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European Respiratory Review : An... Sep 2022There is no consensus on the most effective treatments of pulmonary arterial hypertension (PAH). Our objective was to compare effects of medications for PAH. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is no consensus on the most effective treatments of pulmonary arterial hypertension (PAH). Our objective was to compare effects of medications for PAH.
METHODS
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception to December 2021. We performed a frequentist random-effects network meta-analysis on all included trials. We rated the certainty of the evidence using the Grades of Recommendation, Assessment, Development, and Evaluation approach.
RESULTS
We included 53 randomised controlled trials with 10 670 patients. Combination therapy with endothelin receptor antagonist (ERA) plus phosphodiesterase-5 inhibitors (PDE5i) reduced clinical worsening (120.7 fewer events per 1000, 95% CI 136.8-93.4 fewer; high certainty) and was superior to either ERA or PDE5i alone, both of which reduced clinical worsening, as did riociguat monotherapy (all high certainty). PDE5i (24.9 fewer deaths per 1000, 95% CI 35.2 fewer to 2.1 more); intravenous/subcutaneous prostanoids (18.3 fewer deaths per 1000, 95% CI 28.6 fewer deaths to 0) and riociguat (29.1 fewer deaths per 1000, 95% CI 38.6 fewer to 8.7 more) probably reduce mortality as compared to placebo (all moderate certainty). Combination therapy with ERA+PDE5i (49.9 m, 95% CI 25.9-73.8 m) and riociguat (49.5 m, 95% CI 17.3-81.7 m) probably increase 6-min walk distance as compared to placebo (moderate certainty).
CONCLUSION
Current PAH treatments improve clinically important outcomes, although the degree and certainty of benefit vary between treatments.
Topics: Humans; Network Meta-Analysis; Pulmonary Arterial Hypertension
PubMed: 35948391
DOI: 10.1183/16000617.0036-2022 -
Pulmonary Circulation 2021This systematic review of literature and online reports critically appraised incidence and prevalence estimates of pulmonary arterial hypertension and chronic...
Epidemiology of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: identification of the most accurate estimates from a systematic literature review.
This systematic review of literature and online reports critically appraised incidence and prevalence estimates of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension to identify the most accurate estimates. Medline® and Embase® databases were searched for articles published between 1 January 2003 and 31 August 2020. Studies were grouped according to whether they were registries (population-based estimates), clinical databases (hospital-based estimates) or claims/administrative databases. Registries were classified into systematic and non-systematic registries, according to whether every national centre participated. Of 7309 publications identified, 5414 were screened after removal of duplicates and 33 were included. Inclusion was based on study type, availability of a clear numerator (diagnosed population) and a population- or hospital-based denominator, or all primary data required to calculate estimates. Only the most recent publication from a database was included. Most studies were based on European data and very few included children. In adults, the range of estimates per million was approximately 20-fold for pulmonary arterial hypertension incidence (1.5-32) and prevalence (12.4-268) and of similar magnitude for chronic thromboembolic pulmonary hypertension incidence (0.9-39) and prevalence (14.5-144). Recent (≤5 years) national systematic registry data from centralised healthcare systems provided the following ranges in adult estimates per million: approximately 5.8 for pulmonary arterial hypertension incidence, 47.6-54.7 for pulmonary arterial hypertension prevalence, 3.1-6.0 for chronic thromboembolic pulmonary hypertension incidence and 25.8-38.4 for chronic thromboembolic pulmonary hypertension prevalence. These estimates were considered the most reliable and consistent for the scientific community to plan for resource allocation and improve detection rates.
PubMed: 33456755
DOI: 10.1177/2045894020977300 -
British Journal of Anaesthesia Apr 2021The risk of complications, including death, is substantially increased in patients with pulmonary hypertension (PH) undergoing anaesthesia for surgical procedures,...
BACKGROUND
The risk of complications, including death, is substantially increased in patients with pulmonary hypertension (PH) undergoing anaesthesia for surgical procedures, especially in those with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH). Sedation also poses a risk to patients with PH. Physiological changes including tachycardia, hypotension, fluid shifts, and an increase in pulmonary vascular resistance (PH crisis) can precipitate acute right ventricular decompensation and death.
METHODS
A systematic literature review was performed of studies in patients with PH undergoing non-cardiac and non-obstetric surgery. The management of patients with PH requiring sedation for endoscopy was also reviewed. Using a framework of relevant clinical questions, we review the available evidence guiding operative risk, risk assessment, preoperative optimisation, and perioperative management, and identifying areas for future research.
