Summary: A new study reveals that sildenafil (Viagra) enhances brain blood flow and improves blood vessel function in patients at risk of vascular dementia. This study marks a significant advancement in addressing this condition.
The team found that sildenafil increased blood flow in the brain’s small and large vessels, potentially preventing dementia. These findings highlight the drug’s promise for larger-scale trials to confirm its effectiveness.
Key Facts:
- Sildenafil improved blood flow and cerebrovascular function in at-risk patients.
- The trial involved 75 participants with minor stroke and small vessel disease signs.
- Sildenafil had fewer side effects compared to cilostazol, another similar drug tested.
Source: Oxford University
A new trial conducted by the University of Oxford reveals that sildenafil, commonly known as Viagra, enhances blood flow to the brain and improves the function of brain blood vessels in patients at a heightened risk of vascular dementia.
This study, published in Circulation Research, marks a potentially pivotal step in the fight against this debilitating condition.
Dr. Alastair Webb, as Associate Professor at the Wolfson Center for Prevention of Stroke and Dementia at Oxford University said, “This is the first trial to show that sildenafil gets into the blood vessels in the brain in people with this condition, improving blood flow and how responsive these blood vessels are.
“These two key factors are associated with chronic damage to the small blood vessels in the brain, which is the commonest cause of vascular dementia. This demonstrates the potential of this well-tolerated, widely-available drug to prevent dementia, which needs testing in larger trials.”
The significance of this research lies in its potential to transform the treatment and prevention of vascular dementia, which currently lacks specific therapies.
Chronic damage to the small blood vessels in the brain is not only the leading cause of vascular dementia but also contributes to 30% of strokes and 80% of brain bleeds. High blood pressure, reduced blood flow to the brain, and impaired blood vessel function exacerbate these conditions, making the findings of this trial particularly crucial.
The OxHARP trial was a meticulously designed double-blind, placebo-controlled study involving 75 participants who had experienced a minor stroke and showed signs of mild to moderate small vessel disease.
Each participant received sildenafil, a placebo, and cilostazol (a similar drug) over three-week periods in a randomized order. The study employed cardiovascular physiology tests, ultrasound, and functional MRI scans to evaluate the drugs’ effects.
Key findings include:
- Sildenafil increased blood flow in both large and small brain vessels as measured by ultrasound and MRI scans.
- Sildenafil enhanced the blood flow response to carbon dioxide, indicating improved cerebrovascular function.
- Both sildenafil and cilostazol lowered blood vessel resistance in the brain.
- Sildenafil caused fewer side effects compared to cilostazol, particularly with less incidence of diarrhea.
Looking ahead, the next steps involve larger-scale trials to confirm these findings and explore sildenafil’s potential in preventing vascular dementia on a broader scale.
Professor Peter Rothwell, Founding Director of the Wolfson Center for Prevention of Stroke and Dementia said, “Professor Webb’s findings are very encouraging and highlight the potential for preventing vascular dementia using existing drugs that target the underlying reduction in flow in the small blood vessels in the brain.”
About this dementia and neuropharmacology research news
Author: Alastair Webb
Source: Oxford University
Contact: Alastair Webb – Oxford University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Cerebrovascular Effects of Sildenafil in Small Vessel Disease: The OxHARP Trial” by Alastair Webb et al. Circulation Research
Abstract
Cerebrovascular Effects of Sildenafil in Small Vessel Disease: The OxHARP Trial
BACKGROUND:
Vascular 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.
METHODS:
OxHARP 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% CO2 on transcranial ultrasound (transcranial ultrasound-CVR); blood oxygen-level dependent–magnetic resonance imaging within WMH (CVR-WMH) and normal-appearing white matter (CVR-normal-appearing white matter); cerebral perfusion by arterial spin labeling (magnetic resonance imaging pseudocontinuous arterial spin labeling); and resistance by cerebrovascular conductance. Adverse effects were compared by Cochran Q.
RESULTS:
In 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; P=0.18), or versus cilostazol (−0.01, −0.04 to 0.02; P=0.36), despite increased blood flow (∆ peak systolic velocity, 6.3 cm/s, 3.5–9.07; P<0.001; ∆ end-diastolic velocity, 1.98, 0.66–3.29; P=0.004).
Secondary outcomes improved on sildenafil versus placebo for CVR-transcranial ultrasound (0.83 cm/s per mm Hg, 0.23–1.42; P=0.007), CVR-WMH (0.07, 0–0.14; P=0.043), CVR-normal-appearing white matter (0.06, 0.00–0.12; P=0.048), perfusion (WMH: 1.82 mL/100 g per minutes, 0.5–3.15; P=0.008; and normal-appearing white matter, 2.12, 0.66–3.6; P=0.006) and cerebrovascular resistance (sildenafil-placebo: 0.08, 0.05–0.10; P=4.9×10−8; cilostazol-placebo, 0.06, 0.03–0.09; P=5.1×10−5). Both drugs increased headaches (P=1.1×10−4), while cilostazol increased moderate-severe diarrhea (P=0.013).
CONCLUSIONS:
Sildenafil 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.
