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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.

Published version
Peer-reviewed

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Authors

Scutt, Polly 
Blackburn, Daniel J 
Ankolekar, Sandeep 
Krishnan, Kailash 

Abstract

BACKGROUND: Stroke 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. METHODS: In 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). RESULTS: We 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. CONCLUSION: 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. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. TRIAL REGISTRATION: ISRCTN ISRCTN85562386.

Description

Keywords

Aged, Blood Pressure, Cognition Disorders, Female, Humans, Hypolipidemic Agents, Lipids, Male, Practice Guidelines as Topic, Prospective Studies, Stroke, Stroke Rehabilitation

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

12

Publisher

Public Library of Science (PLoS)
Sponsorship
The trial was funded equally by grants from Alzheimer’s Society and Stroke Association in the UK. There was no commercial support for the trial, and antihypertensive and lipid lowering drugs were prescribed by the responsible physician and sourced locally. The grant applicants conceived and designed the trial and wrote the protocol. Study data were collected, monitored, and analysed by the PODCAST Coordinating Centre in Nottingham, UK. Analysis, interpretation, and report writing were done independently of the funders and sponsor. The corresponding author and two other authors (PS, LW) had full access to all the data in the study; additionally, the corresponding author had final responsibility for the decision to submit for publication, and is the guarantor for the study. This study is registered as ISRCTN85562386 (http://www.isrctn.com/ISRCTN85562386).