The scenarios included a range of conditions from chronic back pain and being drunk, to going into labour and a suspected stroke.

 Two thirds (68) of participants had undertaken some first aid training; 37 had medical training; and 45 had neither. Most were aged between 18 and 44.

Most participants correctly identified when an ambulance was not needed in only two out of the seven scenarios, and between 5% and 48% would have dialled 999.

The authors asserts that much “abuse of ambulance services” results from a lack of first aid awareness, and that those with some basic training were less likely to call inappropriately in all scenarios. They did not find any participant characteristics were predictive of calling an ambulance inappropriately once confounders were taken into account.

The scenarios in which an ambulance was not required were: a woman going into labour; a man with chronic back pain who has run out of painkillers; a drunk man being sick; a three year old with piece of Lego stuck in their nose; a single episode of blood in the urine; a toddler with a bruise on their head; and a knife cut on the palm of a hand that is not bleeding heavily.

“All of these scenarios may require medical advice or help, ranging from first aid at home to an urgent emergency department visit, but none requires ambulance attendance,” say the authors, adding: “It is highly likely that there is confusion between the need for medical treatment and the need for an ambulance”.

The study also found that one in four people don’t realise that an ambulance is required for a suspected stroke, prompting the authors to comment that the finding is “concerning”. They question the efficacy of the government’s recent stroke awareness campaign (FAST), which was launched in 1999.

Almost all participants correctly identified when an ambulance was needed in three out of five scenarios. These were: a middle aged man with sudden severe pains in his chest and arm (heart attack); a paracetamol overdose; an older person slurring their words after not having drunk any alcohol; a road traffic accident victim; a four year old with a high temperature and a stiff neck.

Reference

1. Kirkby HM, Roberts LM. Inappropriate 999 calls: an online pilot survey. Emerg Med J 2011;doi:10.1136/emj.2010.092346
Available online: http://press.psprings.co.uk/emj/february/emj92346.pdf

The CBT programme, which was delivered in 20 two-hour sessions, was focused on reducing experience of daily stress, time urgency and hostility. The programme included five specific goals of education, self-monitoring, skills training, cognitive restructuring, and spiritual development. Results after a mean follow-up of 94 months showed that the group undergoing CBT had a lower rate of fatal and non-fatal first recurrent CVD events (HR 0.59, CI 0.42-0.83, P=0.002); fewer recurrent acute myocardial infractions (HR 0.55, CI 0.36-0.85, P=.007) and a non significant lowering of all-cause mortality (HR0.72, CI 0.40-1.30, P=.28).

These results have led the European Society of Cardiology (ESC) to recommend that stress management programmes should be made more widely available across Europe for patients with coronary artery disease.[2] However, the ESC also asserts that further studies will be needed to define the patient populations who will most benefit from behavioural interventions.

Commenting on the publication, ESC Spokesman Joep Perk from Linneaus University (Kalmar, Sweden) says, “This study adds weight to the case that stress management programmes are important, but leaves open questions about whether we can afford the approach, who are the best target populations and why the study didn’t affect mortality.”

The research, he adds, contains one major bias. “There is a risk that study patients may have been more adherent to drug therapy since they have more frequent contact with health care professionals than patients in the control group”. Additional guidelines on stress management will be included in the upcoming European Guidelines on CVD Prevention in clinical practice, due to be launched in Dublin in 2012 at the 5th Joint European Societies Taskforce on CVD Prevention.

ESC spokesperson Eva Prescott, from Bispebjerg University Hospital of Copenhagen (Denmark), welcomes the research as being one of the first studies looking at psychosocial interventions to demonstrate hard end points. “The study further confirms that we should probably be more active in addressing the psychosocial aspects of patients with cardiovascular disease. The strengths of the study are the long duration of follow-up and the fact that it enrolled consecutive patients. But it’s a single centre study and I’d like to see the results repeated in a multicentre study”.

