scholarly journals SUN-618 Decision Analysis for Glucagon-Like Peptide Receptor Agonists vs. Sodium-Glucose cotransporter2 Inhibitors in Type 2 Diabetes Mellitus

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ali Al khazaali ◽  
Alexis Mckee ◽  
Anjul Sharma ◽  
Stewart Albert
Keyword(s):  
Adverse Events ◽  
Disease Risk ◽  
Relative Rate ◽  
Cardiovascular Disease Risk ◽  
Systemic Review ◽  
Major Adverse Cardiovascular Events ◽  
Number Needed To Treat ◽  
Serious Adverse Events ◽  
Similar Reduction ◽  
Glucagon Like Peptide

Abstract Background: Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes (RO). Objective. Evaluation of data to assist in the prescribing decision with regard to severity of illness and risk for adverse events. Study Design: Systemic review of the major CVOT and previous meta-analyses. Main Outcome Measures: Analysis of six trials on GLP-1 RA and 4 trials on SGLT2i, showed both drug classes reduced MACE and CVD compared to controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: (relative rate, rr MACE= 1.09, 95%CI;0.98,1.22, p= 0.129; rr, CVD =1.04, CI;0.87,1.24, p=0.657). Hospitalization for heart failure (HHF) improved with SGLT2i (rr=0.68, CI; 0.61,0.76, p<0.001) but not with GLP-1 RA, (rr = 0.94, CI; 0.86,1.03, p=0.17). Both GLP-1 RA and SGLT2i showed significant reduction in RO (GLP-1RA, rr=0.83, CI; 0.75,0.912, p=<0.001, SGLT2i, rr=0.0.67, CI; 0.57,0.79, p=0.001) without a preferential difference between the classes (GLP-1 RA vs SGLT2i, relative difference (rd) =0.005, CI;-0.011,0.021, p=0.532, number needed to treat (NNT)=200). Serious adverse events (SAE) for SGLT2i were predominantly mycotic genital infections in women (number needed to harm (NNH) =13 and diabetic ketoacidosis NNH=595. Gastrointestinal intolerance was the major SAE in the GLP1-RA class (NNH=35). Conclusion: Both GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and RO. SGLT2i have advantages over GLP-1 RA in reduction in HHF especially in those with more severe cardiovascular disease risk.

scholarly journals Glucagon-like Peptide-1 Receptor Agonists versus Sodium-Glucose Cotransporter Inhibitors for Treatment of T2DM

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Alexis McKee ◽  
Ali Al-Khazaali ◽  
Stewart G Albert
Keyword(s):  
Adverse Events ◽  
Relative Rate ◽  
Major Adverse Cardiovascular Events ◽  
Serious Adverse Events ◽  
Similar Reduction ◽  
Renal Outcomes ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Context Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes. Objective Assist in the prescribing decision regarding severity of illness and risk for adverse events. Design Meta-analysis of the major CVOT and previous meta-analyses. Main Outcome Measures Six trials of GLP-1 RA (51 762 subjects) and 4 trials of SGLT2i (33 457 subjects) showed both drug classes reduced MACE and CVD versus controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: relative rate [rr] MACE 1.04, 95% confidence interval [CI] 0.94, 1.16, P = ns; rr CVD 1.04, 95% CI 0.87, 1.24, P = ns). Hospitalization for heart failure (HHF) improved with SGLT2i (rr 0.68, CI 0.61, 0.76, P < 0.001) but not with GLP-1 RA, (rr 0.93, CI 0.86,1.03, P = ns). Meta-regression suggested benefits of the SGLT2i on CVD and HHF were accentuated with the underlying rate of MACE in the cohort (i.e., >10 events/1000pt*year). GLP-1 RA and SGLT2i showed reduction in renal outcomes (GLP-1 RA rr 0.83, CI 0.75, 0.91, p ≤ 0.001, SGLT2i rr 0.67, CI 0.57, 0.79, P < 0.001) without a preferential difference (GLP-1 RA vs SGLT2i, rr 1.24, CI 0.95, 1.61, P = ns; relative difference (rd) 0.005, CI -0.011, 0.021, P = ns). Serious adverse events for SGLT2i were mycotic genital infections in women (number needed to harm [NNH] = 13 and diabetic ketoacidosis NNH = 595. Gastrointestinal intolerance was the serious adverse event in the GLP1-RA class (NNH = 35). Conclusion GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and renal outcomes. SGLT2i have advantages over GLP-1 RA in reduction in HHF.

