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Circulation. Cardiovascular... Sep 2023Short-term (≤6 months) dual antiplatelet therapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Short-term (≤6 months) dual antiplatelet therapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome.
METHODS
A systemic search identified randomized controlled trials that included patients with acute coronary syndrome treated using (1) standard DAPT (12 months) with clopidogrel, prasugrel (standard/low dose), or ticagrelor; (2) extended DAPT (≥18 months); (3) short-term DAPT (≤6 months) followed by P2Y inhibitor or aspirin; (4) 12-month DAPT with unguided de-escalation from potent P2Y inhibitors to low-dose potent P2Y inhibitor or clopidogrel at 1 month; and (5) guided selection DAPT with genotype or platelet function tests. The primary efficacy outcome (major adverse cardiovascular events) was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding.
RESULTS
This meta-analysis included 32 randomized controlled trials with 103 497 patients. While there were no differences in efficacy between short, unguided de-escalation and guided selection strategies, unguided de-escalation was associated with reduced risk of major adverse cardiovascular events compared with standard DAPT with clopidogrel or ticagrelor (hazard ratio [95% CI], 0.67 [0.49-0.93] and 0.68 [0.50-0.93]). Both short DAPT followed by P2Y inhibitor and unguided de-escalation were associated with reduced risks in safety compared with other strategies, including guided selection (hazard ratio [95% CI], 0.66 [0.47-0.93] and 0.48 [0.33-0.71]). Short DAPT followed by a P2Y inhibitor was associated with reduced risk of major bleeding and all-cause death compared with standard, extended DAPT (eg, versus DAPT with clopidogrel; hazard ratio [95% CI], 0.64 [0.42-0.97] and 0.60 [0.44-0.82]). By rankogram, unguided de-escalation strategy was the safest and most effective strategy in reducing major adverse cardiovascular events and major or minor bleeding while short DAPT followed by P2Y inhibitor was ranked the best for major bleeding and all-cause death.
CONCLUSIONS
In patients with acute coronary syndrome, unguided de-escalation was associated with the lowest risk of major adverse cardiovascular events and major or minor bleeding outcomes, while short DAPT followed by P2Y inhibitor was associated with the lowest risk of major bleeding and all-cause death.
Topics: Humans; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Network Meta-Analysis; Clopidogrel; Ticagrelor; Treatment Outcome
PubMed: 37609850
DOI: 10.1161/CIRCINTERVENTIONS.123.013242 -
Clinical Gastroenterology and... May 2024Recent studies raise concern for increased risk of major adverse cardiovascular events (MACE) with Janus kinase (JAK) inhibitors used to treat immune-mediated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Recent studies raise concern for increased risk of major adverse cardiovascular events (MACE) with Janus kinase (JAK) inhibitors used to treat immune-mediated inflammatory disorders (IMIDs). We aimed to examine MACE risk with licensed biologics and small molecules used commonly between IMIDs: inflammatory bowel disease, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis.
METHODS
Data were obtained from systematic searches (from inception to May 31, 2022) in PubMed, Embase, Ovid Medline, Scopus, Cochrane Central, and ClinicalTrials.gov. Studies that assessed a predefined MACE (myocardial infarction, cerebrovascular accident, unstable angina, cardiovascular death, or heart failure) risk in those ≥18 years of age with IMIDs treated with anti-interleukin (IL)-23 antibodies, anti-IL-12/23, anti-tumor necrosis factor α antibodies (anti-TNF-α), or JAK inhibitors were included in a network meta-analysis using a random-effects model with pooled odds ratios (ORs) reported with 95% credible intervals (CrIs) by drug class and disease state.
RESULTS
Among 3528 studies identified, 40 (36 randomized controlled trials and 4 cohort studies) were included in the systematic review, comprising 126,961 patients with IMIDs. Based on network meta-analysis of randomized controlled trials, regardless of disease state, anti-TNF-α (OR, 2.49; 95% CrI, 1.14-5.62), JAK inhibitors (OR, 2.64; 95% CrI, 1.26-5.99), and anti-IL-12/23 (OR, 3.15; 95% CrI, 1.01-13.35) were associated with increased MACE risk compared with placebo. There was no significant difference in the magnitude of the MACE risk between classes or based on IMID type.
CONCLUSIONS
Anti-IL-12/23, JAK inhibitors, and anti-TNF-α were associated with higher risk of MACE compared with placebo. The magnitude of the increased MACE risk was not different by IMID type. These results require confirmation in larger prospective studies.