One of the main differences in the current study, says Dr Prescott, is that unlike previous studies interventions were offered to all patients who met the selection criteria, not just those found to be distressed. “In further studies I’d like to see whether the beneficial effect depended on the patient’s baseline psychological characteristics and whether everyone would derive benefit, or only those who have difficulty coping,” says Prescott, adding that in a world of finite health care resources such research would help target the intervention to those who most need it.

“The real question is whether the data are reproducible,” said ESC spokesperson Helmut Gohlke, from Bad Krozingen Heart Centre (Germany). “The study was undertaken by an extremely dedicated team of health care professionals. The question is whether the approach would work in an average centre and whether health care professionals could keep patients motivated to return for repeat sessions”. But with investigators calculating a number needed to treat (NNT) analysis of nine patients to prevent one recurrent CVD event, Gohlke believes that the approach would prove remarkably cost effective. “My approximate calculation – with an NNT of nine – is that it would cost around €18,000 to prevent one event, making the approach at least as cost effective as most interventions”.

The actual mechanism behind the benefit delivered by CBT is open to debate. One possibility is that people who are less stressed are better able to take on board life style interventions such as giving up smoking, taking more physical activity and improving their diets. Additionally, stress is thought to exert detrimental effects on the cardiovascular system through activation of the catecholamine system. Catecholamines are known to raise heart rates. Indeed the SHIFT study presented at the ESC Congress in 2010 supported the concept that reduction of heart rate contributes significantly to the beneficial outcomes in patients with heart failure.

Reference

1. Randomized Controlled Trial of Cognitive Behavioral Therapy vs standard treatment to prevent recurrent cardiovascular events in patients with coronary heart disease, M. Gulliksson, G. Burell, B. Vessby, et al.. (Arch Intern Med, Jan 24 2011; 171: 134-140)
2. ESC Press Statement – Stress reduction may reduce recurrent cardiac events, Sophia Antipolis (28th January 2011)

The patient, an East London engineer, was found lying unconscious in the street and hypothermic last month in temperatures of 14˚F (-10C) when he was rushed to Croydon, where he suffered a cardiac arrest. Under the care of two of Dr. Raghunath and Russell Metcalfe-Smith, Clinical Lead for Resuscitation at Coydon, the patient was placed on the AutoPulse, which delivered 80 compressions per minute, allowing the team to perform other life-saving therapies.

“Without the AutoPulse, we would have needed relay teams of people continually performing chest compressions while we worked around them. With the clock approaching three and a half hours, the patient’s pulse returned and his heart flickered back to life,” said Metcalfe-Smith. “This is the stuff you read about in medical journals, but never expect to experience firsthand.”

Croydon was the first hospital in the United Kingdom to use the AutoPulse when it was installed four years ago, and the first in Europe to standardize on its use for every cardiac arrest in the facility. The hospital also experiences one of the highest cardiac arrest rates in London in the Emergency Department, according to Metcalfe-Smith, with around 350 cardiac arrest cases brought into the department each year and another 185 in-hospital arrests.

The AutoPulse Non-invasive Cardiac Support Pump (shown) is an automated, portable device with a load-distributing LifeBand® that squeezes the entire chest. It may offer a significant advantage over manual CPR, moving blood more consistently than human providers, as it provides uninterrupted chest compressions to maintain myocardial and cerebral perfusion.

Asked whether their hospital had a plan to manage the increased pressure that could result from a third cold winter only two in five said yes and a quarter said no. People were questioned about the impact that current plans for the redevelopment or reconfiguration of their service or department may have on their ability to cope with winter pressures in the future.

Three in five said their service or department was facing reconfiguration, 46% were facing contraction, 17% were merging and 17% said they were expanding. Forty-two per cent said the impact of the changes would be ‘mostly negative’ against ten per cent saying it would be ‘mostly positive’.

Dr Finbarr Martin, Consultant Geriatrician at Guys and St Thomas’ Hospital and President of the BGS, predicted towards the close of 2010 the consequences which continuing cold weather might have: “there will be significantly greater delays in discharging patients from hospitals and this could have major impacts for the quality of care older people receive”.

Martin pointed out that while “the survey response is small it must be remembered that cold weather affects older people disproportionately than the general population, for instance, 90% of winter excess deaths are of people aged over 65.[2] As we have an ageing population, we need to adapt and better integrate our services so that we are able to deliver high quality and efficient care”.

