Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot ‘Prevention of Decline in Cognition after Stroke Trial’ (PODCAST) Randomised Controlled Trial

Abstract

BackgroundStroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial.MethodsIn a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R).ResultsWe enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison.ConclusionIn patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted.Trial RegistrationISRCTN ISRCTN85562386

Longitudinal Effect of Stroke on Cognition: A Systematic Review

“…40 Similarly, there may be less focus on incorporating vascular risk factors into these models because results from a recent clinical trial found that intensively managing vascular risk factors in stroke survivors did not alter cognition after 2 years. 41…”

Hypercholesterolaemia and vascular dementia

“…The Prevention Of Decline in Cognition After Stroke Trial (PODCAST) [145] randomized patients without dementia who were 3 to 7 months after stroke to intensive (systolic <125 mmHg) versus guideline (systolic <140 mmHg) blood pressure lowering. In addition, participants with IS were randomized to intensive (<1.3 mmol/l) versus guideline (<3 mmol/l) lipid-lowering therapy.…”

Effect of Combined Antihypertensive and Lipid-Lowering Therapies on Cognitive Function: A New Treatment Strategy?

“…e Pilot Prevention of Decline in Cognition after Stroke Trial (PODCAST) randomized controlled trial showed that intensive lipid-lowering therapy (target LDL-c < 1.3 mmol/l) was feasible and safe in patients with recent stroke, nondementia, and total cholesterol 3.0-8.0 mmol/l, but it did not change cognition for two years [67].…”

“…Gottesman et al proposed an increasing number of midlife vascular risk factors that were significantly associated with elevated amyloid standardized uptake value ratios, which was not significant for late-life risk factors [7]. e main results from the PODCAST randomized controlled trial showed that, in patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe but did not alter cognition over two years [67]. e small enrolled number, advanced age, and poststroke status may account for these differences.…”