Oral Prostacyclin Pathway Agents Used in PAH: A Targeted Literature Review.

Purpose: Pulmonary arterial hypertension (PAH) is a rare and progressive pulmonary vascular disease that can result in right heart failure and death. Oral prostacyclins play an important role in the management of intermediate-low risk PAH. This targeted literature review (TLR) aimed to identify and compare evidence supporting use of oral prostacyclin pathway agents (PPAs: selexipag and oral treprostinil) in intermediate-low risk PAH. Methods: A targeted literature review was conducted. Literature databases (MEDLINE, Embase, and Cochrane reviews) were searched for studies describing clinical practice and treatment outcomes for oral treprostinil and selexipag globally, published in English (2012 to 2022). Electronic searches were supplemented by manual-searches of targeted conferences (2020 to 2022), and reference lists of identified publications were reviewed. One reviewer assessed studies for eligibility. Results: In total, 95 publications met inclusion criteria: 47 full-text articles (selexipag n = 22; oral treprostinil n = 16; selexipag and oral treprostinil n = 9) and 48 conference materials. Selexipag and oral treprostinil target the prostacyclin pathway differently; their label-supporting trials had different primary endpoints (disease progression and hospitalization vs exercise capacity and disease progression), differing baseline therapy (0, 1 or 2 vs 0 or 1 baseline treatments), titration duration and dosing (personalized dose capped at 1600 ug twice daily (BID) vs increasing doses over time with no maximum dose), respectively. While both oral PPAs have demonstrated reduced risk of disease progression, only selexipag showed reduction in hospitalization rates. Oral PPAs have been shown to reduce healthcare costs in real-world clinical practice. This difference is reflected in labeled indications. Conclusion: Given differences in trial- and real-world outcomes, number of prior therapies, and dosing, personalizing the choice of oral PPA is critical to maximizing the benefit for individual patients.

PAH is a condition that causes heart failure. It is important to take medicines to slow down this process. For people with early disease, there are some medicines that can be taken as a tablet rather than as an injection to slow down disease progression. The differences between two of the tablet options ­ selexipag and oral treprostinil, are unclear. We reviewed publications describing how, when and why these medicines are used and how well they work, to improve our understanding of the value of these medicines to people with PAH.

Individual- and Community-Level Predictors of Hospital-at-Home Outcomes.

Advanced Care at Home is a Mayo Clinic hospital-at-home (HaH) program that provides hospital-level care for patients. The study examines patient- and community-level factors that influence health outcomes. The authors performed a retrospective study using patient data from July 2020 to December 2022. The study includes 3 Mayo Clinic centers and community-level data from the Agency for Healthcare Research and Quality. The authors conducted binary logistic regression analyses to examine the relationship among the independent variables (patient- and community-level characteristics) and dependent variables (30-day readmission, mortality, and escalation of care back to the brick-and-mortar hospital). The study examined 1433 patients; 53% were men, 90.58% were White, and 68.2% were married. The mortality rate was 2.8%, 30-day readmission was 11.4%, and escalation back to brick-and-mortar hospitals was 8.7%. At the patient level, older age and male gender were significant predictors of 30-day mortality (P-value <0.05), older age was a significant predictor of 30-day readmission (P-value <0.05), and severity of illness was a significant predictor for readmission, mortality, and escalation back to the brick-and-mortar hospital (P-value <0.01). Patients with COVID-19 were less likely to experience readmission, mortality, or escalations (P-value <0.05). At the community level, the Gini Index and internet access were significant predictors of mortality (P-value <0.05). Race and ethnicity did not significantly predict adverse outcomes (P-value >0.05). This study showed promise in equitable treatment of diverse patient populations. The authors discuss and address health equity issues to approximate the vision of inclusive HaH delivery.

Hemodynamic response to inhaled nitric oxide in patients with pulmonary hypertension and chronic kidney disease: A retrospective cohort study.

Pulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH-CKD) affects approximately 20%-40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH-CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH-CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end-stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface area who underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3 Wood units were included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7% of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc-PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc-PH groups. Among a small subset (n = 14) who were subsequently treated with PAH-targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH-CKD.

Tyvaso DPI: Drug-device characteristics and patient clinical considerations.

