Types of studies

All RCTs and quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth, or other predictable methods) of individuals with resistant hypertension undergoing renal sympathetic denervation procedures, without duration or language restrictions.

Types of participants

Adults (older than 18 years), with refractory or resistant hypertension, defined by the presence of a clinic blood pressure above target (higher than 140/90 mmHg, or higher than 130/80 mmHg in individuals with type 2 diabetes mellitus), despite the concomitant use of three or more antihypertensive drugs of different classes, including a diuretic.

Types of interventions

Any transcatheter renal sympathetic denervation procedures performed using contemporary percutaneous catheters and radiofrequency probes compared with standard medical therapy or sham intervention.

Types of outcome measures

Electronic searches

The Cochrane Hypertension Information Specialist conducted systematic searches in the following databases for randomised controlled trials without language, publication year or publication status restrictions:

• the Cochrane Hypertension Specialised Register via the Cochrane Register of Studies (CRS‐Web) (searched 16 February 2016);

• the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2) via the Cochrane Register of Studies Online (CRSO) (searched 15 February 2016);

• MEDLINE Ovid (from 1946 onwards), and MEDLINE Ovid In‐Process & Other Non‐Indexed Citations (searched 15 February 2016);

• PubMed (searched 16 February 2016);

• Embase Ovid (searched 15 February 2016);

• ClinicalTrials.gov (www.clinicaltrials.gov) searched 15 February 2016);

• World Health Organization International Clinical Trials Registry Platform (www.who.int/trialsearch) searched 15 February 2016).

The Information Specialist modelled subject strategies for databases on the search strategy designed for MEDLINE. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategy designed by Cochrane for identifying randomised controlled (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.b. (Handbook 2011)). Search strategies for major databases are provided in Appendix 1.

Searching other resources

• The Cochrane Hypertension Information Specialist searched the Hypertension Specialised Register segment (which includes searches of MEDLINE and Epistemonikos for systematic reviews) to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials.

• We checked the bibliographies of included studies and any relevant systematic reviews identified for further references to relevant trials.

• Where necessary, we contacted authors of key papers and abstracts to request additional information about their trials.

• We did not perform a separate search for adverse effects of interventions used for the treatment of hypertension. We considered adverse effects described in included studies only.

• We checked the reference lists of cardiology and nephrology textbooks for additional resources.

Selection of studies

Two authors (AP and LR) independently screened titles and abstracts, and retained studies and reviews that might include relevant data or information on trials for review in detail; studies that were not applicable were excluded. The same authors (AP and LR) independently assessed retrieved abstracts, and if necessary the full text, of these studies to determine which studies satisfied the inclusion criteria.

Data extraction and management

Two authors (AP and LR) independently carried out data extraction using a standard electronic data extraction form. We arranged for translations of studies reported in non‐English language journals before assessment. If more than one publication of a study existed, we grouped the reports together and used the publication with the most complete data in the analyses. If relevant outcomes were published only in earlier versions of the study, we used such data.

Assessment of risk of bias in included studies

Two authors (AP and DB) independently assessed the following items using the 'Risk of bias' assessment tool (Higgins 2011).

• Sequence generation (selection bias);

• Allocation concealment (selection bias);

• Blinding (detection bias)

  • Participants and personnel

  • Outcome assessors;

• Completeness of outcome data (attrition bias);

• Selective outcome reporting (reporting bias);

• Other sources of bias:e.g. funding bias.

Measures of treatment effect

We expressed dichotomous outcome results as risk ratios (RRs) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment, we reported results as mean differences (MD) or standardised mean differences (SMD) if different scales were reported, with 95% CI.

Unit of analysis issues

We appraised unit of analysis issues according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011)

Dealing with missing data

We requested additional information from the corresponding author(s) by email. We carefully evaluated important data, such as numbers of screened and randomised participants, as well as numbers of intention‐to‐treat, as‐treated, and per‐protocol populations. We explored attrition in the study, such as drop‐outs, losses to follow‐up, and withdrawals. We appraised issues of missing data and imputation methods (such as last‐observation‐carried‐forward) according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Assessment of heterogeneity

We tested heterogeneity with a Chi² test on n ‐ 1 degrees of freedom, using an alpha of 0.05 for statistical significance, and used the I² statistic (Higgins 2003). We considered I² values of 25%, 50%, and 75% to correspond to low, medium, and high levels of heterogeneity.

Assessment of reporting biases

Where possible, we had planned to construct funnel plots to assess for the potential existence of small study bias (Higgins 2011).

Data synthesis

We analysed data for each outcome using Review Manager 5.3 (RevMan 2014) in an attempt to estimate the overall effect. We used the Mantel‐Haenszel method for the fixed‐effect model, except when statistical heterogeneity was observed, in which case we applied the random‐effects model, to ensure robustness of the model chosen and susceptibility to outliers.

Subgroup analysis and investigation of heterogeneity

We had planned subgroup analyses to explore possible sources of heterogeneity (e.g. participants, treatments). Heterogeneity among participants could be related to age, the presence of comorbidities (e.g. diabetes, cardiovascular diseases), the presence or severity of renal function impairment, and the duration and severity of hypertension (e.g. number and dosage of antihypertensive drugs used). Heterogeneity in treatments could be related to the type and duration of the renal sympathetic denervation procedure and the type of catheter and radiofrequency probe used. We also planned an exploration of the effect of short‐ and long‐term follow‐up as a source of significant heterogeneity between studies.

Sensitivity analysis

If applicable, we had planned sensitivity analyses to explore the influence of the following factors on effect size:

• repeating the analysis excluding any large studies, to establish how much they impact on the results;

• repeating the analysis taking into account the risk of bias;

• repeating the analysis excluding unpublished studies.