Survey results
The BGS survey got 48 replies from members; the vast majority of respondents were consultant physicians in geriatric medicine.

Q1: What was the impact of the last two cold winters (2008/9, 2009/2010)

Q2: Where were older people treated in your hospital in the last two years and where will they be treated this winter? (Percentages of respondents ticking each location. This does not signify the percentage of older people being treated in those locations):

Q3: Were there delays to discharge to the following places in the last two cold winters and do you expect delays in discharge to the following places this year if it turns out to be a third cold winter? (Where ratios do not add up to 100%, the balance is accounted for by no response).

A number of free text comments were made with relation to this question. These included:

• Inappropriate pressure to move patient to rehabilitation wards when in need of acute services.
• Nearly drowning in numbers.
• Multiple bed moves increasing risk of HAIs [hospital acquired infections] spreading.
• Safari ward rounds to multiple areas lead to prolonged length of stay esp[cially] when ward were temporary and therefore sat feed with nurses/admin unfamiliar with the social services paperwork needed to set up or even restart care.
• A lot of inappropriate boarding.
• Low medical staffing due to sickness.

Q4: Has your hospital/dept got a plan in place for dealing with the winter pressures?

• Yes (40%)
• No (25%)
• Don’t know (35%)

Q5: With the NHS being under significant pressure, one can expect a raft of policy initiatives, reconfiguration and financial pressures. Are there current or future plans to do any of the following in your service/department? (respondents ticked any box which applies, so this does not add up to 100%)?

• Reconfiguration (60%)
• Expansion (17%)
• Contraction (46%)
• Merger (17%)
• Don’t know (19%)

Q6: With reference to your answer to question 5, will these changes have a positive or negative impact on the care and treatment of older people that your service/department deliver over the winter months?

• Mostly negative 42%
• No difference 4%
• Negative and positive 31%
• Mostly positive 10%

Q7. Any other comments? Below is a selection of comments given in answer:

• Despair at times.
• Our Trust is committed to removing older people’s services from the main hospital but has no clue how to do it. A number of geriatrician‐initiated projects are going on with the aim of connecting hospital and community services but while these look promising they are at the mercy of future funding decisions.
• With continuous reduction in medical bed numbers in hospital but without any real increase in social care provision e.g. home help, district nurse, meal on wheel, care home place etc. I am certain that elderly care will suffer and the idea of care closer at home/admission avoidance is just a “dangerous” practice.
• Unbearable sustained multi‐level pressures.
• It is strange that the coming of winter every year is such an unexpected surprise.
• Social services however have already stated that they are unable to provide the usual level of funding for care home placements; limiting this to 3 a month for the region! This has already begun to impact the acute services, as more patients await care home placement in acute wards.

Contact

Tom Thorpe
email: tomthorpe@bgs.org.uk

References

1. British Geriatrics Society poll suggests a third icy winter will bring delays, (BGS Press Release, December 2010) Access online: http://www.bgs.org.uk/index.php?option=com_content&view=article&id=1131:british-geriatrics-society-poll-suggests-a-third-icy-winter-will-bring-delays&catid=6:prindex&Itemid=99
2. Aggregate of figures from ONS (England and Wales), GROS (Scotland), and NISRA (Northern Ireland), 2008, quoted in Help the Aged, Older people in the United Kingdom (May 2010)

This recommendation may be sidelined by the current availability of dabigatran, now approved in some countries as a potential substitute for warfarin in AF treatment. The committee behind the new guidelines made its decisions on this issue before the Food and Drug Administration (FDA) had approved the drug. The report’s authors therefore admit that although they reviewed the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial of dabigatran[3], “recommendations about its use are not included in this focused update because dabigatran was not approved for clinical use by the FDA at the time of organizational approval” [1] (p.163).

