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The role of low molecular weight heparin on recurrent pregnancy loss: A systematic review and meta-analysis.
Jiang, F, Hu, X, Jiang, K, Pi, H, He, Q, Chen, X
Taiwanese journal of obstetrics & gynecology. 2021;(1):1-8
Abstract
To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were retrieved, and the systematic evaluation was conducted. PubMed, Embase, and Cochrane library databases were searched by using keywords, including low-molecular-weight heparin or LMWH, and recurrent miscarriage or recurrent pregnancy loss in pregnant women from their earliest data to February 2020. Two investigators independently evaluated eligibility. Risk ratios (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, this meta-analysis was performed using random-effect model due to the high heterogeneity among these eight studies. A total of eight RCTs involving 1854 participants were included in the meta-analysis involving 963 patients with RPL who were prescribed LMWH (enoxaparin, tinzaparin, or dalteparin) alone and 891 patients who were treated with no LMWH interventions (placebo, folic acid or non-treatment) were compared. Pooled data from the remaining eight RCTs showed the differences between intervention groups and control groups. Compared with control groups, LMWH had significantly improved live births (RR,1.19; 95%CI, 1.03 to 1.38; P = 0.02), and reduced miscarriage rates (RR, 0.62; 95%CI, 0.43 to 0.91; P = 0.01). The study suggested that LMWH could improve the live births and reduce the miscarriage rates of RPL. Therefore, LMWH might be a good treatment choice for women with unexplained PRL.
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Design of a prospective patient-level pooled analysis of two parallel trials of empagliflozin in patients with established heart failure.
Packer, M, Butler, J, Filippatos, G, Zannad, F, Ferreira, JP, Zeller, C, Brueckmann, M, Jamal, W, Pocock, SJ, Anker, SD, et al
European journal of heart failure. 2020;(12):2393-2398
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Abstract
AIM: The EMPEROR-Reduced trial demonstrated that empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with a reduced ejection fraction, and the EMPEROR-Preserved trial is currently evaluating the effect of the drug on the same endpoint in patients with an ejection fraction >40%. However, neither the trial was designed to have adequate statistical power to evaluate the effects of empagliflozin and dapagliflozin on major adverse renal outcomes or on mortality. Herein we describe the design of a prospective individual patient-level pooled analysis of two large-scale trials with empagliflozin (EMPEROR-Reduced and EMPEROR-Preserved) in patients with heart failure across the spectrum of ejection fraction. METHODS The trials were carried out in parallel using the same administrative structure and committees, randomization procedure, schedule of study visits and adjudication criteria and similar groups of investigators and case report forms. The two component trials specified the same primary and key secondary endpoints and used an identical hierarchical testing procedure, which included a pooled analysis of the two trials as a key component of the hierarchy. Consequently, the pooled analysis has been prospectively assigned a false positive error rate, which is conditional on one or both trials first achieving success on their primary and one or both key secondary endpoints. The pooled analysis has its own statistical plan with its own endpoints, and this plan was finalized before either trial had begun recruitment of patients into either study. The primary endpoint of the pooled analysis is a composite of serious adverse renal outcomes, defined by chronic dialysis, renal transplantation and a profound or sustained decrease in glomerular filtration rate. All-cause and cardiovascular mortality are specified as secondary endpoints. CONCLUSION The planned pooled analysis has an unusually high degree of statistical rigour that will allow it to address important questions that cannot be fully addressed by the individual trials.
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Sex Differences in Cardiovascular Medication Prescription in Primary Care: A Systematic Review and Meta-Analysis.
