Is There an Urgent Need for Intervention Studies?

During the last couple of days I have had an email exchange with a colleague about the recent supplements in both EFP’s Journal of Clinical Periodontology and AAP’s Journal of Periodontology where a number of review articles had been published on the relationship between periodontitis and systemic diseases. The papers had been formulated and discussed during a November 11-14, 2012 workshop which had been organized by both organizations in Segovia, Spain. While the update of our current knowledge and opinion is welcome, of course, the effort bringing together the usual suspects (but not so many critical minds) from the United States and Europe was mainly directed in publishing a so-called Manifesto which largely simplified the complex information into easy to digest statements with which politics can be made. I have reported on certain aspects on this blog before.

My colleague last night wondered why the international community has not gained support to get the money to conduct an RCT intervention trial to determine if periodontal treatment will reduce cardiovascular events, calling for an international trial with each country providing funds to support the trial expense. Well, JCP editor Maurizio Tonetti, together with Thomas van Dyke, had actually called for “well-designed intervention trials on the impact of periodontal treatment on prevention of ACVD [artherosclerotic cardiovascular disease] hard clinical outcomes,” see here [pdf].

First of all, I agree that intervention studies would help clarify the so far so long rather blurred situation of undeniable but weak associations, in prospective longitudinal cohort studies, between periodontitis and cardiovascular disease, which might in fact be due to causal albeit weak relationship, a common trait among subjects prone to chronic disease, or, what I tend to believe, incomplete confounder adjustment. In the recent thorough and bracingly critical review on the association by Lockhart et al. (2012) [pdf], which was heavily discussed by “thought leaders” here and across the Atlantic Ocean and which most probably prompted the EFP/AAP enterprise in Segovia, the authors concluded,

“This review highlights significant gaps in our scientific understanding of the interaction of oral health and ASVD [artherosclerotic vascular disease]. Identification of clinically relevant aspects of their association or therapeutic strategies that might improve the recognition or therapy of ASVD in patients with PD [periodontal disease] would require further study in well-designed controlled interventional studies. Such investigations should reflect the longitudinal effectiveness of different approaches to managing periodontal health, given the possibility of PD recurrence after therapy and the extended time course of evolution of ASVD and its manifestations. Uniform criteria for PD case definition, extent, and severity; standardized treatment protocols; and consideration of time course, important confounders, and effect modifiers on the association of PD and ASVD would also improve future studies. Finally, the implications of the observed transient detrimental effects of PD therapy on markers of inflammation and endothelial function should be clarified. In the meantime, statements that imply a causative association between PD and specific ASVD events or claim that therapeutic interventions may be useful on the basis of that assumption are unwarranted.” (Emphasis added.)

Given the expected small effect, thousands of patients, probably at an age of less than 60 years with at least generalized moderate periodontitis have to be enrolled and randomized in an intervention study. (As has been shown in the systematic review by Dietrich et al. 2013 [pdf], there appears to be little evidence for any association between periodontal and cardiovascular disease in older individuals.) Half of them have to be denied any periodontal treatment while the test group must receive proper treatment and maintenance therapy. The study has to be extended for prolonged periods of times since cardiovascular events do not occur frequently in that age group. Whether such a study is ethically acceptable is highly questionable. One then has to ask about final consequences. For example, calculating the number needed to treat for periodontal disease in order to prevent a case of a cardiovascular event is most revealing.

NNT

Consider, as a quick example, hypothetical (!) data in the table to the left. Say, after 10 years, among a study population with periodontitis of 1000 subjects, there were 45 cardiovascular events in the experimental group (properly treated for periodontitis and carefully maintained), while in the control group (no periodontal treatment at all), 55 cases suffered a cardiovascular event. This leads to event rates in the two groups of 9 and 11%, respectively. The number needed to treat (NNT) would then be 1/0.02, or 50. Thus, in order to prevent one single case suffering a cardiovascular event, one had to treat and maintain 50 patients properly for periodontal disease.  The main, established, risk factors for cardiovascular disease, smoking, cholesterol, overweight, lack of physical exercise etc. are not considered at all. One has to be alerted when the focus is now apparently shifted by dentists to not-established risk factors such as periodontal disease. And, as a matter of fact, periodontal treatment has not lowered prevalence, extent and severity of periodontal disease in the Unites States or elsewhere.

10 September 2013 @ 10:55 am.

Last modified March 29, 2014.

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