Trials In Cardiology Research Articles

An Analysis of Global Research Trends in Cardiology Over the Last two Decades.

Heart disease today is a major cause of morbidity and mortality plaguing mankind worldwide. The present research was undertaken to ascertain global research trends in clinical trials in Cardiology involving human subjects over the last two decades. Cross-sectional study. A detailed search strategy was employed in December 2013, using the PubMed database. All papers published in 1993-2013 were evaluated. The research trends of various cardiologic subspecialties in the United States and worldwide have been analysed and detailed statistical analysis was done. United States had maximum number of researches. Clinical trials involving infarction were maximum followed by coronary angiography and coronary angioplasty in that order. The year 2013 had the most researches. The United States was the top country and Boston was the top city. Author Christodoulos Stefanadis had the greatest number of researches in this field. American Journal of Cardiology was the most favored journal and Circulation was the journal with the highest impact factor. This effort may help funding agencies, prospective job seekers, fellowship applicants, policymakers and patients Conclusion: The research output in cardiology has increased and improved significantly over past decade. The publication per diplomat is more in transplant cardiology, Also more clinical trials involving coronary restenosis have to be done to know in depth to add to current knowledge and database.

Commentary on highlighted late breaking trials in interventional cardiology at ESC, VIVA, TCT, and AHA 2013.

With the plethora of clinical trials, it is difficult for busy interventional cardiologists to stay up to date. Therefore, the SCAI publications committee concisely summarizes and provides editorial commentary on the most important trials from recent, large international meetings. The intent is to provide this summary every six months to allow quick assimilation of trial results into interventional practice. © 2014 Wiley Periodicals, Inc.

Top 10 Countdown: Clinical Trials in Cardiology

Throughout the past year, results from multiple clinical trials in the field of cardiology have been released. This article reviews data that were released from the top 10 clinical trials in cardiovascular health during the past year.

Advances in clinical cardiology.

Multiple, potentially practice-changing cardiology trials have been presented or published over the past year. In this paper, we summarize and place in clinical context, new data regarding management of acute coronary syndrome and ST-elevation myocardial infarction (copeptin assessment, otamixaban, cangrelor, prasugrel, sodium nitrite, inclacumab, ranolazine, preventive coronary intervention of non-culprit lesions, immediate thrombolytic therapy versus transfer for primary intervention), new coronary intervention data (thrombectomy, radial access, pressure wire fractional flow reserve, antiplatelet therapy duration and gene-guidance, permanent and biodegradable polymers, coronary bifurcation and strategies), and coronary artery bypass data (off pump vs. on pump). Latest trials in trans-aortic valve implantation, heart failure (eplerenone, aliskiren, spironolactone, sildenafil, dopamine, nesiritide, omecamtiv mecarbil, the algisyl left ventricular augmentation device, and echo-guided cardiac resynchronization), atrial fibrillation (edoxaban, dabigatran, and ablation), cardiac arrest (hypothermia, LUCAS™ mechanical chest compression), and cardiovascular prevention (vitamins, renal denervation for resistant hypertension, renal artery stenting, saxagliptin, alogliptin, and gastric banding) are also discussed.

Omega-3 fatty Acids in cardiovascular disease – An uphill battle

In cardiology, results of recent large intervention trials with eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplements were neutral. In contrast, in epidemiologic studies, an inverse relation between clinical events and intake of EPA+DHA was found which was steeper for higher levels of EPA+DHA. A standardized way of determining levels is the Omega-3 Index, which is the percentage of EPA+DHA of a total of 26 fatty acids measured in erythrocytes. According to current criteria, a low Omega-3 Index is a cardiovascular risk factor. What can explain this contradiction? Trial participants were recruited irrespective of their baseline status in EPA+DHA - an important predictor of events. Levels of EPA+DHA have a statistically normal distribution; together with the large inter-individual variability of levels' responding to increased intake, this created a large overlap of EPA+DHA levels between intervention and control groups. Moreover, trial participants were advised to take EPA+DHA supplements with breakfast, frequently a low fat meal, resulting in poor bioavailability. As a result, there is an urgent need for new intervention trials in cardiology, for which participants with a low baseline omega-3 index are recruited, and then treated with individually tailored doses of EPA+DHA to a prespecified target range.

Commentary on late breaking trials in interventional cardiology at ESC, VIVA, TCT, AHA (Fall 2012), and ACC 2013

With the plethora of clinical trials, it is difficult for busy interventional cardiologists to stay up to date. Therefore, the Society for Cardiovascular Angiography and Interventions (SCAI) publications committee concisely summarized and provided editorial commentary on the most important trials from recent, large international meetings. The intent is to provide this summary every six months to allow quick assimilation of trial results into interventional practice.