RESULTS
Reported 30 day mortality after non-cardiac and non-obstetric surgery ranges between 2% and 18% in patients with PH undergoing elective procedures, and increases to 15-50% for emergency surgery, with complications and death usually relating to acute right ventricular failure. Risk factors for mortality include procedure-specific and patient-related factors, especially markers of PH severity (e.g. pulmonary haemodynamics, poor exercise performance, and right ventricular dysfunction). Most studies highlight the importance of individualised preoperative risk assessment and optimisation and advanced perioperative planning.
CONCLUSIONS
With an increasing number of patients requiring surgery in specialist and non-specialist PH centres, a systematic, evidence-based, multidisciplinary approach is required to minimise complications. Adequate risk stratification and a tailored-individualised perioperative plan is paramount.
Topics: Consensus; Expert Testimony; Humans; Hypertension, Pulmonary; Perioperative Care; Postoperative Complications
PubMed: 33612249
DOI: 10.1016/j.bja.2021.01.005 -
Chest Mar 2019Pulmonary arterial hypertension (PAH) carries a poor prognosis if not promptly diagnosed and appropriately treated. The development and approval of 14 medications over...
BACKGROUND
Pulmonary arterial hypertension (PAH) carries a poor prognosis if not promptly diagnosed and appropriately treated. The development and approval of 14 medications over the last several decades have led to a rapidly evolving approach to therapy, and have necessitated periodic updating of evidence-based treatment guidelines. This guideline statement, which now includes a visual algorithm to enhance its clinical utility, represents the fourth iteration of the American College of Chest Physicians Guideline and Expert Panel Report on Pharmacotherapy for PAH.
METHODS
The guideline panel conducted an updated systematic review to identify studies published after those included in the 2014 guideline. A systematic literature search was conducted using MEDLINE via PubMed and the Cochrane Library. The quality of the body of evidence was assessed for each critical or important outcome of interest using the Grading of Recommendations Assessment, Development and Evaluation approach. Graded recommendations and ungraded consensus-based statements were developed and voted on using a modified Delphi technique to achieve consensus.
RESULTS
Two new recommendations on combination therapy and two ungraded consensus-based statements on palliative care were developed. An evidence-based and consensus-driven treatment algorithm was created to guide the clinician through an organized approach to management, and to direct readers to the appropriate area of the document for more detailed information.
CONCLUSIONS
Therapeutic options for the patient with PAH continue to expand through basic discovery, translational science, and clinical trials. Optimal use of new treatment options requires prompt evaluation at an expert center, utilization of current evidence-based guidelines, and collaborative care using sound clinical judgment.
Topics: Adult; Antihypertensive Agents; Diagnostic Techniques, Respiratory System; Drug Monitoring; Evidence-Based Medicine; Exercise Tolerance; Humans; Pulmonary Arterial Hypertension; Pulmonary Medicine; Respiratory System Agents
PubMed: 30660783
DOI: 10.1016/j.chest.2018.11.030 -
Annals of the Rheumatic Diseases Aug 2017The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new...
The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
Topics: Angiotensin-Converting Enzyme Inhibitors; Delphi Technique; Endothelin Receptor Antagonists; Europe; Fingers; Fluoxetine; Gastrointestinal Diseases; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Hypertension, Pulmonary; Kidney Diseases; Lung Diseases; Phosphodiesterase 5 Inhibitors; Prostaglandins I; Pyrazoles; Pyrimidines; Raynaud Disease; Rheumatology; Scleroderma, Systemic; Selective Serotonin Reuptake Inhibitors; Ulcer
PubMed: 27941129
DOI: 10.1136/annrheumdis-2016-209909 -
Journal of the American Society of... Jul 2017Pulmonary embolism (PE) is a common diagnosis with significant mortality if not appropriately treated. The use of transthoracic echocardiography in patients with PE is... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Pulmonary embolism (PE) is a common diagnosis with significant mortality if not appropriately treated. The use of transthoracic echocardiography in patients with PE is common; however, its diagnostic capabilities in this use are unclear. With the increased use of ultrasonography in medical settings, it is important to understand the strengths and limitations of echocardiography for the diagnosis of PE.
METHODS
We conducted a systematic review of PubMed, CINAHL, and EMBASE through 2016 for articles assessing the diagnostic accuracy of transthoracic echocardiography for PE. Two authors independently abstracted relevant data from the studies. We assessed quality using the QUADAS-2 tool for diagnostic studies.