Tyvaso DPI is a drug-device combination therapy comprised of a small, portable, reusable, breath-powered, dry powder inhaler (DPI) for the delivery of treprostinil. It is approved for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. Tyvaso DPI utilizes single-use prefilled cartridges to ensure proper dosing. Unlike nebulizer devices, administration of Tyvaso DPI is passive and does not require coordination with the device. The low-flow rate design results in targeted delivery to the peripheral lungs due to minimal drug loss from impaction in the oropharynx. The inert fumaryl diketopiperazine (FDKP) excipient forms microparticles that carry treprostinil into the airways, with a high fraction of the particles in the respirable range. In a clinical study in patients with pulmonary arterial hypertension, Tyvaso DPI had similar exposure and pharmacokinetics, low incidence of adverse events, and high patient satisfaction compared with nebulized treprostinil solution. Tyvaso DPI may be considered as a first prostacyclin agent or for those that do not tolerate other prostacyclin formulations, patients with pulmonary comorbidities, patients with mixed Group 1 and Group 3 pulmonary hypertension, or those that prefer an active lifestyle and need a portable, non-invasive treatment. Tyvaso DPI is a patient-preferred, maintenance-free, safe delivery option that may improve patient compliance and adherence.

Impact of Pulmonary Hypertension Hemodynamic Phenotype on Incident Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation/flutter (AF) is common among patients with pulmonary hypertension (PH) and is associated with poor clinical outcomes. AF has been shown to occur more commonly among patients with postcapillary PH, although AF also occurs among patients with precapillary PH. The goal of this study was to evaluate the independent impact of PH hemodynamic phenotype on incident AF among patients with PH. METHODS: We retrospectively identified 262 consecutive patients, without a prior diagnosis of atrial arrhythmias, seen at the PH clinic at Mayo Clinic, Florida, between 1997 and 2017, who had right heart catheterization and echocardiography performed, with follow-up for outcomes through 2021. Kaplan-Meier analysis and Cox-proportional hazards regression modeling were used to evaluate the independent effect of PH hemodynamic phenotype on incident AF. RESULTS: Our study population was classified into two broad PH hemodynamic groups: precapillary (64.9%) and postcapillary (35.1%). The median age was 59.5 years (Q1: 48.4, Q3: 68.4), and 72% were female. In crude models, postcapillary PH was significantly associated with incident AF (HR 2.17, 95% CI: 1.26-3.74, p = 0.005). This association was lost following multivariable adjustment, whereas left atrial volume index remained independently associated with incident AF (aHR 1.30, 95% CI: 1.09-1.54, p = 0.003). CONCLUSION: We found PH hemodynamic phenotype was not significantly associated with incident AF in our patient sample; however, echocardiographic evidence of left atrial remodeling appeared to have a greater impact on AF development. Larger studies are needed to validate these findings and identify potential modifiable risk factors for AF in this population.

Inhaled treprostinil vs iloprost: Comparison of adherence, persistence, and health care resource utilization in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with a substantial clinical and economic burden. Inhaled prostacyclins are a well-established part of pharmacotherapy for PAH. There are differences between inhaled therapies in the burden imposed by administration frequency. Simpler and less time-consuming inhaled PAH therapies may improve both adherence and persistence and potentially affect outcomes. OBJECTIVE: To compare real-world health care resource use, costs, and treatment adherence and persistence in patients with PAH who initiated inhaled treprostinil or iloprost. METHODS: Adult patients with 1 inpatient or 2 outpatient medical claims separated by at least 30 days with a diagnosis of PAH were identified using International Classification of Diseases, Ninth Revision or Tenth Revision, Clinical Modification codes with a pharmacy claim for inhaled treprostinil or iloprost. Patients were required to be continuously enrolled in the health plan for 6 months prior to and 12 months after the index date. A proportion of days covered of 0.8 or more was considered adherent; persistence was no gap in therapy for at least 60 days. All-cause health care resource utilization and all-cause costs were assessed. RESULTS: 405 and 62 patients were included in the inhaled treprostinil and iloprost cohorts, respectively. Adherence (50.9% and 22.6%; P < 0.0001) and persistence (6 months, 65.2% vs 35.5%; 12 months, 46.7% vs 16.1%; log-rank P < 0.001) were significantly better with inhaled treprostinil. Post-index allcause inpatient admissions (39.3% vs 54.8%; P = 0.02) and post-index emergency department (ED) utilization (36.3% vs 50.0%; P = 0.04) were lower with inhaled treprostinil. Among patients who were persistent with therapy through 12 months, there was no significant difference between groups in mean (SD) all-cause total costs ($266,462 [137,324] vs $262,826 [112,452] for inhaled treprostinil vs iloprost, respectively; P = 0.98). CONCLUSIONS: The results suggest that inhaled treprostinil is less burdensome, is associated with greater adherence and persistence, and may reduce all-cause hospitalizations and ED visits. DISCLOSURES: This study was funded by the United Therapeutics Corporation to obtain data for this analysis and compose the manuscript. Dr Burger has served as clinical investigator in multicenter interventional trials sponsored by United Therapeutics but did not receive any direct compensation. Drs Wu and Morland and Mr Classi are employees of United Therapeutics Corporation and own stock/shares in the company.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Portopulmonary Hypertension in Nontransplanted Patients: Results of the Largest US Single-Institution Registry.