Topics: Humans; Cardiovascular Diseases; Biological Products; Network Meta-Analysis; Janus Kinase Inhibitors
PubMed: 37821035
DOI: 10.1016/j.cgh.2023.09.033 -
JAMA Cardiology May 2024Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor.
OBJECTIVE
To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI.
DATA SOURCES
MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction.
STUDY SELECTION
Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI.
DATA EXTRACTION AND SYNTHESIS
Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data.
MAIN OUTCOMES AND MEASURES
The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding.
RESULTS
Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.
Topics: Ticagrelor; Percutaneous Coronary Intervention; Humans; Clopidogrel; Platelet Aggregation Inhibitors; Dual Anti-Platelet Therapy; Purinergic P2Y Receptor Antagonists; Hemorrhage
PubMed: 38506796
DOI: 10.1001/jamacardio.2024.0133 -
European Journal of Neurology Aug 2023Previous studies investigating cardiovascular disorders in patients with Parkinson's disease (PD) showed heterogeneous results regarding whether there is a higher or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Previous studies investigating cardiovascular disorders in patients with Parkinson's disease (PD) showed heterogeneous results regarding whether there is a higher or lower risk of myocardial infarction (MI) in these patients compared to the general population. Because of the inconsistency in findings, herein the aim was to perform a systematic review and meta-analysis to investigate the risk of MI in patients with PD.
METHODS
A comprehensive literature search was performed using four databases, PubMed, Web of Science, Scopus and Embase, in June 2022. Peer-reviewed observational studies comprising case-controls, cohort, cross-sectional and longitudinal studies that reported MI in the PD population were included.
RESULTS
After the screening, 20 studies with a total of 80,441 patients with PD and 802,857 controls were included in our qualitative and quantitative synthesis. The pooled estimated odds ratio for MI in PD patients compared to controls was 0.80 (95% confidence interval [CI] 0.56-1.05) which indicates that there is no association. The pooled prevalence of MI was 5% (95% CI 3%-7%) with a range of 1%-20% amongst patients with PD. The men (6%, 95% CI 1%-13%) and women (6%, 95% CI 1%-14%, Q = 29.27, I = 98.50%, p < 0.001) had similar MI prevalence.
CONCLUSION
This comprehensive systematic review and meta-analysis provide compelling evidence that PD is associated with a reduced risk of MI. Whilst the exact mechanism underlying this association remains to be fully elucidated, it is clear that certain risk factors for cardiac events appear to be less present in PD patients, which may serve as a protective factor. However, given the reports of increased risk for cerebrovascular events in PD patients, it is possible that the major risk factors for MI and cardiovascular accidents in this population differ. These findings have important implications for clinical management and further research in this area is warranted.
Topics: Male; Humans; Female; Parkinson Disease; Cross-Sectional Studies; Myocardial Infarction; Risk Factors; Prevalence
PubMed: 37151196
DOI: 10.1111/ene.15838 -
Cardiovascular Diabetology Nov 2023Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia.
METHODS
PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867).
RESULTS
Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy.
CONCLUSIONS
The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Cholesterol; Myocardial Infarction; Gout; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38017541
DOI: 10.1186/s12933-023-02022-z -
European Journal of Preventive... Jul 2023While regular physical activity has clear benefits to cardiovascular health, physical exertion can trigger acute myocardial infarction (AMI). We aimed to estimate how... (Meta-Analysis)
Meta-Analysis
AIMS
While regular physical activity has clear benefits to cardiovascular health, physical exertion can trigger acute myocardial infarction (AMI). We aimed to estimate how many AMIs may be attributed to bouts of physical exertion and to explore possible modifiers of this association.
METHODS AND RESULTS
MEDLINE, ISI Web of Science, and Scopus databases were searched for case-crossover studies reporting the relative risk (RR) of exertion-related AMI and exposure prevalence in the control periods. We used the random-effects model to pool the RR estimates and the mixed-effects model and random-effects meta-regression for subgroup analyses and estimated the population attributable fraction (PAF) at the population level and in different subgroups. The study met the Preferred Reporting Items for Systematic Reviews and Meta-Analyses requirements. Twelve studies including 19 891 AMI patients met the criteria for inclusion. There was a strong overall association between episodic physical exertion and AMI [RR = 3.46; 95% confidence interval (CI), 3.16-3.78]. The total PAF was 10.6% (95% CI, 9.44-11.83). For each additional year of age, the RR of exertion-related AMI increased by ∼3%, but the PAF decreased by 2%. For each additional time of habitual activity per week, the RR of exertion-related AMI decreased by ∼43%. The impact was greater among those engaged in physical exertion one to three times a week (≥20% of cases) and among those who did not take compared with those who took β-blockers (P = 0.049).
