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Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.
Willeit, P, Tschiderer, L, Allara, E, Reuber, K, Seekircher, L, Gao, L, Liao, X, Lonn, E, Gerstein, HC, Yusuf, S, et al
Circulation. 2020;(7):621-642
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Abstract
BACKGROUND To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
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Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis.
Lombardi, M, Chiabrando, JG, Vescovo, GM, Bressi, E, Del Buono, MG, Carbone, S, Koenig, RA, Van Tassell, BW, Abbate, A, Biondi-Zoccai, G, et al
Current atherosclerosis reports. 2020;(9):45
Abstract
PURPOSE OF REVIEW Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention. RECENT FINDINGS Fourteen studies were identified providing data on 125,763 patients. A prespecified cut-off value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.
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The effect of nicorandil in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a systematic review and meta-analysis.
Ji, Z, Zhang, R, Lu, W, Ma, G, Qu, Y
Irish journal of medical science. 2020;(1):119-131
Abstract
AIMS: To study the effect of nicorandil on prognosis of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS We retrieved literatures from Web of Science, Pubmed, Embase, and Cochrane Library. The retrieval time was limited from inception to December 2018. RESULTS Nineteen randomized controlled trials involving 2176 patients were finally selected for this study. Meta-analysis showed that nicorandil can significantly reduce corrected TIMI frame count (cTFC) (WMD = - 5.27; 95% CI (- 6.61, - 3.93); P < 0.00001) and improve the no-reflow or slow-reflow phenomenon of coronary arteries (thrombolysis in myocardial infarction (TIMI) ≤ 2) (RR = 0.52; 95% CI (0.40, 0.68); P < 0.001). Compared with control group, nicorandil group has higher left ventricular ejection fraction (LVEF) (WMD = 3.42; 95% CI (1.32, 5.51); P = 0.001), and subgroup analysis showed that sex ratio was one source of heterogeneity (male/female ratio < 4 for low M/F group, M/F > 4 for high M/F group). In the low M/F group, LVEF in nicorandil group was increased significantly (WMD = 4.61; 95% CI (3.03, 6.20); P < 0.001), while there was no significant difference in LVEF between two groups in the high M/F group (WMD = 1.00; 95% CI (- 1.09, 3.09); P = 0.350). In addition, the incidence of in-hospital reperfusion arrhythmia (RR = 0.47; 95% CI (0.36, 0.63); P < 0.00001) and major adverse cardiovascular events (MACEs) (RR = 0.49; 95% CI (0.35, 0.69); P < 0.001) were significantly lower in the nicorandil group than that in control group. CONCLUSIONS Nicorandil can improve coronary microcirculation and left ventricular function of patients with AMI after PCI. Interestingly, female patients may benefit more from nicorandil than male patients in improving heart function.
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Effects of Intracoronary Nicorandil on Myocardial Microcirculation and Clinical Outcomes in Patients with Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials.
Shi, L, Chen, L, Qi, G, Tian, W, Zhao, S
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020;(2):191-198
Abstract
BACKGROUND The amelioration of myocardial reperfusion in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PPCI) remains a significant issue. OBJECTIVE We conducted a meta-analysis of randomized controlled trials (RCTs) to better assess the effects of intracoronary nicorandil administration on myocardial microcirculation and clinical outcomes in these patients. METHODS The meta-analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. A literature search was performed in the PubMed, Embase, Cochrane Library, and Web of Science databases up to April 2019, with no time or language limitations. Pooled risk ratios (RRs) were calculated to evaluate the treatment effects. RESULTS Seven RCTs involving a total of 562 patients were included. Compared with control, intracoronary nicorandil significantly reduced the incidence of thrombolysis in myocardial infarction (TIMI) grade ≤ 2 (RR 0.349; 95% confidence interval [CI] 0.199-0.611; P < 0.001) and TIMI myocardial perfusion grade ≤ 2 (RR 0.611; 95% CI 0.438-0.852; P = 0.004) and was associated with higher complete ST-segment resolution rates (RR 1.326; 95% CI 1.090-1.614; P = 0.005). However, no significant benefits were observed on clinical outcomes, including death (RR 0.370; 95% CI 0.085-1.618; P = 0.187), recurrent myocardial infarction (RR 0.507; 95% CI 0.156-1.655; P = 0.261), heart failure (RR 0.528; 95% CI 0.224-1.247; P = 0.145), and target lesion/vessel revascularization (RR 1.109; 95% CI 0.553-2.224; P = 0.770). CONCLUSIONS Intracoronary nicorandil can significantly improve myocardial microcirculation in patients with AMI undergoing PPCI, but it failed to offer clinically significant benefits.
