The quality of evidence is downgraded by study limitations (lack of blinding) and by suspected publication bias (in labetalol studies).
A Cochrane review [Abstract] 1 included 8 studies with a total of 1 493 hypertensive subjects. Four studies examined the blood pressure (BP) lowering efficacy of 6.25 to 50 mg/day carvedilol in 1 381 mild to moderate hypertensive patients, and 4 studies examined the BP lowering efficacy of 400 to 800 mg/day labetalol in 112 hypertensive patients.
The average trough BP lowering effect of once (12.5 mg/day) and twice (25 mg/day) the recommended starting dose of carvedilol was -4 (95% CI -6 to -2) / -3 (95% CI -4 to -2) mmHg (>1000 subjects). Carvedilol, within the recommended dose range, did not show a significant dose response effect for systolic blood pressure (SBP) or diastolic blood pressure (DBP). Carvedilol had little or no effect on pulse pressure (-1 mm Hg) and did not change BP variability. The average peak BP lowering effect of labetalol at twice (400 mg/day labetalol) the recommended starting dose was -10 (95% CI -14 to -7) / -7 (95% CI -9 to -5) mmHg (n=110). Data for 200 mg/day labetalol (the recommended starting dose) was not found.
Overall results for once and twice the starting dose of carvedilol and labetalol are shown in table T1. Based on indirect comparison with other classes of drugs, the blood pressure lowering effect of dual alpha- and beta-receptor blockers was less than non-selective, beta1-selective and partial agonist beta blockers, as well as thiazides and drugs inhibiting the renin angiotensin system. Dual blockers also had little or no effect on reducing pulse pressure, which is similar to the other beta-blocker classes, but less than the average reduction of pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin system.
| Outcome | Mean estimate (95% CI)* | Participants (studies) |
|---|---|---|
| Systolic blood pressure | MD -5.59 (95% CI -7.47 to -3.70) mmHg | 1 007 (8 studies) |
| Diastolic blood pressure | MD -3.88 (95% CI -4.95 to -2.82) mmHg | 1 007 (8 studies) |
| Heart rate | MD -4.62 (95% CI -5.71 to -3.54) mmHg | 977 (7 studies) |
| Pulse pressure | MD -1.89 (95% CI -3.58 to -0.20) mmHg | 1 007 (8 studies) |
| Withdrawal due to adverse effects | RR 0.88 (95% CI 0.54 to 1.42) | 1 412 (5 studies) |
| * Mean estimates of combining once and twice starting dose; MD = mean difference; RR = relative risk | ||
Clinical comments
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