The update also recommends that catheter ablation “is useful in maintaining sinus rhythm in selected patients with significantly symptomatic, paroxysmal AF who have failed treatment with an antiarrhythmic drug and have normal or mildly dilated left atria, normal or mildly reduced LV function, and no severe pulmonary disease” (p.166). Catheter ablation is already widely recommended and practiced in the treatment of atrial fibrillation patients without severe lung disease who have not had success with drug therapy.

Amongst other recommendations, it is asserted that strict heart rate control has no benefit over less aggressive control in patients with atrial fibrillation. Previous guidelines advised keeping the heart rate of an atrial fibrillation patient at less than 80 beats/min at rest and less than 110 beats/min during a 6-minute walk. The updated guidelines advise keeping a resting heart rate of less than 110 beats/min in patients with persistent AF who also have stable ventricular function and have no symptoms, or symptoms deemed acceptable, related to their arrhythmia.

The updated guidelines also suggest the use of dronedarone to reduce hospitalizations for cardiovascular events in patients with paroxysmal AF or after conversion of persistent AF. However, the study also recommends that dronedarone “should not be administered to patients with class IV heart failure or patients who have had an episode of decompensated heart failure in the past 4 weeks, especially if they have depressed left ventricular function” (p.163).

References

1. 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline), Wann et al, (Heart Rhythm 2011;8:157–176)
2. Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation, The ACTIVE Investigators, (N Engl J Med 2009;360:2066­78) http://www.nejm.org/doi/pdf/10.1056/NEJMoa0901301
3. Dabigatran versus warfarin in patients with atrial fibrillation, Connolly SJ, Ezekowitz MD, Yusuf S, et al., (N Engl J Med. 2009;361:1139 –51)

• To ensure that primary healthcare professionals (predominantly GPs and practice nurses) are screening, diagnosing and treating AF to optimum levels.
• To raise awareness of AF as a risk factor for stroke amongst the public.
• To lobby national policy makers for improvement in and better implementation of guidance around AF detection/treatment.

Efforts will also include an organised advertising campaign on the dangers of AF, targeting the public, and a parliamentary reception in June to spread awareness amongst and gain support from policymakers. The Stroke Association has also carried out a survey of 1000 GPs to gauge clinical awareness levels of the link between the two conditions, and to ascertain their concerns over the current diagnosis, treatment and management of AF – the results will be published early in the new year.

The Stroke Association’s planned campaign will follow on the heels of a report it published recently with the Atrial Fibrillation Association[1] analysing widespread weaknesses in management of the AF/stroke problem. Their report highlights the general under-diagnosis and under-treatment of AF by clinicians, as well as the scant attention given to it by policymakers.

Its authors suggest that despite the dangers and great economic toll of the condition, AF rarely attracts the attention its severity and epidemiology warrants. Based on the results of a clinician survey, they claim that “clinicians do not regard AF as especially life threatening”, despite the immediate, well-recognised dangers posed by stroke itself, indicating that clinicians “may not fully appreciate the strength of the association between stroke and AF” [1] (p.15).

The report refers to a survey conducted by the AF Aware group[2] which found that 31% of UK patients with AF had never seen a cardiologist, a further 24% saw their cardiologist less than once a year, and 35% of patients only saw their GP once a year or less. The report’s authors recommend more thorough scrutiny in AF care, including specialist nurses and clinics for dedicated treatment.

It also evaluates the presence of AF within the NHS’ Quality and Outcomes Framework (QOF) for GPs, stating the need for greater encouragement of monitoring and treatment. The QOF currently rewards practices for producing a register of AF patients and for the percentages, firstly, diagnosed by ECG or a specialist and, secondly, treated with anticoagulants or anti-platelet therapy. However, the report’s authors point out that QOF indicators do not encourage active identification of AF in patients with associated risk factors, such as age or obesity, who may benefit from additional treatment to anticoagulation alone.

