scholarly journals Nintedanib, Pirfenidone and Pirfenidone Versus Nintedanib: A Systematic Review And Meta-Analysis

Author(s):  
Tyler Pitre ◽  
Renata Husnudinov ◽  
Muhammad Faran Khalid ◽  
Melanie C. Zhang ◽  
Sonya Cui ◽  
...  

Abstract Background: Patients with idiopathic pulmonary fibrosis have a poor overall prognosis. Only nintedanib and pirfenidone have been shown to reduce mortality. Objective: This systematic review and meta-analysis aims to assess the efficacy of nintedanib, pirfenidone, and pirfenidone vs nintedanib on patient important outcomes. Methods: Randomized trials were retrieved from MEDLINE, Cochrane, and EMBASE. The primary outcome was mortality. The secondary outcomes included change in FVC, acute exacerbations and hospitalizations and adverse drug effects leading to discontinuation. We used an inverse variance random effects meta-analysis method to calculate pooled relative risk (RR), standardized mean difference (SMD) and mean difference (MD).Results: A total of 13 studies were included. Both nintedanib [RR 0.63 (0.47,0.85); moderate certainty] and pirfenidone [RR 0.68 (0.47,0.99); moderate certainty] probably reduce all-cause mortality when compared to placebo, but only nintedanib [SMD 0.47 (0.34, 0.60); high certainty] reduces change in FVC. Nintedanib [RR 0.69 (0.48,0.99); moderate certainty],but not pirfenidone probably reduces acute exacerbations or hospitalizations compared to placebo. Compared with placebo, neither nintedanib nor pirfenidone increased risk of drug discontinuation due to adverse effect but there is probably risk of patient drug discontinuation with pirfenidone compared to nintedanib [RR 4.34 (1.72 to 10.98); moderate certainty].Conclusion: Both nintedanib and pirfenidone probably reduce all-cause mortality. Nintedanib is probably more tolerable to pirfenidone in regard to compliance and may be more effective than pirfenidone in reducing mortality rate and in slowing disease progression. Larger head to head randomized trials are needed.

2019 ◽  
Vol 42 (2) ◽  
pp. E26-32 ◽  
Author(s):  
Rebecca Mathew ◽  
Sarah M. Visintini ◽  
F. Daniel Ramirez ◽  
Pietro DiSanto ◽  
Trevor Simard ◽  
...  

Purpose: Patients in cardiac intensive care units (ICU) are admitted with increasingly higher disease acuity and a larger burden of non-cardiac critical illness. Accordingly, positive inotropes are being used with increased frequency and little comparative data to support drug selection. We compared the effectiveness and safety of dobutamine and milrinone in low cardiac output states (LCOS) and/or cardiogenic shock (CS). Methods: We performed a systematic review comparing dobutamine to milrinone on all-cause mortality, length of stay in the ICU (LOS-ICU), length of stay in hospital (LOS-H) and significant arrhythmias in hospitalized patients with LCOS and/or CS. Results: We identified 11 studies that meet eligibility requirements and which were published between 2001 and 2016 and included 23,056 patients. Only one randomized clinical trial was identified, with the remaining studies comprising observational cohort studies. The primary outcome, all-cause mortality, trended towards a benefit with milrinone but did not meet pre-specified significance (OR 1.13, 95% CI 1.00-1.29, p=0.06). While LOS-ICU (mean difference -0.72, 95% CI -1.10- -0.34, p=0.0002) was shorter with dobutamine, there was no difference in LOS-H (mean difference -1.22, 95% CI -4.68 – 2.24, p=0.49). Significant arrhythmias, specifically symptomatic and/or requiring antiarrhythmic therapy, were no different between the groups (OR 1.78, 95% CI 0.85-3.76, p=0.13). Conclusions: Currently available data comparing milrinone to dobutamine in patients requiring inotropic support is limited. Dobutamine may be associated with a shorter LOS in the ICU, with a worrisome signal of increased risk of allcause mortality. Randomized data are needed to guide inotrope selection in patients with LCOS and/or CS.


2021 ◽  
pp. 1-8
Author(s):  
Huiyang Li ◽  
Peng Zhou ◽  
Yikai Zhao ◽  
Huaichun Ni ◽  
Xinping Luo ◽  
...  

