Testosterone trial stopped due to cardiovascular events 

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A trial testing testosterone gel in older men with mobility limitations has been stopped early because of an increased risk of cardiovascular events in the treated group.

The trial, supported by the US National Institute on Aging, was being conducted to investigate whether testosterone treatment would increase muscle mass and strength in older men with limited mobility.

In the trial, 209 men were randomly assigned to receive 10 g of a transdermal gel, containing either placebo or 100 mg of testosterone, to be applied to the skin once daily for six months. The men in the trial were an average 74 years old and had high rates of chronic diseases such as diabetes and cardiovascular disease.

The trial was stopped after a review by the study’s data and safety monitoring board, which found that 23 of the 106 men who had received testosterone experienced adverse cardiovascular-related events during the study, compared with five of the 103 men who received placebo. In addition, seven men in the testosterone group and one in the placebo group had atherosclerosis-related events. The cardiovascular-related events included myocardial infarction (MI), arrhythmias, hypertension, and one death from a suspected MI. The testosterone group did show significantly greater improvements in muscle strength.

Reporting the findings in a paper published online on June 30, 2010, in The New England Journal of Medicine, the trial investigators say that chance may have played a role in the outcomes observed and that the diversity of the adverse cardiac events that were seen makes them less easily explained by a single mechanistic explanation. They also caution against extrapolating the findings to other doses and formulations of testosterone or to other populations, particularly young men who have hypogonadism, without cardiovascular disease or limitations in mobility.

Apixaban beneficial in atrial fibrillation 

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A study of a new drug for atrial fibrillation, apixaban (Pfizer/Bristol-Myers Squibb), has been stopped early because of benefit.

The trial was stopped after a predefined interim analysis by the independent data monitoring committee “revealed clear evidence of a clinically important reduction in stroke and systemic embolism”, a company statement announced.

The AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Strokes) study included 5,600 patients with all types of atrial fibrillation who were intolerant of or unsuitable for warfarin. They were randomised to 5 mg of apixaban or 81–324 mg of aspirin for up to 36 months.

The primary efficacy outcome is the time from the first dose of the study drug to the first occurrence of ischaemic stroke, haemorrhagic stroke, or systemic embolism. The secondary efficacy outcome includes the time to the first occurrence of ischaemic stroke, haemorrhagic stroke, systemic embolism, myocardial infarction, or vascular death.

Full results from the AVERROES study will be presented at the European Society of Cardiology 2010 Congress in Stockholm, Sweden.

Eplerenone beneficial in mild heart failure 

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Another trial stopped early because of benefit is EMPHASIS-HF (Eplerenone in Mild Patients Hospitalisation And SurvIval Study in Heart Failure) which looked at the aldosterone inhibitor, eplerenone, in mild heart-failure patients.

According to Pfizer, an interim analysis of the trial showed that patients treated with eplerenone in addition to current standard of care experienced a significant reduction in risk of cardiovascular death or heart failure hospitalisation compared with those in the placebo arm of the trial. 

The company says it is now working to ensure that all patients are informed of this decision, and an amendment to the protocol will be requested to allow all consenting patients to start treatment with eplerenone in an open-label extension of the study, after completing a close-out visit ending the double-blind, placebo-controlled phase. 

Eplerenone is currently approved for hypertension and for use in addition to optimal medical therapy early after acute myocardial infarction in patients with congestive heart failure.

The routine use of oxygen in the treatment of myocardial infarction (MI) patients is questioned in a new analysis in the Cochrane Database of Systematic Reviews. 

The authors, led by Dr Juan Cabello (Hospital General Universitario de Alicante, Spain) and Professor Tom Quinn (University of Surrey, Guildford) say there is no conclusive evidence from randomised controlled trials to support the routine use of inhaled oxygen in patients with acute MI, and the available clinical trial data suggest that oxygen might actually be harmful. 

A definitive randomised controlled trial is urgently required given the mismatch between trial evidence suggestive of possible harm from routine oxygen use and recommendations for its use in clinical practice guidelines, they add. 

