Statins, triple antihypertensive combination may lower ICH recurrence risk

Statin therapy, as well as triple antihypertensive combination therapy, may reduce the risk of recurrence in patients who have survived an intracerebral haemorrhage (ICH), according to new local findings presented at HKMF 2023.

“Post-ICH statin therapy can be considered for patients with cerebral amyloid angiopathy [CAA]–associated disease or asymptomatic atherosclerosis. However, it is important to avoid LDL-cholesterol [LDL-C] levels <1.8 mmol/L in these patients,” suggested Dr Kay-Cheong Teo of School of Clinical Medicine, the University of Hong Kong (HKU). “Additionally, triple antihypertensive therapy is required for long-term blood pressure [BP] control after ICH.”

Statins in ICH survivors with low LDL-C

No consensus has been reached on the use of statins in ICH survivors with CAA-associated disease or asymptomatic atherosclerosis. [Stroke 2022;53:2161-2170] “To explore the association of recurrent ICH with follow-up LDL-C and statin use, we performed an analysis using 2011–2019 data from the HKU stroke registry,” Teo said.

The study involved 508 ICH survivors with LDL-C measurement during follow-up (mean, 71.5 months). Among these patients, 141 and 367 had mean LDL-C levels <1.8 mmol/L and >1.8 mmol/L, respectively. [Teo KC, HKMF 2023]

“In multivariate analysis, a significant increase in risk of recurrent ICH was demonstrated with mean follow-up LDL-C levels <1.8 mmol/L [adjusted hazard ratio (adjHR), 1.91; 95 percent confidence interval (CI), 1.02–3.57; p=0.045],” Teo reported. “Interestingly, no significant association was found for post-ICH statin use [adjHR, 0.86; 95 percent CI, 0.47–1.59; p=0.636].”

After adjusting for confounding factors, subset analyses revealed that the elevated risk of recurrent ICH associated with follow-up LDL-C levels <1.8 mmol/L were primarily observed in men (p=0.005), patients aged >75 years (p=0.040), those diagnosed with CAA-associated disease (p=0.046), and those who did not receive statins after ICH (p=0.022).

“These findings indicate that statins can be considered for these patients, but vigilance is required to avoid LDL-C levels <1.8 mmol/L,” highlighted Teo.

“Patients with naturally low LDL-C levels may be at risk of developing a bleeding-prone brain. Previous research showed reduced LDL-C concentrations in patients with a high burden of cerebral microbleeds,” he explained. [Stroke 2002;33:2845-2849]

Triple antihypertensive combination in ICH survivors

“BP control remains essential for preventing ICH,” noted Teo. “Our joint study with US researchers demonstrated that targeting systolic BP <120 mm Hg after ICH may reduce the risk of recurrence and major adverse cardiovascular and cerebrovascular events, without increasing mortality.” [Stroke 2023;54:78-86]

Teo and colleagues suggest early initiation of triple antihypertensive therapy after ICH. Their combined cohort study showed that most ICH survivors required treatment with ≥3 antihypertensive agents, particularly if the patients were young (<65 years), had admission systolic BP >190 mm Hg, or had a history of hypertension prior to ICH (p<0.001 for all). [Teo KC, ISC 2020, abstract 15]

However, >60 percent of ICH survivors had uncontrolled hypertension (BP ≥140/90 mm Hg) at 3 months after ICH. Among these patients, approximately two-thirds were undertreated with ≤2 antihypertensive classes, and most of these patients had inadequate treatment during follow-up care. [JAHA 2021;10:e020392]

“Therapeutic inertia among both clinicians and patients may contribute to inadequate antihypertensive treatment. In my view, using single-pill combination antihypertensive therapy could improve patients’ treatment adherence,” Teo commented. “To address therapeutic inertia, we will conduct the randomized MOBILE trial comparing mobile app vs usual care for managing hypertension in ICH survivors.” [NCT05830305]