Pharmacological Interventions for Hypertensive Emergencies

Summary

A Cochrane review [Abstract] 1 included 15 studies with a total of 869 subjects. Participants included patients with marked elevation of blood pressure in the presence of acute end organ damage like myocardial infarction, unstable angina, acute left ventricular failure with pulmonary oedema, acute aortic dissection, encephalopathy, stroke, and life-threatening bleeding (intracerebral haemorrhage, subarachnoid haemorrhage). Inclusion treshold was SBP ≥180 and or DBP ≥ 110 mm Hg except in acute aortic dissection or with left ventricular failure and pulmonary oedema a SBP greater or equal to 120 mm Hg and or DBP ≥70 mm Hg, and for patients with intracranial haemorrhage or subarachnoid haemorrhage a SBP ≥ 160 mm Hg. Two trials included a placebo arm. All studies (except one) were open-label trials. Seven drug classes were evaluated: nitrates (9 trials), ACE-inhibitors (7), diuretics (3), calcium channel blockers (6), alpha-1 adrenergic antagonists (4), direct vasodilators (2) and dopamine agonists (1). The follow-up range was short (6-24 hours).

Mortality event data were reported in 7 trials and totalled 6 deaths in 3 RCTs. No trial reported cardiovascular events as a composite. One placebo-controlled trial and three head to head trials reported myocardial infarction as an outcome. There was no statistically significant difference between ACEi and placebo (RR 0.72, 95% CI 0.31 to 1.72). There was no statistical difference in myocardial infarctions between nitrates (2.7%) and alfa-adrenergic antagonist (5%) (RR 0.55, 95% CI 0.09 to 3.17); or nitrates (16%) vs. diuretics (12.5%) (RR 1.30, 95% CI 0.40 to 4.19); or between diazoxide (3.5%) vs. dihydralazine (4%) (RR 0.86, 95% CI 0.06 to 12.98). Three trials reported pulmonary edema requiring mechanical ventilation as outcome. There was no statistically significant difference between captopril and placebo (RR 0.40, 95% CI 0.09 to 1.86), nitrates and alfa-adrenergic antagonist (RR 4.12, 95% CI 0.20 to 84.24) or between nitrates and ACE-Inhibitor (RR 0.33, 95% CI 0.01 to 7.78). The pooled effect of 3 different anti-hypertensive drugs in one placebo-controlled trial showed a statistically significant greater reduction in both systolic (WMD -13, 95% CI -19 to -7) and diastolic (WMD -8, 95% CI, -12 to -3) blood pressure with antihypertensive therapy.

Although it is unproven, it is highly likely that antihypertensive therapy is an overall benefit in a hypertensive emergency and therefore a placebo controlled trial to prove this would be unethical. Properly conducted randomised trials comparing different drug classes and treatment strategies are badly needed.