-
Global Heart 2023This systematic review and meta-analysis aimed to determine the efficacy of macitentan in patients with pulmonary hypertension (PH). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aimed to determine the efficacy of macitentan in patients with pulmonary hypertension (PH).
METHODS
A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo or blank, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs).
RESULTS
Six RCTs (enrolling 1,003 participants) met the inclusion criteria. Macitentan showed significant effects on 6-min walk distance (6MWD) (WMD 12.06 m, 95% CI 2.12 to 21.99 m), pulmonary vascular resistance (PVR) (WMD -186.51 dyn·s/cm, 95% CI -232.72 to -140.29 dyn·s/cm), mean pulmonary artery pressure (mPAP) (WMD -3.20 mmHg, 95% CI -5.93 to -0.47 mmHg), N-terminal pro-brain natriuretic peptide (NT-proBNP) (WMD -232.47 ng/L, 95% wCI -318.22 to -146.72 ng/L), and cardiac index (WMD 0.39 L/min/m, 95% CI 0.20 to 0.58 L/min/m).
CONCLUSION
Macitentan significantly improved 6MWD, PVR, mPAP, NT-proBNP, and cardiac index in patients with PH. Macitentan should be further validated in patients with PH.
Topics: Humans; Hypertension, Pulmonary; Treatment Outcome; Randomized Controlled Trials as Topic; Pyrimidines
PubMed: 37901601
DOI: 10.5334/gh.1274 -
The European Respiratory Journal Jun 2024Pulmonary arterial hypertension (PAH) has been described in patients treated with proteasome inhibitors (PIs). Our objective was to evaluate the association between PIs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary arterial hypertension (PAH) has been described in patients treated with proteasome inhibitors (PIs). Our objective was to evaluate the association between PIs and PAH.
METHODS
Characteristics of incident PAH cases previously treated with carfilzomib or bortezomib were analysed from the French pulmonary hypertension registry and the VIGIAPATH programme from 2004 to 2023, concurrently with a pharmacovigilance disproportionality analysis using the World Health Organization (WHO) global database (VigiBase) and a meta-analysis of randomised controlled trials.
RESULTS
11 incident cases of PI-associated PAH were identified (six with carfilzomib and five with bortezomib) with a female:male ratio of 2.7:1, a median age of 61 years, and a median delay between PI first exposure and PAH of 6 months. Four patients died (two from right heart failure, one from respiratory distress and one from an unknown cause). At diagnosis, six were in New York Heart Association Functional Class III/IV with severe haemodynamic impairment (median mean pulmonary arterial pressure 39 mmHg, cardiac index 2.45 L·min·m and pulmonary vascular resistance 7.2 WU). In the WHO pharmacovigilance database, 169 cases of PH associated with PI were reported since 2013 with significant signals of disproportionate reporting (SDR) for carfilzomib, regardless of the definition of cases or control group. However, SDR for bortezomib were inconsistent. The systematic review identified 17 clinical trials, and carfilzomib was associated with a significantly higher risk of dyspnoea, severe dyspnoea and PH compared with bortezomib.
CONCLUSION
PIs may induce PAH in patients undergoing treatment, with carfilzomib emitting a stronger signal than bortezomib, and these patients should be monitored closely.
Topics: Humans; Middle Aged; Bortezomib; France; Oligopeptides; Pharmacovigilance; Proteasome Inhibitors; Pulmonary Arterial Hypertension; Randomized Controlled Trials as Topic; Registries
PubMed: 38697649
DOI: 10.1183/13993003.02158-2023 -
Internal and Emergency Medicine Apr 2024The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of... (Meta-Analysis)
Meta-Analysis
The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.
Topics: Humans; Antihypertensive Agents; Connective Tissue Diseases; Peptide Fragments; Pulmonary Arterial Hypertension; Randomized Controlled Trials as Topic
PubMed: 38378970
DOI: 10.1007/s11739-024-03539-1 -
Journal of Cardiovascular Development... Oct 2023Obesity is reported to have a protective effect on mortality in pulmonary hypertension (PH), a phenomenon known as obesity paradox. However, the data are conflicting,... (Review)
Review
Obesity is reported to have a protective effect on mortality in pulmonary hypertension (PH), a phenomenon known as obesity paradox. However, the data are conflicting, with some studies showing decreased mortality while other studies found no effect of obesity on mortality. Therefore, we performed a systematic review and meta-analysis to examine whether there is an association between obesity and mortality in PH. Only patients with PH diagnosed by right heart catheterization were included. We also performed a sub-group analysis of subjects with pre-capillary PH only. A total of six studies met the inclusion criteria, with a sample size of 13,987 patients. Obese subjects had lower mortality compared to non-obese subjects in the combined pre- and post-capillary PH group (hazard ratio 0.79, 95% CI 0.66-0.95, = 0.01). While obesity was associated with reduction in mortality in the pre-capillary PH group (hazard ratio 0.77, 95% CI 0.60 to 0.98, = 0.03), this was not uniform across all studies.
