Thirty trials involving 53 interventions (eight classes of hypertensive drugs) were included in the review (n=20,006). Jadad scores ranged from 2 to 4 in studies with blood pressure outcomes and from 3 to 5 in studies with morbidity and mortality outcomes. Most of the studies were conducted in USA; other countries included South Africa, Nigeria, Jamaica, Bahamas and Zimbabwe.
Blood pressure:
For systolic blood pressure, mean difference ranged from -13.20 (95% CI -16.72 to -9.68) for centrally acting agents to -3.53 (95% CI -7.51 to 0.45) for β-blockers. For diastolic blood pressure, mean difference ranged from -8.06 (95% CI -10.01 to -6.11) for diuretics to -2.09 (95% CI -3.28 to -0.91) for angiotensin II receptor blockers.
There was no pooled effect for calcium channel blockers due to heterogeneity. Calcium channel blockers, diuretics, central sympatholytics, α-blockers and angiotensin II receptor blockers were significantly more effective than placebo in reducing blood pressure (systolic and diastolic).
No statistically significant difference from placebo was found either for β-blockers in reducing systolic blood pressure (WMD -3.53mmHg, 95% CI -7.51 to 0.45) or ACE inhibitors in achieving diastolic blood pressure goals (RR 1.35, 95% CI 0.81 to 2.26).
Evidence of moderate to substantial heterogeneity was found for calcium channel blockers and β-blockers for systolic blood pressure outcomes and calcium channel blockers, diuretics, ACE inhibitors and α-blockers for diastolic blood pressure outcomes. Only calcium channel blockers remained effective in all prespecified subgroups, including patients with a baseline diastolic blood pressure of 110mmHg or more.
Diastolic blood pressure goal was defined as diastolic blood pressure ≤90mmHg or reduction of diastolic blood pressure of ≥10mmHg (or 10% reduction). The percentage of patients who reached diastolic blood pressure goal was 23%; this ranged from 0% (postganglionic sympathetic neuron blockers) to 46% (calcium channel blockers).
Sensitivity analyses:
These revealed a significant difference in favour of β-blockers compared to placebo for systolic blood pressure and a significant difference in favour of ACE inhibitors for reaching blood pressure goal. Sensitivity analyses did not significantly alter the magnitude of effect for any other outcome reported.
Morbidity and mortality:
When drugs were combined to reach blood pressure goals, no statistically significant between-group differences were found for morbidity and mortality outcomes (based on data from four trials).
Adverse effects:
Adverse events were reported in 12 trials and occurred more frequently with drugs than with placebo. In particular, a greater incidence of diabetes was found with diuretics and a higher risk of cardiovascular events was found with drug regimens that included angiotensin-converting enzyme inhibitors. Studies with higher drug doses did not appear to report greater frequency of adverse events.