Early in-hospital exposure to statins and outcome after intracerebral haemorrhage – Results from the Virtual International Stroke Trials Archive

Abstract

Introduction: Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome. Patients and methods: Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome. Results: A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n ¼ 89, 9.7%) was associated with better functional outcome (modified Rankin Scale 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3-3.6).Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n ¼ 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3-5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors. Discussion: It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias. Conclusion: Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days.

Secondary mechanisms of injury and viable pathophysiological targets in intracerebral hemorrhage

“…62 Targeting ICH mechanisms using combination therapy on patients that can be accrued on an adaptive trial design may also result in better therapeutic combined stratified strategies and algorithms than targeting single mechanisms individually (Figure 4) and less investigator bias with proper statistical Bayesian implementation. 26 Knowledge of various mechanisms of ICH as delineated in this review have increased over the last decade. Adaptive trial design will allow for the optimization of the various mechanisms that have shown promise in the last few decades but have not been able to produce a definitive Phase 3 trial demonstrating improved outcome.…”

“… 3 , 14 Calcium influences physiological homeostasis by playing a critical role in the coagulation cascade and neuronal, skeletal, smooth muscle, and hormone secretion. 26 – 28 Serum calcium is normally found ionized and charged (active physiological form), in a free state and protein bound, or as an anion bound complex. 14 , 15 Calcium is regulated by parathyroid hormone, vitamin D metabolites, and calcitonin.…”

“… 28 These G-coupled receptors modulate calcium concentrations to maintain vascular tone 28 , 31 , 32 and are expressed in perivascular nerves, vascular smooth muscle cells, and endothelial cells. 28 , 30 Lower serum calcium correlates with increased microbleeds, pre-existing unstable cardiac arrhythmias and rheumatic heart disease, 26 larger hematoma volume, and worse outcome in ICH. 14 , 31 , 32 Strategies to improve serum calcium and decrease the influx of intracellular calcium may be useful for mitigating secondary injury.…”

“… 62 Targeting ICH mechanisms using combination therapy on patients that can be accrued on an adaptive trial design may also result in better therapeutic combined stratified strategies and algorithms than targeting single mechanisms individually ( Figure 4 ) and less investigator bias with proper statistical Bayesian implementation. 26 …”

Effect of Statin Therapy on Mortality and Recurrence of Intracerebral Hemorrhage in Patients With Spontaneous Intracerebral Hemorrhage

“…However, these meta-analyses reported a significant decrease in all-cause mortality and all-stroke types [ 11 - 12 ]. Several retrospective studies showed promising mortality and functional outcomes with an early continuation of statin therapy and poor outcomes in post-ICH patients who discontinued statins [ 13 - 14 ]. According to several meta-analyses, statin use in ICH patients is linked to better functional outcomes and reduced mortality, which suggests that patients who start taking statins or continue taking them after admission are more likely to have positive clinical results [ 15 - 16 ].…”