The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine

BackgroundWhole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care.Methods/DesignThis pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients’ genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes, behaviors and outcomes of physician and patient participants at multiple time points before and after the disclosure of these results.DiscussionThe impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine will evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies.Trial registrationClinicalTrials.gov identifier NCT01736566

Randomized trials of PCIs versus CABG surgery: why coronary stenting should remain the first choice of revascularization in non-diabetic patients and why the controversy is still present in diabetics

Knowing the best revascularization option for diabetic patients with multiple vessel disease is a challenge without a definitive answer. There have been several randomized clinical trials and subsequent meta-analyses comparing current available technology trying to reach an exhaustive conclusion; comparisons between coronary artery bypass grafts and bare-metal stents, coronary artery bypass grafts and first generation drug-eluting stents and, most recently, first generation versus latest generation drug-eluting stents generated some interesting results. Information provided by pooled data from some of the most important randomized clinical cardiology trials from the last two decades have produced surprising results. The authors analyze these data to discuss the best therapeutic procedures for each patient.

Abstract T P344: Clopidogrel Resistance in Stroke Patients (The CRISP Trial)

Background: Clopidogrel is a thienopyridine with ADP antagonising effects that is widely used in the secondary prevention of ischemic strokes and transient ischemic attacks (TIAs). Despite this some patients will go on to have recurrent strokes or TIAs. Cardiology trials have identified patients with clopidogrel resistance, defined as a vasodilator-stimulated phosphoprotein (VASP) index of >50% after at least 7 days of clopidogrel treatment. This was associated with recurrent cardiac events. The VASP-index measures phosphorylation of VASP in the resting state and activated states using flow cytometry techniques. As phosphorylation of VASP is dependent upon activation of the platelet P2Y12 receptor that is targeted by clopidogrel the difference in phosphorylation between the two states provides an indirect measure of platelet inhibition. Previous trials have shown a prevalence of clopidogrel resistance in stroke patients of between 8 and 18%, but no study to date has shown whether this is associated with significantly more recurrent cerebrovascular events. We are testing the hypothesis that amongst patients treated with clopidogrel for secondary prevention of cerebrovascular disease, those with resistance are more likely to have recurrent Strokes or TIAs. Should this hypothesis be confirmed, then further research would be needed to identify treatment strategies that may minimise this risk. Design A prospective cohort study recruiting 120 patients from the acute stroke unit at the Royal Liverpool hospital with a diagnosis of stroke or TIA that will be commenced on clopidogrel therapy and expected to continue it for at least one year. We will compare outcomes between those found to be 'clopidogrel responders' and 'clopidogrel resistant'. A sample size of 120 patients was chosen based on the concept of 'reproducibility probability', taking into account the number of patients needed for similar studies in cardiology patients, the prevalence of 'clopidogrel resistance' amongst stroke patients and the potential for patients to later be excluded. Outcome Recurrent cerebrovascular event within 6 months of entering trial. Trial Status Recruitment ongoing.

Clinical Trials in Cardiology

Controlled clinical trials conduct the research that completes the causal argument between a treatment and a disease's control. Yet, this pinnacle of clinical research is itself afflicted. Chronic problems with recruitment failure vitiate the potency of our research efforts. In addition, the collision of end-point multiplicity (the drive to measure multiple end points) with the requirement of statistical parsimony (ie, the need to reduce the number of interpretable end points to control the overall type I error) induces a core inefficiency in clinical trial productivity by reducing the number of endpoints findings that are generalizable to the population at large. Unless clinical trialists engage these problems with vigor and imagination, our pinnacle may be nothing more than an inflection point leading to decline.

The Landscape of Clinical Trials in Nephrology: A Systematic Review of ClinicalTrials.gov

Well-designed trials are of paramount importance in improving the delivery of care to patients with kidney disease. However, it remains unknown whether contemporary clinical trials within nephrology are of sufficient quality and quantity to meet this need. Systematic review. Studies registered with ClinicalTrials.gov. Interventional (ie, nonobservational) studies (both randomized and nonrandomized) registered between October 2007 and September 2010 were included for analysis. Studies were reviewed independently by physicians and classified by clinical specialty. Nephrology versus cardiology versus other trials. Select clinical trial characteristics. Of 40,970 trials overall, 1,054 (2.6%) were classified as nephrology. Most nephrology trials were for treatment (75.4%) or prevention (15.7%), with very few diagnostic, screening, or health services research studies. Most nephrology trials were randomized (72.3%). Study designs included 24.9% with a single study group, 64.0% that included parallel groups, and 9.4% that were crossover trials. Nephrology trials, compared with2,264 cardiology trials (5.5% overall), were more likely to be smaller (64.5% vs 48.0% enrolling≤100 patients), phases 1-2 (29.0% vs 19.7%), and unblinded (66.2% vs 53.3%; P<0.05 for all). Nephrology trials also were more likely than cardiology trials to include a drug intervention (72.4% vs 41.9%) and less likely to report having a data monitoring committee (40.3% vs 48.5%; P<0.05 for all). Finally, there were few trials funded by the National Institutes of Health (NIH; 3.3%, nephrology; 4.2%, cardiology). Does not include all trials performed worldwide, and frequent categorization of funding source as university may underestimate NIH support. Critical differences remain between clinical trials in nephrology and other specialties. Improving care for patients with kidney disease will require a concerted effort to increase the scope, quality, and quantity of clinical trials within nephrology.

