The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment

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.

Automated summary

This study investigated the effects of tadalafil on cerebral blood flow in older people with symptomatic small vessel disease and found that it did not have a significant treatment effect. Unexpectedly, tadalafil also had effects on blood pressure. Future research may require different dosing regimens.