The Stroke Association, in collaboration with Stroke Alliance for Europe (SAFE), Atrial Fibrillation Association (AFA) and Sanofi-Aventis, have commissioned two research studies around AF in the past two years. Initially, the Sanofi-sponsored ‘AF Aware’ campaign was launched to highlight differences in information provision for AF patients in Europe. Patients were surveyed about their treatment and the amount and quality of information about AF they were offered, the results of which were then compared with the perceptions of AF healthcare professionals.[3]

As a result of the survey, SAFE and The Stroke Association obtained a larger grant from Sanofi to commission a health economics based study in 2010 about the provision of AF services across Europe, and how they compared, with a particular emphasis on Eastern Europe. The results from this study were very recently presented to the SAFE annual conference in Slovenia. They are also planning further research commissions around AF in 2011, and are currently beginning the process of identifying further gaps and areas of AF research needing further study on a Europe-wide basis.

According to Dr Peter Coleman, Deputy Director of Research, the Association is particularly interested in recent Lancet publications from Professor Peter Rothwell[4, 5, 6, 7] and colleagues in Oxford, who have shown in the OXVASC cohort that patients exhibiting significant variability in their blood pressure may be at significantly higher risk of stroke than patients who have stable hypertension, and that certain blood pressure medications actually promote and increase blood pressure variability. Coleman tells Arrhythmia Watch that the findings “are particularly applicable to people suffering from AF, as it may be that individuals suffering the combination of variable blood pressure and AF could be hugely at risk of stroke”.

The Association also recognises that the fast and reliable diagnosis of AF is a key area for future developments, and have had recent talks with a medical devices manufacturer regarding their wearable ECG monitors. The Stroke Association carries out regular testing of the public in their ‘Know Your Blood Pressure’ campaign, emphasising the importance of getting any palpitations checked by a healthcare professional, but appreciate that infrequent blood pressure monitoring and ECG is unlikely to pick up idiosyncratic AF and that a more focused intervention is required in people who suspect they have AF.

References

1. ‘Keeping Our Finger on the Pulse: Why Wales Must Address the Personal, Clinical and Economic Impact of Atrial Fibrillation’, Atrial Fibrillation Association & Stroke Association in Wales (2010) http://www.stroke.org.uk/media_centre/press_releases/wales/keeping_our_finger.html
2. Close the Gap, AF Aware survey (2009)
3. An international survey of physician and patient understanding, perception, and attitudes to atrial fibrillation and its contribution to cardiovascular disease morbidity and mortality, European Society of Cardiology (2009)
4. Blood pressure variability and risk of new-onset atrial fibrillation: a systematic review of randomized trials of antihypertensive drugs, Webb AJ, Rothwell PM., (Stroke. 2010 Sep;41(9):2091-3. Epub 2010 Jul 22)
5. Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke, Rothwell PM, Howard SC, Dolan E, O’Brien E, Dobson JE, Dahlöf B, Poulter NR, Sever PS; ASCOT-BPLA and MRC Trial Investigators, (Lancet Neurol. 2010 May;9(5):469-80. Epub 2010 Mar 11)
6. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis, Webb AJ, Fischer U, Mehta Z, Rothwell PM., (Lancet. 2010 Mar 13;375(9718):906-15)
7. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension, Rothwell PM, Howard SC, Dolan E, O’Brien E, Dobson JE, Dahlöf B, Sever PS, Poulter NR., (Lancet. 2010 Mar 13;375(9718):895-905)

The private healthcare market, currently worth more than £5.5 billion, is of growing importance due to an ageing population, improved medical outcomes and higher life expectancy. Ongoing government initiatives which allow NHS patients to seek treatment from private healthcare providers in certain circumstances make it an important issue for the organisation. The NHS currently accounts for almost one quarter of revenues paid to private healthcare providers. The OFT proposes to explore four possible areas of concern:

• The level of concentration amongst providers of private healthcare at the national, regional and local levels, and whether this limits the extent of competition in the market.
• The existence of any barriers preventing private healthcare providers from entering or expanding in the market.
• The existence of any restrictions on the ability of consultants and other medical professionals to practice.
• How consumers access and assess information, and how they exercise choice in the provision of private healthcare. The OFT makes clear that, following their consultation with interested parties, it is possible that these initial areas of interest may change. While the study will not focus directly on the market for private medical insurance, aspects of this market’s operation will be considered in so far as they affect the provision of private healthcare.