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PCSK9 inhibitor therapy: A systematic review and meta-analysis of metabolic and cardiovascular outcomes in patients with diabetes.
Monami, M, Sesti, G, Mannucci, E
Diabetes, obesity & metabolism. 2019;(4):903-908
Abstract
AIMS: Pro-protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors bring about a wide reduction in low-density lipoprotein (LDL) cholesterol, greater than that of other lipid-lowering agents. The aim of this metanalysis was assessment of the effects of PCSK9 inhibitors on glucose metabolism, LDL cholesterol, cardiovascular morbidity and mortality in individuals with and without diabetes. MATERIALS AND METHODS A Medline and Clinicaltrials.gov search for eligible studies published before 1 December 2017 was performed. All randomized trials comparing PCSK-9 inhibitors with placebo or active drugs were included. Primary endpoints included (a) incident diabetes, fasting glucose and HbA1c, (b) LDL cholesterol at endpoint in patients with diabetes and in the total sample, and (c) major cardiovascular events (MACE) and mortality in individuals with and without diabetes. RESULTS A total of 38 trials was identified. The risk of incident diabetes was not increased by PCSK-9 inhibitors, vs placebo or any comparator. The reduction in LDL cholesterol vs placebo in patients with diabetes was 52.6 [41.3;63.8] mg/dL; the corresponding figure for all patients was 66.9 [62.4;71.3] mg/dL. Meta-regression analysis showed an inverse correlation between proportion of patients with diabetes and drug effect on LDL cholesterol in trials vs ezetimibe, but not in those vs placebo. In studies reporting data on MACE and mortality separately for individuals with and without diabetes, the effect of PCSK-9 did not appear to be affected by diabetes. CONCLUSION PCSK-9 inhibitors do not affect glucose metabolism. Their efficacy on LDL cholesterol and MACE in patients with diabetes does not seem to be very dissimilar to that observed in non-diabetic participants.
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Contribution of the polymorphism rs1800469 of transforming growth factor β in the development of myocardial infarction: meta-analysis of 5460 cases and 8413 controls (MOOSE-compliant article).
Du, L, Gong, T, Yao, M, Dai, H, Ren, HG, Wang, H
Medicine. 2019;(26):e15946
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Abstract
Studies investigating the association between transforming growth factor (TGF-β-509C/T, rs1800469) promoter polymorphism and myocardial infarction (MI) risk reported inconsistent results. The aim of our study was to assess the association between the 509C/T polymorphism of the TGF-β gene (rs1800469) and MI risk.A total of 5460 cases and 8413 controls in 7 case-control studies were incorporated in our current meta-analysis. The original studies were selected through searching the databases of the PubMed and EMBASE. The odds ratio (OR) and 95% confidence interval (95% CI) of TGF-β 509C/T (rs1800469) for MI risk were applied to estimate the strength of the association.Our results showed that T allele carriers had a 13% increased risk of MI, when compared with the C allele carriers (OR = 1.13, 95% CI: 1.00-1.27). In the subset analysis by the type of MI, significantly elevated risk of MI was associated with the homozygote TT and heterozygote C/T in no-AMI subjects, when compared with the CC homozygote carriers (OR = 1.12, 95% CI:1.02-1.23).Our meta-analysis shows that the polymorphism with homozygote TT and heterozygote C/T of TGF-β 509C/T (rs1800469) is significantly associated with the increased risk of MI.
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Evaluation of a meta-analysis of air quality and heart attacks, a case study.
Stanley Young, S, Kindzierski, WB
Critical reviews in toxicology. 2019;(1):85-94
Abstract
It is generally acknowledged that claims from observational studies often fail to replicate. An exploratory study was undertaken to assess the reliability of base studies used in meta-analysis of short-term air quality-myocardial infarction risk and to judge the reliability of statistical evidence from meta-analysis that uses data from observational studies. A highly cited meta-analysis paper examining whether short-term air quality exposure triggers myocardial infarction was evaluated as a case study. The paper considered six air quality components - carbon monoxide, nitrogen dioxide, sulphur dioxide, particulate matter 10 μm and 2.5 μm in diameter (PM10 and PM2.5), and ozone. The number of possible questions and statistical models at issue in each of 34 base papers used were estimated and p-value plots for each of the air components were constructed to evaluate the effect heterogeneity of p-values used from the base papers. Analysis search spaces (number of statistical tests possible) in the base papers were large, median = 12,288 (interquartile range = 2496 - 58,368), in comparison to actual statistical test results presented. Statistical test results taken from the base papers may not provide unbiased measures of effect for meta-analysis. Shapes of p-value plots for the six air components were consistent with the possibility of analysis manipulation to obtain small p-values in several base papers. Results suggest the appearance of heterogeneous, researcher-generated p-values used in the meta-analysis rather than unbiased evidence of real effects for air quality. We conclude that this meta-analysis does not provide reliable evidence for an association of air quality components with myocardial risk.
