Intracranial hemorrhage (ICH) is a rare event that is difficult to predict and often has devastating consequences. Clinical predictors of ICH in stable patients with atherosclerosis are not well described.
Methods:
We evaluated the clinical correlates of ICH risk in patients randomized to placebo (N=13,166) in the TRA 2°P-TIMI 50 trial, a multinational trial of patients with atherothrombosis randomized to vorapaxar or placebo added to standard therapy. Eligible patients had a history of myocardial infarction, peripheral arterial disease, or recent ischemic stroke (2 wks to 12 mo.). ICH was adjudicated by an independent CEC.
Results:
A total of 53 ICH events (0.5% at 3 years) occurred during follow up in the placebo group. 94% of patients were receiving aspirin, 5% a thienopyridine alone, and 57% dual antiplatelet therapy. Overall, age, sex, prior ischemic stroke, and renal dysfunction were significantly associated with ICH (Table 1). After adjustment age, male gender, and prior ischemic stroke remained significantly associated with an increased hazard of ICH (Figure 1). Notably, the predictors differed between qualifying groups. After adjustment renal dysfunction (p=0.018) and diabetes (p=0.073) were associated with ICH in the MI/PAD group. In contrast, only male gender was associated with ICH in the CVD group (p=0.048).
Conclusions:
Advanced age, male gender, and history of ischemic stroke are associated with an increased hazard of ICH in patients with a history of atherothrombosis. Predictors of ICH vary depending on background vascular disease. In patients with MI/PAD and no recent stroke, traditional risk factors including diabetes and renal dysfunction are associated with ICH.
The Epigenome in Atherosclerosis