Types of studies

We included randomised controlled trials (RCT) that aimed to test the effects of different periodontal therapies for people diagnosed with chronic periodontitis, with or without cardiovascular disease (CVD), with follow‐up times of at least one year. The studies could be primary prevention studies or secondary prevention studies. In the former, the focus would be on using periodontal treatment to prevent the occurrence of CVD. Participants in the secondary prevention studies would have CVD, or have been previously diagnosed with CVD, so the focus would be on preventing recurrence.

Types of participants

We considered trials with participants who met the following criteria, regardless of age, sex, race, social or economic status.

1. Diagnosis of at least moderate chronic periodontitis with pocketing greater than or equal to 4 mm.

2. Absence of any known genetic or congenital heart defects and aggressive periodontitis.

3. For primary prevention, no existing or previous diagnosis of CVD (including angina, myocardial infarction, stroke); for secondary prevention, an existing or previous diagnosis of CVD.

4. Absence of other sources of inflammation, such as pulpal infections and active caries.

5. No periodontal treatment within preceding six months (participants should have active disease and not be in a periodontal maintenance programme).

We did not include participants for whom periodontal therapy was contraindicated (including pregnant or lactating women, people with severe systemic diseases other than CVD), or participants who were unable to complete assessments during the follow‐up period.

Types of interventions

• Experimental: periodontal therapy of subgingival scaling and root planing (SRP), or SRP in combination with systemic antibiotic or host modulation, with or without other active remedies.

• Control: maintenance therapy (supragingival scaling, antimicrobial rinses), or no periodontal treatment, with or without the same basic remedies as those in the intervention group.

Types of outcome measures

We classified outcomes as primary (the main outcomes we considered when drawing conclusions) and secondary. We considered only long‐term outcomes, i.e. those measured at one year or more.

Electronic searches

Cochrane Oral Health’s Information Specialist conducted systematic searches in the following databases for RCTs and controlled clinical trials, with no language, publication year, or publication status restrictions:

• Cochrane Oral Health’s Trials Register (searched 17 November 2021; Appendix 1);

• Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 10) in the Cochrane Library (searched 17 November 2021; Appendix 2);

• MEDLINE Ovid (1946 to 17 November 2021; Appendix 3);

• Embase Ovid (1980 to 17 November 2021; Appendix 4);

• CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 17 November 2021; Appendix 5);

• OpenGrey (searched 17 November 2021; Appendix 6).

Subject strategies were modelled on the search strategy designed for MEDLINE Ovid. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategies designed by Cochrane for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions, Version 6.3 (Lefebvre 2022)).

We also searched the following databases:

• Chinese BioMedical Literature Database (CBM; 1978 to 4 March 2022);

• China National Knowledge Infrastructure (CNKI; 1994 to 4 March 2022);

• VIP (1989 to 4 March 2022).

The search attempted to identify all relevant studies, irrespective of language. We translated non‐English papers. We searched the Open Grey database for previous versions of this review but discontinued the search for this update due to poor yield. The search strategy used for Open Grey can be found in Appendix 6.

Searching other resources

Cochrane Oral Health's Information Specialist searched the following databases for ongoing trials:

• US National Institutes of Health Trials Register (http://clinicaltrials.gov; to 17 November 2021; Appendix 7);

• World Health Organization (WHO) Clinical Trials Registry Platform (http://apps.who.int/trialsearch/default.aspx; to 17 November 2021; Appendix 8).

We also searched Sciencepaper Online (2003 to 4 March 2022).

We checked the reference lists of all included studies for additional studies. We contacted the first authors of all included studies by email for any ongoing or unpublished studies examining the efficacy and safety of periodontal therapy for the prevention of CVD.

Selection of studies

Two review authors carried out the study selection in duplicate, according to the selection criteria. We had designed the search to be sensitive, and include controlled clinical trials, which we filtered out early in the selection process if they were not randomised. We initially screened the titles and abstracts from the search results to look for possible eligible studies. We retrieved full texts of these studies, which were independently assessed by both review authors to further assess eligibility. We discussed any disagreements on study inclusion to reach consensus, and when necessary, a third review author arbitrated. We developed a PRISMA flow diagram of the whole process, as recommended (Liberati 2009).

Data extraction and management

Two review authors carried out the data extraction in duplicate. Disagreements were resolved by discussion, and an arbitrator was involved when the disagreement remained unresolved. We designed a customised data extraction form, using Microsoft Access 2007, in accordance with guidance from the Cochrane Handbook for Systematic Reviews of Interventions version (Higgins 2011). We pilot‐tested this, using a sample of the studies focusing on this topic, and then applied it to all the included studies. We collected the following data.

• Source: study identification (ID), reviewer ID, citation, and contact details.

• Eligibility: reasons for inclusion and exclusion.

• Methods of the study: centres and their location, duration, design, sequence generation, allocation concealment, blinding, and statistical methods.

• Participants: total number, setting, age and sex, diagnostic criteria for both cardiovascular disease and periodontitis, inclusion and exclusion criteria.

• Interventions: number of groups; content details, including periodontal therapy, control treatment, and other active treatment; time, frequency, dose, and usage of drugs administered.

• Outcomes: definition of measures and units of the measurements, time points of measurement, sample size calculation, number of participants allocated to each group, numbers lost to follow‐up and the reasons, detailed summary data for each group.