CONCLUSION
Every tenth AMI may be assigned to physical exertion. The impact was more pronounced among younger patients, those exposed to exertion one to three times a week, and those not taking β-blockers.
Topics: Humans; Physical Exertion; Myocardial Infarction; Risk
PubMed: 36790838
DOI: 10.1093/eurjpc/zwad045 -
Progress in Cardiovascular Diseases 2023With expanding commercial space programs, uncertainty remains about the cardiovascular effects of space environmental exposures including microgravity, confinement,... (Review)
Review
BACKGROUND
With expanding commercial space programs, uncertainty remains about the cardiovascular effects of space environmental exposures including microgravity, confinement, isolation, space radiation, and altered bacterial virulence. Current limited data suggests additional health threats compared to Earth.
METHODS
We systematically reviewed PubMed, CENTRAL, Web of Science, EMBASE and Cochrane databases for prospective studies on spaceflight and cardiovascular outcomes. Search terms combined cardiovascular disease topics with spaceflight concepts. No date or language restrictions were imposed.
RESULTS
35 studies representing 2696 space travelers met inclusion criteria. Studies were grouped into spaceflight associations with: atherosclerosis, mortality, cardiac function, orthostatic intolerance, and arrhythmias. Atherosclerosis evidence was limited, with animal studies linking space radiation to endothelial damage, oxidative stress, and inflammation. However, human data showed no significantly increased atherosclerotic disease in astronauts. Mortality studies demonstrated lower cardiovascular mortality in astronauts compared to the general population however there was conflicting data. Cardiac function studies revealed physiologic ventricular atrophy, increased arterial stiffness, and altered blood flow distribution attributed to microgravity exposure. Effects appeared transient and reversible post-flight. Orthostatic intolerance studies found astronauts experienced altered heart rate variability, baroreflex response, and blood pressure changes post-flight. Arrhythmia studies showed increased ventricular ectopy during spaceflight, but limited data on long term flights.
CONCLUSIONS
Environmental space hazards impact the cardiovascular system through multiple mechanisms. Microgravity causes cardiac atrophy and orthostatic intolerance while space radiation may potentially accelerate atherosclerosis. Further research is needed, especially regarding long-term spaceflights.
Topics: Humans; Cardiovascular Diseases; Orthostatic Intolerance; Prospective Studies; Space Flight; Hemodynamics; Arrhythmias, Cardiac; Atherosclerosis; Atrophy
PubMed: 37531984
DOI: 10.1016/j.pcad.2023.07.009 -
Current Problems in Cardiology Dec 2023Myocardial regeneration has been a topic of interest in literature and research in recent years. An evolving approach reported is glucocorticoid (GC) receptor antagonism... (Review)
Review
Myocardial regeneration has been a topic of interest in literature and research in recent years. An evolving approach reported is glucocorticoid (GC) receptor antagonism and its role in the regeneration of cardiomyocytes. The authors of this study aim to explore the reported literature on GC receptor antagonism and its effects on cardiomyocyte remodeling, hypertrophy, scar formation, and ongoing cardiomyocyte death following cardiac injury. This article overviews cellular biology, mechanisms of action, clinical implications, challenges, and future considerations. The authors of this study conducted a systematic review utilizing the Cochrane methodology and PRISMA guidelines. This study includes data collected and interpreted from 30 peer-reviewed articles from 3 databases with the topic of interest. The mammalian heart has regenerative potential during its embryonic and fetal phases which is lost during its developmental processes. The microenvironment, intrinsic molecular mechanisms, and systemic and external factors impact cardiac regeneration. GCs influence these aspects in some cases. Consequently, GC receptor antagonism is emerging as a promising potential target for stimulating endogenous cardiomyocyte proliferation, aiding in cardiomyocyte regeneration following a cardiac injury such as a myocardial infarction (MI). Experimental studies on neonatal mice and zebrafish have shown promising results with GC receptor ablation (or brief pharmacological antagonism) promoting the survival of myocardial cells, re-entry into the cell cycle, and cellular division, resulting in cardiac muscle regeneration and diminished scar formation. Transient GC receptor antagonism has the potential to stimulate cardiomyocyte regeneration and help prevent the dreaded complications of MI. More trials based on human populations are encouraged to justify their applications and weigh the risk-benefit ratio.
