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Cochrane Database of Systematic Reviews

Guanylate cyclase stimulators for pulmonary hypertension

Overview of attention for article published in Cochrane database of systematic reviews, August 2016
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Guanylate cyclase stimulators for pulmonary hypertension
Published in
Cochrane database of systematic reviews, August 2016
DOI 10.1002/14651858.cd011205.pub2
Pubmed ID

Andrew J Wardle, Matthew J Seager, Richard Wardle, Robert MR Tulloh, J Simon R Gibbs


Pulmonary hypertension is a condition of complex aetiology that culminates in right heart failure and early death. Soluble guanylate cyclase (sGC) stimulators are a promising class of agents that have recently gained approval for use. To evaluate the efficacy of sGC stimulators in pulmonary hypertension. We searched CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE and the reference lists of articles. Searches are current as of 12 February 2016. We selected randomised controlled trials (RCTs) involving participants with pulmonary hypertension of all ages, severities and durations of treatment. AW, MS and RW independently selected studies, assessed evidence quality and extracted data. This process was overseen by RT and SG. All included studies were sponsored by the drug manufacturer. Five trials involving 962 participants are included in this review. All trials were of relatively short duration (< 16 weeks). Due to the heterogenous aetiology of pulmonary hypertension in participants, results are best considered according to each pulmonary hypertension subtype.Pooled analysis shows a mean difference (MD) increase in six-minute walking distance (6MWD) of 30.13 metres (95% CI 5.29 to 54.96; participants = 659; studies = 3). On subgroup analysis, for pulmonary arterial hypertension (PAH) there was no effect noted (6MWD; MD 11.91 metres, 95% CI -44.92 to 68.75; participants = 398; studies = 2), and in chronic thromboembolic pulmonary hypertension (CTEPH) sGC stimulators improved 6MWD by an MD of 45 metres (95% CI 23.87 to 66.13; participants = 261; studies = 1). Data for left heart disease-associated PH was not available for pooling. Importantly, when participants receiving phosphodiesterase inhibitors were excluded, sGC stimulators increased 6MWD by a MD of 36 metres in PAH. The second primary outcome, mortality, showed no change on pooled analysis against placebo (Peto odds ratio (OR) 0.57, 95% CI 0.18 to 1.80).Pooled secondary outcomes include an increase in World Health Organization (WHO) functional class (OR 1.53, 95% CI 0.87 to 2.72; participants = 858; studies = 4), no effect on clinical worsening (OR 0.45, 95% CI 0.17 to 1.14; participants = 842; studies = 3), and a reduction in mean pulmonary artery pressure (MD -2.77 mmHg, 95% CI -4.96 to -0.58; participants = 744; studies = 5). There was no significant difference in serious adverse events on pooled analysis (OR 1.12, 95% CI 0.66 to 1.90; participants = 818; studies = 5) or when analysed at PAH (MD -3.50, 95% CI -5.54 to -1.46; participants = 344; studies = 1), left heart disease associated subgroups (OR 1.56, 95% CI 0.78 to 3.13; participants = 159; studies = 2) or CTEPH subgroups (OR 1.29, 95% CI 0.65 to 2.56; participants = 261; studies = 1).It is important to consider the results for PAH in the context of a person who is not also receiving a phosphodiesterase-V inhibitor, a contra-indication to sGC stimulator use. It should also be noted that CTEPH results are applicable to inoperable or recurrent CTEPH only.Evidence was rated according to the GRADE scoring system. One outcome was considered high quality, two were moderate, and eight were of low or very low quality, meaning that for many of the outcomes the true effect could differ substantially from our estimate. There were only minor concerns regarding the risk of bias in these trials, all being RCTs largely following the original protocol. Most trials employed an intention-to-treat analysis. sGC stimulators improve pulmonary artery pressures in people with PAH (who are treatment naive or receiving a prostanoid or endothelin antagonist) or those with recurrent or inoperable CTEPH. In these settings this can be achieved without notable complication. However, sGC stimulators should not be taken by people also receiving phosphodiestase-V inhibitors or nitrates due to the risks of hypotension, and there is currently no evidence supporting their use in pulmonary hypertension associated with left heart disease. There is no evidence supporting their use in children. These conclusions are based on data with limitations, including unavailable data from two of the trials.

X Demographics

X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 235 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Unknown 234 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 36 15%
Student > Bachelor 29 12%
Researcher 19 8%
Student > Doctoral Student 16 7%
Student > Ph. D. Student 15 6%
Other 43 18%
Unknown 77 33%
Readers by discipline Count As %
Medicine and Dentistry 76 32%
Nursing and Health Professions 27 11%
Psychology 8 3%
Social Sciences 7 3%
Agricultural and Biological Sciences 6 3%
Other 24 10%
Unknown 87 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 November 2016.
All research outputs
of 25,655,374 outputs
Outputs from Cochrane database of systematic reviews
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Outputs of similar age
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Outputs of similar age from Cochrane database of systematic reviews
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Altmetric has tracked 25,655,374 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,151 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 35.0. This one is in the 17th percentile – i.e., 17% of its peers scored the same or lower than it.
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