Trial reportCirculation research2024
Cerebrovascular Effects of Sildenafil in Small Vessel Disease: The OxHARP Trial.
Trial report in Circulation research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03855332 (Oxford Haemodynamic Adaptation to Reduce Pulsatility), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Oxford Haemodynamic Adaptation to Reduce Pulsatility: Randomised, Placebo-controlled, Double-blind Crossover Trial of Effects of Sildenafil on Cerebral Arterial Pulsatility in Patients With Cryptogenic or Lacunar Stroke and Small Vessel Disease
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Phosphodiesterase-5 inhibitors for cerebral small vessel disease-related ischemic stroke and cognitive decline: systematic review and meta-analysis.Frontiers in neurologyPooled it
- Oral phosphodiesterase-5 inhibitor does not augment red blood cell deformability at rest or during handgrip exercise.European journal of applied physiology · 2026Trial
- Neurovascular effects of tadalafil in patients with cerebral small vessel disease: ETLAS-2 substudy.Brain communications · 2026Trial
- Optimal markers of treatment response to vasodilatory drugs in small vessel disease: An OxHARP trial analysis.International journal of stroke : official journal of the International Stroke Society · 2026Trial
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Selective vulnerability of cerebral vasculature toScience advances · 2026Article
- Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy.Cell · 2026Article
- Cerebrovascular Reactivity Assessment with Breath-Hold Functional MRI in Patients with Moyamoya Angiopathy: Which Time Period to Analyze?Diagnostics (Basel, Switzerland) · 2026Article
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- Vascular cognitive impairment and dementia: Prevention, treatments, mechanisms and management options for the future.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- The international society of vascular behavioural and cognitive disorders: highlights from VasCog 2025 in the UK.Cerebral circulation - cognition and behavior · 2026Article
- Phosphodiesterase-5 Inhibition and Alzheimer's Disease Risk: A Mendelian Randomisation Study.Aging cell · 2025Article
- Photobiomodulation in cardiovascular diseases: molecular mechanisms and pharmacological approaches to enhance the therapeutics effects of light.Lasers in medical science · 2025Review
- The vascular contribution to cognitive decline in ageing and dementia.Nature reviews. Neuroscience · 2025Review
- Compatibility Studies of Sildenafil-HPBCD Inclusion Complex with Pharmaceutical Excipients.Pharmaceutics · 2025Article
- Aortic Stiffness and Alzheimer's Disease: The Medin Connection.Biomolecules · 2025Review
- Genetically Proxied Phosphodiesterase Type 5 (PDE5) Inhibition and Risk of Dementia: A Drug Target Mendelian Randomization Study.Molecular neurobiology · 2025Article
- Towards advanced regenerative therapeutics to tackle cardio-cerebrovascular diseases.American heart journal plus : cardiology research and practice · 2025Review
- Carotid Blood Flow Assessment during Dynamic Respiratory Maneuvers Demonstrates a Shift toward Vasoconstriction with Increasing Age.Journal of medical ultrasoundArticle
- Alzheimer's disease model explains Alzheimer's disease incidences.Journal of Alzheimer's disease reportsArticle
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundVascular cognitive impairment due to cerebral small vessel disease is associated with cerebral pulsatility, white matter hypoperfusion, and reduced cerebrovascular reactivity (CVR), and is potentially improved by endothelium-targeted drugs such as cilostazol. Whether sildenafil, a phosphodiesterase-5 inhibitor, improves cerebrovascular dysfunction is unknown.
methodsOxHARP trial (Oxford Haemodynamic Adaptation to Reduce Pulsatility) was a double-blind, randomized, placebo-controlled, 3-way crossover trial after nonembolic cerebrovascular events with mild-moderate white matter hyperintensities (WMH), the most prevalent manifestation of cerebral small vessel disease. The primary outcome assessed the superiority of 3 weeks of sildenafil 50 mg thrice daily versus placebo (mixed-effect linear models) on middle cerebral artery pulsatility, derived from peak systolic and end-diastolic velocities (transcranial ultrasound), with noninferiority to cilostazol 100 mg twice daily. Secondary end points included the following: cerebrovascular reactivity during inhalation of air, 4% and 6% CO
resultsIn 65/75 (87%) patients (median, 70 years;79% male) with valid primary outcome data, cerebral pulsatility was unchanged on sildenafil versus placebo (0.02, -0.01 to 0.05;
conclusionsSildenafil did not reduce pulsatility but increased cerebrovascular reactivity and perfusion. Sildenafil merits further study to determine whether it prevents the clinical sequelae of small vessel disease. REGISTRATION: URL: https://www.clinicaltrials.gov/study/NCT03855332; Unique identifier: NCT03855332.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.