Effect of early treatment with anti-hypertensive drugs on short and long-term mortality in patients with an acute cardiovascular event.
BACKGROUND
Acute cardiovascular events represent a therapeutic challenge. Blood pressure lowering drugs are commonly used and recommended in the early phase of these settings. This review analyses randomized controlled trial (RCT) evidence for this approach.


OBJECTIVE
To determine the effect of immediate and short-term administration of anti-hypertensive drugs on all-cause mortality, total non-fatal serious adverse events (SAE) and blood pressure, in patients with an acute cardiovascular event, regardless of blood pressure at the time of enrollment.


METHODS
MEDLINE, EMBASE, and Cochrane clinical trial register from Jan 1966 to February 2009 were searched. Reference lists of articles were also browsed. In case of missing information from retrieved articles, authors were contacted.


METHODS
Randomized controlled trials (RCTs) comparing anti-hypertensive drug with placebo or no treatment administered to patients within 24 hours of the onset of an acute cardiovascular event.


METHODS
Two reviewers independently extracted data and assessed risk of bias. Fixed effects model with 95% confidence intervals (CI) were used. Sensitivity analyses were also conducted.


RESULTS
Sixty-five RCTs (N=166,206) were included, evaluating four classes of anti-hypertensive drugs: ACE inhibitors (12 trials), beta-blockers (20), calcium channel blockers (18) and nitrates (18). Acute stroke was studied in 6 trials (all involving CCBs). Acute myocardial infarction was studied in 59 trials. In the latter setting immediate nitrate treatment (within 24 hours) reduced all-cause mortality during the first 2 days (RR 0.81, 95%CI [0.74,0.89], p<0.0001). No further benefit was observed with nitrate therapy beyond this point. ACE inhibitors did not reduce mortality at 2 days (RR 0.91,95%CI [0.82, 1.00]), but did after 10 days (RR 0.93, 95%CI [0.87,0.98] p=0.01). No other blood pressure lowering drug administered as an immediate treatment or short-term treatment produced a statistical significant mortality reduction at 2, 10 or >/=30 days. There was not enough data studying acute stroke, and there were no RCTs evaluating other acute cardiovascular events.


CONCLUSIONS
Nitrates reduce mortality (4-8 deaths prevented per 1000) at 2 days when administered within 24 hours of symptom onset of an acute myocardial infarction. No mortality benefit was seen when treatment continued beyond 48 hours. Mortality benefit of immediate treatment with ACE inhibitors post MI at 2 days did not reach statistical significance but the effect was significant at 10 days (2-4 deaths prevented per 1000). There is good evidence for lack of a mortality benefit with immediate or short-term treatment with beta-blockers and calcium channel blockers for acute myocardial infarction.
Perez
Marco I
MI
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Science Mall, Vancouver, BC, Canada, V6T 1Z3.
Musini
Vijaya M
VM
Wright
James M
JM
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000401:mortality*; D002423:Cause of Death; D004334:Drug Administration Schedule; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D009566:Nitrates / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D009566:Nitrates