Risk of Hypertension Associated with Antivascular Endothelial Growth Factor Monoclonal Antibodies: A Meta-Analysis From 51088 Patients with Cancer

2020 ◽  
Vol 22 (7) ◽  
Author(s):  
Weilan Wang ◽  
Le Cai ◽  
Bingkun Xiao ◽  
Rongqing Huang

Context: Hypertension events are the dominant adverse events observed in patients receiving the antivascular endothelial growth factor (anti-VEGF) monoclonal antibodies bevacizumab and ramucirumab treatment, which severe hypertension, particularly hypertensive emergencies, may cause acute target organ injury and major cardiovascular events, that has limited the administration of anti-VEGF monoclonal antibodies. The current meta-analysis aimed to examine the relative risk (RR) of hypertension associated with anti-VEGF monoclonal antibodies. Evidence Acquisition: PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library, and Clinical Trials.gov were searched until July 2019 for relevant phase II and III randomized controlled trials (RCTs). Statistical analyses were performed to examine the RR (with 95% confidence intervals (CIs)) of hypertension associated with the anti-VEGF monoclonal antibodies. Results: Ninety four RCTs and 51088 patients were included in the current meta-analysis. According to the results, compared with the control arms, anti-VEGF monoclonal antibodies increased the risk of all-grade (RR: 3.45, 95% CI: 2.98 - 4.00) and high-grade (RR: 5.63, 95% CI: 5.05 - 6.26) hypertension. In the subgroup analyses, the risk of high-grade hypertension varied significantly with cancer type, so that the highest RR was for patients with ovarian cancer (17.27, 95% CI: 8.50 - 35.08), whereas the risk of all-grade hypertension did not vary significantly. When stratified based on drug types and drug dose, no significant difference was discovered. Conclusions: Anti-VEGF monoclonal antibodies significantly increased the risk of hypertension. The risk may vary with tumor type. Clinicians should be aware of the adverse reaction and clinical monitoring as well as effective management of such situations, particularly for high-risk patients.

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e042384
Author(s):  
Qihang Kong ◽  
Wai-kit Ming ◽  
Xue-Song Mi

ObjectiveTo determine the effects of the intraocular injection of antivascular endothelial growth factor (anti-VEGF) drugs on the refractive status of infants with retinopathy of prematurity (ROP).DesignSystematic review and meta-analysis of the refractive status of infants with ROP who receive anti-VEGF drugs.Data sourcesThe PubMed, Web of Science and Embase databases and the ClinicalTrials.gov website were searched up to June 2020.Eligibility criteria when selecting studiesWe included randomised controlled trials (RCTs) and observational studies that compared refractive errors between anti-VEGF drug and laser therapies.Data extraction and synthesisData extraction and risk-of-bias assessments were conducted by two independent reviewers. We used a random-effect model to pool outcomes. The outcome measures were the spherical equivalents, axial length (AL), anterior chamber depth (ACD) and lens thickness (LT).ResultsThirteen studies involving 1850 eyes were assessed: 914 in the anti-VEGF drug group, and 936 in the control (laser) group. Children who received anti-VEGF drug treatment had less myopia than those who received laser therapy (mean difference=1.80 D, 95% CI 0.97 to 2.63, p<0.0001, I2=78%). The AL, ACD and LT did not reach statistical significance difference between the two groups. The current evidence indicates that the refractive safety in children with ROP is better for anti-VEGF drug treatment than for laser therapy.ConclusionsThis meta-analysis indicates that anti-VEGF drug therapy results in less myopia compared with laser therapy. However, there are relatively few published articles on refractive errors in ROP, and so high-quality and powerful RCTs are needed in the future.PROSPERO registration numberCRD42020160673.


2017 ◽  
Vol 102 (8) ◽  
pp. 1077-1085 ◽  
Author(s):  
Xin-yu Zhao ◽  
Song Xia ◽  
You-xin Chen

Background/aimsTo evaluate the efficacy of antivascular endothelial growth factor (anti-VEGF) agents pretreatment before vitrectomy for patients with complicated proliferative diabetic retinopathy (PDR).MethodsThe PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched up to June 2017 to identify related studies. The Peferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. The StataSE V.12.0 software was used to analyse the relevant data. The weighted mean difference, relative risk and their 95% CIs were used to assess the strength of the association.Results14 randomised controlled trials involving 613 patients were assessed, the anti-VEGF pretreatment group included 289 patients and the control group included 324 patients. Our analysis indicated that anti-VEGF pretreatment before vitrectomy for complicated PDR could facilitate much easier surgery regarding less intraoperative bleeding, less endodiathermy, shorter duration of surgery, less iatrogenic retinal breaks, less frequency of using silicone oil and relaxing retinotomy (P<0.05). Additionally, anti-VEGF pretreatment could also achieve better postoperative best-corrected visual acuity, less early recurrent vitreous haemorrhage (VH) and quicker absorption of recurrent VH (P<0.05). However, the incidence of late recurrent VH, recurrent retinal detachment or related secondary surgery could not be reduced (P>0.05).ConclusionThe pretreatment of anti-VEGF agents before vitrectomy for patients with complicated PDR might facilitate much easier surgery and better visual rehabilitation, reduce the rate of early recurrent VH and accelerate its absorption. Moreover, future better-designed studies with larger sample sizes are required to further evaluate the efficacy of different anti-VEGF agents and reach a firmer conclusion.


