ALPHA-2 AGONISTS





Acronyms


DRUGS IN CLASS


MECHANISM OF ACTION


HYPERTENSION | Clonidine


RCT
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
RCT
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.





HYPERTENSIVE URGENCY


SIDE EFFECTS




CONTRAINDICATIONS


PRECAUTIONS




STOPPING CLONIDINE


DRUG INTERACTIONS


LONG-TERM SAFETY


DOSING


BIBLIOGRAPHY