Can Periodontal Treatment Reduce CV Events in Stroke Patients?

February 11, 2022

The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.

The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI) or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.

Both groups had a much lower event rate compared with a historical control group made up of similar patients.

In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.  

"My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients," lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine, told | Medscape Cardiology.

"Even standard periodontal care — a dental clean every 3 months — was beneficial."

Sen presented the study February 9 at the International Stroke Conference (ISC), taking place in New Orleans and virtually.

"This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group," he said.  

Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so ended up comparing standard treatment with intensive treatment.

"We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study," he said.

Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the US population. It is particularly prevalent in the southeastern part of the United States, known as the "Stroke Belt" because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.

For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.

Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.

The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics, and patients were given an electric toothbrush, mouthwash, and air flosser for dental care.

All patients received comprehensive conventional stroke risk factor treatment.

The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.   

Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group vs 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% CI, 0.30 - 1.38; P = .26).

But both groups had a much lower rate if recurrent events compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.

In both standard treatment and intensive treatment groups, combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.

Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Sen noted was very similar to that of the historical controls. The P value for this trend was "very significant" (P = .0017), he said.

Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment — in both standard treatment and intensive treatment.

"Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven't had any randomized data," Sen noted.

He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. "This is not something we currently think about, but it could make a big difference in future event rates."

Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.

"We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don't know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk," Sen said. "Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.

"I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this," he said.  

But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.

"Even in individuals who haven't had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of MI and stroke, and that regular dental care (one or more visits per year) can reduce this risk. I don't think we can do a randomized trial in the general population — that would need enormous numbers. We will have to rely on the observational studies here," he added.

Commenting on the current study for | Medscape Cardiology, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.

"There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow up," said McCullough, chair of the Department of Neurology, McGovern Medical School, University of Texas Health Science Center, Houston. "Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked etc, made a dramatic difference."

The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).

International Stroke Conference 2022. Abstract LBS3. Presented February 9, 2022.

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