Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis

2020 ◽  
Author(s):  
Paul Guedeney ◽  
Sabato Sorrentino ◽  
Gennaro Giustino ◽  
Celine Chapelle ◽  
Silvy Laporte ◽  
...  
Keyword(s):  
Systematic Review ◽  
Injection Site ◽  
Meta Analysis ◽  
Injection Site Reaction ◽  
Indirect Comparison ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Efficacy And Safety ◽  
Site Reaction ◽  
Increased Risk

Abstract Aims Although alirocumab and evolocumab have both been associated with improved outcomes in patients with dyslipidaemia or established atherosclerotic cardiovascular disease, data on their respective performances are scarce. This study aimed at providing an indirect comparison of the efficacy and safety of alirocumab vs. evolocumab. Methods and results We conducted a systematic review and network meta-analysis of randomized trials comparing alirocumab or evolocumab to placebo with consistent background lipid-lowering therapy up to November 2018. We estimated the relative risk (RR) and the 95% confidence intervals (CIs) using fixed-effect model in a frequentist pairwise and network meta-analytic approach. A total of 30 trials, enrolling 59 026 patients were included. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. Compared with evolocumab, alirocumab was associated with a significant reduction in all-cause death (RR 0.80, 95% CI 0.66–0.97) but not in cardiovascular death (RR 0.83, 95% CI 0.65–1.05). This study did not find any significant differences in myocardial infarction (RR 1.15, 95% CI 0.99–1.34), stroke (RR 0.96, 95% CI 0.71–1.28), or coronary revascularization (RR 1.13, 95% CI 0.99–1.29) between the two agents. Alirocumab was associated with a 27% increased risk of injection site reaction compared to evolocumab; however, no significant differences were found in terms of treatment discontinuations, systemic allergic reaction, neurocognitive events, ophthalmologic events, or new-onset of or worsening of pre-existing diabetes. Conclusion Alirocumab and evolocumab share a similar safety profile except for injection site reaction. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to the heterogeneity of the studied populations treated with the two drugs.

P5367Indirect comparison of the safety and efficacy of alirocumab and evolocumab: from a comprehensive meta-analysis of 30 randomized controlled trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Guedeney ◽  
S Sorrentino ◽  
G Giustino ◽  
C Chapelle ◽  
B Claessen ◽  
...  
Keyword(s):  
Injection Site ◽  
Meta Analysis ◽  
Injection Site Reaction ◽  
Fixed Effect Model ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Site Reaction ◽  
Eligibility Criteria ◽  
Safety And Efficacy ◽  
Increased Risk

Abstract Background Alirocumab and evolocumab, two proprotein convertase subtilisin–kexin type 9 inhibitors, have both been associated with improved outcomes in patients with atherosclerotic cardiovascular disease in addition to standard lipid-lowering therapies. However, their comparative safety and efficacy profiles are unknown. Purpose To compare the safety and efficacy of alirocumab versus evolocumab. Methods We conducted a systematic review and network meta-analysis of placebo-controlled randomized trials available up to November 2018 evaluating the safety and efficacy of alirocumab and evolocumab. We estimated risk ratio and 95% confidence intervals using fixed effect model in a frequentist pairwise and network metanalytic approach. The primary safety endpoints were any adverse events leading to treatment-discontinuation, injection site reaction, systemic allergic reaction, neurocognitive events, ophthalmologic events and new-onset of diabetes mellitus (DM) or worsening of pre-existing DM. The primary efficacy endpoints were all-cause and cardiovascular (CV) death, myocardial infarction (MI) and stroke. This study was registered in PROSPERO (CRD42018090768). Results A total of 30 trials, enrolling 59,026 patients were included in this analysis, of whom 13,607 received alirocumab and 17,931 received evolocumab. Mean weighted follow-up time was 2.5 years, with an exposure time of 144,907 patients-years. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. There were no significant differences between alirocumab and evolocumab in terms of safety endpoints, except for injection site reaction with a 27% increased risk of injection site reaction with alirocumab compared to evolocumab (Figure). Compared with evolocumab, alirocumab was associated with a reduction of all-cause death but not CV death. There were no significant differences in MI or stroke between alirocumab and evolocumab. Conclusion Alirocumab and evolocumab share a similar safety profile. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to heterogeneity of the studied populations between the two drugs.