OBJECTIVE: To explore clinical characteristics, risk profiles, and outcomes of patients with portopulmonary hypertension (PoPH) who have contraindications to liver transplant (LT). METHODS: From the largest US single-institution registry of patients with PoPH, we analyzed 160 patients who did not receive LT between 1988 to 2019. Pulmonary arterial hypertension (PAH)-pertinent characteristics, hemodynamic features, treatments, and risk stratification were compared at baseline, first follow-up visit, and censor/death time. RESULTS: Median survival for the entire cohort was 27.5 months from the diagnosis of PoPH. Overall survival was 89%, 77%, 51%, and 38% at 6 months, 1 year, 3 years, and 5 years, respectively. Survival was significantly affected by the severity of liver disease (P<.001). Most patients received PAH-specific therapies (136 [85%]), predominantly monotherapy (123 [77%)]. With treatment, significant improvements were noted in World Health Organization functional class (P=.04), 6-minute walk distance (P<.001), right ventricular function (P<.001), pulmonary vascular resistance (P<.001), and Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) Lite 2 score (P=.02) univariately. Per European Society of Cardiology risk stratification, no patient met full criteria for low risk at baseline or at follow-up. In a multivariate Cox risk model, 6-minute walk distance, right atrial pressure, pulmonary capillary wedge pressure, bilirubin level, and Model for End-Stage Liver Disease-sodium score of 15 or higher were associated with increased risk of death. CONCLUSION: Patients with PoPH who did not undergo LT had a poor prognosis. This persisted despite use of PAH-specific therapies and significant improvements in hemodynamics, echocardiography parameters of right ventricle function, 6-minute walk distance, and World Health Organization functional class.

Delphi consensus recommendation for optimization of pulmonary hypertension therapy focusing on switching from a phosphodiesterase 5 inhibitor to riociguat.

Dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate-risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined. We developed an expert consensus statement on the transition to sGC and other treatment escalations and transitions in PAH using a modified Delphi process. The Delphi process used a panel of 20 physicians with expertise in PAH. Panelists answered three questionnaires on the management of treatment escalations and transitions in PAH. The initial questionnaire included open-ended questions. Later questionnaires consolidated the responses into statements that panelists rated on a Likert scale from -5 (strongly disagree) to +5 (strongly agree) to determine consensus. The Delphi process produced several consensus recommendations. Escalation should be considered for patients who are at high risk or not achieving treatment goals, by adding an agent from a new class, switching from oral to parenteral prostacyclins, or increasing the dose. Switching to a new class or within a class should be considered if tolerability or other considerations unrelated to efficacy are affecting adherence. Switching from a PDE5i to an SGC activator may benefit patients with intermediate risk who are not improving on their present therapy. These consensus-based recommendations may be helpful to clinicians and beneficial for patients when evidence-based guidance is unavailable.

BREEZE: Open-label clinical study to evaluate the safety and tolerability of treprostinil inhalation powder as Tyvaso DPI™ in patients with pulmonary arterial hypertension.

