Periodontal Disease Treatment After Stroke or Transient Ischemic Attack: The PREMIERS Study, a Randomized Clinical Trial

Abstract

Background: Patients with stroke/transient ischemic attack and periodontal disease (PD) are at increased risk for cardiovascular events. PD treatments that can improve stroke risk factors were tested if they might assist patients with cerebrovascular disease.

Methods: In this multicenter phase II trial, patients with stroke/transient ischemic attack and moderately severe PD were randomly assigned to intensive or standard PD treatment arms. The primary outcome measure was a composite of death, myocardial infarction, and recurrent stroke, as well as adverse events. Secondary outcome included changes in stroke risk factors.

Results: A total of 1209 patients with stroke/transient ischemic attack were screened, of whom 481 met the PD eligibility criteria; 280 patients were randomized to intensive arm (n=140) and standard arm (n=140). In 12-month period, primary outcome occurred in 11 (8%) in the intensive arm and 17 (12%) in the standard arm. The intensive arm was nonsuperior to the standard arm (hazard ratio, 0.65 [95% CI, 0.30-1.38]) with similar rates of adverse events (sepsis 2.1% versus 0.7%; dental bleeding 1.4% versus 0%; and infective endocarditis 0.7% versus 0%). Secondary-outcome improvements were noted in both arms with diastolic blood pressure and high-density lipoprotein cholesterol (P<0.05).

Conclusions: In patients with recent stroke/transient ischemic attack and PD, intensive PD treatment was not superior to standard PD treatment in prevention of stroke/myocardial infarction/death. Fewer events were noted in the intensive arm and the 2 arms were comparable in the safety outcomes. Secondary-outcome measures showed a trend toward improvement, with significant changes noted in diastolic blood pressure and high-density lipoprotein in both the treatment arms.

Trial registration: ClinicalTrials.gov NCT 02541032.

Keywords: endocarditis; myocardial infarction; periodontal diseases; sepsis; stroke.

Figure 1:. Consort Diagram.

Summary of the trial population – including patient numbers who were screened, randomized into each arm of the trial, and follow-up analysis. TIA – Transient Ischemic Attack, PD – Periodontal Disease

Figure 2:. Kaplan Meier Curve for time to composite event (Stroke/MI/Death) in Intensive and Standard Treatment Arm.

Summary of total composite events as survival probability by time to event in months, showing no statistically significant difference between the two treatment arms (Logrank test). The image was created using SAS Version 9.4. The number of patients at each timepoint, as indicated in the panel below the x axis.