Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38
Guarantor: R C Turner.
Objective: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes.
Design: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of <150/85 mm Hg (with the use of an angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment) with less tight control aiming at a blood pressure of <180/105 mm Hg.
Setting: 20 hospital based clinics in England, Scotland, and Northern Ireland.
Subjects: 1148 hypertensive patients with type 2 diabetes (mean age 56, mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years.
Main outcome measures: Predefined clinical end points, fatal and non-fatal, related to diabetes, deaths related to diabetes, and all cause mortality. Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography.
Results: Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg) (P<0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related end points (95% confidence interval 8% to 38%) (P=0.0046), 32% in deaths related to diabetes (6% to 51%) (P=0.019), 44% in strokes (11% to 65%) (P=0.013), and 37% in microvascular end points (11% to 56%) (P=0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34% reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P=0.0004) and a 47% reduced risk (7% to 70%) (P=0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart. After nine years of follow up 29% of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures.
Conclusion: Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity.
This study showed that tight control of blood pressure based on captopril or atenolol as first agents and aiming for both a systolic blood pressure <150 mm Hg and diastolic pressure <85 mm Hg achieved a mean 144/82 mm Hg compared with 154/87 mm Hg in a control group
29% of patients in the tight control group required three or more hypotensive treatments
Tight control of blood pressure reduced the risk of any non-fatal or fatal diabetic complications and of death related to diabetes; deterioration in visual acuity was also reduced
Reducing blood pressure needs to have high priority in caring for patients with type 2 diabetes
HDL=high density lipoprotein.
LDL=low density lipoprotein.
We appreciate the cooperation of the patients and many NHS and non-NHS staff at the centres. We thank Philip Bassett for editorial assistance, and Caroline Wood, Kathy Waring, and Lorraine Mallia for typing the manuscripts.
Members of the study group are given at the end of the paper.
Funding: The UK prospective diabetes study and the hypertension in diabetes study was funded by grants from the Medical Research Council, British Diabetic Association, Department of Health, the United States National Eye Institute and the United States National Institute of Diabetes, Digestive and Kidney Disease in the National Institutes of Health, the British Heart Foundation, the Charles Wolfson Charitable Trust, the Clothworkers’ Foundation, the Health Promotion Research Trust, the Alan and Babette Sainsbury Trust, the Oxford University Medical Research Fund Committee, and pharmaceutical companies, including Novo-Nordisk, Bayer, Bristol-Myers Squibb, Hoechst, Lilly, Lipha, and Farmitalia Carlo Erba. GlaxoWellcome, SmithKline Beecham, Pfizer, Zeneca, Pharmacia and Upjohn, and Roche provided grants for health economics and epidemiological studies. Boehringer Mannheim, Becton Dickinson, Owen Mumford, Securicor, Kodak, and Cortecs Diagnostics gave additional help.
Conflict of interest: None.
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