For the review, published on June 16, 2010, the authors pooled the results of three randomised trials involving 387 MI patients. Results showed that oxygen use was associated with a relative risk of death of 2.88 in an intention-to-treat analysis and 3.03 in patients with confirmed MI. While suggestive of harm, the small number of deaths (14) meant that this could be a chance occurrence, they point out. 

They note that as long ago as 1950, it was demonstrated that the administration of pure oxygen not only failed to reduce the duration of angina pain but also prolonged the electrocardiographic changes indicative of an MI, adding that: “It is surprising that a definitive study to rule out the possibility that oxygen may do more harm than good has not been done”. 

Treat individual risk factors not ‘metabolic syndrome’ 

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A new study suggests that patients with metabolic syndrome are no more at risk of future myocardial infarction (MI) than those with diabetes or hypertension alone, and that doctors should focus on treating individual risk factors.

The study, published in the May 25, 2010 issue of the Journal of the American College of Cardiology, analysed data from the INTERHEART study, a case control study of incident acute MI, to investigate whether the risk of MI associated with the metabolic syndrome is greater than that conferred by its constituent components (such as abdominal obesity, elevated glucose, abnormal lipids, and elevated blood pressure).Results showed that metabolic syndrome was associated with a two- to three-times increased risk of MI, but the same risk was conferred by having either hypertension or diabetes alone. 

The authors explain that supporters of the metabolic syndrome concept believe that when the component risk factors occur together this would have an additive or greater effect on risk. They add that their results do not support this idea, and therefore adds to the evidence that a diagnosis of metabolic syndrome is not useful.

The British Valve Group – a new special interest group

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The influence and importance of valve disease is increasing and yet the subject remains under-represented. There is, for example, no group affiliated to the British Cardiovascular Society and no National Services Framework on valve disease. A number of interested individuals have recently convened to discuss the formation of a specialist group suggesting it could issue comments on topical issues, plan collaborative research and organise study days. The group will bring together all disciplines interested in valve disease and will be concerned with wider issues like variations in care as well as those more immediately related to clinical practice.

Its first study day will be held on 25 October 2010 at the Royal Society of Medicine in London. Topics will include: the epidemiology, health economics, bioengineering, biology and genetics of valve disease; temporal and regional variations in valve surgery; advances in techniques of repair; exercise-testing, the use of neurohormones, and risk-stratification for valve surgery; the case for specialist clinics and for screening. The day will appeal to all interested in valve disease including cardiologists and surgeons, nurses and sonographers, anatomists, bioengineers and geneticists and epidemiologists. The group welcomes registrants (Becky West on [email protected]) and also expressions of interest ([email protected]).

Lp(a) screening recommended by European Atherosclerosis Society 

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Patients at moderate to high risk of cardiovascular disease should be screened for elevated Lp(a) and take niacin to lower levels to under 50 mg/dL (1.3 mmol/L), according to a consensus statement from the European Atherosclerosis Society (EAS).

A preview of the EAS statement was announced during the EAS 2010 Congress held in June in Hamburg, Germany, by Dr Børge Nordestgaard (University of Copenhagen, Denmark). He said bringing a patient’s Lp(a) level under 50 mg/dL should be a treatment priority, after the management of LDL cholesterol.

It is thought that about 20% of people have plasma Lp(a) levels over
50 mg/dL, with no gender differences, but there are some racial differences, with whites and Asians having lower levels while black and Hispanics generally have somewhat higher levels.

Since lifestyle appears to have little impact on Lp(a) level, the EAS recommends that 1 to 3 g of niacin daily is the best treatment. But it notes that further studies are needed in both primary- and secondary-prevention settings to better define which patients should be targeted for treatment and what the target level of Lp(a) should be.

England sees MI reduction after smoking ban 

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A new study has confirmed that there has been a significant drop in hospital admissions for myocardial infarction (MI) after the introduction of smoke-free legislation in England.