Inhaled treprostinil is an approved therapy for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease in the United States. Studies have confirmed the robust benefits and safety of nebulized inhaled treprostinil, but it requires a time investment for nebulizer preparation, maintenance, and treatment. A small, portable treprostinil dry powder inhaler has been developed for the treatment of PAH. The primary objective of this study was to evaluate the safety and tolerability of treprostinil inhalation powder (TreT) in patients currently treated with treprostinil inhalation solution. Fifty-one patients on a stable dose of treprostinil inhalation solution enrolled and transitioned to TreT at a corresponding dose. Six-minute walk distance (6MWD), device preference and satisfaction (Preference Questionnaire for Inhaled Treprostinil Devices [PQ-ITD]), PAH Symptoms and Impact (PAH-SYMPACT®) questionnaire, and systemic exposure and pharmacokinetics for up to 5 h were assessed at baseline for treprostinil inhalation solution and at Week 3 for TreT. Adverse events (AEs) were consistent with studies of inhaled treprostinil in patients with PAH, and there were no study drug-related serious AEs. Statistically significant improvements occurred in 6MWD, PQ-ITD, and PAH-SYMPACT. Forty-nine patients completed the 3-week treatment phase and all elected to participate in an optional extension phase. These results demonstrate that, in patients with PAH, transition from treprostinil inhalation solution to TreT is safe, well-tolerated, and accompanied by statistically significant improvements in key clinical assessments and patient-reported outcomes with comparable systemic exposure between the two formulations at evaluated doses (trial registration: clinicaltrials.gov identifier: NCT03950739).

Utilization of an Electronic Health Record Integrated Risk Score to Predict Hospitalization Among COVID-19 Patients.

OBJECTIVE: To evaluate the performance of an Electronic Health Record (EHR) integrated risk score for COVID-19 positive outpatients to predict 30-day risk of hospitalization. PATIENTS AND METHODS: A retrospective observational study of 67 470 patients with COVID-19 confirmed by polymerase chain reaction (PCR) test between March 12, 2020 and February 8, 2021. Risk scores were calculated based on data in the chart at the time of the incident infection. RESULTS: The Mayo Clinic COVID-19 risk score consisted of 13 components included age, sex, chronic lung disease, congenital heart disease, congestive heart failure, coronary artery disease, diabetes mellitus, end stage liver disease, end stage renal disease, hypertension, immune compromised, nursing home resident, and pregnant. Univariate analysis showed all components, except pregnancy, have significant (P < .001) association with admission. The Mayo Clinic COVID-19 risk score showed a Receiver Operating Characteristic Area Under Curve (AUC) of 0.837 for the prediction of admission for this large cohort of COVID-19 positive patients. CONCLUSION: The Mayo Clinic COVID-19 risk score is a simple score that is easily integrated into the EHR with excellent predictive performance for severe COVID-19. It can be leveraged to stratify risk for severe COVID-19 at initial contact, when considering therapeutics or in the allocation of vaccine supply.

Comparing Diagnosis and Treatment of Pulmonary Hypertension Patients at a Pulmonary Hypertension Center versus Community Centers.

Once patients are diagnosed with pulmonary hypertension it is important to identify the correct diagnostic group as it will have implications on the disease state management. Pulmonary hypertension is increasingly diagnosed and treated in general medical practices; however, evidence-based guidelines recommend evaluation and treatment in pulmonary hypertension centers for accurate diagnosis and appropriate treatment recommendations. We conducted a retrospective cohort study of 509 random patients 18 years and older who were evaluated in our pulmonary hypertension clinic from January 2005 to December 2018. 68.4% (n = 348) had their diagnostic group clarified or changed. Pulmonary hypertension was deemed an incorrect diagnosis in 12.4% (n = 63). A total of 114 patients (22.4%) had been initiated on pulmonary hypertension specific treatment prior to presentation. Pulmonary hypertension specific medication was stopped in 57 (50.0%) cases. The estimated monthly saving of the stopped medication based on wholesale acquisition costs was USD 396,988.05-419,641.05, a monthly saving of USD 6964.70-7362.12 per patient. Evaluation outside of a pulmonary hypertension center may lead to misdiagnosis and inappropriate or inadequate treatment. Pulmonary arterial hypertension directed therapy improves median survival, but inappropriate therapy may cause harm; therefore, patients benefit from a specialized center with multiple resources to secure an accurate diagnosis and tailored treatment for their condition.

Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial.

BACKGROUND: The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. METHODS: In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04351152, and is completed. FINDINGS: Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41-137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79-89) participants in the lenzilumab group and in 190 (78%; 72-83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02-2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. INTERPRETATION: Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. FUNDING: Humanigen.

Improving Patient Selection and Prioritization for Hospital at Home Through Predictive Modeling.

Hospital at home is designed to offer patients hospital level care in the comfort of their own home. The process by which clinicians select eligible patients that are clinically and socially appropriate for this model of care requires labor-intensive manual chart reviews. We addressed this problem by providing a predictive model, web application, and data pipeline that produces an eligibility score based on a set of clinical and social factors that influence patients' success in the program. Providers used this predictive model to prioritize the order in which they perform chart reviews and patient screenings. Training performance area under the curve (AUC) was 0.77. Testing 'in production' had an AUC of 0.75. Admission criteria in training rapidly changed over the course of the study due to the novelty of the clinical model. The current algorithm successfully identified many inconsistencies in enrollment and has streamlined the process of patient identification.

Facemasks and Walk Distance in Pulmonary Arterial Hypertension Patients.

Little is known about the effect of wearing a facemask on the physiological and perceptual responses to exercise in patients with pulmonary arterial hypertension (PAH). We performed a single-center retrospective study to evaluate whether facemask wearing impacted distanced covered, rating of perceived exertion (RPE), and arterial oxygen saturation (SpO2) during a 6-minute walk test (6MWT) in PAH patients. Forty-five patients being treated for group 1 PAH and who performed a 6MWT before and after implementation of a facemask mandate were included in the analysis. Each included patient performed a 6MWT without (test 1) and with (test 2) a facemask between October 1, 2019, and October 31, 2020. At both time points, all patients also underwent a submaximal cardiopulmonary exercise test, echocardiogram, and blood laboratory tests, with a Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2.0 score calculated. The two 6MWTs were performed 81±51 days apart, and all patients were clinically stable at both testing timepoints. Six-minute walk test distance was not different between test 1 and test 2 (405±108 m vs 400±103 m, P=.81). Similarly, both end-test RPE and lowest SpO2 during the 6MWT were not different in test 1 and test 2 (RPE: 2.5±1.7 vs 2.5±2.1, P=.91; SpO2 nadir: 92.8±3.4% vs 93.3±3.3%, P=.55). Our findings show that wearing a facemask has no discernable impact on the arterial oxygen saturation and perceptual responses to exercise or exercise capacity in patients with moderate-to-severe PAH. This study reinforces the evidence that wearing a facemask is safe in PAH patients, even during exercise.

Topic-Based, Recent Literature Review on Pulmonary Hypertension.

Pulmonary hypertension is a complex condition but a relatively common manifestation of severe cardiopulmonary disease. By contrast, pulmonary arterial hypertension is uncommon and is more prevalent in young women. To better categorize patients and to guide clinical decision-making, 5 diagnostic groups and associated subgroups characterize the spectrum of disease. A multidisciplinary approach to evaluation and treatment is recommended by published guidelines and often entails referral to a designated pulmonary hypertension center. Several key publications during the last couple of years merit review. The PubMed database was searched for English-language studies and guidelines relating to pulmonary hypertension. The following terms were searched, alone and in combination: pulmonary hypertension, pulmonary arterial hypertension, portopulmonary hypertension, and chronic thromboembolic pulmonary hypertension. The focus was on those publications with new information on evaluation and management of pulmonary hypertension between January 1, 2019, and January 31, 2021. Of the subgroups, 2 were of particular interest for this review: portopulmonary hypertension and chronic thromboembolic pulmonary hypertension. Last, available data on the impact of the coronavirus disease 2019 pandemic and newer treatment agents in early trials were selectively reviewed. The review is therefore intended to serve as a practical, focused review of important topics germane to those clinicians caring for patients with pulmonary hypertension.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Lung Cancer.

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. METHODS: This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. RESULTS: In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). CONCLUSIONS: This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.