RESULTS
Undefined "right heart strain" was the most common sign used, and it had a sensitivity of 53% (95% CI, 45%-61%) and a specificity of 83% (95% CI, 74%-90%). Eleven other distinct signs were identified: ventricle size ratio, abnormal septal motion, tricuspid regurgitation, 60/60 sign, McConnell's sign, right heart thrombus, right ventricle hypokinesis, pulmonary hypertension, right ventricular end-diastolic diameter, tricuspid annular plane systolic excursion, and right ventricular systolic pressure.
CONCLUSIONS
Studies show a consistently high specificity and low sensitivity for echocardiography in the diagnosis of PE, making it potentially adequate as a rule-in test at the bedside in critical care settings such as the emergency department and intensive care unit for patients with a suspicion of PE, especially those unable to get other confirmatory studies. Future research may continue to clarify the role of bedside echocardiography in conjunction with other tests and imaging in the overall management of PE.
Topics: Diagnosis, Differential; Echocardiography; Humans; Pulmonary Embolism
PubMed: 28495379
DOI: 10.1016/j.echo.2017.03.004 -
European Journal of Obstetrics,... Oct 2020Traditionally, pulmonary hypertension during pregnancy has been associated with increased risk of adverse maternal and fetal outcomes. The aim of this study to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Traditionally, pulmonary hypertension during pregnancy has been associated with increased risk of adverse maternal and fetal outcomes. The aim of this study to systematically analyze the published literature mentioning pregnancy outcomes in pregnant women with pulmonary hypertension in recent decades.
STUDY METHODS
A Comprehensive electronic literature search of MEDLINE, EMBASE and Cochrane library was done to find studies published in English literature from 1 Jan 1990 to 31 May 2018. Prospective and retrospective observational studies describing pregnancy outcomes in at least 4 women with pulmonary hypertension were included in this study. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale. The primary outcomes included maternal mortality and any pregnancy loss. The analysis included absolute risks and 95% confidence intervals (CI) for adverse outcomes using the DerSimonian-Laird random effects model. Heterogeneity was assessed by I statistic and visual plot.
RESULTS
Twenty studies captured data from 589 parturient describing 610 pregnancies. The pooled unadjusted data yielded maternal mortality of 11.5 (95% CI; 7.6-17.2) and the total pregnancy loss was 22.8 (95% CI; 16.2-31.1). Prematurity and IUGR/SGA were reported by 7 and 8 studies and had pooled estimates of 51.7 (95% CI; 37.6-65.7) and 29.3 (95% CI; 20.9-39.5), respectively. The pooled estimates of cesarean delivery and general anesthesia were 72.1 (95% CI; 60.6-81.93) and 40.1 (95% CI; 26.4-55.5), respectively.
CONCLUSIONS
Fetomaternal outcomes have improved in recent decades in parturient with moderate to severe pulmonary hypertension. These findings have implications for preconceptional counselling and risk stratifications.
Topics: Female; Humans; Hypertension, Pulmonary; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Outcome; Prospective Studies; Retrospective Studies
PubMed: 32862030
DOI: 10.1016/j.ejogrb.2020.08.028 -
Thrombosis Research Nov 2023Life-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Life-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral anticoagulants (DOAC) for CTEPH is yet to be established. We performed a systematic review and meta-analysis to clarify the outcomes of CTEPH in patients who used DOAC or vitamin K antagonists (VKA).
METHODS
We reviewed literature in PubMed and EMBASE through March 2023. We included studies involving patients with CTEPH where DOAC and VKA were compared. We collected data including intervention history for CTEPH, bleeding events, recurrence of VTE (venous thromboembolism), and mortality. We performed a meta-analysis using the Mantel-Haenszel method with a fixed-effects model.
RESULTS
We included one randomized clinical trial and six observational studies, with a total of 2969 patients. Six studies investigated major bleeding outcomes, and seven investigated all bleeding outcomes. There were no differences in major bleeding (RR 0.59, 95 % CI [0.34-1.02], I = 0 %) and all-bleeding (RR 0.87, 95 % CI [0.67-1.13], I = 0 %). Based on the five studies we included, DOAC was associated with a lower risk of mortality (RR 0.54, 95 % CI: 0.37-0.79, I = 5 %). However, a higher risk of recurrent pulmonary embolism (PE) was seen in three studies (RR 3.80, 95 % CI: [1.93-7.50], I = 11 %). No significant differences were noted in terms of VTE.
CONCLUSION
DOAC compared to VKA was associated with a significantly lower mortality and higher risk of recurrent PE. Since most of the included studies are observational, we must consider the existence of multiple biases and confounding factors.
