A Network Meta-Analysis of Clinical Management Strategies for Treatment-Resistant Hypertension: Making Optimal Use of the Evidence

Journal of General Internal Medicine, Mar 2017

Background With the addition of surgical interventions to current medicinal treatments, it is increasingly challenging for clinicians to rationally choose among the various options for treating patients with apparent treatment-resistant hypertension (ATRHTN). This study aims to establish the comparative effectiveness of mineralocorticoid receptor antagonists (MRA), renal denervation (RDN), darusentan and central arteriovenous anastomosis (CAA) for patients with ATRHTN by performing a network meta-analysis. Methods Data Sources: Studies from recent meta-analyses for RDN and placebo effect were supplemented with a systematic search for MRAs in ATRHTN in the Pubmed, EMBASE, CINAHL and Cochrane databases through November 2016. Study Selection: Randomized controlled trials comparing treatment options for patients with ATRHTN. Data Extraction and Synthesis: Data were extracted using predefined data extraction forms, including the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. A Bayesian random effects model was used to conduct a network meta-analysis. Spironolactone was used as the main comparator. Main Outcomes and Measures: Reduction in 24-h ambulatory blood pressure measurement (ABPM). Results Twenty articles met our inclusion criteria, and seven treatment alternatives were compared. Compared to MRA, CAA had the highest probability of being more effective, further reducing 24-h SBP (−4.8 mmHg [−13.0, 3.7]) and 24-h DBP (−9.7 mmHg [−18, -0.63]). This difference is likely to be clinically meaningful, with a probability of 78 and 96% at a threshold of a 2-mmHg reduction in blood pressure. Conclusions When compared to MRA as anchor, darusentan, CAA and RDN are not more effective in achieving a clinically significant reduction in ambulatory blood pressure in individuals with apparent treatment-resistant hypertension.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://link.springer.com/content/pdf/10.1007%2Fs11606-017-4000-7.pdf

A Network Meta-Analysis of Clinical Management Strategies for Treatment-Resistant Hypertension: Making Optimal Use of the Evidence

KEY WORDS: treatment-resistant hypertension; network meta-analysis; MRAs. J Gen Intern Med A Network Meta-Analysis of Clinical Management Strategies for Treatment-Resistant Hypertension: Making Optimal Use of the Evidence Peter Makai 1 Joanna IntHout 1 Jaap Deinum 1 Kevin Jenniskens Gert Jan van der Wilt 1 0 Julius Center, University Medical Center Utrecht , Utrecht , The Netherlands 1 Department for Health Evidence, Health Technology Assessment Group, Radboud Institute for Health Sciences, Radboud University Medical Center , Nijmegen , The Netherlands BACKGROUND: With the addition of surgical interventions to current medicinal treatments, it is increasingly challenging for clinicians to rationally choose among the various options for treating patients with apparent treatment-resistant hypertension (ATRHTN). This study aims to establish the comparative effectiveness of mineralocorticoid receptor antagonists (MRA), renal denervation (RDN), darusentan and central arteriovenous anastomosis (CAA) for patients with ATRHTN by performing a network meta-analysis. METHODS: Data Sources: Studies from recent meta-analyses for RDN and placebo effect were supplemented with a systematic search for MRAs in ATRHTN in the Pubmed, EMBASE, CINAHL and Cochrane databases through November 2016. Study Selection: Randomized controlled trials comparing treatment options for patients with ATRHTN. Data Extraction and Synthesis: Data were extracted using predefined data extraction forms, including the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. A Bayesian random effects model was used to conduct a network meta-analysis. Spironolactone was used as the main comparator. Main Outcomes and Measures: Reduction in 24-h ambulatory blood pressure measurement (ABPM). RESULTS: Twenty articles met our inclusion criteria, and seven treatment alternatives were compared. Compared to MRA, CAA had the highest probability of being more effective, further reducing 24-h SBP (−4.8 mmHg [−13.0, 3.7]) and 24-h DBP (−9.7 mmHg [−18, -0.63]). This difference is likely to be clinically meaningful, with a probability of 78 and 96% at a threshold of a 2-mmHg reduction in blood pressure. CONCLUSIONS: When compared to MRA as anchor, darusentan, CAA and RDN are not more effective in achieving a clinically significant reduction in ambulatory blood pressure in individuals with apparent treatmentresistant hypertension. INTRODUCTION Hypertension (HTN) is the most common condition seen in primary care,1 with a global prevalence of 41% in the general population.2 Uncontrolled HTN is a risk factor for cardiovascular and renal disease, sources of significant morbidity and cost to society, and is therefore an important public health target.1,3,4 An estimated 14–16% of hypertensive patients have apparent treatment-resistant hypertension (ATRHTN).5 This proportion will be even higher if more stringent criteria are adopted for adequate blood pressure control.6–9 ATRHTN is defined as inadequately controlled blood pressure despite receiving three or more adequately dosed hypertensive medications, of which at least one is a diuretic.10 Adherence is a key factor in ATRHTN, and according to some estimates, 50% of patients with ATRHTN do not adhere to their medication.11–13 The most common fourth-line treatment is the addition of a mineralocorticoid receptor antagonist (MRA) to the treatment regimen.14 In recent years, other pharmacological interventions have been developed, including darusentan,15 an endothelin receptor antagonist, as well as various devicebased strategies such as renal denervation (RDN) and central arteriovenous anastomosis (CAA).16 A lack of data on the comparative effectiveness of these new treatment strategies poses challenges to the production and interpretation of relevant clinical evidence and to choosing optimal treatment strategies for patients. Direct comparison trials and conventional pairwise meta-analyses have demonstrated different conclusions regarding the efficacy of RDN, likely because of the heterogeneity in control treatments. Trials of RDN, for example, have compared RDN with standard medication therapy (no additional treatment),17 with a sham procedure (mimicking RDN without actually performing the intervention)18 and with MRA as add-on therapy.19 While a recent medium-sized trial showed that RDN was superior to MRA,19 another trial of the same size failed to show a difference in the primary endpoint.20 Among direct comparisons of RDN with other active treatments, results have been mixed. Three conventional pairwise meta-analyses show RDN to be superior,17,21,22 while a fourth meta-analysis, based exclusively on randomized controlled trials (RCTs), casts doubt on these conclusions.23 Conventional pairwise meta-analysis is unable to deal with heterogeneity in control interventions. A more appropriate approach in such cases is a network meta-analysis.24 In a network-meta analysis, effect sizes associat (...truncated)


This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1007%2Fs11606-017-4000-7.pdf

Peter Makai PhD, Joanna IntHout PhD, Jaap Deinum MD PhD, Kevin Jenniskens MSc, Prof. Gert Jan van der Wilt PhD. A Network Meta-Analysis of Clinical Management Strategies for Treatment-Resistant Hypertension: Making Optimal Use of the Evidence, Journal of General Internal Medicine, 2017, pp. 921-930, Volume 32, Issue 8, DOI: 10.1007/s11606-017-4000-7