Is it Worth CANVASing for CREDENCE? A Benefit-risk Analysis

2020 ◽  
Vol 16 (5) ◽  
pp. 509-514
Author(s):  
Binayak Sinha ◽  
Samit Ghosal
Keyword(s):  
Adverse Events ◽  
Fungal Infections ◽  
Absolute Risk ◽  
Pooled Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Number Needed To Treat ◽  
Pooled Data ◽  
The Individual ◽  
Fracture Risks ◽  
Number Needed To Harm

Background and Aims: A number of significant positive and negative signals emerged from the CANVAS Program and CREDENCE trial with the use of canagliflozin. These signals are confusing. A Likelihood of being Helped of Harmed (LHH) analysis was conducted to determine the risk, benefit ratio associated with canagliflozin use and address the signals as a continuum. Materials &Methods: LHH was calculated from the number needed to treat (NNT) and number needed to harm (NNH) available from the absolute risk reductions reported with the outcomes of interest, in these two trials. Results: In the CANVAS Program, LHH for major adverse cardiovascular events (MACE) points at a significant benefit with canagliflozin use in comparison to amputation (1.65), fractures (1.65) and euglycaemic diabetic ketoacidosis (euDKA) (16.67) risks. Only genital fungal infections were significant more in both sexes (0.21-M and 0.1-F) when LHH was matched against the positive outcomes. In contrast, the hHF benefits were outweighed by amputation (0.95) and fracture risks (0.95). : In CREDENCE trial, the LHH for Primary composite, Renal composite and MACE, all supported the benefits in comparison to any adverse events encountered in the trial. : The LHH from pooled data (CANVAS Program and CREDENCE trial) was in favour of all the benefits (hHF and renal composites) except for MACE matched against amputation (0.66). Conclusion: The outcome benefits were in favour of canagliflozin in comparison to all reported adverse events, when hHF and renal composite were under consideration, in both the individual and pooled LHH analysis. However, the MACE benefits were overwhelmed by amputation risk in the pooled analysis.

scholarly journals Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence

2018 ◽  
Vol 89 (7) ◽  
pp. 741-753 ◽  
Author(s):  
Emily Stockings ◽  
Dino Zagic ◽  
Gabrielle Campbell ◽  
Megan Weier ◽  
Wayne D Hall ◽  
...  
Keyword(s):  
Adverse Events ◽  
Seizure Frequency ◽  
Observational Studies ◽  
Number Needed To Treat ◽  
Seizure Freedom ◽  
Low Grade ◽  
Serious Adverse Events ◽  
Seizure Reduction ◽  
Increased Risk ◽  
Randomised Controlled

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.PROSPERO registration numberCRD42017055412.

scholarly journals Adjudication of cardiovascular events in patients with chronic obstructive pulmonary disease: SUMMIT trial

2020 ◽  
Vol 17 (4) ◽  
pp. 430-436
Author(s):  
Robert A Wise ◽  
Julie A Anderson ◽  
Pierre Amarenco ◽  
Nicholas J Cowans ◽  
Courtney Crim ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Adverse Events ◽  
Pulmonary Disease ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Chronic Obstructive ◽  
Clinical Endpoint ◽  
Serious Adverse Events ◽  
Obstructive Pulmonary Disease ◽  
Medical Dictionary

Background: Adjudicated cause-specific mortality has been used in major trials of chronic obstructive pulmonary disease. However, there is less experience with adjudicated major adverse cardiovascular events as a key efficacy outcome in chronic obstructive pulmonary disease trials. The Study to Understand Mortality and Morbidity in chronic obstructive pulmonary disease trial required a Clinical Endpoint Committee to adjudicate the outcomes of modified major adverse cardiovascular events and cause-specific mortality. Methods and results: A six-member Clinical Endpoint Committee reviewed adverse event and serious adverse event reports included in a list of 204 Medical Dictionary for Regulatory Activities terms. Adverse events were triaged by one Clinical Endpoint Committee member, and then reviewed by three reviewers (round 1). If these three disagreed on the adjudication, the event was discussed by the full committee to reach a consensus (round 2). Among 16,485 participants, 48,105 adverse events were reported, among which 3314 were reviewed by the Clinical Endpoint Committee. After triage, 1827 were adjudicated in round 1; 338 required committee consensus in round 2, yielding 450 myocardial infarctions, strokes, unstable anginas or transient ischaemic attacks. Only 20/1627 (1%) non-serious adverse events were adjudicated as cardiovascular events. Only 45/204 Medical Dictionary for Regulatory Activities terms reviewed yielded cardiovascular events. A total of 430 deaths were adjudicated in round 1 and 631 in round 2, yielding 459 cardiovascular deaths. Adjudication of chest pain and sudden death often required additional information from site investigators. Site assessment of cardiovascular death was moderately specific (501/602 = 83%) but not sensitive (256/459 = 56%). Conclusion: A Clinical Endpoint Committee is useful for adjudication of major adverse cardiovascular events in chronic obstructive pulmonary disease trials but requires considerable resources and effort by investigators. This process can be streamlined by reviewing only serious adverse events and filtering by selected Medical Dictionary for Regulatory Activities terms.

