2 Common Heart Disease Treatments May Work to Slow or Prevent Vascular Dementia, UK Study Finds

Vijaya Iyer, PhD avatar

by Vijaya Iyer, PhD |

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vascular disease and dementia

Two prescription treatments for heart disease and angina — cilostazol and isosorbide mononitrate — show a potential to prevent or reduce vascular dementia, a study reports.

They also can be safely used in people with a history of stroke, which was the focus of this research.

Because vascular dementia and evidence of disease affecting small blood vessels in the brain are found in Alzheimer’s patients, these results may also point to a way of slowing or preventing the cognitive decline associated with this disease’s development. Recent research also identifies stroke as a major factor for both vascular dementia and Alzheimer’s disease.

The study, “Tolerability, safety and intermediary pharmacological effects of cilostazol and isosorbide mononitrate, alone and combined, in patients with lacunar ischaemic stroke: The LACunar Intervention-1 (LACI-1) trial, a randomised clinical trial,” was published in the journal EClinicalMedicine.

Researchers in the U.K. reviewed literature and identified two current medications with the potential to improve blood vessel function in the brain after a stroke, especially what’s known as a lacunar ischaemic stroke that’s brought on by obstructed blood flow, and subsequently oxygen supply, in the brain.

Cilostazol (brand name Pletal, among others) is an oral vasodilator that works by improving blood flow while alleviating pain caused by poor circulation, especially in the legs. Isosorbide mononitrate (brand name Imdur, among others) helps prevent angina (chest pain) caused by heart disease. It relaxes blood vessels to improve blood flow and oxygen supply.

The research team then conducted a nine-week Phase 2 clinical study (NCT02481323) to evaluate the safety, tolerability, and efficacy of cilostazol and isosorbide mononitrate, either alone or in combination, in 57 patients with a history of lacunar stroke being treated at two large stroke centers in that country. Participants mean age was 66.1, and 32% (18) were women.

In addition to these medications given as treatment in this open-label trial, patients continued using prescribed medications, including those treating stroke.

People were randomly assigned to one of four treatment groups – cilostazol only (13); isosorbide mononitrate only (15); cilostazol and isosorbide mononitrate combined, with an immediate start (14); and cilostazol and isosorbide mononitrate combined, with a three-week delayed treatment start (15). This last group served as a ‘no drug’ comparison group for the trial’s opening weeks.

Oral cilostazol was given at 50 mg twice a day, which gradually increased over two or three weeks to 100 mg twice daily, if tolerated. Oral isosorbide mononitrate, likewise, was started at 25 mg once a day and slowly increased to 25 mg twice daily.

Patients completed health questionnaires to assess their tolerance for these treatments and perceived side effects.

At the end of eight weeks, the study found 40 (72%) of patients were taking either full doses (a group that also includes no missed doses) or partial doses (which includes missing between one and up to half of the allocated dose), with no difference seen among groups.

“Most participants, including those in the dual drug groups, were taking target, or near to target dose, by the end of the treatment period,” the study reported.

Headaches and heart palpitations were reported across all groups in the study’s initial weeks, but normalized as treatment progressed. And “there were no drug-related adverse events or bleeding complications, despite all participants also taking prescribed antiplatelet drugs,” the researchers noted.

Blood pressure, platelet function, pulse rate, and periodic magnetic resonance imaging brain scans were used to monitor treatment efficacy.

No significant differences in blood pressure and platelets were found in people on either treatment. Pulse rates were statistically higher in the cilostazol group compared to those not using this medication.

All treatments were reported to improved patients’ cognitive abilities, as measured in timed tests, and cerebrovascular reactivity — measured by imaging — improved from baseline  or study start in all patients excepts those in the delayed start group, but the difference was not significant.

The small size of the study population, however, was considered a limiting factor and further trials are necessary to confirm these findings.

“We are delighted that the results of this trial show promise for treating a common cause of stroke and the commonest cause of vascular dementia since currently there are no effective treatments. Further trials are underway,” Joanna Wardlaw, the study’s lead researcher and a professor at the University of Edinburgh’s Centre for Clinical Brain Sciences ,said a press release.

“There hasn’t been a new drug for dementia for 15 years, so finding evidence that these cheap existing drugs could prevent dementia after a stroke would be a huge breakthrough,” added James Pickett, PhD, head of research at Alzheimer’s Society in the U.K.

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