Pharmacological interventions for hypertensive emergencies.
BACKGROUND
Hypertensive emergencies, marked hypertension associated with acute end-organ damage, are life-threatening conditions. Many anti-hypertensive drugs have been used in these clinical settings. The benefits and harms of such treatment and the best first-line treatment are not known.


OBJECTIVE
To answer the following two questions using randomized controlled trials (RCTs): 1) does anti-hypertensive drug therapy as compared to placebo or no treatment affect mortality and morbidity in patients presenting with a hypertensive emergency? 2) Does one first-line antihypertensive drug class as compared to another antihypertensive drug class affect mortality and morbidity in these patients?


METHODS
Electronic sources: MEDLINE, EMBASE, Cochrane clinical trial register. In addition, we searched for references in review articles and trials. We attempted to contact trialists. Most recent search August 2007.


METHODS
All unconfounded, truly randomized trials that compare an antihypertensive drug versus placebo, no treatment, or another antihypertensive drug from a different class in patients presenting with a hypertensive emergency.


METHODS
Quality of concealment allocation was scored. Data on randomized patients, total serious adverse events, all-cause mortality, non-fatal cardiovascular events, withdrawals due to adverse events, length of follow-up, blood pressure and heart rate were extracted independently and cross checked.


RESULTS
Fifteen randomized controlled trials (representing 869 patients) met the inclusion criteria. Two trials included a placebo arm. All studies (except one) were open-label trials. Seven drug classes were evaluated in those trials: nitrates (9 trials), ACE-inhibitors (7), diuretics (3), calcium channel blockers (6), alpha-1 adrenergic antagonists (4), direct vasodilators (2) and dopamine agonists (1). Mortality event data were reported in 7 trials. No meta-analysis was performed for clinical outcomes, due to insufficient data. 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,-7] and diastolic [WMD -8, 95%CI, -12,-3] blood pressure with antihypertensive therapy.


CONCLUSIONS
There is no RCT evidence demonstrating that anti-hypertensive drugs reduce mortality or morbidity in patients with hypertensive emergencies. Furthermore, there is insufficient RCT evidence to determine which drug or drug class is most effective in reducing mortality and morbidity. There were some minor differences in the degree of blood pressure lowering when one class of antihypertensive drug is compared to another. However, the clinical significance is unknown. RCTs are needed to assess different drug classes to determine initial and longer term mortality and morbidity outcomes.
Perez
M I
MI
University of British Columbia, Anesthesiology, Pharmacology and Therapeutics, 2176 Health Science Mall, Vancouver, BC, Canada V6T 1Z3. maiperez@interchange.ubc.ca
Musini
V M
VM
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004630:Emergencies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic
D000959:Antihypertensive Agents