Abstract A037: The Effect of Antihypertensive Medication Classes on Cerebral Small Vessel Disease: A Secondary Analysis of the SPS3 Trial

Background: Hypertensive cerebral small vessel disease (CSVD) causes lacunar stroke, intraparenchymal hemorrhage (IPH), and cognitive impairment. Blood pressure (BP) control is the cornerstone of CSVD treatment; however, it is unknown if specific classes of antihypertensive medication exhibit distinct efficacy in CSVD. We explored the effect of antihypertensive class exposure on clinical manifestation of CSVD after lacunar stroke. Methods: This secondary analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial included 2,993 patients with MRI-confirmed lacunar stroke. Participants were followed every three months to assess medication compliance and BP measurement. The primary model assessed the effect of antihypertensive class (thiazide, ACE-I/ARB, beta-blocker, calcium channel blocker, and non-first-line medications) exposure on recurrent stroke due to CSVD (lacunar stroke or IPH). Multivariable, competing-risk cumulative incidence function was utilized with antihypertensive class exposure and BP control input as time-dependent covariates. Secondary analyses assessed: 1) the effect of medication class on all major adverse cardiovascular events (MACE) and 2) excess cognitive decline in Cognitive Abilities Screening Instrument (CASI) using mixed-effects regression. Results: Over an average follow-up of 3.7 years, 179 (6%) participants experienced a recurrent lacunar stroke and 23 (1%) had IPH. Participants with recurrent lacunar stroke/IPH were more likely to have diabetes, higher BP over follow-up, prescribed non-first line antihypertensives, and less likely to be prescribed thiazides ( P <0.05) at baseline. No specific anti-hypertensive class was significantly associated with reduced recurrent lacunar stroke/IPH (Table 1). Thiazide exposure was associated with a marginally significant reduction in MACE (HR 0.55, CI: 0.30 - 0.99, P =0.05) (Table 2). Among 2,659 participants with available CASI assessments, non-first line antihypertensives were associated with higher adjusted annual cognitive score (average marginal effects of 0.19 points, CI: 0.18 – 0.19) (Table 3). Conclusions: We did not detect a consistent protective effect of any antihypertensive class in CSVD, however, thiazide diuretics were associated with fewer MACE events and non-first line antihypertensives were associated with improved cognition. Assessing the effect of specific antihypertensive regiments on CSVD progression will require future trials.