2018 ◽  
Vol 103 (4) ◽  
pp. 442-451 ◽  
Author(s):  
Allison Low ◽  
Ambar Faridi ◽  
Kavita V Bhavsar ◽  
Glenn C Cockerham ◽  
Michele Freeman ◽  
...  

Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on best-corrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (≥ 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.


2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Gan-Lin He ◽  
Duo-Rong Xu ◽  
Wai-Yi Zou ◽  
Sui-Zhi He ◽  
Juan Li

The VAD (vincristine-doxorubicin-dexamethasone) regimen has been used for decades to treat multiple myeloma (MM). Based on reports that vascular endothelial growth factor- (VEGF-) mediated angiogenesis is critical for MM pathogenesis, the antiangiogenic compound thalidomide has been added to VAD (T-VAD). However, it remains unclear whether T-VAD is more efficacious than VAD for serum VEGF reduction or if the difference influences clinical outcome. Pubmed, Cochrane library, China Biomedical Literature (CBM) database, China National Knowledge Infrastructure (CNKI) database, Vip database, and Wanfang database were searched for relevant studies published up to June 2017. RevMan5.2 was used for methodological quality evaluation and data extraction. Thirteen trials (five randomized, seven nonrandomized, and one historically controlled) involving 815 cases were included. Serum VEGF was significantly higher in MM cases than non-MM controls (MD=353.01, [95%CI 187.52–518.51], P<0.01), and the overall efficacy of T-VAD was higher than that of VAD (RR=1.36, [1.21–1.53], P <0.01). Further, T-VAD reduced VEGF to a greater extent than VAD does ([MD=-49.85, [-66.28− -33.42], P<0.01). The T-VAD regimen also reduced VEGF to a greater extent in newly diagnosed MM patients than it did in recurrent patients ([MD=-120.20, [-164.60–-39.80], P<0.01). There was no significant difference in VEGF between T-VAD patients (2 courses) and nontumor controls (MD=175.94, [-26.08–377.95], P=0.09). Greater serum VEGF reduction may be responsible for the superior efficacy of T-VAD compared to VAD.


2020 ◽  
pp. 247412642095306
Author(s):  
John D. Pitcher ◽  
Andrew A. Moshfeghi ◽  
Genevieve Lucas ◽  
Nick Boucher ◽  
Hadi Moini ◽  
...  

Purpose: We assessed the effect of treatment frequency with intravitreal antivascular endothelial growth factor (anti-VEGF) agents on visual acuity (VA) in diabetic macular edema (DME). Methods: This retrospective analysis assessed electronic medical records of eyes newly diagnosed with DME and treated with an anti-VEGF agent at US clinics using the Vestrum Health (Naperville, Illinois) treatment and outcomes database. Eyes were divided into 2 injection frequency subcohorts (≤ 6 vs > 6 injections/y); treatment frequency and change in mean VA (Early Treatment Diabetic Retinopathy Study letters) were evaluated. Results: Among 155 240 eyes assessed, 3028 met inclusion criteria for analysis in year 1 and 1292 in year 2. During year 1 of treatment, 57% (n = 1725) received > 6 injections; most continued to receive the same injection frequency during year 2. Mean VA gain from baseline at year 1 was lower in the ≤ 6 than in the > 6 injections/year subcohort (3.7 vs 8.0 letters, respectively; P < .001). Mean VA change from the end of year 1 to year 2 for eyes receiving ≤ 6 injections in year 1 generally remained unchanged, irrespective of year 2 dosing frequency. In eyes that received > 6 injections in year 1, mean VA loss was significantly greater for eyes receiving less-frequent dosing in year 2 than in those maintained on > 6 injections. Conclusions: More than 50% of eyes with DME in routine clinical practice that completed at least 1 year of follow-up received > 6 injections of an anti-VEGF agent during the first year, resulting in better VA gains than eyes treated less frequently.


