DIRECT Programme Baseline Characteristics

Summary of Programme objective and study populations

The primary objective of the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme was to examine primary prevention (incidence) and secondary prevention (progression) of diabetic retinopathy with candesartan in normoalbuminuric, normotensive patients with Type 1 diabetes and secondary prevention only in normoalbuminuric, normotensive or treated hypertensive patients with Type 2 diabetes.

A total of 5,231 patients were randomised to the DIRECT Programme:

1,421 in the primary prevention study in patients with Type 1 diabetes (DIRECT-Prevent 1)
1,905 in the secondary prevention study in patients with Type 1 diabetes (DIRECT-Protect 1)
1,905 in the secondary prevention study in patients with Type 2 diabetes (DIRECT-Protect 2)

Baseline measures

Baseline characteristics of a range of markers were determined in each study group prior to initiation of treatments (Table 1):

HbA1c baseline levels were 8.1%, 8.5% and 8.2% in DIRECT-Prevent 1, DIRECT-Protect 1 and 2 studies, respectively.
The mean baseline systolic/diastolic blood pressure in DIRECT-Prevent 1 was 116/72 mmHg and in DIRECT-Protect 1 117/74 mmHg.
For patients in DIRECT-Protect 2 not treated for hypertension (37%), the mean systolic/diastolic blood pressure was 123/76 mmHg and in patients receiving treatment for hypertension (63%) (Figure 1), the mean systolic/diastolic blood pressure was 139/79 mmHg.
Overnight urine collections showed low urinary albumin excretion rates (UAER) at baseline in all three studies.

Table 1. The DIRECT Programme baseline characteristics, mean (SD)

Baseline characteristics

TIA=transient ischaemic attack, BMI=body mass index, S-HDL=high density lipoprotein, UAER=urinary albumin excretion rate.

Figure 1. Antihypertensive treatment in the patients with Type 2 diabetes and hypertension at baseline. (A) Proportion of patients in specific antihypertensive drug classes, (B) Number of antihypertensive drugs used

Figure 1A

Figure 1B

Baseline eye examinations

Baseline eye examinations revealed that:

In the Type 1 secondary prevention study, DIRECT-Protect 1, 49% of the patients had retinopathy level 20 in at least one eye and only 9% had moderate–moderately severe non-proliferative retinopathy (level 43–47) (Figure 2).
In the Type 2 secondary prevention study, DIRECT-Protect 2, the retinopathy was more pronounced at baseline, with 17% of patients having retinopathy level 43–47 (Figure 3).
Significant correlation with retinopathy levels was found with duration of diabetes (p<0.0001), HbA1c (p<0.0001) and systolic blood pressure (p=0.003) in both the Type 1 and Type 2 patient populations. Diastolic blood pressure was significantly correlated with retinopathy level in patients with Type 1 diabetes (p=0.001).
In the Type 1 population, >90% of patients had visual acuity of ≥1.0 in at least one eye (Figure 4 A and B).
A small proportion of patients with Type 2 diabetes had visual acuity between 0.5 and 0.9 in the worst eye (Figure 4 C).
None of the patients had reduced visual acuity due to diabetic retinopathy in accordance with the exclusion criteria.

Further information

Further details of the baseline characteristics from the three studies in the DIRECT Programme are given in the baseline publication (The DIRECT Programme Study Group. The DIabetic REtinopathy Candesartan Trials (DIRECT) Programme: baseline characteristics. JRAAS 2005;6:25–32).

To download a copy of the publication please click here.

Figure 2. Distribution of retinopathy levels in Direct-Protect 1 at baseline (worst eye)

Figure 3. Distribution of retinopathy levels in DIRECT-Protect 2 at baseline (worst eye)

Figure 4. Baseline visual acuity in DIRECT-Prevent 1 (A), in DIRECT-Protect 1 (B) and DIRECT-Protect 2 (C), worst eye (%) in intervals converted to the Decimal Scale

Figure 4A

Figure 4B

Figure 4C