PubMed: 37887866
DOI: 10.3390/jcdd10100419 -
Journal of Cardiovascular Development... Dec 2023Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is... (Review)
Review
Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is scant and conflicting evidence about the use of pulmonary hypertension (PH) specific therapy in patients with PH-COPD. PubMed, OVID, CINAHL, Cochrane, Embase, and Web of Science were searched using various MESH terms to identify randomized controlled trials (RCTs) or observational studies investigating PH-specific therapies in patients with severe PH-COPD, defined by mean pulmonary artery pressure (mPAP) of more than 35 mm Hg or pulmonary vascular resistance (PVR) of more than 5 woods units on right heart catheterization. The primary outcome was a change in mPAP and PVR. Secondary outcomes were changes in six-minute walk distance (6MWD), changes in the brain-natriuretic peptide (BNP), New York Heart Association (NYHA) functional class, oxygenation, and survival. Thirteen studies satisfied the inclusion criteria, including a total of 328 patients with severe PH-COPD. Out of these, 308 patients received some type of specific therapy for PH. There was a significant reduction in mPAP (mean difference (MD) -3.68, 95% CI [-2.03, -5.32], < 0.0001) and PVR (MD -1.40 Wood units, 95% CI [-1.97, -0.82], < 0.00001). There was a significant increase in the cardiac index as well (MD 0.26 L/min/m, 95% CI [0.14, 0.39], < 0.0001). There were fewer patients who had NYHA class III/lV symptoms, with an odds ratio of 0.55 (95% CI [0.30, 1.01], = 0.05). There was no significant difference in the 6MWD (12.62 m, 95% CI [-8.55, 33.79], = 0.24), PaO (MD -2.20 mm Hg, 95% CI [-4.62, 0.22], = 0.08), or BNP or NT-proBNP therapy (MD -0.15, 95% CI [-0.46, 0.17], = 0.36). The use of PH-specific therapies in severe PH-COPD resulted in a significant reduction in mPAP and PVR and increased CI, with fewer patients remaining in NYHA functional class III/IV. However, no significant difference in the 6MWD, biomarkers of right ventricular dysfunction, or oxygenation was identified, demonstrating a lack of hypoxemia worsening with treatment. Further studies are needed to investigate the use of PH medications in patients with severe PH-COPD.
PubMed: 38132665
DOI: 10.3390/jcdd10120498 -
Medicina Clinica Jun 2024Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart...
BACKGROUND AND OBJECTIVES
Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart failure and death. While pulmonary endarterectomy is the treatment of choice, some patients might benefit from medical therapy or balloon pulmonary angioplasty. Sex differences in outcomes of these therapies are not well characterized.
MATERIAL AND METHODS
We conducted a systematic review and meta-analysis to investigate sex differences in outcomes of various therapies for CTEPH. We searched MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library databases between January 1, 2010 and April 30, 2021, published in English. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I statistic. We assessed publication bias using Begg's and Egger's tests. This study is registered in PROSPERO, CRD42021268504.
RESULTS
A total of 19 studies met the eligibility criteria, but only 3 trials provided separate outcomes for women and men. Two studies evaluated the efficacy of BPA, and one study evaluated the efficacy of riociguat (129 patients). Overall, 57.3% of patients were women and 62.6% were in functional class III. Mean time of follow-up was 55.5 (SD 26.1) weeks. Women showed a significantly better response in cardiac index (mean difference [MD], 0.10L/min/m; 95% confidence interval [CI], 0.04-0.16; I=0%; P=0.001). Alternatively, the reduction of pulmonary vascular resistances was significantly higher for men than for women (MD, 161.17dynscm; 95% CI, 67.99-254.35; I=0%; P=0.0007).
CONCLUSIONS
Women and men might show different hemodynamic responses to riociguat or BPA for CTEPH.
PubMed: 38908993
DOI: 10.1016/j.medcli.2024.03.014 -
Chest May 2024Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances.