scholarly journals Indirect Meta-Analysis of Brexpiprazole Versus Aripiprazole in the Acute Treatment of Schizophrenia

2021 ◽  
Author(s):  
Erich Seifritz ◽  
Michael Friede ◽  
Jörg Schnitker
Keyword(s):  
Adverse Events ◽  
Acute Treatment ◽  
Dopamine D2 Receptor ◽  
Meta Analysis ◽  
D2 Receptor ◽  
Number Needed To Treat ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Safety Indices ◽  
Number Needed To Harm

Abstract Background: Brexpiprazole and aripiprazole are atypical antipsychotics that act as partial agonists at the dopamine D2 receptor. No head-to-head trial comparing brexpiprazole and aripiprazole in the treatment of schizophrenia is available. Here, we carry out a systematic review and comparison of the efficacy and safety of brexpiprazole and aripiprazole in schizophrenia treatment.Methods: We employed an indirect meta-analysis to determine effect sizes from randomised placebo-controlled trials with brexpiprazole and aripiprazole in the acute treatment of schizophrenia. We compared responder rates, incidences of adverse events and serious adverse events, the number needed to treat (NNT) for response, number needed to harm (NNH) for adverse events or treatment discontinuation, and likelihood to be helped or harmed (LHH) as efficacy and safety indices of the two drugs. Results: Five studies for each drug were included in the analysis. Similar risk differences vs. placebo were observed for responder rates under brexpiprazole (10.2%, p = 0.0015) and aripiprazole (10.3%, p = 0.0003). Higher incidences of adverse events and serious adverse events were seen under aripiprazole compared with brexpiprazole, however, the risk differences were not statistically significant. The NNT for response was 11 for both substances. For brexpiprazole compared with placebo, we did not find an increase of adverse events (NNH = 27, not significant), however, we found an increased number of adverse events for aripiprazole versus placebo (NNH = 17, p < 0.05). For both drugs, benefits were encountered more often than harms, with an LHH for any adverse event of 2.41 for brexpiprazole and 1.56 for aripiprazole, respectively. Conclusions: The likelihood to be helped rather than harmed was greater with brexpiprazole compared to aripiprazole for the total rate of adverse events (ratio of brexpiprazole LHH/aripiprazole LHH = 1.54).

scholarly journals Personalized Statin Therapy and Coronary Atherosclerotic Plaque Burden in Asymptomatic Low/Intermediate-Risk Individuals

2018 ◽  
Vol 8 (2) ◽  
pp. 140-150 ◽  
Author(s):  
Ranganath Muniyappa ◽  
Radwa A. Noureldin ◽  
Khaled Z. Abd-Elmoniem ◽  
Riham H. El Khouli ◽  
Jatin Raj Matta ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Risk Reduction ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Coronary Plaque ◽  
Plaque Burden ◽  
Number Needed To Treat ◽  
Atherosclerotic Cardiovascular Disease ◽  
Asymptomatic Individuals

Background: Current guidelines for the primary prevention of atherosclerotic cardiovascular disease are based on the estimation of a predicted 10-year cardiovascular disease risk and the average relative risk reduction estimates from statin trials. In the clinical setting, however, decision-making is better informed by the expected benefit for the individual patient, which is typically lacking. Consequently, a personalized statin benefit approach based on absolute risk reduction over 10 years (ARR10 benefit threshold ≥2.3%) has been proposed as a novel approach. However, how this benefit threshold relates with coronary plaque burden in asymptomatic individuals with low/intermediate cardiovascular disease risk is unknown. Aims: In this study, we compared the predicted ARR10 obtained in each individual with plaque burden detected by coronary computed tomography angiography. Methods and Results: Plaque burden (segment volume score, segment stenosis score, and segment involvement score) was assessed in prospectively recruited asymptomatic subjects (n = 70; 52% male; median age 56 years [interquartile range 51–64 years]) with low/intermediate Framingham risk score (< 20%). The expected ARR10 with statin in the entire cohort was 2.7% (1.5–4.6%) with a corresponding number needed to treat over 10 years of 36 (22–63). In subjects with an ARR10 benefit threshold ≥2.3% (vs. < 2.3%), plaque burden was significantly higher (p = 0.02). Conclusion: These findings suggest that individuals with higher coronary plaque burden are more likely to get greater benefit from statin therapy even among asymptomatic individuals with low cardiovascular risk.