165-img-1The study, published online in the British Medical Journal on June 8, 2010, found that, after accounting for a pre-existing decline in admissions, trends in population size, and seasonal variation in admissions, there was a 2.4% drop in the number of emergency admissions for MI after the smoking ban legislation came into force on July 1, 2007. This equates to 1,200 fewer emergency admissions in the first year after the law came into effect (1,600 including readmissions).

The researchers, from the University of Bath, note that the largest impacts of smoking bans on MI rates have been reported in smaller studies in the US, with reductions in the range of 27% to 40%, while larger studies have reported more modest reductions. But they point out that there is some uncertainty around the extent to which some of these studies have effectively accounted for other factors that might influence patterns of admissions for MI, such as a general decline in MI rate anyway and seasonal issues.

They suggest that the reduction found in this study was smaller than other studies partly because of better control for such factors and also because exposure to secondhand smoke before the ban was lower in England. Visit Website for experts’ take on smoking and its health effects.  In some other countries, with 55% of employed adults in England already working in a smoke-free environment and many bars and restaurants having already gone smoke-free.

Is the EWTD failing the welfare of junior doctors?

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To find out how the European Working Time Directive set up to help improve the welfare of junior doctors seems to be failing in one of its primary objectives, why women may benefit more from cardiac resynchronisation therapy defibrillators than men, and why telehealth heart failure patients experience a significant improvement in their care and quality of life, visit our sister website:

www.arwatch.co.uk

A glossary of terms used in interventional cardiology: part 2

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We continue our series in which Consultant Interventionist Dr Michael Norell takes a sideways look at life in the cath lab…and beyond. In this column, he updates the definitions of terms used in interventional cardiology.

Some years ago I put together some definitions of words, phrases and acronyms, commonly encountered in the practice of angioplasty (percutaneous coronary intervention [PCI]), which I thought might be of assistance to the aspiring balloonist. It was cleverly (sic) headlined “Ten Atmospheres and All That” as a homage to the iconic non-textbook of English history that some of us may recall, and appeared in Cardiology News in its August 2006 issue; reprints are available.

The technology around PCI has expanded enormously in the last four years, so an update is now timely. On this occasion, and in the spirit of fairness, I felt that the British Journal of Cardiology should have its own turn to shoulder the, probably unwanted, literary burden of such an article, which, given the rated burst pressure of modern balloons, might perhaps be better titled “Twenty Atmospheres and All That”.

Retrograde (approach to) CTO: A novel, if tiresome, method of reopening Chronic Total Occlusions when the more commonly used anterograde approach, atenolol and feigning deafness to symptoms, have all failed. Very rarely one has to ‘encourage’ patients that intervention is unnecessary and that their chest pain can be safely ignored. This can be achieved using a heavy blunt implement in order to convince them; a so-called ‘CTO Club’. Treatment of bifurcation lesions (see below) can be avoided using a similar technique.

OCT: Optical Coherence Tomography – an intravascular imaging modality using light rather than ultrasound and thereby producing superior spatial resolution. This results in an aesthetically more pleasing and sepia-tinted image, akin to a sandstorm rather than a snowstorm.

MDT: Multi-Disciplinary Team – an increasingly important forum in which the management plan of an individual patient is devised by agreement among all relevant specialities (e.g. surgery, intervention, social work, etc.). The final decision is reached transparently and by consensus. Depending on a unit’s criteria dictating which cases are to be presented, the number of patients involved can be huge (note alternative: Minimum Discussion Time).

SYNTAX: Recently presented pivotal trial examining the ‘real world’ use of correct grammar when advising a patient as to the best mode of coronary revascularisation.

2b/3a (inhibitor): A potent platelet paralyser of inestimable value in the treatment of complex anatomy and in the setting of unstable clinical presentations. However, the resultant increased bleeding risk invariably prompts the serious operator to consider the pros and cons of its use and share their concerns with the catheter lab staff: “2b or not 2b; that is the question”.