Sonya Branch, OFT Senior Director of Services and Public Markets said: “We are keen to establish whether patients and buyers of private healthcare services, including the NHS, are getting the full benefit of choice and competition. As this is a complex area, we want to engage with providers, patients and government first to ensure that we identify and focus on the correct issues prior to launching the market study in 2011”.

The OFT plans to launch the study in Spring 2011 before publishing a final report by the end of 2011, and will be contacting key parties directly. Other interested parties can submit views on the market study’s proposed scope by writing to the OFT by 1 February 2011. Comments can be submitted by email to privatehealthcare@oft.gsi.gov.uk or sent to:
Private Healthcare Market Study

Office of Fair Trading

Fleetbank House,
2-6 Salisbury Square
London EC4Y 8JX

Contact

Laura Osborne
phone: 020 7211 8899
email: enquiries@oft.gov.uk

References

1. A document outlining the proposed scope of the market study can be found on the Private Healthcare Market Study page: link: http://www.oft.gov.uk/OFTwork/markets-work/current/private-healthcare/

Interest in the device was boosted by a recent study in the New England Journal of Medicine (1) from Dr Gust Bardy and others. Using this system they evaluated four subcutaneous ICD configurations in 78 candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. They also evaluated long-term use of S-ICDs in a pilot of six patients, which was followed by a European trial involving 55 patients.

The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator, similar to that illustrated. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation (VF), but requiring a significantly higher mean energy requirement, 36.6 versus 11.1 Joules.

Among those who received a permanent S-ICD, VF was successfully detected in all 137 induced episodes. Induced VF was terminated twice in 58 of 59 patients with the delivery of 65 Joules in two consecutive tests.

In the European single-group trial of 55 patients (53 of whom were evaluated) the mean time to delivery of a shock was 14 secs. The mean duration of the procedure, including device insertion and testing, was 67 mins, a time which was reduced to 55 mins by practitioners who had done at least three implantations. After ten months follow-up 54 of 55 patients were alive, one having died from renal failure. A pocket infection developed in two patients but no cases of pocket erosion occurred. There were no lead fractures and no generator migration occurred.

The new device is reported to cost around £12,000 and does not need replacement for five years.

Speaking at a meeting in London recently, Dr Andrew Grace, Consultant Cardiologist, Papworth Hospital, Cambridge, UK, described leads as “the Achilles heel of defibrillator therapy”. He described also how about 36% of shocks from conventional ICDs are inappropriate. “This is absurd” said Dr Grace, who helped develop the new device and who is also a senior author on the NEJM paper.

He summarised the benefits of the new device saying that it delivered significantly fewer false shocks, it was faster to implant and safe to remove. It also eliminated the need for fluoroscopic guidance for lead placement and it “leaves the venous system alone”.

The device is approved in the UK and approximately 50 have been implanted.

Reference

1. Bardy GH, Smith WM, Hood MA et al. An entirely subcutaneous implantable-defibrillator. New Engl J Med 2010. ((10.1056/NEJMoa0909545) published 12 May 2010.

We will feature news about subcutaneous lead ICDs again in the near future.  We will also soon feature news about newer ICD systems which are also less prone to inappropriate shock delivery

Anticoagulants can reduce the risk of stroke by up to 80% here,“ says  Prof. Einhäupl. New substances such as dabigatran and rivaroxaban which can be taken orally, and overcome the need for INR monitoring, should make life easier for doctors and patients once they are approved, in his view.

Fewer side effects  – equal effectiveness

The effects of dabigatran were tested in the  RE-LY study on 18,000 participants, and its findings were discussed at the neurology congress in Berlin. “In general, the substance proved to be well tolerated. With the same efficacy, dabigatran had fewer side effects, and with higher efficacy approximately the same side effects as standard drugs,“ says Prof. Einhäupl. However it is too early for euphoria. „”We still don’t know enough about the long term effects of the drugs. Dabigatran has yet to be approved and is expected to be on the market by year’s end. The effects of  rivaroxaban are now being tested on patients with atrial fibrillation. There is of course always some level of risk „that a patient becomes a ‘bleeder’ as a result of the drugs,“  says Prof. Einhäupl. „Each individual case must be carefully weighed up. But as soon as an additional risk factor arises, when atrial fibrillation is already present, these measures should be employed.“ Among patients at risk are those over 60, diabetics and heavy smokers.