• Miscellaneous: funding, key conclusions, whether we required correspondence, and miscellaneous comments from review authors.

For studies that had multiple groups, we had planned to extract data for all groups relevant to this review and record these in the 'Characteristics of included studies' section.

Where there was any missing information, we contacted the original investigators of the included studies for clarification.

Assessment of risk of bias in included studies

We carried out 'Risk of bias' assessments, following the approach described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions version (Higgins 2011). We contacted authors of the included studies by email to obtain or clarify any unreported or unclear information on the risk of bias of the studies. Two review authors independently assessed the risk of bias according to the published article and the trial authors' responses. They discussed any discrepancies, and a third review author arbitrated when necessary.

Measures of treatment effect

Our selection of statistical methods was dependent on whether the data were dichotomous, continuous, or presented as time‐to‐event. We treated both primary outcomes as dichotomous data or time‐to‐event data.

For dichotomous data, we calculated risk ratios (RR) and 95% confidence intervals (CIs). We used the Peto odds ratio (Peto OR) with 95% CI if the incidence of the events observed was very low.

For continuous data, we calculated mean differences (MD) and 95% CIs for change from baseline or the final values, if they were measured by similar indices. If the data had been measured using different indices, we would have used standardised mean differences (SMD) and 95% CIs.

Unit of analysis issues

We had planned to analyse cluster‐randomised trials and studies with more than two intervention groups differently from RCTs. For cluster‐randomised trials, to avoid any inappropriate analyses in the original studies, we would have adopted approximate analyses‐effective sample sizes, following the guidance of the first edition of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). For studies with more than two intervention groups, as each meta‐analysis addressed only a single pair‐wise comparison, we would have considered two approaches. The first was to combine groups to create a single pair‐wise comparison; if this first approach failed, we had planned to select the most relevant pair of interventions.

Dealing with missing data

For trials with missing data, we contacted the trial authors for clarification and supplementation of the data. If there was no reply, we planned to adopt the following statistical methods, following guidance in the first edition of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). If the standard deviation (SD) of the continuous data was not reported, we would calculate it: (i) from the standard error (SE), 95% CIs, P values or t values, ranges or interquartile ranges reported in the article; or (ii) if the SD of change from baseline values was missing, we would calculate it using the correlation coefficient. We planned to conduct Intention‐to‐treat (ITT) analysis if there were sufficient data. If ITT could not be adopted, we planned to analyse the available data and interpret results with caution

Assessment of heterogeneity

We planned to use the Chi² test for heterogeneity to examine if heterogeneity existed among the included studies. We used the I² statistic to estimate the impact of the heterogeneity:

• 0% to 40% may indicate slight heterogeneity;

• 30% to 60% may indicate moderate heterogeneity;

• 50% to 90% may indicate substantial heterogeneity;

• 75% to 100% may indicate very substantial (considerable) heterogeneity.

Assessment of reporting biases

To avoid reporting biases, we carried out a comprehensive search that included grey literature and ongoing studies (seeSearch methods for identification of studies). We planned to assess publication bias and other reporting biases with the help of funnel plots, if there were more than 10 trials providing results for one outcome. Asymmetry of the funnel plot could suggest potential publication bias, and would have been further tested by the methods introduced by Egger 1997 (continuous outcomes) and Rücker 2008 (dichotomous outcomes).

Data synthesis

We had planned to pool data if there was more than one study with similar comparisons that reported the same outcome, using a fixed‐effect meta‐analysis model for two or three studies, and random‐effects for four or more.

The method of meta‐analysis for computing different kinds of data varied. We used the Review Manager 5 default fixed‐effect model, Mantel‐Haenszel method, for dichotomous data and calculated MD or SMD for continuous data, unless the data were only in the appropriate form for generic inverse variance for continuous data (Review Manager 2014). In addition, we planned to use the Peto or inverse variance method for time‐to‐event data.

Subgroup analysis and investigation of heterogeneity

Had there been sufficient studies, we would have investigated any heterogeneity by carrying out subgroup analyses according to the different courses and instruments of periodontal therapy and different adjuvant treatments.

Sensitivity analysis

To test the stability of the conclusions, we had planned to carry out sensitivity analyses based on different assumptions, such as excluding studies with evident biases, using different methods to deal with missing data, different models of meta‐analysis, exclusion of studies causing significant statistical heterogeneity, or ITT analysis. We would have reported the results in detail, and evaluated their impact on the stability of the conclusions, in the discussion section.

Summary of findings and assessment of the certainty of the evidence

To provide key information on the effects and safety of periodontal therapy for CVD management in a quick and accessible format, we developed a 'Summary of findings' table for each comparison. This shows the certainty of the body of evidence for the primary outcomes (all‐cause death, all CVD‐related death, all cardiovascular events). Our assessment of the body of evidence involved consideration of risk of bias at the outcome level, directness of the evidence, heterogeneity, precision of effect estimates, and risk of publication bias (see Assessment of reporting biases). We used the GRADE system to evaluate the certainty of the evidence for each comparison and outcome, and GRADEpro GDT software (Atkins 2004; Guyatt 2008; Higgins 2011; GRADEpro GDT). We assessed the certainty of the evidence as high, moderate, low, or very low.