Fibrates are effective for modifying atherogenic dyslipidaemia, and particularly for lowering serum triglycerides. However, evidence that fibrates reduce mortality and morbidity associated with ...cardiovascular disease (CVD), or overall mortality and morbidity, in the primary prevention of CVD is lacking.
This Cochrane Review and meta-analysis aimed to evaluate the clinical benefits and harms of fibrates versus placebo or usual care or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone for the primary prevention of cardiovascular disease (CVD) morbidity and mortality.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), and Web of Science (all from inception to 19 May 2016). We searched four clinical trial registers (last searched on 3 August 2016) with the help of an experienced professional librarian. We searched the databases to identify randomised controlled trials (RCTs) evaluating the clinical effects of fibrate therapy in the primary prevention of CVD events. We did not impose any language restrictions.
We aimed to include all RCTs comparing the effects of fibrate monotherapy versus placebo or usual care, or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone. Included studies had a follow-up of at least six months for the primary prevention of CVD events. We excluded trials with clofibrate, because it was withdrawn from the market in 2002.
Two review authors independently screened titles and abstracts for potential study inclusion. Two review authors independently retrieved the full-text papers and extracted data. Disagreements were resolved by consensus. We calculated risk ratios (RRs) and accompanying 95% confidence intervals (CIs) for aggregate data on primary and secondary outcomes. We tested for heterogeneity with the Cochrane Q-test and used the I
statistic to measure inconsistency of treatment effects across studies. Using the GRADE approach, we assessed the quality of the evidence and used the GRADE profiler software (GRADEpro GDT) to import data from Review Manager 5 to create 'Summary of findings' tables.
We identified six eligible trials including 16,135 individuals. The mean age of trial populations varied across trials; between 47.3 and 62.3 years. Four trials included individuals with diabetes mellitus type 2 only. The mean treatment duration and follow-up of participants across trials was 4.8 years. We judged the risks of selection and performance bias to be low; risks of detection bias, attrition bias, and reporting bias were unclear. Reporting of adverse effects by included trials was very limited; that is why we used discontinuation of therapy due to adverse effects as a proxy for adverse effects. Patients treated with fibrates had a reduced risk for the combined primary outcome of CVD death, non-fatal myocardial infarction, or non-fatal stroke compared to patients on placebo (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74 to 0.96; participants = 16,135; studies = 6; moderate-quality of evidence). For secondary outcomes we found RRs for fibrate therapy compared with placebo of 0.79 for combined coronary heart disease death or non-fatal myocardial infarction (95% CI 0.68 to 0.92; participants = 16,135; studies = 6; moderate-quality of evidence); 1.01 for overall mortality (95% CI 0.81 to 1.26; participants = 8471; studies = 5; low-quality of evidence); 1.01 for non-CVD mortality (95% CI 0.76 to 1.35; participants = 8471; studies = 5; low-quality of evidence); and 1.38 for discontinuation of therapy due to adverse effects (95% CI 0.71 to 2.68; participants = 4805; studies = 3; I
= 74%; very low-quality of evidence). Data on quality of life were not available from any trial. Trials that evaluated fibrates in the background of statins (2 studies) showed no benefits in preventing cardiovascular events.
Moderate-quality evidence suggests that fibrates lower the risk for cardiovascular and coronary events in primary prevention, but the absolute treatment effects in the primary prevention setting are modest (absolute risk reductions < 1%). There is low-quality evidence that fibrates have no effect on overall or non-CVD mortality. Very low-quality evidence suggests that fibrates are not associated with increased risk for adverse effects.
The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear.
To ...determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication.
Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013.
Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys.
After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% 95% CI, 22.3%-27.6%). Only 96 of 253 discontinuations (37.9% 95% CI, 32.0%-44.3%) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% 95% CI, 8.2%-12.0%). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio OR, 0.25 95% CI, 0.15-0.43; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 95% CI, 0.92-1.00; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 95% CI, 2.29-4.43; P < .001).
In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.
The Epidemiology of Coronary Heart Disease Ferreira-González, Ignacio
Revista española de cardiología (English ed.),
February 2014, 2014-Feb, 2014-02-00, 20140201, Letnik:
67, Številka:
2
Journal Article
Recenzirano
Understanding the societal impact and trends of coronary heart disease through basic epidemiological measures is essential to evaluate treatment effectiveness and organize resource distribution. In ...the following narrative review, data are presented on the prevalence, incidence, and prognosis of coronary heart disease in general and of acute coronary syndrome in particular.
Conocer el impacto de la enfermedad coronaria en la sociedad a través de las medidas epidemiológicas básicas y su evolución es fundamental para evaluar la efectividad de los tratamientos y organizar la distribución de recursos. En la siguiente revisión narrativa, se presentan datos sobre prevalencia, incidencia y pronóstico de la enfermedad coronaria en general y del síndrome coronario agudo en particular.