Stent strut: Celebratory dance performed when a particularly inaccessible or difficult lesion has eventually been treated. Such a reaction, often reminiscent of the gyrations produced by the Rolling Stones’ Mick Jagger, is characteristically the proclivity of operators who had not appreciated the complexity of the case in the first place. This deficiency is termed strut thickness.

Polymer: A compound that is combined with an anti-proliferative agent and used in the manufacture of some drug-eluting stents. The stent is coated with the resulting mixture, the composition of which dictates the active drug’s release kinetics. The science of this technology can be mindboggling and it is, therefore, important that the concepts involved are presented to clinicians at meetings or conferences, in a simple and easily understood manner. This is called an absorbable polymer.

Abluminal: This is the point at which your Latin ‘O’ level is now seen to be valuable. Had the Romans used drug-eluting devices, they too would have realised the logic of applying anti-proliferative agent only to the surface of the stent in contact with the vessel wall (i.e. away from the lumen). However, they would also have more correctly described this drug elution as being directed towards the vessel wall, in other words, ‘admural’.

Bifurcation: Given that most coronary lesions are either before, after or at a branch point, this anatomy can be notoriously common. The recently published BBC-ONE study confirmed what most of us already knew: when considering the treatment of such cases, rather than embarking on a complex ‘two-stent’ strategy, you are much better off watching television.

‘Take-off’ angle: The angle at which a side branch leaves the parent vessel can impact on the outcome when treating bifurcation disease. If particularly acute, or severely obtuse, the appearances can strike such anxiety in an operator that he is obliged to leave the catheter lab and take off.

FAME: Another pivotal trial, this time assessing the value of pressure-wire guided PCI when compared with giving free rein to our occulo-stenotic reflex. It exposed the shortcomings of previous – and widely used – technology (the ‘Mark One Eyeball’), and confirmed that what we see on the angiogram is not necessarily the truth. Perhaps any form of revascularisation – surgical or percutaneous – should be preceded by such functional testing in order to limit unnecessary stenting or pointless bypass grafting.

Soprano: A new ‘family’ of guide wires derived from the internal workings of a piano. They are particularly valuable when the operator’s assistant is severely underperforming, in which case they can be ‘suspended’ using this technology. Other varieties of this type of wire, used punitively in similar circumstances, include the Castrati and the Falsetto.

Delivery system: Once stock is ordered from the manufacturer it is important for an interventional unit to ensure a robust method by which new catheters, wires, stents and balloons actually arrive on the catheter lab shelves and so be available for use.

Platform: Occasionally, ordered stock (see above) may be sent by rail in which case the exact knowledge of the place of arrival is vital.

Wall coverage: Technique for ensuring that at least one abstract will be presented at a forthcoming scientific meeting or conference by submitting a vast number on similar topics to the programme committee.

MACE: Major Adverse Cardiac Events – a composite end point including death, non-fatal infarction, target lesion failure, etc., used universally in interventional trials.

ACME: Accumulation of a Concocted Myriad of Events – an alternative and infrequently used composite incorporating a host of clinically less important events in a desperate attempt to drive the end point in the direction of significance, e.g. procedural palpitation, skin rash at 30 days or readmission with a sore throat.

Non-superiority: Strategy or device A is no better than strategy or device B.

Non-inferiority: Strategy or device A is no worse than strategy or device B.

Equivalence: Both strategies or devices are equally good (or bad).

Equipoise: 1. A position in which data supporting one of two approaches is exactly counterbalanced by evidence for the other.
2. A cross between a horse and a dolphin.

Meeting the psychological needs of cardiac patients: an integrated stepped-care approach within a cardiac rehabilitation setting

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Depression and anxiety are commonly experienced by cardiac patients and are associated with reduced quality of life and mortality, but the evidence for the effectiveness of medical and psychological treatments for depression has been mixed.

Continue reading Meeting the psychological needs of cardiac patients: an integrated stepped-care approach within a cardiac rehabilitation setting