Abstract Objective: The aim of this meta-analysis was to investigate the association between malnutrition assessed by the controlling nutritional status (CONUT) score and all-cause mortality in patients with heart failure. Design: Systematic review and meta-analysis. Settings: A comprehensively literature search of PubMed and Embase databases was performed until 30 November 2020. Studies reporting the utility of CONUT score in prediction of all-cause mortality among patients with heart failure were eligible. Patients with a CONUT score ≥2 are grouped as malnourished. Predictive values of the CONUT score were summarized by pooling the multivariable-adjusted risk ratios (RR) with 95 % CI for the malnourished v. normal nutritional status or per point CONUT score increase. Participants: Ten studies involving 5196 patients with heart failure. Results: Malnourished patients with heart failure conferred a higher risk of all-cause mortality (RR 1·92; 95 % CI 1·58, 2·34) compared with the normal nutritional status. Subgroup analysis showed the malnourished patients with heart failure had an increased risk of in-hospital mortality (RR 1·78; 95 % CI 1·29, 2·46) and follow-up mortality (RR 2·01; 95 % CI 1·58, 2·57). Moreover, per point increase in CONUT score significantly increased 16% risk of all-cause mortality during the follow-up. Conclusions: Malnutrition defined by the CONUT score is an independent predictor of all-cause mortality in patients with heart failure. Assessment of nutritional status using CONUT score would be helpful for improving risk stratification of heart failure.


Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215322
Author(s):  
Hyun Woo Lee ◽  
Chang-Hwan Yoon ◽  
Eun Jin Jang ◽  
Chang-Hoon Lee

BackgroundThe association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.MethodsWe searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.ResultsACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence).ConclusionsACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Sripal Bangalore ◽  
Shruthi Chandrashekhar ◽  
Sandeep Pulimi ◽  
Franz H Messerli

Background: The 2007 ACC/AHA guideline on perioperative evaluation recommends perioperative β-blockers for non-cardiac surgery. However, some clinical trials seem to be at odds with these recommendations. Methods: PUBMED/EMBASE/CENTRAL search for randomized trials (RCTs) evaluating β-blockers for non-cardiac surgery. Efficacy outcomes of all-cause mortality, cardiovascular (CV) mortality, nonfatal MI, nonfatal stroke, heart failure, and myocardial ischemia (30 days), and safety outcomes of perioperative bradycardia, hypotension, and bronchospasm. Results: Among 33 RCTs which evaluated 12,306 patients, β-blockers were not associated with any significant reduction in the risk of all-cause mortality, CV mortality, or heart failure, but were associated with a 35% decrease in nonfatal MI, 64% decrease in myocardial ischemia at the expense of a 101% increase (Figure ) in nonfatal strokes. The beneficial effects were driven mainly by trials with high-bias risk, while analyses of low-biased trials showed a 28% and 101% increase in all-cause mortality and stroke with only a 29% and 59% reduction in nonfatal MI and 59%myocardial ischemia. For the safety outcomes, β-blockers were associated with a significantly increased risk of peri-op bradycardia and peri-op hypotension. Conclusions: In patients undergoing non-cardiac surgery, we estimate that treatment of 1000 patients with β-blockers results in 16 fewer nonfatal MI, but at the expense of 3 disabling strokes and 45 and 59 patients with clinically significant perioperative bradycardia and hypotension respectively, and suggests an increase in all-cause mortality.


2017 ◽  
Vol 32 (5) ◽  
pp. 607-618 ◽  
Author(s):  
Michelle N McDonnell ◽  
Briony Rischbieth ◽  
Tenille T Schammer ◽  
Chantel Seaforth ◽  
Alex J Shaw ◽  
...  

Objective: The technique called Lee Silverman Voice Treatment (LSVT)-LOUD has previously been used to improve voice quality in people with Parkinson’s disease. The objective of this study was to assess the effectiveness of an alternate intervention, LSVT-BIG (signifying big movements), to improve functional mobility. Design: Systematic review with meta-analysis of randomized trials. Data sources: Medline, Embase, CINAHL, AgeLine, Scopus and Cochrane Library were searched from inception to September 2017 using multiple search terms related to Parkinson’s disease and LSVT-BIG. Review method: Two researchers searched the literature for studies of the LSVT-BIG intervention of 16 sessions, delivered by a certified instructor over four weeks, to any other intervention. Outcomes related to functional ability were included. Study quality was appraised using the Cochrane Risk of Bias tool. Results: Four studies were included, reporting on three randomized trials of 84 participants with mild Parkinson’s disease. Compared to physiotherapy exercises, or a shorter training protocol, there was a significant improvement in motor function assessed with the Unified Parkinson’s Disease Rating Scale part III (mean difference = −3.20, 95% confidence interval = −5.18 to −1.23) and a trend towards faster Timed Up and Go performance (mean difference = −0.47, 95% confidence interval = −0.99 to 0.06) and 10-metre walk test (mean difference = −0.53, 95% confidence interval = −1.07 to 0.01). Conclusion: Compared to shorter format LSVT-BIG or general exercise, LSVT-BIG was more effective at improving motor function. This provides preliminary, moderate quality evidence that amplitude-oriented training is effective in reducing motor impairments for people with mild Parkinson’s disease.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jie Wang ◽  
Yangjing Xue ◽  
Saroj Thapa ◽  
Luping Wang ◽  
Jifei Tang ◽  
...  