ObjectivesThe aim of this study was to create a new Vall d’Hebron Risk Score-II (VH-RS-II) for non-fatal myocardial infarction (MI) and/or cardiac death (CD), excluding patients with coronary ...revascularisation (CR) during the follow-up.MethodsWe analysed 5215 consecutive patients underwent gated single photon emission CT (SPECT); 2960 patients (age 64.2±11, male 58.1%) had no previous MI and/or CR, and 2255 patients (age 63.3±11, male 81.9%) had previous MI and/or CR. During a follow-up of 4.3±2.6 years, the cardiac event (MI and CD) was evaluated. This study was reviewed and approved by the ethics committee of our institution (number form trial register, PR(AG)168.2012). To obtain the predictor model, multivariate Cox regression analysis and multivariate logistic regression analysis were used. RS-VH-II was validated with 679 patients.ResultsIn patients without previous MI and/or CR, age (HR: 1.01; p<0.001), diabetes (HR: 2.1, p=0.001), metabolic equivalent (METs) (HR: 0.89, p=0.038), ST segment depression (HR: 1.4, p=0.011), ejection fraction (EF) (HR: 0.97, p<0.001) and summed stress score (HR: 1.2, p<0.001) were the independent predictors of CE (C-statistic: 0.8). In patients with previous MI and/or CR, age (HR: 1.06, p<0.001), male (HR: 1.9, p=0.047), smoker (HR: 1.5, p=0.047), METs (HR: 0.8, p<0.001), ST segment depression (HR: 1.4, p=0.002), EF (HR: 0.96; p<0.001) and summed difference score (HR: 1.03, p=0.06) were the independent predictors of CE (C-statistic:0.8).ConclusionThe VH-RS-II obtained from different clinical exercise and gated SPECT variables allow the risk stratification for MI and CD in patients with or without previous MI and/or CR in due form.
While on his first hospital duty, a second-year cardiology resident receives a message in his pager about a patient who has just been admitted to the emergency room with chest pain. Specifically, he ...is asked to discard that the pain is of coronary origin. The resident questions the patient on his symptoms, examines his risk factors, and analyzes the electrocardiogram (ECG). With the ECG data, the qualitative information of pain provided by the patient, together with his past medical history, the presence of coronary pain is eventually discarded. The patient's past medical history reads «the symptoms described by the patient, the presence of hypertension as the only risk factor, and the lack of specific changes on the ECG suggest that the chances of coronary pain are extremely low». Intuitively, the resident considers that the chances the pain is due to coronary artery disease (CAD) with the data available (qualitative data of pain, risk factors, ECG) is lower than, let's say, 5%. In other words, the resident instinctively concludes that: p(CAD |qualitative data, risk factors, ECG) < .05, that is, the probability of having CAD according to all the abovementioned information (qualitative data, risk factors, and ECG) is < 5%. However, before the patient...
Predictors of antiplatelet therapy discontinuation (ATD) during the first year after drug-eluting stent implantation are poorly known.
This was a prospective study with 3-, 6-, 9-, and 12-month ...follow-up of patients receiving at least 1 drug-eluting stent between January and April 2008 in 29 hospitals. Individual- and hospital-level predictors of ATD were assessed by hierarchical-multinomial regression analysis. ATD could be assessed in 1622 candidates for follow-up (82.5%). A total of 234 patients (14.4%) interrupted at least 1 antiplatelet therapy drug, predominantly clopidogrel (n=182, 11.8%). Bleeding events or invasive procedures led to ATD in 109 patients. This was predicted by renal impairment (odds ratio OR 2.81, 95% confidence interval CI 1.48 to 5.34), prior major hemorrhage (OR 3.77, 95% CI 1.41 to 10.03), and peripheral arterial disease (OR 1.78, 95% CI 1.01 to 3.15). Medical decisions led to ATD in 70 patients; this was predicted by long-term use of anticoagulant therapy (OR 3.88, 95% CI 1.26 to 11.98), undergoing the procedure in a private hospital (OR 13.3, 95% CI 1.69 to 105), and not receiving instructions about medication (OR 2.8, 95% CI 1.23 to 6.36). Thirty-nine patients interrupted ATD on their own initiative, mainly immigrants (OR 3.78, 95% CI 1.2 to 11.98) and consumers of psychotropic drugs (OR 2.58, 95% CI 1.3 to 5.12).
ATD during the first year after drug-eluting stent implantation is based mainly on patient decision or a medical decision not associated with major bleeding events or major surgical procedures. Individual- and hospital-level variables are important to predict ATD.
TRPV4 channels, which respond to mechanical activation by permeating Ca
into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 ...involvement in pathological and physiological remodeling through Ca
-dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca
dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4-/- mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4-/-, displayed significant TRPV4 overexpression, elevated Ca
influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4-/- mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca
-dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response.
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