ALPHA-2 AGONISTS













Clonidine vs Propranolol vs Placebo for Hypertension, Br J Clin Pharmacol (1977) [PubMed abstract]
  • A small crossover study published in 1977 enrolled 32 patients with hypertension
Main inclusion criteria
  • DBP 105 - 129 mmHg on at least 3 separate occasions over a month
  • Hypertension that was previously untreated or uncontrolled on meds
Main exclusion criteria
  • Renal failure
  • Heart failure
  • MI in the previous year
Baseline characteristics
  • Median age 54 years
  • Average SBP ∼ 187 mmHg, DBP ∼ 116 mmHg
  • Median duration of hypertension - 2 years
  • Previous treatment with BP meds - 63%
Randomized treatment groups
  • Group 1 - Clonidine titrated to effect. Average dose at the end of 12 weeks was 0.540 mg/day.
  • Group 2 - Propranolol titrated to effect. Average dose at the end of 12 weeks was 576 mg/day.
  • Group 3 - Placebo
  • Patients received each therapy for 12 weeks with a 2-week washout period between each regimen
Primary outcome: average blood pressure at the end of the 12-week treatment period
Results

Duration: 12 weeks on each regimen
Outcome Clonidine Propranolol Placebo Comparisons
Primary outcome (average BP) 167/101 168/101 185/114 1 and 2 vs 3 p<0.01 | 1 vs 2 p>0.05
Average pulse 74 66 80 1 and 2 vs 3 p<0.05 | 1 vs 2 p<0.01
  • Two-thirds of the patients in the clonidine group complained of drowsiness and dry mouth while taking clonidine

Findings: Clonidine and propranolol were equipotent in reducing blood pressure, but clonidine has more initial side-effects than propranolol
Clonidine vs Others for Hypertension in Male Veterans, NEJM (1993) [PubMed abstract]
  • The Veterans Affairs Cooperative study enrolled 1292 men with hypertension
Main inclusion criteria
  • Male veteran
  • DBP 95 - 109 mmHg off medications
Baseline characteristics
  • Average age 59 years
  • Average BP 152/99 mmHg
  • Black race - 48%
  • Current smoker - 32%
Randomized treatment groups
  • Group 1 (188 patients) - Hydrochlorothiazide 12.5 - 50 mg once daily
  • Group 2 (176 patients) - Atenolol 25 - 100 mg once daily
  • Group 3 (188 patients) - Captopril 25 - 100 mg/day given in 2 divided doses
  • Group 4 (177 patients) - Clonidine 0.2 - 0.6 mg/day given in 2 divided doses
  • Group 5 (182 patients) - Diltiazem SR 120 - 360 mg/day given in 2 divided doses
  • Group 2 (186 patients) - Prazosin 4 - 20 mg/day given in 2 divided doses
  • Group 2 (186 patients) - Placebo
  • There was a washout period of 4 - 8 weeks before randomization
  • Patients were titrated over a period of 4 - 8 weeks to a DBP < 90 mmHg or until they reached the maximum drug dose
Primary outcome: Attainment of blood pressure goal during titration (DBP < 90 mmHg) and DBP of < 95 mmHg at one year
Results

Average BP reduction at the end of the titration phase (SBP/DBP mmHg)
HCTZ Atenolol Captopril Clonidine Diltiazem Prazosin Placebo
14 / 10 11 / 12 9 / 10 16 / 12 13 / 14 12 / 11 3 / 5
  • Primary outcome: Diltiazem - 59%, Atenolol - 51%, Clonidine - 50%, HCTZ - 46%, Captopril - 42%, Prazosin - 42%, Placebo - 25%
  • All medications were significantly better than placebo for blood pressure reduction
  • Side effects (clonidine vs placebo): fatigue 17% vs 8%; sleepiness 30% vs 6%; dry mouth 37% vs 6% (all statistically significant)

Findings: Among men, race and age have an important effect on the response to single-drug therapy for hypertension. In addition to cost and quality of life, these factors should be considered in the initial choice of drug.