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

ReferenceUK 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.

UKHDS (UKPDS): UK Hypertension in Diabetes Study- TRIAL DESIGN -

DesignRandomized, open, controlled trial

Patients1148 hypertensive patients with type 2 diabetes, mean age 56 years, mean BP at entry 160/94 mmHg

Follow up and primary endpointMean follow up 8.4 years. Primary endpoints morbidity and mortality related to diabetes and all-cause mortality

TreatmentTight 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)

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)

UKHDS (UKPDS): UK Hypertension in Diabetes Study- RESULTS: BP Control and side effects -

Mean systolic and diastolic BP

Years from randomization

0

80

321 4 5 6 7 8 9

100

140

160Blood pressure(mmHg)

Less tight control(n=156)

Tight control(n=297)

UK Prospective Diabetes Study Group. BMJ 1998;317:703–13.

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

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 tightcontrol (n=390)

Relative risk for tightcontrol (95% CI)

Clinical end point

aAny diabetes-related endpoint 50.9 67.4 0.76 (0.62– 0.92) 0.0046 bDeath related to diabetes 13.7 20.3 0.68 (0.49– 0.94) 0.019

All-cause mortality 22.4 27.2 0.82 (0.63– 1.08) 0.17 cMyocardial infarction 18.6 23.5 0.79 (0.59– 1.07) 0.13

Stroke (fatal and non-fatal) 6.5 11.6 0.56 (0.35– 0.89) 0.013

Peripheral vascular disease 1.4 2.7 0.51 (0.19– 1.37) 0.17

Microvascular disease 12.0 19.2 0.63 (0.44– 0.89) 0.0092 Retinal photocoagulation 10.2 16.6 0.65 (0.39 – 1.06) 0.023 Heart failure 3.6 8.1 0.44 (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/hypoglycemiac Fatal/non-fatal MI, or sudden death

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 tightcontrol (%)

Relative risk for tightcontrol (95% Cl)

Progression of retinopathyby > 2 steps

Median 1.5 yearsMedian 4.5 yearsMedian 7.5 years

Deterioration in visionby > 3 ETDRS lines a

Median 1.5 yearsMedian 4.5 yearsMedian 7.5 years

20.227.534.0

5.47.5

10.2

23.136.751.3

6.88.919.4

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)

0.380.019

0.0038

0.390.47

0.0036

a ETDRS = early treatment of diabetic retinopathy study

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