Key Advances in Clinical Cardiology

Multiple key cardiology trials with the potential to change practice or advance understanding have been presented over the past 12 months at international meetings, including the American College of Cardiology (ACC, Chicago, USA, March 2012), European Association for Percutaneous Cardiovascular Interventions (EuroPCR, Paris, France, May 2012), European Society of Cardiology (ESC, Munich, Germany, August 2012), Transcatheter Cardiovascular Therapeutics (TCT, Miami, USA, October 2012), and the American Heart Association (AHA, Los Angeles, USA, November 2012). In this paper, the authors describe and place in clinical context new acute coronary syndrome data, including use of oral antiplatelets and anticoagulants (prasugrel, rivaroxaban, vorapaxar), personalized antiplatelet therapy guided by platelet aggregometry, glucose-insulin-potassium infusion, and changing trends in myocardial infarction. New trial data are also described for interventional cardiology (revascularization in multivessel disease, fractional flow reserve-guided intervention, radial access, bioabsorbable polymer stents, drug-eluting balloons, intraaortic balloon pump use, transcatheter aortic valve implantation), in heart failure (copeptin, angiotensin receptor neprilysin inhibition, aldosterone blockade in diastolic heart failure, biventricular pacing), atrial fibrillation (surgical ablation, antithrombotic strategy after stenting), implantable defibrillator use, and in prevention (renal denervation in hypertension, dalcetrapib, lomitapide, proprotein convertase subtilisin/kexin type 9 in dyslipidemia, insulin glargine/fish oils, and bariatric surgery in diabetes).

Are All Clinical Trial Sites Created Equal?

Physicians seem increasingly skeptical of the results of randomized clinical trials. The reasons are multifactorial but might be due, in part, to concerns about generalizability and reproducibility of trial results. Contemporary cardiology trials routinely involve thousands of patients and hundreds

Competing time-to-event endpoints in cardiology trials: A simulation study to illustrate the importance of an adequate statistical analysis

Clinical trials in cardiology commonly consider time-to-event endpoints that are often influenced by competing risks. In the presence of competing risks, standard survival analysis techniques, such as the Kaplan-Meier estimator, can yield seriously biased results. Although methods to account for competing risks are well known in the statistical literature, they are rarely applied in clinical trials. Simulation study, to demonstrate the appropriate application and interpretation of the competing risks methodology with respect to time-to-event endpoints. In this paper, different statistical approaches to account for competing risks are systematically compared, based on a simulation study and using the original data from a cardiology trial. Group comparisons in clinical trials that have competing time-to-event endpoints should be based on the cause-specific hazard functions. In contrast, group comparisons based on event rates should be carried out with care, as event rates are directly influenced by competing events. Ignoring or not fully accounting for competing risks may yield misleading or even erroneous results, which could hinder understanding of survival trends; therefore, it is important that competing risks methodology be routinely incorporated into clinical trial standards.

The Need for Large Clinical Studies in Perioperative Medicine

The Need for Large Clinical Studies in Perioperative Medicine

Motivation and frustration in cardiology trial participation: The patient perspective

OBJECTIVE:The participation of humans in clinical cardiology trials remains essential, but little is known regarding participant perceptions of such studies. We examined the factors that motivated participation in such studies, as well as those that led to participant frustration.METHODS:Patients who had participated in hypertension and coronary arterial disease (phases II, III, and IV) clinical trials were invited to answer a questionnaire. They were divided into two groups: Group I, which included participants in placebo-controlled clinical trials after randomization, and Group II, which included participants in clinical trials in which the tested treatment was compared to another drug after randomization and in which a placebo was used in the washout period.RESULTS:Eighty patients (47 patients in Group I and 33 patients in Group II) with different socio-demographic characteristics were interviewed. Approximately 60% of the patients were motivated to participate in the trial with the expectation of personal benefit. Nine participants (11.2%) expressed the desire to withdraw, which was due to their perception of risk during the testing in the clinical trial (Group I) and to the necessity of repeated returns to the institution (Group II). However, the patients did not withdraw due to fear of termination of hospital treatment.CONCLUSIONS:Although this study had a small patient sample, the possibility of receiving a benefit from the new tested treatment was consistently reported as a motivation to participate in the trials.

