scholarly journals Efficacy and Safety of Antiplatelet Therapies in Symptomatic Peripheral Artery Disease: A Systematic Review and Network Meta-Analysis

2020 ◽  
Vol 18 ◽  
Author(s):  
Marco De Carlo ◽  
Giovanni Di Minno ◽  
Tobias Sayre ◽  
Mir Sohail Fazeli ◽  
Gaye Siliman ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
Major Adverse Cardiovascular Events ◽  
Limb Ischaemia ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Randomised Controlled

Background: Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD. Methods: We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses. Results: We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65- 0.93) and ticagrelor (HR 0.80; 95%CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95%CrI 0.43- 1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk. Conclusion: This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.

scholarly journals Clinical Outcomes of Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongzhou Guo ◽  
Zhishuai Ye ◽  
Rongchong Huang
Keyword(s):  
Antiplatelet Therapy ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Gi Bleeding ◽  
Coronary Syndrome ◽  
All Cause Mortality

Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]

Abstract 14325: Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events and Mortality in Clinical Trials of Time-constrained Dual-antiplatelet Therapy After Percutaneous Coronary Intervention

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jennifer Ramsay ◽  
John McClure ◽  
Colin Berry
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Pooled Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Bleeding Events ◽  
P2y12 Inhibitor ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Reduced Risk

Introduction: The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events (MACE). A time-constrained approach to DAPT has been recently investigated in five multicenter trials including GLOBAL LEADERS, STOP-DAPT2, SMART-CHOICE, TWIGHLIGHT and TICO. Methods: We undertook a pooled analysis of these trials to assess the overall associations between time-constrained P2Y12 inhibitor monotherapy (“aspirin free regimen”) for bleeding events, MACE and all-cause mortality as compared to standard care with DAPT for at least 12 months post-PCI. We implemented a DerSimonian and Laird random effects meta-analysis using the metafor package in R. Results: 32,361 randomized trial participants, including 16,898 (52.2%) with a history of ACS, underwent PCI and had outcome data available. P2Y12 inhibitor monotherapy from 1 - 3 months was associated with a reduced risk for bleeding (hazard ratio (HR) (95% confidence interval (CI)) 0.60 (0.45, 0.81); p=0.024), including in the ACS group in which the magnitude of risk reduction was greatest (HR (95% CI) 0.50 (0.41, 0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the hazard were also favorable for MACE (0.88 (0.77, 1.02)) and all-cause mortality (95% CI 0.85 (0.71, 1.03)). Conclusions: Compared with DAPT for 12 months post-PCI, P2Y12 inhibitor monotherapy from 1-3 months substantially reduces the risk of major and fatal bleeding and, in addition, potentially protective effects, for MACE and all-cause mortality. Considering patient safety, the results support a strategy of DAPT for 1-3 months followed by ‘aspirin free’ P2Y12 inhibitor monotherapy.

scholarly journals Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

2018 ◽  
Vol 40 (2) ◽  
pp. 208-215 ◽  
Author(s):  
Qian-jie Tang ◽  
He-ping Lei ◽  
Hong Wu ◽  
Ji-yan Chen ◽  
Chun-yu Deng ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Major Adverse Cardiovascular Events

Abstract 16401: Duration of Dual Antiplatelet Therapy in Coronary Heart Disease: A 60,000-patient Meta-analysis of Randomised Controlled Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anda Bularga ◽  
Mohammed Meah ◽  
Dimitrios Doudesis ◽  
Anoop S Shah ◽  
Nicholas L Mills ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Major Bleeding ◽  
Randomised Controlled Trials ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Short Term ◽  
All Cause Mortality ◽  
Standard Duration ◽  
Randomised Controlled

Introduction: Dual antiplatelet therapy (DAPT) is the cornerstone of pharmacological treatment for patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention for stable coronary disease. Despite widespread use, the optimal duration of DAPT remains uncertain. We present an updated meta-analysis comparing outcomes in short-term DAPT (≤ 6 months) versus long-term DAPT (≥ 12 months). Methods: Four major databases were searched for randomised controlled trials of interest. The primary outcome was all-cause mortality. Secondary safety outcomes included any bleeding and major bleeding. Efficacy outcomes included cardiovascular death, myocardial infarction, stent thrombosis, coronary revascularization and thrombotic stroke. Further subgroup analysis stratified by index presentation and a sensitivity analysis to evaluate shorter duration DAPT (≤3 months) was performed. Results: Nineteen randomised controlled trials were included (n=60,879) of which 8 compared shorter duration DAPT (≤3 months) with standard duration (12 months) (n=38,036). Short-term DAPT was associated with an apparent modest increase in myocardial infarction (risk ratio [RR] 1.09; 95% confidence interval [CI], 0.98-1.22) with a major reduction in bleeding (RR 0.68; 95% CI, 0.55-0.83) for major bleeding and (RR 0.66; 95% CI, 0.56-0.77 for any bleeding) and an overall apparent reduction in all-cause mortality (RR 0.90; 95% CI 0.81-1.01). These associations persisted when comparing shorter duration DAPT to standard duration. Subgroup analysis of patients with stable disease or ACS identified no significant heterogenicity in efficacy, safety or mortality outcomes. Conclusion: In the largest meta-analysis to date comparing duration of DAPT, we show that short (≤ 6 months) and shorter (≤ 3 months) DAPT is associated with continuing trends for small reductions in all-cause mortality irrespective of index presentation.

A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes

2018 ◽  
Vol 25 (8) ◽  
pp. 844-853 ◽  
Author(s):  
Safi U Khan ◽  
Swapna Talluri ◽  
Haris Riaz ◽  
Hammad Rahman ◽  
Fahad Nasir ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bayesian Network ◽  
Cardiovascular Mortality ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Credible Interval ◽  
Major Adverse Cardiovascular Events ◽  
Pcsk9 Inhibitors ◽  
Adverse Cardiovascular Event ◽  
All Cause Mortality

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.

scholarly journals Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study

BMJ ◽  
2020 ◽  
pp. m3342 ◽  
Author(s):  
Kristian B Filion ◽  
Lisa M Lix ◽  
Oriana HY Yu ◽  
Sophie Dell’Aniello ◽  
Antonios Douros ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Retrospective Cohort ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Major Adverse Cardiovascular Events ◽  
Site Specific ◽  
Sodium Glucose Cotransporter ◽  
All Cause Mortality

Abstract Objective To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice. Design Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis. Setting Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18. Population 209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years. Main outcome measures The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis. Results Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87). Conclusions In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors. Trial registration ClinicalTrials.gov NCT03939624 .

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