Zhao, M, Woodward, M, Vaartjes, I, Millett, ERC, Klipstein-Grobusch, K, Hyun, K, Carcel, C, Peters, SAE
Journal of the American Heart Association. 2020;(11):e014742
Abstract
Background Sex differences in the management of cardiovascular disease have been reported in secondary care. We conducted a systematic review with meta-analysis of systematically investigated sex differences in cardiovascular medication prescription among patients at high risk or with established cardiovascular disease in primary care. Methods and Results PubMed and Embase were searched between 2000 and 2019 for observational studies reporting on the sex-specific prevalence of aspirin, statins, and antihypertensive medication prescription, including beta blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and diuretics, in primary care. Random effects meta-analysis was used to obtain pooled women-to-men prevalence ratios for each cardiovascular medication prescription. Metaregression models assessed the impact of age and year on the findings. A total of 43 studies were included, involving 2 264 600 participants (28% women) worldwide. Participants' mean age ranged from 51 to 76 years. The pooled prevalence of cardiovascular medication prescription for women was 41% for aspirin, 60% for statins, and 68% for any antihypertensive medications. Corresponding rates for men were 56%, 63%, and 69% respectively. The pooled women-to-men prevalence ratios were 0.81 (95% CI, 0.72-0.92) for aspirin, 0.90 (95% CI, 0.85-0.95) for statins, and 1.01 (95% CI, 0.95-1.08) for any antihypertensive medications. Women were less likely to be prescribed angiotensin-converting enzyme inhibitors (0.85; 95% CI, 0.81-0.89) but more likely with diuretics (1.27; 95% CI, 1.17-1.37). Mean age, mean age difference between the sexes, and year of study had no significant impact on findings. Conclusions Sex differences in the prescription of cardiovascular medication exist among patients at high risk or with established cardiovascular disease in primary care, with a lower prevalence of aspirin, statins, and angiotensin-converting enzyme inhibitors prescription in women and a lower prevalence of diuretics prescription in men.
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Effects of the Antianginal Drugs Ranolazine, Nicorandil, and Ivabradine on Coronary Microvascular Function in Patients With Nonobstructive Coronary Artery Disease: A Meta-analysis of Randomized Controlled Trials.
Zhu, H, Xu, X, Fang, X, Zheng, J, Zhao, Q, Chen, T, Huang, J
Clinical therapeutics. 2019;(10):2137-2152.e12
Abstract
PURPOSE The goal of this study was to investigate the effects of the antianginal drugs ranolazine, nicorandil, and ivabradine on coronary microvascular function. METHODS Electronic scientific databases were searched for randomized trials investigating the effects of antianginal drugs on coronary microvascular function. Primary outcomes were changes in the coronary flow reserve (CFR), index of microvascular resistance (IMR), and myocardial perfusion reserve index (MPRI). The secondary outcome was the Seattle Angina Questionnaire scores. The standardized mean difference or weighted mean difference (WMD) (95% CI) served as a summary statistic. FINDINGS The antianginal drugs ranolazine, nicorandil, and ivabradine did not increase the CFR compared with the control drugs (standardized mean difference, 0.39; 95% CI, -0.08 to 0.85; P = 0.10). Ranolazine did not increase the global MPRI compared with the control drugs (weighted mean difference [WMD], 0.11; 95% CI, -0.06 to 0.29; P = 0.21). However, in the subgroups with a baseline CFR <2.5 or a global MPRI <2, ranolazine increased the global MPRI (WMD, 0.19; 95% CI, 0.10 to 0.27; P < 0.0001). In addition, the subendocardial midventricular MPRI (mid-subendocardial MPRI) was improved after ranolazine treatment (WMD, 0.12; 95% CI, 0.03 to 0.20; P = 0.007). Moreover, nicorandil significantly reduced the IMR compared with the control drugs (WMD, -7.63; 95% CI, -11.82 to -3.44; P = 0.0004). In addition, ranolazine and ivabradine improved 3 of the 5 Seattle Angina Questionnaire scores. IMPLICATIONS Ranolazine improved the global MPRI in patients with definite coronary microvascular dysfunction and the mid-subendocardial MPRI with suspicious coronary microvascular dysfunction, and nicorandil reduced the IMR. In addition, ranolazine and ivabradine reduced angina. Moreover, it is possible that the IMR and mid-subendocardial MPRI are more sensitive than the CFR and global MPRI for evaluating coronary microvascular function.
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The Identification of Calcified Coronary Plaque Is Associated With Initiation and Continuation of Pharmacological and Lifestyle Preventive Therapies: A Systematic Review and Meta-Analysis.