Topics: Humans; Venous Thromboembolism; Hypertension, Pulmonary; Anticoagulants; Blood Coagulation; Hemorrhage; Pulmonary Embolism; Fibrinolytic Agents; Administration, Oral; Vitamin K; Randomized Controlled Trials as Topic
PubMed: 37839150
DOI: 10.1016/j.thromres.2023.10.003 -
Frontiers in Cardiovascular Medicine 2021Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with poor prognosis, conferring up to a 10-fold increase in mortality in patients with sarcoidosis,...
BACKGROUND
Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with poor prognosis, conferring up to a 10-fold increase in mortality in patients with sarcoidosis, but the actual prevalence of SAPH is unknown.
METHODS
The PubMed, Embase, and Cochrane Library databases were systematically searched for epidemiological studies reporting the prevalence of SAPH up to July 2021. Two reviewers independently performed the study selection, data extraction, and quality assessment. Studies were pooled using random-effects meta-analysis.
RESULTS
This meta-analysis included 25 high-quality studies from 12 countries, with a pooled sample of 632,368 patients with sarcoidosis. The prevalence of SAPH by transthoracic echocardiography in Europe, the United States and Asia was 18.8% [95% confidence interval (CI): 11.1-26.5%], 13.9% (95% CI: 5.4-22.4%) and 16.2% (95% CI: 7.1-25.4%) separately, and the overall pooled prevalence was 16.4% (95%CI: 12.2-20.5%). By right heart catheterization (RHC), the pooled prevalence of SAPH was 6.4% (95% CI: 3.6-9.1%) in general sarcoidosis population, and subgroup analyses showed that the prevalence of SAPH was 6.7% (95% CI: 2.4-11.0%) in Europe and 8.6% (95% CI: -4.1 to 21.3%) in the United States. Further, the prevalence of pre-capillary PH was 6.5% (95% CI: 2.9-10.2%). For the population with advanced sarcoidosis, the pooled prevalence of SAPH and pre-capillary PH by RHC was as high as 62.3% (95% CI: 46.9-77.6%) and 55.9% (95% CI: 20.1-91.7%), respectively. Finally, the pooled prevalence of SAPH in large databases with documented diagnoses (6.1%, 95% CI: 2.6-9.5%) was similar to that of RHC. Substantial heterogeneity across studies was observed for all analyses ( > 80%, < 0.001).
CONCLUSIONS
The sarcoidosis population has a relatively low burden of PH, mainly pre-capillary PH. However, as the disease progresses to advanced sarcoidosis, the prevalence of SAPH increases significantly.
PubMed: 35111830
DOI: 10.3389/fcvm.2021.809594 -
Annals of Palliative Medicine Oct 2021Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic significance for other types of pulmonary hypertension (PH). Our purpose was to evaluate the specific impact of riociguat on all types of PH.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of riociguat treatment for PH through databases of the Cochrane Library, PubMed, Embase, and Web of Science from inception to the present. Duplicate publications, studies with no full text, incomplete information or inability to extract data, animal experiments and reviews, and systematic reviews were excluded. The software RevMan 5.4 was used for data synthesis.
RESULTS
There were 8 RCTs included in our study, involving 1,606 participants. For PAH and CTEPH patients, riociguat treatment extended 6-minute walk distance (6MWD) by 39.84 meters, decreased mean pulmonary arterial pressure (PAP) by 4.20 mmHg, lowered pulmonary vascular resistance (PVR) by 218.76 dynes/sec/cm-5, cut down right atrial pressure (RAP) by 0.9 mmHg, increased cardiac index (CI) by 0.49 L/min/m2, improved cardiac output (CO) by 0.89 L/min, reduced N-terminal pro-type B natriuretic peptide (NT-proBNP) by 436.21 pg/mL, and decreased adverse events and clinical worsening as compared with placebo. For other types of PH including PH due to left heart disease and PH due to lung disease, riociguat was reported as having improved CI by 0.42 L/min/m2 and CO was increased by 0.92 L/min compared with placebo. Other efficacy outcomes and safety outcomes did not attain statistical difference in other types of PH.
CONCLUSIONS
For PAH and CTEPH, riociguat treatment is safe and effective, but for other types of PH, it can only improve some hemodynamic parameters.
Topics: Chronic Disease; Humans; Hypertension, Pulmonary; Pyrazoles; Pyrimidines
PubMed: 34763472
DOI: 10.21037/apm-21-2656