BACKGROUND
Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances.
RESEARCH QUESTION
What are the diagnostic evaluation, epidemiologic features, associated factors, prognostic significance, and outcome measures in interventional trials for PH in patients with ILD in the current literature?
STUDY DESIGN AND METHODS
Ovid MEDLINE, Embase, and CENTRAL databases were searched for original research evaluating PH in participants with ILD of any cause. The definition of PH was based on the investigators' criteria.
RESULTS
Three hundred two studies were included, with varying diagnostic evaluations used to define PH. Commonly used diagnostic tests were right heart catheterization (RHC; 56%) and transthoracic echocardiography (TTE; 50%). The pooled prevalence for PH in general populations with ILD was 36% (95% CI, 30%-42%) using RHC and 34% (95% CI, 29%-38%) using TTE. Lower diffusion capacity of the lungs for carbon monoxide, worse oxygenation status, reduced exercise capacity, increased pulmonary artery to aorta ratio and pulmonary artery diameter, and elevated serum brain natriuretic peptide consistently were associated with the presence of PH in at least 60% of reported studies. The presence of PH was associated with increased symptom burden and worse prognosis. Outcome measures in interventional trials of PH in ILD focused on changes in pulmonary vascular hemodynamics and 6-min walk distance.
INTERPRETATION
PH is a common complication in ILD with significant health impacts. A standardized definition with prospective evaluation of risk-stratified assessments for PH using identified associated risk factors is warranted. Our findings provide an evidence base for validation as surrogate end points in future PH interventional trials in ILD.
TRIAL REGISTRY
International Prospective Register of Systematic Reviews; No.: CRD42021255394; URL: https://www.crd.york.ac.uk/prospero/.
PubMed: 38821182
DOI: 10.1016/j.chest.2024.04.025 -
Sleep Medicine Dec 2023Sleep disorders, including obstructive sleep apnea (OSA), restless leg syndrome (RLS) and insomnia, are present in chronic obstructive pulmonary disease (COPD) with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sleep disorders, including obstructive sleep apnea (OSA), restless leg syndrome (RLS) and insomnia, are present in chronic obstructive pulmonary disease (COPD) with varied prevalence. The aim of this systematic review and meta-analysis was to investigate prevalence of OSA, RLS and insomnia in patients with COPD and summarize their clinical characteristics.
METHODS
We searched PubMed, Web of Science and Scopus for eligible articles reporting the prevalence of OSA, RLS, and insomnia in COPD patients. The Newcastle‒Ottawa scale was applied for quality assessment. Odds ratios or mean differences with 95 % confidence intervals (CIs) were applied for the overall prevalence calculation and clinical characteristics assessment. Sensitivity analysis, subgroup analysis and meta-regression were conducted to evaluate the heterogeneity of the results.
RESULTS
Sixty articles reporting the prevalence of sleep disorders in patients with COPD were included, and the prevalence of OSA, RLS, and insomnia reached 29.1 %(95%CI 27.2%-30.9 %), 21.6 %(95%CI 11.8%-33.3 %) and 29.5 %(95%CI 16.9%-44.0 %), respectively. COPD patients with OSA were characterized by male sex (OR 1.631 95 % CI: 1.231-2.161), obesity(kg/m) (MD 4.435, 95 % CI 3.218-5.652), higher Epworth Sleepiness Scale (MD: 3.741, 95 % CI: 0.655-6.828, p = 0.018), better pulmonary function (MD 5.66, 95 % CI 3.546-7.774) and higher risks of hypertension (OR 1.933 95 % CI 1.382-2.70) and diabetes (OR 1.898 95 % CI 1.264-2.849). COPD patients with RLS were associated with a higher Epworth sleepiness scale (ESS) score (MD 3.444, 95 % CI 1.880-5.008) and a longer COPD duration(year) (MD: 3.656, 95 % CI: 2.209-5.103). COPD patients with insomnia were characterized by female sex(OR 0.556, 95%CI 0.545,0.567, p < 0.001).
CONCLUSION
Our study suggests that OSA, RLS and insomnia are common in COPD patients with specific clinical characteristics. Further studies are needed to explore the interactions between COPD and sleep disorders.