Gupta, A, Lau, E, Varshney, R, Hulten, EA, Cheezum, M, Bittencourt, MS, Blaha, MJ, Wong, ND, Blumenthal, RS, Budoff, MJ, et al
JACC. Cardiovascular imaging. 2017;(8):833-842
Abstract
OBJECTIVES The aim of this study was to assess the odds of initiation or continuation of pharmacological and lifestyle preventive therapies in patients with nonzero versus zero coronary artery calcium (CAC) score detected on cardiac computed tomography. BACKGROUND Detection of calcified coronary plaque could serve as a motivational tool for physicians and patients to intensify preventive therapies. METHODS We searched PubMed, EMBASE (Excerpta Medica database), Web of Science, Cochrane CENTRAL (Cochrane central register of controlled trials), ClinicalTrials.gov, and the International Clinical Trials Registry Platform for studies evaluating the association of CAC scores with downstream pharmacological or lifestyle interventions for prevention of cardiovascular disease. Pooled odds ratios (ORs) of downstream interventions were obtained using the DerSimonian and Laird random effects model. RESULTS After a review of 6,256 citations and 54 full-text papers, 6 studies (11,256 participants, mean follow-up time: 1.6 to 6.0 years) were included. Pooled estimates of the odds of aspirin initiation (OR: 2.6; 95% confidence interval [CI]: 1.8 to 3.8), lipid-lowering medication initiation (OR: 2.9; 95% CI: 1.9 to 4.4), blood pressure-lowering medication initiation (OR: 1.9; 95% CI: 1.6 to 2.3), lipid-lowering medication continuation (OR: 2.3; 95% CI: 1.6 to 3.3), increase in exercise (OR: 1.8; 95% CI: 1.4 to 2.4), and dietary change (OR: 1.9; 95% CI: 1.5 to 2.5) were higher in individuals with nonzero CAC versus zero CAC scores, but not for aspirin or blood pressure-lowering medication continuation. When assessed within individual studies, these findings remained significant after adjustment for baseline patient characteristics and cardiovascular risk factors. CONCLUSIONS This systematic review and meta-analysis suggests that nonzero CAC score, identifying calcified coronary plaque, significantly increases the likelihood of initiation or continuation of pharmacological and lifestyle therapies for the prevention of cardiovascular disease.
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Do polypills lead to neglect of lifestyle risk factors? Findings from an individual participant data meta-analysis among 3140 patients at high risk of cardiovascular disease.
Selak, V, Bullen, C, Stepien, S, Arroll, B, Bots, M, Bramley, D, Cass, A, Grobbee, D, Hillis, GS, Molanus, B, et al
European journal of preventive cardiology. 2016;(13):1393-400
Abstract
AIM: The aim of this study was to investigate whether polypill-based care for the prevention of cardiovascular disease (CVD) is associated with a change in lifestyle risk factors when compared with usual care, among patients with CVD or high calculated cardiovascular risk. METHODS We conducted an individual participant data meta-analysis of three trials including patients from Australia, England, India, Ireland, the Netherlands and New Zealand that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior CVD event or who were at high risk of their first event. Analyses investigated any differential effect on anthropometric measures and self-reported lifestyle behaviours. RESULTS Among 3140 patients (75% male, mean age 62 years and 76% with a prior CVD event) there was no difference in lifestyle risk factors in those randomised to polypill-based care compared with usual care over a median of 15 months, either across all participants combined, or in a range of subgroups. Furthermore, narrow confidence intervals (CIs) excluded any major effect; for example differences between the groups in body mass index was -0.1 (95% CI -0.2 to 0.1) kg/m(2), in weekly duration of moderate intensity physical activity was -2 (-26 to 23) minutes and the proportion of smokers was 16% vs 17% (RR 0.98, 0.84 to 1.15) at the end of trial. DISCUSSION This analysis allays concern that polypill-based care may lead to neglect of lifestyle risk factors, at least among high-risk patients. Maximally effective preventive approaches should address lifestyle factors alongside pharmaceutical interventions, as recommended by major international guidelines.
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Generic versus brand-name drugs used in cardiovascular diseases.
Manzoli, L, Flacco, ME, Boccia, S, D'Andrea, E, Panic, N, Marzuillo, C, Siliquini, R, Ricciardi, W, Villari, P, Ioannidis, JP
European journal of epidemiology. 2016;(4):351-68
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Abstract
This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider use.
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Omega 3 Fatty acids and cardiovascular outcomes: systematic review and meta-analysis.