P5317Prevalence of cardiovascular diseases in the Middle-East: systemic review and meta-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Shehab ◽  
A S Bhagavathula
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Cardiovascular Diseases ◽  
Middle East ◽  
Disease Risk ◽  
Meta Analysis ◽  
Cardiovascular Disease Risk ◽  
Random Effect ◽  
Systemic Review ◽  
Significant Independent Risk Factor

Abstract Background Cardiovascular diseases are the leading cause of mortality in the world and CVDs are responsible for 34% of all deaths in the middle east population. To better understanding of the current CVD prevalence in the middle east population we conducted this systematic review and meta-analysis. Aim To assess the prevalence and risk factors of CVD among middle east adult population from the published literature. Methods Electronic data basis such as PubMed, Sciencedirect, Embase and Google scholar were searched, from the year 2011 to December 2018. All the original articles published in English and have investigated the prevalence of CVD and risk factors. Study characteristics, participants demographics and risk factors of CVD were recorded. To pull the CVD prevalence, we used random effect meta-analysis. we assess heterogeneity using both the formal tests and subgroup analysis. We also assessed the quality of the studies and examined the publication bias. Results We retrieved 2931 potentially relevant papers through searches of electronic and gray literatures, of which 44 articles met inclusion criteria after the screening and were included in systematic review and meta-analysis (N=191,979). The weighted pooled prevalence of CVD was 13.7% (95% CI: 11.1%-16.3%) in the Middle-East. The prevalence of cardiovascular disease risk factors such as dyslipidemia accounts 43.1% (95% CI: 17%-69.3%), diabetes mellitus 32.3%, 95% CI: 23.8%-40.8%), hypertension 30.7% (95% CI: 25.2%-36.3%). Other traditional CVD risk factors, smoking 16.3% (95% CI: 12.9%-19.7%), and family history of CVDs 18.7% (95% CI: 15.2%-22.2%). Conclusion A high CVD prevalence of 13.7% was identified and dyslipidemia remain to be a significant independent risk factor for CVD in the Middle-East. Interventional strategies are urgently required for primary prevention of CVD and its associated risk factors in Middle East population.

scholarly journals Safety and Efficacy of SGLT2 Inhibitors: A Multiple-Treatment Meta-Analysis of Clinical Decision Indicators

2021 ◽  
Vol 10 (12) ◽  
pp. 2713
Author(s):  
Vicente Martínez-Vizcaíno ◽  
Ana Díez-Fernández ◽  
Celia Álvarez-Bueno ◽  
Julia Martínez-Alfonso ◽  
Iván Cavero-Redondo
Keyword(s):  
Heart Failure ◽  
Meta Analysis ◽  
Clinical Decision ◽  
Renal Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Number Needed To Treat ◽  
Cochrane Central Register ◽  
Serious Adverse Events ◽  
Multiple Treatment ◽  
All Cause Mortality

To jointly assess the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiorenal outcomes and all-cause mortality in type 2 diabetes mellitus (T2DM) with or at high risk of cardiovascular disease (CVD). We performed a systematic review and network meta-analysis, systematically searching the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science databases up to September 2020. Primary outcomes were composite major adverse cardiovascular events (MACEs), hospitalization for heart failure, all-cause mortality and a composite renal outcome. We performed a random effects network meta-analysis estimating the pooled hazard ratio (HR), risk ratio and number needed to treat (NNT). Six trials evaluating empagliflozin, canagliflozin, dapagliflozin and ertugliflozin met the inclusion/exclusion criteria, which comprised 46,969 patients, mostly with established CVD. Pooled estimates (95% CI) of benefits of SGLT2i in terms of HR and NNT were as follows: for all-cause mortality, 0.85 (0.75, 0.97) and 58 (28, 368); for MACE, 0.91 (0.85, 0.97) and 81 (44, 271); for hospitalization for heart failure, 0.70 (0.62, 0.78) and 32 (20, 55); and for composite renal outcome, 0.61 (0.50, 0.74) and 20 (11, 44). Pooled estimates for serious adverse events were 0.92 (95% CI 0.89, 0.95). In patients with T2DM at cardiovascular risk, ertugliflozin is a less potent drug than empagliflozin, canagliflozin or dapagliflozin to prevent cardiorenal events and all-cause mortality. In addition, our data endorse that empagliflozin is the best treatment option among SGLT2i for this type of patient, but the evidence is not consistent enough.

scholarly journals Urate, Blood Pressure, and Cardiovascular Disease

Hypertension ◽  
2020 ◽  
Author(s):  
Dipender Gill ◽  
Alan C. Cameron ◽  
Stephen Burgess ◽  
Xue Li ◽  
Daniel J. Doherty ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Meta Analysis ◽  
Cardiovascular Disease Risk ◽  
Serum Urate ◽  
Major Adverse Cardiovascular Events ◽  
Randomized Controlled

Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10–1.30]; P =4×10 −5 ), peripheral artery disease (1.12 [95% CI, 1.03–1.21]; P =9×10 −3 ), and stroke (1.11 [95% CI, 1.05–1.18]; P =2×10 −4 ). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, −2.55 mm Hg [95% CI, −4.06 to −1.05]; P =1×10 −3 ) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22–0.73]; P =3×10 −3 ) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44–1.03]; P =0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.

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