Stroke prevention through rhythm control in AF

A new antiarrhythmic drug (dronedarone) could be of great importance in future in treating atrial fibrillation. A major international study (ATHENA) demonstrated that stroke risk was reduced relatively by 34%. Because stroke was not the primary objective of the study, further investigations are now necessary to confirm this surprising result. „And the mechanisms by which this effect is achieved are still unclear,“ says Prof. Einhäupl. The lower rate of side effects observed, compared to the precursor chemical amiodarone, is also a benefit.

Secondary prevention in stroke patients

Further study results on the theme of operative secondary prevention of stroke were also presented. The German Stroke Society compared carotid endarterectomy with the insertion of stents in the carotid artery. Our suspicions were confirmed. Stent implantation offers no advantage over a well conducted carotid operation, but probably carries disadvantages,“ says Prof. Einhäupl. “The mortality risk or the risk of a further stroke are  marginally higher for patients with stents. “I would then, other than in a  few exceptions, always give preference to a well conducted carotid operation“, he said.

Longer therapeutic window for thrombolysis

Studies on thrombolysis presented at the neurology congress also demonstrate improved prospects for stroke victims. Medical guidelines until now have stipulated that thrombolysis should be carried out only within three hours of a stroke. “For this reason, and others, this treatment has been available to only a few patients,“ says Prof. Einhäupl. A large scale European study has now demonstrated that thrombolysis can be used safely and effectively up to four and a half hours later.

Experience at the Berlin Charité has shown that comprehensive rapidly conducted MRI examinations on acute stroke patients can offer new treatment options. In the course of clinical observation of 11 stroke patients with ischaemia, after MRI examination thrombolysis was safely conducted. This was done although it was unclear when the patient had suffered the stroke. “The results show that those patients in whom the course of the stroke is unclear can also receive  thrombolysis. The precondition is that the decision be made on the basis of precise MRT results,“ says Prof. Einhäupl. Further examinations show that thrombolysis can also be carried out on patients with acute stroke but mild symptoms.

Allopurinol is a drug used primarily to treat individuals with excess uric acid. Hyperuricemia can lead to gout and, in extreme cases, kidney failure. Elevated uric acid may also increase risk of developing hypertension and heart disease. Patients with CKD–who most often die from heart disease.

To investigate, Marian Goicoechea, PhD, Jose Luño, MD, Hospital General Universitario Gregorio Marañón, in Madrid, Spain) and their colleagues conducted a prospective, randomized trial of 113 CKD patients who received either allopurinol (100 mg/day) or who continued taking their usual therapy. The researchers assessed kidney disease progression, cardiovascular events and hospitalizations among patients in the study over two years.

The blood levels of uric acid and C-reactive protein significantly decreased in patients treated with allopurinol. In the control group, kidney function declined after two years, but in the allopurinol-treated group, kidney function improved. Allopurinol treatment slowed down kidney disease progression regardless of patients’ age, gender, and diabetes status; their blood levels of uric acid and C-reactive protein; the amount of  protein patients lost in the urine; and the other types of medications patients used. In addition, compared with usual therapy, allopurinol treatment reduced the risk of cardiovascular events by 71% and the risk of hospitalizations by 62%.

While allopurinol has significant potential benefits for CKD patients, “these results have to be confirmed in larger prospective trials and are the basis for a hypothesis that still needs to be tested,” the authors wrote.

Study co-authors include Soledad García de Vinuesa, Ursula Verdalles, Caridad Ruiz-Caro, Jara Ampuero, Abraham Rincón, and David Arroyo of Hospital General Universitario Gregorio Marañón.

Allopurinol in angina pectoris

Another study (2) in the Lancet shows that the drug prolongs exercise capacity in chronic stable angina, and could thus be a cheap alternative to conventional treatments. The study, from Professor Allan D Struthers, University of Dundee, UK, and colleagues.