Kotwal, S, Jun, M, Sullivan, D, Perkovic, V, Neal, B
Circulation. Cardiovascular quality and outcomes. 2012;(6):808-18
Abstract
BACKGROUND Early trials evaluating the effect of omega 3 fatty acids (ω-3 FA) reported benefits for mortality and cardiovascular events but recent larger studies trials have variable findings. We assessed the effects of ω-3 FA on cardiovascular and other important clinical outcomes. METHODS AND RESULTS We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for all randomized studies using dietary supplements, dietary interventions, or both. The primary outcome was a composite of cardiovascular events (mostly myocardial infarction, stroke, and cardiovascular death). Secondary outcomes were arrhythmia, cerebrovascular events, hemorrhagic stroke, ischemic stroke, coronary revascularization, heart failure, total mortality, nonvascular mortality, and end-stage kidney disease. Twenty studies including 63030 participants were included. There was no overall effect of ω-3 FA on composite cardiovascular events (relative risk [RR]=0.96; 95% confidence interval [CI], 0.90-1.03; P=0.24) or on total mortality (RR=0.95; 95% CI, 0.86-1.04; P=0.28). ω-3 FA did protect against vascular death (RR=0.86; 95% CI, 0.75-0.99; P=0.03) but not coronary events (RR=0.86; 95% CI, 0.67-1.11; P=0.24). There was no effect on arrhythmia (RR=0.99; 95% CI, 0.85-1.16; P=0.92) or cerebrovascular events (RR=1.03; 95% CI, 0.92-1.16; P=0.59). Adverse events were more common in the treatment group than the placebo group (RR=1.18, 95% CI, 1.02-1.37; P=0.03), predominantly because of an excess of gastrointestinal side effects. CONCLUSIONS ω-3 FA may protect against vascular disease, but the evidence is not clear-cut, and any benefits are almost certainly not as great as previously believed.
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Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients.
Naderi, SH, Bestwick, JP, Wald, DS
The American journal of medicine. 2012;(9):882-7.e1
Abstract
OBJECTIVE Combination therapy, specifically with aspirin, cholesterol and blood pressure-lowering drugs, substantially reduces the risk of coronary heart disease, but the full preventive effect is only realized if treatment continues indefinitely. Our objective was to provide a summary estimate of adherence to drugs that prevent coronary heart disease, according to drug class and use in people who have had a myocardial infarction (secondary prevention) and people who have not (primary prevention). METHODS A meta-analysis of data on 376,162 patients from 20 studies assessing adherence using prescription refill frequency for the following 7 drug classes was performed: aspirin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium-channel blockers, thiazides, and statins. Meta-regression was used to examine the effects of age, payment, and treatment duration. RESULTS The summary estimate for adherence across all studies was 57% (95% confidence interval [CI], 50-64) after a median of 24 months. There were statistically significant differences in adherence between primary and secondary prevention: 50% (CI, 45-56) and 66% (CI, 56-75), respectively (P=.012). Adherence was lower for thiazides (42%) than for angiotensin receptor blockers (61%) in primary prevention (P=.02). There were no other statistically significant differences between any of the drug classes in primary or secondary prevention studies. Adherence decreased by 0.15% points/month (P=.07) and was unrelated to age or whether patients paid for their pills. CONCLUSION Adherence to preventive treatment is poor and little related to class of drug, suggesting that side effects are not the main cause. General, rather than class-specific, measures at improving adherence are needed.
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Effects of coenzyme Q10 on vascular endothelial function in humans: a meta-analysis of randomized controlled trials.
Gao, L, Mao, Q, Cao, J, Wang, Y, Zhou, X, Fan, L
Atherosclerosis. 2012;(2):311-6
Abstract
OBJECTIVE The purpose of this study was to quantify the effect of coenzyme Q10 on arterial endothelial function in patients with and without established cardiovascular disease. BACKGROUND Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis. METHODS AND RESULTS The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 July 2011. Eligible studies were randomized controlled trials on the effects of coenzyme Q10 compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Five eligible trials enrolled a total of 194 patients. Meta-analysis using random-effects model showed treatment with coenzyme Q10 significantly improvement in endothelial function assessed peripherally by flow-mediated dilatation (SMD 1.70, 95% CI: 1.00-2.4, p<0.0001). However, the endothelial function assessed peripherally by nitrate-mediated arterial dilatation was not significantly improved by using fix-effects model (SMD -0.19, 95% CI: -1.75 to 1.38, p = 0.81). CONCLUSION Coenzyme Q10 supplementation is associated with significant improvement in endothelial function. The current study supports a role for CoQ10 supplementation in patients with endothelial dysfunction.