Low-Dose Aspirin after an Episode of Haemorrhagic Stroke Is Associated with Improved Survival

Abstract

We aimed at investigating how antiplatelet drug use affected mortality in patients with a history of haemorrhagic stroke (HS). Thus, starting 30 days after an HS episode, we followed 1,004 patients with intracerebral haemorrhage (ICH) and 929 patients with subarachnoid haemorrhage (SAH) for a median of 6.4 years. We estimated the effect of time-dependent exposure to antiplatelets after HS on all-cause mortality. Cox proportional hazard models were used to compute adjusted hazard ratios (aHRs) and 95% confidence intervals (CI). We found that current use of low-dose aspirin was associated with a 32% improved survival (aHR = 0.68; 95% CI: 0.53–0.88), with a similar association among ICH (aHR = 0.66; 95% CI: 0.49–0.89) and SAH (aHR = 0.61; 95% CI: 0.36–1.04) patients. A statistically significant improved survival associated with current use of low-dose aspirin during follow-up was only observed among individuals who used antithrombotic drugs in the year before the HS (prior use: aHR = 0.56; 95% CI: 0.39–0.80; non-prior use: aHR = 0.87; 95% CI: 0.61–1.24). Current use of clopidogrel was not associated with survival (aHR = 1.35; 95% CI: 0.88–2.08). Statin use was associated with improved survival (aHR = 0.38; 95% CI: 0.31–0.47). On the other hand, discontinuation of statins (aHR = 1.31; 95% CI: 1.02–1.68) or low-dose aspirin (aHR = 1.54; 95% CI: 1.21–1.97) was associated with decreased survival. In our study, use of low-dose aspirin after an episode of HS to reduce vascular risks is safe, particularly in patients who were on antithrombotic therapy before the episode. Our results suggest an improved survival associated with low-dose aspirin. This finding must be interpreted with care due to the observational nature of the study, and warrants further studies.

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

“…Therefore, starting antiplatelet therapy seems to be safe and might be beneficial in patients who survived a median of 76 days after intracerebral haemorrhage, most of whom had good functional ability at baseline and a higher probability of good functional outcome at 6-month follow up (table 1, appendix). 19 Our findings, alongside published observational studies,9, 10, 11, 12, 13, 14 provide reassurance about the use of long-term antiplatelet therapy in a range of patients after intracerebral haemorrhage associated with antithrombotic therapy.…”

“…In the longer term (months to years), findings from a systematic review and meta-analysis 9 of observational studies of patients with any type of intracranial haemorrhage (ie, intracerebral, subarachnoid, or subdural haemorrhage) showed lower risks of occlusive vascular events and no difference in haemorrhagic events associated with resumption compared with avoidance of antiplatelet therapy. Small, non-randomised observational studies of patients with intracerebral haemorrhage have reported similar associations with starting antiplatelet therapy compared with its avoidance 10, 11, 12, 13, 14. Because of the paucity of evidence, no guidelines with strong recommendations about long-term antiplatelet therapy after intracerebral haemorrhage are available,15, 16 so variations in clinical practice occur 3 .…”

Risk of intracranial hemorrhage (RICH) in users of oral antithrombotic drugs: Nationwide pharmacoepidemiological study

“…Patients who survive ICH may have risk factors for future thromboembolic events, but the role of antithrombotic medications remains a therapeutic dilemma with conflicting evidence and contradictory recommendations [ 36 – 41 ]. There is currently a lack of solid evidence to guide decisions on whether and when to start or restart treatment in ICH survivors, and both well designed randomized trials and observational studies should be encouraged [ 42 ].…”

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: statistical analysis plan for a randomised controlled trial

“…A recent systematic review and meta-analysis of observational studies of all sub-types of intracranial haemorrhage found lower risks of ischaemic events and no difference in haemorrhagic events associated with antiplatelet drug resumption [9]. Small, non-randomised observational studies restricted to patients with stroke due to ICH have reported similar associations [10–14], but these associations were not ‘dramatic’ so randomised controlled trials (RCTs) are needed to resolve this therapeutic dilemma [15]. However, such RCTs have not been published [16].…”