Effects of lipid-lowering therapy on major adverse limb events in patients with peripheral arterial disease: A meta-analysis of randomized clinical trials

Vascular ◽  
2021 ◽  
pp. 170853812110439
Author(s):  
Walter Masson ◽  
Martín Lobo ◽  
Leandro Barbagelata ◽  
Graciela Molinero ◽  
Ignacio Bluro
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Arterial Disease ◽  
Lipid Lowering ◽  
Placebo Control ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Increased Risk ◽  
Peripheral Arterial

Objective Patients with peripheral artery disease (PAD) are at increased risk of major adverse limb events (MALE). Furthermore, MALE have several clinical implications and a poor prognosis, so prevention is a fundamental issue. The main objective of the present meta-analysis of randomized clinical trials is to evaluate the effect of different lipid-lowering therapies on MALE incidence in patients with PAD. Methods A meta-analysis of randomized studies that evaluated the use of lipid-lowering therapy in patients with PAD and reported MALE was performed, after searching the PubMed/MEDLINE, Embase, ScieLO, Google Scholar, and Cochrane Controlled Trials databases. A fixed- or random-effects model was used. Results Five randomized clinical trials including 11,603 patients were identified and considered eligible for the analyses (5903 subjects were allocated to receive lipid-lowering therapy, while 5700 subjects were allocated to the respective placebo/control arms). The present meta-analysis revealed that lipid-lowering therapy was associated with a lower incidence of MALE (OR: 0.76, 95% confidence interval: 0.66–0.87; I2: 28%) compared to placebo/control groups. The sensitivity analysis shows that the results are robust. Conclusion This study demonstrated that the use of lipid-lowering therapy compared with the placebo/control arms was associated with a marked reduction in the risk of MALE. Physicians involved in the monitoring and treatment of patients with PAD must work hard to ensure adequate lipid-lowering medication in these patients.

scholarly journals Efficacy and Safety of CGRP Monoclonal Antibodies for the Prevention of Migraine Compared with Placebo: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Xiaojing Yi ◽  
Yun Chen ◽  
Kun Chen ◽  
Mo Liu ◽  
Jiale Yi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Monoclonal Antibodies ◽  
Adverse Events ◽  
Injection Site ◽  
Response Rate ◽  
Meta Analysis ◽  
Upper Respiratory Tract ◽  
Efficacy And Safety ◽  
Upper Respiratory ◽  
Secondary Outcomes

Abstract Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are a novel class of drugs for migraine that includes erenumab, fremanezumab, galcanezumab and eptinezumab. In clinical trials, CGRP mAbs have been reported to show good efficacy in the prevention of episodic migraines or chronic migraines. Our aim was to evaluate the efficacy and safety of CGRP monoclonal antibodies in this study.Methods: We systematically searched for randomized controlled trials in the PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. The primary outcome was overall mean change from baseline to end of treatment in the number of monthly migraine headache days (MMHDs). The secondary outcomes included 50% response rate, in the number of monthly headache days (MHDs), in the number of monthly headache hours (MHHs), and in the number of monthly acute migraine-specific medication days (MSMDs). The safety outcomes were evaluated in terms of reported adverse events. Results: Eighteen studies including 11,099 patients were included in the meta-analysis. The meta-analysis showed that CGRP mAbs exhibited a significant benefit in reducing the number of MMHDs compared to placebo (Episodic migraine: Std. MD -0.42, 95% CI -0.47 to -0.36; Chronic migraine: Std. MD -0.28, 95% CI -0.35 to -0.21). Similarly, CGRP mAbs were superior to placebo in the secondary outcomes of 50% response rate, MHDs, MHHs, and MSMDs. With respect to safety, serious adverse events and withdrawal due to adverse events were not significantly associated with CGRP mAbs. Fremanezumab was associated with a significantly higher incidence of any adverse event compared with placebo (RR 1.10, 95% CI 1.03 to 1.17). Galcanezumab was associated with significantly higher treatment-emergent adverse events compared with placebo (RR 1.11, 95% CI 1.04 to 1.17). Constipation and injection site pain were significantly higher with erenumab than placebo. Injection site erythema and injection site induration were significantly higher with fremanezumab than placebo. Upper respiratory tract infection, injection site erythema, injection site pruritus and injection site reaction were significantly higher with galcanezumab than placebo. Conclusions: This study confirms that CGRP mAbs are effective as preventive treatments for episodic migraines and chronic migraines. Adverse reactions at the injection site were associated with erenumab, fremanezumab and galcanezumab therapy. Constipation was more common with erenumab. The risk of upper respiratory tract infection was higher with galcanezumab.Systematic review registration: Our PROSPERO protocol registration number: CRD42019125928. Registered 26 November 2019.

