Twenty-two studies (492 patients) were included: 6 RCTs (164 patients) and 16 non-comparative studies (328 patients).
Of the 6 RCTs, one RCT was a parallel-group unblinded study (70 patients), 3 RCTs were crossover, placebo-controlled blinded studies (44 diabetic patients), and 2 RCTs were randomised open crossover studies with no placebo control (40 patients).
The number of patients per study ranged from 5 to 70. The included studies scored 0.11 to 0.48 on quality. The maximum quality score possible was not reported.
Blood-pressure. The mean decrease in systolic blood-pressure for patients on alpha-blockers (16 studies) was 15.90 mmHg (95% confidence interval, CI: 11.36, 20.44, p<0.0001). Significant heterogeneity was detected (Q=141.41).
The mean decrease in systolic blood-pressure for patients on doxazosin (12 studies) was 15.98 mmHg (95% CI: 10.69, 21.26, p<0.0001). Significant heterogeneity was detected (Q=109.35).
The mean decrease in diastolic blood-pressure for patients on alpha-blockers (18 studies) was 12.11 mmHg (95% CI: 10.09, 14.13, p<0.0001). Significant heterogeneity was detected (Q=57.82).
The mean decrease in diastolic blood-pressure for patients on doxazosin (15 studies) was 12.43 mmHg (95% CI: 10.26, 14.60, p<0.0001). Significant heterogeneity was detected (Q=39.83).
Lipid parameters. The mean change in total cholesterol was -0.26 mmol/L (95% CI: -0.46, -0.06, p<0.02) for all selective alpha1-blockers (12 studies), and -0.28 mmol/L (95% CI: -0.50, -0.05, p<0.002) in the 11 studies that evaluated doxazosin. Significant heterogeneity was found (Q=42.41 and Q=34.43 respectively).
The mean change in HDL cholesterol was 0.12 mmol/L (95% CI: 0.05, 0.19, p<0.02) for all selective alpha1-blockers (12 studies). Significant heterogeneity was found (Q=36.45). The mean change in HDL cholesterol was 0.13 mmol/L (95% CI: 0.06, 0.21, p<0.001) in the 11 studies that evaluated doxazosin. No significant heterogeneity was found (Q=31.94).
The mean change in LDL cholesterol was -0.23 mmol/L (95% CI: -0.42, -0.03, p<0.02) in the 5 studies that evaluated doxazosin. Significant heterogeneity was found (Q=2.43).
Glucose metabolism.
The mean change in glycated haemoglobin was -0.21 (95% CI: -0.51, +0.08), p<0.17) for all selective alpha1-blockers (14 studies). Significant heterogeneity was found (Q=20.64). The mean change was -0.11 (95% CI: -0.41, +0.19, p=0.48) in the 12 studies that evaluated doxazosin. There was no evidence of heterogeneity (Q=7.56).
Side-effects.
The pooled risk difference (14 studies) for withdrawal due to any side-effect was 0.08 (95% CI: 0.06, 0.10). After excluding the 2 studies involving indoramin, the risk difference was zero. No case of syncope was reported in the 10 studies that were monitoring for this effect. Postural hypotension was reported in one doxazosin-treated patient and in three indoramin-treated patients.
Other results that were reported in the review included the triglyceride levels, the ratio of HDL cholesterol to total cholesterol, the insulin sensitivity index, the integrated (AUC) insulin, fasting glucose, and fasting insulin.