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Predictors of mortality in patients with lacunar stroke in the secondary prevention of small subcortical strokes trial
Journal article   Open access   Peer reviewed

Predictors of mortality in patients with lacunar stroke in the secondary prevention of small subcortical strokes trial

Mukul Sharma, Lesly A Pearce, Oscar R Benavente, David C Anderson, Stuart J Connolly, Santiago Palacio, Christopher S Coffey and Robert G Hart
Stroke (1970), Vol.45(10), pp.2989-2994
10/2014
DOI: 10.1161/STROKEAHA.114.005789
PMCID: PMC4175186
PMID: 25158772
url
http://doi.org/10.1161/STROKEAHA.114.005789View
Open Access

Abstract

The Secondary Prevention of Small Subcortical Stroke trial (SPS3) recruited participants meeting clinical and radiological criteria for symptomatic lacunes. Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin. We investigated the factors associated with mortality in this well-characterized population. We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial. Separately, we examined the effect on mortality of nonfatal bleeding during the trial. During a mean follow-up of 3.6 years, the mortality rate was 1.78% per year for the 3020 participants (mean age, 63 years). Significant independent predictors of mortality at study entry were age, diabetes mellitus, history of hypertension, systolic blood pressure (hazard ratio [HR], 1.3 per 20 mm Hg increase), serum hemoglobin<13 g/dL (HR, 1.6), renal function (HR, 1.3 per estimated glomerular filtration rate decrease of 20 mL/min), and body mass index (HR, 1.8 per 10 kg/m2 decrease). Participants with ischemic heart disease (P=0.01 for interaction) and normotensive/prehypertensive participants (P=0.03 for interaction) were at increased risk if assigned to dual antiplatelet therapy. Nonfatal major hemorrhage increased mortality in both treatment arms (HR, 4.5; 95% confidence interval, 3.1-6.6; P<0.001). Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy. Despite extensive exploratory analyses, the mechanisms underlying these interactions are uncertain. http://www.SPS3ClinicalTrials.gov. Unique identifier: NCT00059306.
Hemorrhage - epidemiology Humans Middle Aged Proportional Hazards Models Male Stroke, Lacunar - drug therapy Secondary Prevention Stroke, Lacunar - mortality Stroke, Lacunar - prevention & control Ticlopidine - analogs & derivatives Aspirin - administration & dosage Aspirin - adverse effects Ticlopidine - adverse effects Ticlopidine - administration & dosage Female Aged Drug Therapy, Combination Platelet Aggregation Inhibitors - adverse effects

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