Topics: Animals; Mice; Humans; Myocytes, Cardiac; Receptors, Glucocorticoid; Zebrafish; Cicatrix; Regeneration; Myocardial Infarction; Mammals
PubMed: 37481215
DOI: 10.1016/j.cpcardiol.2023.101986 -
The American Journal of Cardiology Dec 2023Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use for circulatory support in cardiogenic shock results in increased left ventricular (LV) afterload. The use... (Meta-Analysis)
Meta-Analysis
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use for circulatory support in cardiogenic shock results in increased left ventricular (LV) afterload. The use of concomitant Impella or intra-aortic balloon pump (IABP) have been proposed as adjunct devices for LV unloading. The authors sought to compare head-to-head efficacy and safety outcomes between the 2 LV unloading strategies. We conducted a search of Medline, EMBASE, and Cochrane databases to identify studies comparing the use of Impella to IABP in patients on VA-ECMO. The primary outcome of interest was in-hospital mortality. The secondary outcomes included transition to durable LV assist devices/cardiac transplantation, stroke, limb ischemia, need for continuous renal replacement therapy, major bleeding, and hemolysis. Pooled risk ratios (RRs) with 95% confidence interval and heterogeneity statistic I were calculated using a random-effects model. A total of 7 observational studies with 698 patients were included. Patients on VA-ECMO unloaded with Impella vs IABP had similar risk of short-term all-cause mortality, defined as either 30-day or in-hospital mortality- 60.8% vs 64.9% (RR 0.93 [0.71 to 1.21], I = 71%). No significant difference was observed in transition to durable LV assist devices/cardiac transplantation, continuous renal replacement therapy initiation, stroke, or limb ischemia between the 2 strategies. However, the use of VA-ECMO with Impella was associated with increased risk of major bleeding (57.2% vs 39.7%) (RR 1.66 [1.12 to 2.44], I = 82%) and hemolysis (31% vs 7%) (RR 4.61 [1.24 to 17.17], I2 = 66%) compared with VA-ECMO, along with IABP. In conclusion, in patients requiring VA-ECMO for circulatory support, the concomitant use of Impella or IABP had comparable short-term mortality. However, Impella use was associated with increased risk of major bleeding and hemolysis.
Topics: Humans; Extracorporeal Membrane Oxygenation; Hemolysis; Shock, Cardiogenic; Intra-Aortic Balloon Pumping; Heart-Assist Devices; Stroke; Hemorrhage; Treatment Outcome
PubMed: 37812867
DOI: 10.1016/j.amjcard.2023.09.023 -
Catheterization and Cardiovascular... Aug 2023Pretreatment with oral P2Y12 inhibitors is a standard practice for ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pretreatment with oral P2Y12 inhibitors is a standard practice for ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). However, the efficacy and safety of P2Y12 inhibitors pretreatment remain unclear.
OBJECTIVES
We conducted a meta-analysis to investigate the impact of P2Y12 inhibitor pretreatment on thrombotic and hemorrhagic endpoints in STEMI patients.
METHODS
We searched multiple databases for studies that compared P2Y12 inhibitor pretreatment with no pretreatment in STEMI patients and reported endpoints of interest. Random effects model was used for the meta-analysis.
RESULTS
Our meta-analysis included 3 randomized controlled trials and 14 observational studies, comprising 70,465 patients assigned to either P2Y12 inhibitor pretreatment (50,328 patients) or no pretreatment (20,137 patients). Compared to no pretreatment, P2Y12 inhibitor pretreatment did not result in significant reductions in all-cause mortality (risk ratio [RR] 0.73; 95% confidence interval [CI]: 0.52-1.03; p = 0.07), myocardial infarction (RR 0.75; 95% CI: 0.53-1.07; p = 0.11), or major bleeding (RR 0.80; 95% CI: 0.56-1.16; p = 0.22) at 30 days. However, our subgroup analysis revealed that P2Y12 inhibitor pretreatment administered in the pre-hospital setting was associated with a significant reduction in the incidence of myocardial infarction compared to no pretreatment (RR 0.73; 95% CI: 0.56-0.91; p < 0.01).
CONCLUSION
Our analysis suggests that pretreatment with oral P2Y12 inhibitors before PCI in patients with STEMI was not associated with reduced all-cause mortality, myocardial infarction, or major bleeding. However, pretreatment with P2Y12 inhibitors in the pre-hospital setting appears to be beneficial in reducing reinfarction.
Topics: Humans; ST Elevation Myocardial Infarction; Platelet Aggregation Inhibitors; Percutaneous Coronary Intervention; Treatment Outcome; Myocardial Infarction; Hemorrhage; Purinergic P2Y Receptor Antagonists; Observational Studies as Topic
PubMed: 37350287
DOI: 10.1002/ccd.30750