Magnesium for treatment of acute lacunar stroke syndromes: further analysis of the IMAGES trial.
OBJECTIVE
A prespecified interaction analysis of the neutral Intravenous Magnesium Efficacy in Stroke (IMAGES) trial revealed significant benefit from magnesium (Mg) in patients with noncortical stroke. Post hoc analysis indicated that this effect was seen in lacunar clinical syndromes (LACS), interaction P=0.005. We have now examined whether this interaction could be explained by confounding baseline factors.


METHODS
LACS was defined on the basis of neurological signs and did not include imaging. We investigated the interaction between baseline variables and Mg treatment on global outcome. We used logistic-regression models to test whether the Mg-LACS interaction remained significant after adjusting for stratification variables, sex, a novel stroke severity score, and baseline variables that had an interaction with treatment (P<0.1).


RESULTS
The Mg (n=383) and placebo (n=382) groups of LACS patients were well matched on baseline factors. In addition to LACS, we found an interaction between beneficial Mg treatment effect and younger age (P=0.003), higher baseline diastolic blood pressure (P=0.02), higher mean blood pressure (P=0.02), and absence of ischemic heart disease (P=0.07). Even so, the adjusted Mg-LACS interaction remained significant (odds ratio [OR] 0.57; 95% CI, 0.39 to 0.83; P=0.003). In the LACS subgroup, Mg improved Barthel Index <95 (OR 0.73; 95% CI, 0.55 to 0.98), modified Rankin Scale >1 (OR 0.67; 95% CI, 0.50 to 0.91), and global outcome (OR 0.70; 95% CI, 0.53 to 0.92) but not Barthel Index <60 or mortality.


CONCLUSIONS
The positive treatment effect of Mg in LACS cannot be ascribed to general issues of severity, time to treatment, blood pressure, or other baseline factors; equally, this finding may be due to chance. A large trial of Mg treatment in LACS appears justified.
Aslanyan
Stella
S
Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. stella_s_aslanyan@hotmail.com
Weir
Christopher J
CJ
Muir
Keith W
KW
Lees
Kennedy R
KR
D000208:Acute Disease; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D020520:Brain Infarction / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008274:Magnesium / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015203:Reproducibility of Results; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D008274:Magnesium