Experimental evidence on allopurinol suggests that it inhibits the enzyme xanthine oxidase, which in turn reduces the energy used by the heart in each beat or ‘stroke’. If such an effect also occurs in man, this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris, since it would allow more oxygen and energy to reach heart tissue suffering inadequate blood supply in angina patients. In this study, the authors assessed whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina.

65 patients (aged 18–85 years) with clinically diagnosed coronary artery disease, a positive exercise tolerance test*, and stable chronic angina pectoris (for at least 2 months) were recruited into a double-blind, randomised, placebo-controlled, crossover study in a hospital and two infirmaries in the UK. Patients were assigned to allopurinol (600 mg per day) or placebo for 6 weeks and then crossed over to take placebo or allopurinol, so that each patient received both treatments in a randomised fashion. The primary endpoint was the time to ST depression, and the secondary endpoints were total exercise time and time to chest pain.

In the first treatment period, 31 patients were allocated to allopurinol and 28 were analysed, and 34 were allocated to placebo and 32 were analysed. In the second period, all 60 patients were analysed. Allopurinol increased the median time to ST depression to 298 s from a baseline of 232 s, and placebo increased it to 249 s. The absolute difference between allopurinol and placebo was 43 s. Allopurinol increased median total exercise time** to 393 s from a baseline of 301 s, and placebo increased it to 307 s, giving an absolute difference between groups of 58 s. Allopurinol also increased the time to chest pain from a baseline of 234 s to 304 s, and placebo increased it to 272 s, an absolute difference between groups of 38 s. No adverse effects of treatment were reported.

The authors say: “Allopurinol is inexpensive compared with some other antianginal drugs such as ranolazine and ivabradine, and has a favourable long-term (>40 years) safety record for the treatment of gout. Compared with older antianginal drugs (nitrates, β blockers), allopurinol is better tolerated because it does not reduce blood pressure or heart rate, and does not cause many side-effects, such as headaches and tiredness, that occur frequently with nitrates and β blockers.”

They conclude: “High-dose allopurinol significantly prolonged the time to ST depression, the total exercise time, and the time to angina in patients with chronic stable angina during a standard exercise test, suggesting that endogenous xanthine oxidase activity contributes somehow to exercise-induced myocardial ischaemia. These results also show that high-dose allopurinol prolongs exercise in stable angina pectoris…on the basis of our results, allopurinol is a useful anti-ischaemic treatment option in patients with angina that has the advantage of being inexpensive, well tolerated and safe in the long term. The precise place of allopurinol in the management of angina pectoris now needs to be explored further, but this drug might be especially appealing for use in developing countries where coronary artery disease is rapidly increasing in frequency and where access to expensive drugs or invasive treatments (angioplasty and bypass surgery) is often restricted.”

In an accompanying Comment, Dr Henry J Dargie, Scottish Advanced Heart Failure Service, Golden Jubilee National Hospital, Clydebank, West Dunbartonshire, UK and Western Infirmary, Glasgow, UK and Dr Renjith Antony Scottish Advanced Heart Failure Service, Golden Jubilee National Hospital, Clydebank, West Dunbartonshire, say: “Although further work is needed to confirm allopurinol’s putative anti-ischaemic effects and to better understand its mechanism of action, allopurinol joins a growing list of compounds that tests the conventional wisdom on what constitutes antianginal therapy. Although prevention of coronary artery disease remains important, protecting the heart muscle from ischaemia is a logical and pragmatic approach to a disabling condition for which several mechanisms might be responsible.”

References

1. The article, entitled “Effect of Allopurinol in Chronic Kidney Disease Progression and Cardiovascular Risk,” will appear online at http://cjasn.asnjournals.org/ on June 10, 2010, doi10.2215/CJN.01580210.
2. Norman A, Ang DSC, Lang CC, Struthers AD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina:a randomized, placebo controlled crossover trial. Lancet 2010 published online 8 June 2010. DOI:10.1016/so140-6736(10)60391-1.

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