Data on the association between age-related macular degeneration (AMD) and cardiovascular disease and mortality are conflicting. The purpose of this report is to conduct a systematic review to better understand the role of AMD as a risk factor for CVD events and mortality. We searched Medline (Ovid) and Embase (Ovid) for trials published from 1980 to 2015. We included 20 cohort studies that reported relative risks with 95% confidence intervals for the association of AMD and cardiovascular events and mortality, involving 29,964,334 participants. In a random-effects model, the adjusted RR (95% confidence interval [CI]) associated with AMD was 1.08 (1.00–1.117) for all-cause mortality (8 studies) and 1.18 (0.98–1.43) for cardiovascular disease mortality (5 studies). The pooled RR (95% CI) was 1.17 (0.94–1.45) for coronary heart disease (CHD; 3 studies) and 1.13 (0.93–1.36) for stroke (8 studies). Findings from this systematic review support that AMD is associated with increased risk of all-cause mortality. The evidence that AMD predicts incident CVD events or CVD mortality remains inclusive and warrants further study in the future.


Pulse ◽  
2021 ◽  
Vol 9 (1-2) ◽  
pp. 38-46
Author(s):  
Angkawipa Trongtorsak ◽  
Natchaya Polpichai ◽  
Sittinun Thangjui ◽  
Jakrin Kewcharoen ◽  
Ratdanai Yodsuwan ◽  
...  

<b><i>Background:</i></b> Gender-related differences in phenotypic expression and outcomes have been established in many cardiac conditions; however, the impact of gender in hypertrophic cardiomyopathy (HCM) remains unclear. We conducted a systematic review and meta-analysis to assess the differences in clinical outcomes between female and male HCM patients. <b><i>Methods:</i></b> We searched MEDLINE and EMBASE from inception to October 2020. Included were cohort studies that compared outcomes of interest including all-cause mortality, HCM-related mortality, and worsening heart failure (HF) or HF hospitalization between male and female. Data from each study were combined using the random effects model to calculate pooled odds ratio (OR) with 95% confidence interval (CI). <b><i>Results:</i></b> Eleven retrospective cohort studies with a total of 9,427 patients (3,719 females) were included. Female gender was significantly associated with an increased risk of all-cause mortality (pooled OR = 1.63, 95% CI: 1.26–2.10, <i>p</i> ≤ 0.001), HCM-related mortality (pooled OR = 1.47, 95% CI: 1.08–2.01, <i>p</i> = 0.015), and worsening HF or HF hospitalization (pooled OR = 2.05, 95% CI: 1.76–2.39, <i>p</i> ≤ 0.001). <b><i>Conclusions:</i></b> Female gender was associated with a worse prognosis in HCM. These findings suggest the need for improved care in women including early identification of disease and more possible aggressive management. Moreover, gender-based strategy may benefit in HCM patients.


2019 ◽  
Vol 180 (4) ◽  
pp. 243-255 ◽  
Author(s):  
Guodong Xu ◽  
Dingyun You ◽  
Liping Wong ◽  
Donghui Duan ◽  
Fanqian Kong ◽  
...  

Objective Previous studies have shown sex-specific differences in all-cause and CHD mortality in type 2 diabetes. We performed a systematic review and meta-analysis to provide a global picture of the estimated influence of type 2 diabetes on the risk of all-cause and CHD mortality in women vs men. Methods We systematically searched PubMed, EMBASE and Web of Science for studies published from their starting dates to Aug 7, 2018. The sex-specific hazard ratios (HRs) and their pooled ratio (women vs men) of all-cause and CHD mortality associated with type 2 diabetes were obtained through an inverse variance-weighted random-effects meta-analysis. Subgroup analyses were used to explore the potential sources of heterogeneity. Results The 35 analyzed prospective cohort studies included 2 314 292 individuals, among whom 254 038 all-cause deaths occurred. The pooled women vs men ratio of the HRs for all-cause and CHD mortality were 1.17 (95% CI: 1.12–1.23, I2 = 81.6%) and 1.97 (95% CI: 1.49–2.61, I2 = 86.4%), respectively. The pooled estimate of the HR for all-cause mortality was approximately 1.30 in articles in which the duration of follow-up was longer than 10 years and 1.10 in articles in which the duration of follow-up was less than 10 years. The pooled HRs for all-cause mortality in patients with type 2 diabetes was 2.33 (95% CI: 2.02–2.69) in women and 1.91 (95% CI: 1.72–2.12) in men, compared with their healthy counterparts. Conclusions The effect of diabetes on all-cause and CHD mortality is approximately 17 and 97% greater, respectively, for women than for men.


PLoS Medicine ◽  
2021 ◽  
Vol 18 (9) ◽  
pp. e1003738
Author(s):  
Mercedes Yanes-Lane ◽  
Edgar Ortiz-Brizuela ◽  
Jonathon R. Campbell ◽  
Andrea Benedetti ◽  
Gavin Churchyard ◽  
...  

Background Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials. Methods and findings We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children. Conclusions Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.


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