The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment. Issue 12 (8th February 2022)

• Record Type: Journal Article
• Authors: Pauls, Mathilde M.H.; Binnie, Lauren R.; Benjamin, Philip; Betteridge, Shai; Clarke, Brian; Dhillon, Mohani‐Preet K.; Ghatala, Rita; Hainsworth, Fearghal A.H.; Howe, Franklyn A.; Khan, Usman; Kruuse, Christina; Madigan, Jeremy B.; Moynihan, Barry; Patel, Bhavini; Pereira, Anthony C.; Rostrup, Egill; Shtaya, Anan B.Y.; Spilling, Catherine A.; Trippier, Sarah; Williams, Rebecca; Young, Robin; Barrick, Thomas R.; Isaacs, Jeremy D.; Hainsworth, Atticus H.
• Is Part Of: Alzheimer's & dementia. Volume 18:Issue 12(2022)
• Page Start: 2393
• Page End: 2402
• Publication Date: 2022-02-08
• Subjects: cerebral blood flow -- clinical trials -- PDE5 -- small vessel disease -- tadalafil -- vascular cognitive impairment -- vascular cognitive impairment and dementia; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.12559
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Introduction: There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI. Methods: In a double‐blind, placebo‐controlled, cross‐over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling. Results: Tadalafil increased CBF non‐significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (–7.8, –4.9 mmHg; P < .001). No serious adverse events were observed. Discussion: This trial did not identify a significant treatment effect of single‐administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.