scholarly journals Apixaban in Comparison to Warfarin for Stroke Prevention in Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Observational Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Muhammad U. Siddiqui ◽  
David Scalzitti ◽  
Zunaira Naeem
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Nonvalvular Atrial Fibrillation ◽  
Safety Outcome ◽  
Increased Risk

Introduction. Atrial fibrillation leads to increased risk of systemic embolism and stroke. To decrease these adverse events, anticoagulation is routinely prescribed. Nonvitamin K anticoagulants like apixaban and rivaroxaban are becoming popular and being used more frequently nowadays. We here compare the efficacy and safety of apixaban with those of warfarin. Methods and Analysis. This systematic review aims to assess the efficacy and safety of apixaban compared to those of warfarin. Eligible participants were adults diagnosed with nonvalvular atrial fibrillation. The intervention was apixaban, and the comparator was warfarin. The primary efficacy endpoint is the first admission with systemic embolism or stroke, and the primary safety outcome is the occurrence of major bleeding. Relevant studies were searched in the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, and clinicaltrials.gov. After being independently reviewed by two authors, five articles were included in the systematic review. The risk of bias of included studies was assessed using the Cochrane risk of bias tool and SIGN methodology. The RevMan software was used to assess the effect size and perform meta-analysis. Results. Apixaban was found to be superior to warfarin in terms of safety (RR 0.58; CI 0.52–0.66) but not superior to warfarin in terms of efficacy (RR 0.93; CI 0.70–1.24). Conclusion. Apixaban is superior to warfarin in terms of safety, but no difference in efficacy is noted. The choice of anticoagulation should be individualized based on the risk factor profile of the patient.

A systematic review and meta-analysis of the role of statins and their intensity in peripheral artery disease

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Sagris ◽  
J Katsaros ◽  
S Giannopoulos ◽  
DG Kokkinidis
Keyword(s):  
Systematic Review ◽  
Peripheral Artery Disease ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Free Survival ◽  
Low Intensity ◽  
All Cause Mortality ◽  
Artery Disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Peripheral artery disease (PAD) affects more than eight million Americans. However, several studies have shown that those patients are often undertreated, and that statin utilization is suboptimal.  American Heart Association guidelines highlight statins as the first-line lipid-lowering therapy to treat patients with PAD. Our objective with this meta-analysis was to further explore the impact of statins on PAD outcomes and examine whether the actual statin (high vs low intensity) dose impacts outcomes. Methods We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented a comparison of statins vs no statins for PAD patients or compared high vs low intensity statins and provided outcomes with hazard ratio was considered as potentially eligible. The Medline (PubMed) database was searched up to August 30, 2020. A random effects meta-analysis was performed. Results In total, 38 studies and 275,670 patients were included in this meta-analysis. In total, 136,025 (49.34%) were on statins vs 139,645 (50.66%) who were not on statins. Statins had an association with a reduction in all cause-mortality by 42% (HR:0.58, 95% CI: 0.49-0.67, I2= 96.26%) and cardiovascular death by 43% (HR:0.57, 95% CI: 0.40-0.74, I2= 80.39%). Statins use was associated with an increase in amputation-free survival by 56% (HR:0.44, 95% CI: 0.30-0.58, I2 = 15%). The risk of amputation and loss of patency was reduced by 35% (HR:0.65, 95% CI:0.41-0.89, I2 = 86.91%), 46% (HR:0.54, 95% CI: 0.34-0.74, Ι2 = 0%), respectively. Statins use was also associated with a reduction in the risk of major adverse cardiovascular events (MACE) by 35% (HR:0.65, 95% CI: 0.51-0.80, I2= 93.22%) and the incidence of myocardial infarction (MI) by 41% (HR:0.59, 95% CI: 0.33-0.86, I2 = 76.78%). Among patients treated with statins, high-intensity treatment group was associated with a reduction in all cause-mortality by 36% (HR:0.64, 95% CI: 0.54-0.74, I2 = 96.49%) compared to patients treated with low intensity statins. Conclusion Statin treatment among patients with PAD was associated with a statistically significant reduction in all-cause mortality, cardiovascular mortality, MI, MACE, risk for amputation or loss of patency. Statins were also associated with a higher amputation free survival.

scholarly journals Cardiovascular and safety events of PCSK9 inhibitors in statin-treated patients with cardiovascular risk: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 23 ◽  
pp. 422-436
Author(s):  
Zinan ZHAO ◽  
Xin HU ◽  
Yatong ZHANG ◽  
Deping LIU
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Cardiovascular Risk ◽  
Injection Site ◽  
Randomized Clinical Trials ◽  
Adverse Drug Events ◽  
Meta Analysis ◽  
Injection Site Reaction ◽  
Nonfatal Myocardial Infarction ◽  
Site Reaction