2019 ◽  
Vol 4 (1) ◽  
pp. 6-12
Author(s):  
Zofia Michalewska ◽  
Jerzy Nawrocki

Purpose: This article studies visual outcome and frequency of antivascular endothelial growth factor (anti-VEGF) injections continued in patients with neovascular age-related macular degeneration (AMD) who had an earlier vitrectomy for postinjection endophthalmitis. Methods: A retrospective interventional study was conducted reviewing our database for patients with a diagnosis of endophthalmitis in the course of anti-VEGF injections. Endophthalmitis diagnosis was made on clinical examination of pain, rapid decrease in visual acuity (VA), conjunctival hyperemia, hypopyon, and vitritis. In all eyes, core vitrectomy with intravitreal antibiotics was performed. Spectral-domain optical coherence tomography was performed monthly before and after surgery during follow-up. Anti-VEGF injections were continued after surgery in all cases. Results: Eight eyes with postinjection endophthalmitis were included. Mean VA immediately before endophthalmitis was 20/50 Snellen with a mean of 19 intravitreal anti-VEGF injections ( P = .45). At time of endophthalmitis diagnosis, mean VA was 20/1000 (range, 20/2000-20/200). Mean time from injection to when the patient noted first symptoms was 4.3 days (range, 1-8 days). Mean time from first symptoms to surgery was 12 hours (range, 2.5-26 hours). Final mean VA at the end of follow-up (range, 12-84 months) did not statistically differ from VA at the visit immediately before endophthalmitis diagnosis ( P = .69). Mean frequency of injections after vitrectomy did not significantly differ from the presurgical course of treatment ( P =.97). Conclusions: Anti-VEGF treatment might be continued after vitrectomy for endophthalmitis and results in satisfactory anatomical and visual outcome. Surgery did not influence the frequency of anti-VEGF injections for neovascular AMD.


2014 ◽  
Vol 132 (11) ◽  
pp. 1317 ◽  
Author(s):  
Marie Thulliez ◽  
Denis Angoulvant ◽  
Marie Laure Le Lez ◽  
Annie-Pierre Jonville-Bera ◽  
Pierre-Jean Pisella ◽  
...  

2021 ◽  
Vol 14 (7) ◽  
pp. 1092-1099
Author(s):  
Bo-Hao Cui ◽  
◽  
Wen-Wen Wang ◽  
Hao Yang ◽  
Ya-Lan Dong ◽  
...  

AIM: To evaluate the efficacy and safety of intravitreal corticoid as an adjunctive therapy to anti-vascular endothelial growth factor (VEGF) treatment of neovascular age-related macular degeneration (nvAMD). METHODS: Four databases including PubMed, Embase, Cochrane Library, and the clinicaltrials.gov were comprehensively searched for studies comparing intravitreal corticoid plus anti-VEGF (IVC/IVA) vs anti-VEGF monotherapy (IVA) in patients with nvAMD. GRADE profiler was used to assess the quality of outcomes. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events including the occurrence of severe elevation of intraocular pressure (IOP) and the progress of cataract were extracted from the eligible studies. Review Manager (RevMan) 5.3 was used to analyze the data. RESULTS: There was no statistic difference of mean change in BCVA at 6 and 12mo between IVC/IVA and IVA group [95% confidence interval (CI): -2.28 to 4.24, P=0.55; 95%CI: -3.01 to 8.70, P=0.34]. No statistic difference was found in the change of CMT between two groups at 6mo time point (95%CI: -17.98 to 16.42, P=0.93) while the CMT reduction in IVC/IVA group was significantly more obvious than IVA group at 12mo time point [mean difference (MD)=-44.08, 95%CI: -80.52 to -7.63, P=0.02]. The risk of occurrence of severe elevation of IOP in the IVC/IVA group was higher than that in the IVA group (95%CI: 1.92 to 9.48; P=0.0004). Cataract progression risk was calculated no statistic difference between two groups (95%CI: 0.74 to 4.66; P=0.18). CONCLUSION: No visual or anatomical benefits are observed in IVC/IVA group at 6mo. At 12mo, the CMT of the IVC/IVA group is significantly lower than that of the IVA group. Risk of severe elevation of IOP is significantly higher when treated by IVC/IVA.


2020 ◽  
Vol 4 (5) ◽  
pp. 401-410
Author(s):  
Amy Q. Lu ◽  
Bozho Todorich

Purpose: This work evaluates the effects of combined intravitreal antivascular endothelial growth factor (anti-VEGF) and modified panretinal photocoagulation (PRP) for management of proliferative diabetic retinopathy (PDR). Methods: This retrospective case series included 37 eyes of 33 patients with high-risk PDR. Anti-VEGF injections (≥ 2) were followed by modified, midperipheral PRP performed in 2 or more sessions. Visual and anatomic outcomes were tracked for 1 year after treatment. Regression analysis was performed for factors predictive of final outcomes. Results: Mean visual acuity (VA) at initial and final visit were 20/50 and 20/40 ( P = .22), respectively, over a mean follow-up duration of 341.4 days. Central foveal thickness decreased from 321.8 µm to 258.6 µm ( P = .01). Resolution of PDR was achieved in 94.6% of eyes, with 5.4% of eyes requiring additional anti-VEGF for persistent neovascularization. Final VA was significantly associated with baseline VA, VA at 1 month, and any adverse anatomical events. Treatment noncompliance was present in 24.3%; compliance decreased with increasing medical comorbidities, but was not significantly associated with final VA. Conclusions: Combination of anti-VEGF and modified PRP preserved VA and yielded PDR regression in the majority of eyes. This combination provides rapid PDR regression with anti-VEGF while achieving durable disease suppression in this real-world cohort without traditional PRP.


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