83 (0.44–1.59) 0.53 (0.30–0.93) 0.38 0.019 0.0038 0.39 0.47 0.0036 a ETDRS = early treatment of diabetic retinopathy study

8. UKHDS (UKPDS): UK Hypertension in Diabetes Study - SUMMARY - In hypertensive patients with type 2 diabetes, long-term tight BP control aiming to keep BP <150/85 mmHg by use of an ACE inhibitor or beta-blocker (plus additional anti-hypertensive treatment if necessary): Achieved mean BP of 144/82 mmHg Reduced risk of diabetic complications and death related to diabetes Reduced risk of progression of diabetic retinopathy and deterioration in visual acuity