Effects of Statin Therapy on the Risk of Intracerebral Hemorrhage in Korean Patients with Hyperlipidemia

Abstract

Study ObjectiveStatins are widely used for primary and secondary prevention of cardiovascular and cerebrovascular disease. Several large randomized trials have suggested that statins might increase the risk of intracerebral hemorrhage (ICH); studies have also shown interethnic variability in responses to statins. This study aimed to determine the association between statin use and the risk of ICH in patients with hyperlipidemia among a Korean population.DesignPopulation‐based, retrospective cohort study.Data SourceKorean National Health Insurance Service–National Sample Cohort database (2002–2015).PatientsA total of 313,368 patients, aged 40–85 years, without a history of hemorrhagic stroke were included after being diagnosed with hyperlipidemia between January 2003 and December 2013 (for follow‐up through December 2015). Of those, statin users were compared with nonusers by using propensity score matching in a 1:1 ratio (21,797 in each group). The study groups were matched for age, sex, Charlson Comorbidity Index score, follow‐up duration, comorbidities, and concurrent medications.Measurements and Main ResultsThe primary endpoint was occurrence of an ICH event. Secondary endpoints were mortality (all‐cause, major adverse cardiovascular and cerebrovascular event related, and stroke related) and outcomes after ICH (e.g., recurrent ICH and mortality after primary ICH event). The Cox proportional hazard model was used to evaluate the ICH risk of statins. Subgroup analyses were performed based on ICH‐related risk factors. During a mean follow‐up period of 6.4 years, ICH occurred in 456 of the 43,594 patients (1.05%). Statin use was significantly associated with a decreased ICH risk (adjusted hazard ratio [aHR] 0.78, 95% confidence interval [CI] 0.65–0.94). Compared with nonusers, statin users showed significantly lower all‐cause mortality (aHR 0.61, 95% CI 0.57–0.64), cardiovascular and cerebrovascular disease‐related mortality (aHR 0.75, 95% CI 0.65–0.85), and stroke‐related mortality (aHR 0.69, 95% CI 0.54–0.88). No significant differences in recurrence and mortality after an ICH event were noted between study groups.ConclusionStatin therapy was associated with a decreased ICH risk and improvements in ischemic cardiovascular and cerebrovascular outcomes in Korean patients with hyperlipidemia. Further large‐scale clinical studies are needed to clarify the impact of statins on the risk of developing ICH.

Association between statin adherence and the risk of stroke among South Korean adults with hyperlipidemia

“…Therefore, these factors were not included. Second, only patients with hyperlipidemia were included in this study to analyze the effects of statin adherence because statins are used as first-line therapy to reduce LDL-C levels in such patients [9]. Therefore, further research including other CVDs is required.…”

“…Evidence suggests that LDL-C levels are significant predictors of the risks associated with residual cardiovascular events [8]. Statins are used as first-line therapy to reduce LDL-C levels in patients with hyperlipidemia [9]. Over the past few decades, statins have also been used to treat dyslipidemia [10].…”

Cerebrovascular Disease and Statins

“…This risk seemed particularly enhanced in patients with prior intracerebral hemorrhage ( 52 ). However, subsequent sub-analysis of these trials and later studies including the TST trial (as discussed before) have not confirmed this association ( 16 – 19 , 21 , 53 – 56 ). For instance, a meta-analysis of 31 randomized clinical trials of statins did not find any increase in the risk of intracerebral hemorrhage among statin-treated patients, while reporting a reduction in all-cause mortality and all stroke types with statin therapy ( 53 ).…”

“…The same group reported that, in a population without prior history of stroke, those taking statins had lower intracerebral hemorrhage risk compared with those who did not receive statin therapy ( 55 ). Another large population-based study in Korean hyperlipidemic patients without history of haemorrhagic stroke, found that statin therapy was associated with a decreased risk of intracerebral hemorrhage and with improvements in ischemic cardiovascular and cerebrovascular outcomes ( 56 ). According to some observational studies, the potential link between statin use and intracerebral hemorrhage may be enhanced in patients with a background of cerebral angiopathies such as cerebral amyloid angiopathy or CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy) ( 57 ).…”

Comparing the Sensitivities of Measures of Adherence to Antihypertensive Drugs Using Korean National Health Insurance Claims Data

“…A pre-index of 365 days, our base-case, is quite common in previous studies on chronic medications. [29][30][31] In addition, we defined the basecase for the minimum period of medication use, which was referred to how long medications were taken, as 90 days and set the observation period of 3 years in the current study. 32…”