Topics: Humans; Male; Female; Sleep Initiation and Maintenance Disorders; Prevalence; Sleepiness; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Sleep Wake Disorders; Restless Legs Syndrome
PubMed: 37950939
DOI: 10.1016/j.sleep.2023.10.034 -
Clinical Therapeutics Jan 2024To systematically evaluate the safety, dosing regimen, and efficacy of selexipag for pediatric patients with pulmonary hypertension (PH). (Review)
Review
PURPOSE
To systematically evaluate the safety, dosing regimen, and efficacy of selexipag for pediatric patients with pulmonary hypertension (PH).
METHODS
A literature search of the electronic databases of PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar was performed from inception through February 28, 2023. Two reviewers independently searched and evaluated the quality of the studies and pooled data when appropriate. Full-text articles of studies of children diagnosed with PH and treated with selexipag were eligible. Pediatric patients with PH were classified into 2 groups: the add-on therapy group, in which selexipag was used as a third therapy in addition to the baseline treatment, and the transition therapy group, in which patients were switched from parenteral prostacyclin analogs to selexipag.
FINDINGS
Fourteen studies involving 58 pediatric patients with PH were included. All studies were either case reports or case series. Overall, 30 and 28 patients were in the add-on and transition therapy groups, respectively. In both groups, selexipag was initially administered as 50-200 µg twice daily and titrated to a tolerated dosage of 200-1,600 µg twice daily. Prostacyclin analogs were simultaneously weaned for patients in the transition group. In the add-on therapy group, 16 patients (80.0%) were at low risk of the World Health Organization functional class (WHO FC I/II), 12 (76.9%) were at low risk of the 6-minute walk distance (6MWD; >350 m), and 21 (95.5%) were at low risk of the pulmonary vascular resistance index (PVRi; <20 WU/m). Furthermore, N-terminal pro-brain natriuretic peptide and mean pulmonary arterial pressure were significantly improved. More than 70% of patients experienced common tolerable side effects, such as headache, nausea, and diarrhea. In the transition therapy group, 5 patients (55.6%) were at low risk according to WHO FC I/II, 6 (66.7%) were at low risk according to 6MWD, and 14 (87.5) were at low risk according to PVRi; however, selexipag had no significant effect on their hemodynamic parameters. Additionally, more than 80% of patients experienced no side effects.
IMPLICATIONS
Selexipag as add-on therapy or for transition from prostacyclin analogs may have a favorable safety profile and potential efficacy for pediatric patients with PH. Further high-quality evidence of the efficacy and safety of selexipag for the treatment of pediatric PH is warranted.
Topics: Humans; Child; Hypertension, Pulmonary; Antihypertensive Agents; Acetamides; Prostaglandins I
PubMed: 37945502
DOI: 10.1016/j.clinthera.2023.09.026 -
Clinical and Experimental Rheumatology Nov 2023The prevalence and outcome of mixed connective tissue disease-associated pulmonary arterial hypertension (MCTD-PAH) has not been well understood. Our aim was to review... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The prevalence and outcome of mixed connective tissue disease-associated pulmonary arterial hypertension (MCTD-PAH) has not been well understood. Our aim was to review the current knowledge on the prevalence, severity, and mortality of MCTD-PAH. We also aimed to examine the prevalence trend of MCTD-PAH over the years.
METHODS
PubMed/Medline, Embase, Scopus and Web of Science electronic databases were searched for the published randomised controlled clinical trials (RCTs) and observational/original studies on PAH in patients with MCTD from January 1972 to December 2020.
RESULTS
The results were pooled using random-effects meta-analysis based on DerSimonian and Laird method. A total of 983 patients from eight studies were included in the meta-analysis (K=8, n=983). Pooled prevalence of PAH in MCTD patients was 12.53% [95% CI 8.30-18.48%] with significant level statistical heterogeneity (tau2=0.30, tau=0.55, i2 83.3%, H=2.13 Q(df,7)=31.90, p=0.001). There was no association between PAH and female gender or age. The percentage of deaths in MCTD patients due to PAH varied and reached up to 81.8%.
CONCLUSIONS
This is the first systematic review and meta-analysis investigating the prevalence of PAH in patients with MCTD and it revealed an overall prevalence of PAH in patients with MCTD of 12.53%. Our results showed trends of reduced prevalence of MCTD-PAH over last four decade, reconfirmed the lower prevalence rate in recent studies, but revealed an increased mortality rate. We also determined the low impact of the age, gender, and interstitial lung disease on MCTD-PAH.
Topics: Humans; Female; Mixed Connective Tissue Disease; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Prevalence
PubMed: 37497727
DOI: 10.55563/clinexprheumatol/srma43