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Effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery: protocol for a systematic review, meta-analysis, and trial sequential analysis.
Suzumura, EA, Ribeiro, RA, Kawano-Dourado, L, de Barros E Silva, PG, Oliveira, C, Figueiró, MF, Cavalcanti, AB, Lopes, RD, Berwanger, O
Systematic reviews. 2017;(1):116
Abstract
BACKGROUND Preliminary evidence suggests statins may reduce major perioperative vascular events. However, evidence is limited to observational studies, underpowered trials, and non-comprehensive systematic reviews. This review aims to assess the effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery. METHODS We will search MEDLINE/PubMed, EMBASE, LILACS, CENTRAL, Web of Science, and CINAHL for randomized controlled trials assessing the effects of perioperative statin use in adults undergoing non-cardiac surgery and reporting cardiovascular complications. For patients already using statins for hyperlipidemia, a preoperative loading dose of statin is required in the experimental group. We will place no language or publication restriction on our search. Teams of two reviewers will independently assess eligibility and risk of bias, and will extract data from the included trials. Our primary outcome is a combination of cardiovascular mortality or non-fatal myocardial infarction. We will also assess the following outcomes: individual components of the primary outcome, all-cause mortality, total myocardial infarction, elevated troponin in the first seven postoperative days, total stroke, total venous thromboembolism, postoperative atrial fibrillation, elevation of creatine phosphokinase or liver enzymes, and rates of myalgia or rhabdomyolysis. We will conduct meta-analyses using random-effects model and will use trial sequential analysis to establish monitoring boundaries to limit global type I error due to repetitive testing for our primary outcome. We will rate the quality of evidence using the GRADE system. DISCUSSION The results of this systematic review may help to inform clinical practice and also the design of future large-scale randomized trials. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016035987.
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Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic Review and Meta-Analysis.
Murthy, SB, Gupta, A, Merkler, AE, Navi, BB, Mandava, P, Iadecola, C, Sheth, KN, Hanley, DF, Ziai, WC, Kamel, H
Stroke. 2017;(6):1594-1600
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Abstract
BACKGROUND AND PURPOSE The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism. METHODS We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes. RESULTS Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25-0.45; Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58-1.77; Q=24.68, P for heterogeneity <0.001). No significant publication bias was detected in our analyses. CONCLUSIONS In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk-benefit profile of anticoagulation resumption after ICH.
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Risk of myocardial infarction and death in patients with atrial fibrillation treated with dabigatran or vitamin K antagonists. Meta-analysis of observational analyses.
Darwiche, W, Bejan-Angoulvant, T, Angoulvant, D, Babuty, D, Fauchier, L
Thrombosis and haemostasis. 2016;(6):1150-1158
Abstract
The safety of dabigatran versus adjusted-dose vitamin K antagonist (VKA) treatment is the subject of debate. We evaluated the risk of myocardial infarction (MI) or mortality in patients with atrial fibrillation (AF) treated in clinical practice with dabigatran or a VKA. We performed a meta-analysis of observational studies that included an adjusted or matched analysis and reported MI, or death in AF patients treated with dabigatran or a VKA. Ten published analyses met the inclusion criteria. Of the 539,559 patients, 17,365 (3 %) patients were on dabigatran 110 mg twice daily (bid), 150,948 (28 %) were on dabigatran 150 mg bid, and 371,246 (69 %) were on VKA. Adjusted risk for MI versus VKA was 0.71 (0.47-1.07; p=0.10) in patients starting oral anticoagulant (OAC) treatment with dabigatran 110 mg, 0.82 (0.71-0.96; p=0.01) in patients starting dabigatran 150 mg, 1.40 (1.04-1.88; p=0.03) in patients switching OAC treatment to dabigatran 110 mg, and 1.28 (0.88-1.87; p=0.19) in patients switching OAC treatment to dabigatran 150 mg, with statistical homogeneity in each subgroup. Risk of death was consistently lower in patients treated with dabigatran 110 mg (HR 0.79; 0.65-0.96; p=0.02) or 150 mg (HR 0.65; 0.57-0.73; p<0.00001) versus VKA. In conclusion, dabigatran use, as currently prescribed in routine practice for AF patients, was associated with a lower risk of MI in OAC-naïve patients treated with dabigatran 150 mg compared with VKA, and a higher risk of MI in patients switching from VKA to dabigatran 110 mg. Risk of death was lower in AF patients treated with either dose of dabigatran versus VKA.