Objectives: To evaluate whether proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is associated with cardiovascular and safety events in statin-treated patients with cardiovascular risk. Methods: Electronic databases (Pubmed, Cochrane, MEDLINE, EMBASE, ClinicalTrials.gov) were searched through March 31, 2020. Included randomized clinical trials (RCTs) compared PCSK9i use with no PCSK9i in statin treated patients. Two investigators abstracted data and appraised risks of bias. A meta-analysis was performed to calculate risk ratios (RRs) and 95% CIs using fix-effects models. Adjudicated cardiovascular events (CVE) and adverse drug events (ADE) were defined as the primary outcome. Secondary outcomes were cardiovascular (CV) death, all-cause death, nonfatal myocardial infarction, ischemic stroke, serious ADE and injection-site reaction. Results: A total of 10 RCTs 50 053 participants were included. PCSK9i use was associated with signigicant reductions in the CVE (RR, 0.87 [95%CI, 0.83-0.91]; NNT, 54; P<0.00001; I2=0%, heterogeneity P=0.86), nonfatal myocardial infarction (RR, 0.86 [95% CI, 0.78-0.96]; NNT, 95; P=0.005; I2=0%, heterogeneity P=0.88), and ischemic stroke (RR, 0.75 [95%CI 0.64-0.87]; NNT, 244; P=0.00; I2=0%, heterogeneity P=0.82) compared with no PCSK9i in statin-treated patients with CV risk. No significant associations were found between PCSK9i use and no PCSK9i in ADE and serious ADE. PCSK9i use was associated with signigicant increasing in injection-site reaction (RR, 1.55 [95%CI 1.38-1.75]; NNT, 101; P<0.00001; I2=0%, heterogeneity P=0.44). Conclusions: Among statin-treated patients with CV risk, the use of PCSK9i was associated with improving CV outcomes. The use of PCSK9i was well tolerated, but had significantly injection-site reactions.

scholarly journals Meta‐Analysis of Intensive Lipid‐Lowering Therapy in Patients With Polyvascular Disease

2021 ◽  
Author(s):  
Mohammad Alkhalil ◽  
Michał Kuzemczak ◽  
Nicholas Whitehead ◽  
Charalampos Kavvouras ◽  
Vladimír Džavík
Keyword(s):  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Vascular Events ◽  
End Point ◽  
Lowering Therapy ◽  
Increased Risk ◽  
End Point Rate

Background Polyvascular atherosclerotic disease is associated with an increased risk of future cardiovascular events. Intensive lipid‐lowering therapy (ILT) may mitigate this risk. The aims of this study‐level meta‐analysis were to examine the effects of ILT in patients with polyvascular disease and whether baseline low‐density lipoprotein cholesterol (LDL‐C) may determine the level of benefit. Methods and Results Electronic databases were searched through January 2020 to identify randomized controlled trials of treatments targeting upregulation of LDL‐C receptors (ie, statins, ezetimibe, and PCSK9 [proprotein convertase subtilisin–kexin type 9] inhibitors). The primary end point was major adverse vascular events as defined by the included studies. A total of 94 362 patients (14 821 [18.6%] with polyvascular disease) from 7 studies were included. In patients with monovascular disease, ILT was associated with a 13% reduction in the primary end point (rate ratio [RR] 0.87; 95% CI, 0.81–0.93 [ P =0.0002]) (absolute RR, 1.8%) compared with less ILT, while patients with polyvascular disease had 15% relative RR (0.85; 95% CI, 0.80–0.90 [ P <0.00001]) (absolute RR, 6.5%) ( P =0.66 for interaction). When factoring LDL‐C, unlike patients with monovascular disease, the relative benefits of ILT, compared with less ILT, in patients with polyvascular disease were comparable with LDL‐C >100 mg/dL (RR, 0.85; 95% CI, 0.80–0.90 [ P <0.00001]) and LDL‐C <100 mg/dL (RR, 0.88; 95% CI, 0.81–0.96 [ P =0.003]) ( P =0.23 for interaction). Conclusions Patients with polyvascular disease experienced comparable benefits to those with monovascular disease in response to ILT. The benefits of ILT in patients with polyvascular disease were not dependent on baseline LDL‐C, challenging the approach of using LDL‐C as a prerequisite to commence ILT for this high‐risk subgroup.

Sign in / Sign up

Export Citation Format

Share Document