Antihypertensives for combating dementia? A perspective on candidate molecular mechanisms and population-based prevention.

Age-related increases in prevalent dementia over the next 30–40 years risk collapsing medical resources or radically altering the way we treat patients. Better prevention of dementia therefore needs to be one of our highest medical priorities. We propose a perspective on the pathological basis of dementia based on a cerebrovascular-Alzheimer disease spectrum that provides a more powerful explanatory framework when considering the impact of possible public health interventions. With this in mind, a synthesis of evidence from basic, clinical and epidemiological studies indeed suggests that the enhanced treatment of hypertension could be effective for the primary prevention of dementia of either Alzheimer or vascular etiology. In particular, we focus on candidate preventative mechanisms, including reduced cerebrovascular disease, disruption of hypoxia-dependent amyloidogenesis and the potential neuroprotective properties of calcium channel blockers. Following the successful translation of large, long-term and resource-intense trials in cardiology into improved vascular health outcomes in many countries, new multinational prevention trials with dementia-related primary outcomes are now urgently required.

Reporting of radiation exposure in contemporary interventional cardiology trials

To determine reporting of radiation exposure in contemporary interventional cardiology randomized trials published in leading journals. Interventional cardiology procedures are a significant source of ionizing radiation, which can have detrimental effects on both patients and medical personnel. The EuroIntervention 2010 supplement served as a source of randomized trials in interventional cardiology published in scientific literature from 2000 to 2010. Of all the trials in the supplement, 204 represented original research and were examined for reporting of radiation dose and fluoroscopy times. Only eight trials (3.92%) reported either radiation exposure or fluoroscopy time, covering 16,563 patients (4.55% of the total patient population of 363,727). All of these trials were published after 2006. The average fluoroscopy time reported in seven trials was 13.6 min and the mean radiation dose reported in three trials was 58.67 Gy cm(2) . Radiation exposure is not consistently reported in contemporary interventional cardiology trials. Even when reporting occurs, trials may not report detailed data such as radiation dose, radiation exposure time, or fluoroscopy time. Although reporting of radiation exposure has not been a requirement in research studies, efforts by professional societies and regulatory authorities toward standardized reporting should aid clinicians in making a more informed decision on specific interventional procedures and devices.

Independent Data and Safety Monitoring in Psychiatric Intervention Research

A data and safety monitoring board (DSMB) is a multidisciplinary group of scientists that monitors a randomized clinical trial. Although DSMBs have been used for clinical trials in cardiology, oncology, and infectious disease for decades, it was not until the late 1990s that the National Institute of Mental Health (NIMH) initially required a DSMB for some of its larger trials. The NIMH mandate expanded during the succeeding decade to require DSMBs for many of the clinical trials in psychiatry. In turn, the need for board members has grown quickly. The objective of this commentary is to consider the purpose of a DSMB and to describe its roles, responsibilities, composition, and implementation. The rationale for a DSMB is to ensure the integrity and validity of the trial and, most importantly, to protect the safety of trial participants. A board conducts comprehensive reviews of accumulating unblinded data for safety and, in some trials, for efficacy. Reviewers examine adverse events and serious adverse events at regular intervals during the course of the trial. In addition, a DSMB monitors recruitment, randomization, retention, adherence, and follow-up in an effort to evaluate the validity of a trial. Because it is unethical to expose a participant to the risks of an experiment that will be unable to answer the scientific question that was postulated, a board should also evaluate the study protocol prior to trial commencement. Ultimately, a DSMB's responsibilities are broader than that of the trial being monitored. It will protect potential study participants and eventually could affect patients seeking clinical treatment for the disorder being studied.

Pediatric Cardiovascular Drug Trials, Lessons Learned

Few drugs have been labeled for pediatric cardiovascular indications, and many children with cardiac disease are prescribed drugs off-label. Recent initiatives have narrowed this gap, and as a result, there are an increasing number of cardiology trials in the pediatric population. Many studies, however, have either failed to show a dose response in children or have not shown efficacy in children when they have established efficacy in adults. Clinical trials are challenging in children; many factors such as lack of development of a liquid formulation, failure to fully incorporate pharmacokinetic information into trial design, poor dose selection, the lack of clinical equipoise, and the use of difficult surrogate and composite primary endpoints have led to the difficulties and failures observed in several pediatric cardiovascular trials. These lessons learned may help to inform future pediatric clinical trial development.