GENETIC DISORDER MAY HELP FIND A WAY TO REDUCE HEART DISEASE

From the News Desk of Jeanne Hambleton
Posted July 2014
Source : Clinical Center National Institute of Health

New insights into a rare genetic disorder affecting the immune system may lead to treatments for atherosclerosis, the arterial plaques or blockages that are one cause of heart disease. Dr. John I. Gallin, director of the Clinical Center, presented on the advancements at a recent Contemporary Clinical Medicine: Great Teachers Grand Rounds Lecture.Dr. David Bluemke, director of Radiology and Imag ing Sciences at the hospital, also presented on the use of new medical imaging techniques to detect atherosclerosis.

Gallin gave a brief history of the genetic immune disorder, chronic granulomatous disease, and explained the important role it may play in protecting a person from the consequences of atherosclerosis. Bluemke highlighted the advances medical imaging has provided for early diagnosis of atherosclerosis.

Chronic granulomatous disease affects roughly 1 in 200,000 people, said Gallin. The disorder prevents white blood cells known as phagocytes from producing chemicals that eliminate harmful pathogens in the body.

The disease is characterized by recurrent infections and granulomas, or small areas of inflammation, on the skin and inside the body that can lead to severe lung, skin, bone and other organ damage.

Gallin said the cause of the disease can be traced to five mutations in an enzyme complex called NAPDH oxidase. Conditions range in terms of severity depending on which type of mutation a person has.

Gallin and his colleagues have used what they learned about each mutation to develop individualized therapeutic approaches for different types of chronic granulomatous disease.

Over the years, Gallin noticed that people with the disease developed atherosclerosis at a slower rate than those without it. Soon, other researchers began publishing articles with similar conclusions.

A protocol was developed at the Clinical Center to assess the prevalence of atherosclerosis in patients with immune system disorders compared to those without. The results of the protocol confirmed Gallin’s hypothesis.

“What we’ve shown is that chronic granulomatous disease patients are protected from carotid artery thickening,” Gallin said.

Now, his team is working with the NIH’s National Center for Advancing Translational Sciences to identify potential drug targets. To continue advancements, Bluemke highlighted that researchers are using new medical imaging techniques such as CT, MRI and PET to detect atherosclerosis, as early as possible.

The research on these disorders, which is still ongoing, could have profound impacts on cardiovascular disease, which is the leading cause of death in the U.S. and costing health care more than $400 billion annually according to the American Heart Association.

Bluemke noted that doctors need noninvasive imaging methods to detect early atherosclerosis. Traditionally, doctors look at atherosclerosis risk factors, such as age, gender, blood pressure, family history and cholesterol levels to determine risk. These risk factors work well for large populations, but are less helpful for each individual patient.

At the Clinical Center, new medical imaging techniques are allowing researchers to identify early signs of atherosclerosis before a patient shows any symptoms using CT and MRI of the blood vessels in the heart and neck.

The next step is figuring out how to treat it. Clinical trials are underway at the hospital to compare image-guided approaches to lowering atherosclerosis risk factors with standard care guided by traditional risk factors.

Preliminary evidence suggests that atherosclerosis is a reversible condition, according to Bluemke. In one trial, patients were treated with statins, which are a cholesterol-lowering medication, for a year and a half. The statins decreased the amount of plaque in the arteries.

“A disease which we didn’t really envision as being reversible has a possibility of being regressed in this manner,” said Bluemke.

An additional benefit is that the image-guided approaches to treating atherosclerosis are non-invasive and the risk of radiation exposure is low.


STOP ASPIRIN TRY ANTICOAGULANTS, SAYS NICE

From the News Desk of Jeanne Hambleton
Source Pulse magazine
Posted 22 July 2014

NICE’s guidance to stop using aspirin in AF patients (atrial fibrillation) is clinically sound, but comes with little sign of the necessary additional resources, finds Caroline Price

Practices will face a major drive to review all patients with atrial fibrillation who are on aspirin and switch most of them to an oral anticoagulant, after NICE published its long-awaited updated guidance on management of the arrhythmia.

All parties are agreed on the evidence behind the main recommendation of the guideline – that anticoagulation therapy should be the only option for stroke prevention – but it has sparked concerns for practices on how they will be able to implement the recommendations systematically without additional resources being made available.

It could even leave GPs with little option other than to refer patients on to secondary care, the GPC warns.

The numbers of patients affected will differ by practice, but various studies suggest 20-40% of those with atrial fibrillation across the UK – anywhere between 200,000 and 350,000 patients – are still on aspirin, 90% of whom are eligible for anticoagulation.1-3
The guidance also adds some additional elements of complexity for GPs, advising them to adopt the CHA2DS2-VASc risk score instead of tholder CHADS2 score. They should also use the unfamiliar HAS-BLED score to weigh up and then modify patients’ risk of bleeding.

Up to date

The updated guidance has been warmly received by cardiology experts, mainly because it brings the NICE recommendations up to date and in line with European Society of Cardiology guidelines, published in 2010.

In particular, it draws on overwhelming evidence that anticoagulation is much more effective than antiplatelet treatment in terms of reducing stroke and all-cause mortality, while aspirin treatment is no longer considered beneficial because any effect on the risk of ischaemic stroke is offset by the harms of bleeding.

For practices, though, the workload issues are significant and will require extra resources. CCG leads estimate practices will have an average of 140 patients with atrial fibrillation on their list, of whom around 45 will be on aspirin and therefore need review and then several follow-up consultations to manage the transition to anticoagulation.

Dr Peter Scott, a GP in Solihull and GPC representative for the West Midlands, says: ‘It’s not going to happen unless it’s resourced and incentivised as part of a DES or LES, or through the QOF. Until then, I don’t think a systematic approach to this will happen.’

The GPC, while welcoming the guidance, in particular the clarification of the role of aspirin, has also warned the updated recommendations will be too complex for GPs to manage within normal routine care and has called on CCGs to develop enhanced services to support the process.

Dr Andrew Green, chair of the GPC clinical and prescribing subcommittee, says unless GPs are given more resources and support, they may feel they need to refer patients to secondary care.

Dr Green says: ‘I would expect GPs as part of their normal work to consider whether [atrial fibrillation] patients not on anticoagulation should be, in the light of the new guidance.

‘If they should be, then the choice is between anticoagulation with warfarin or one of the newer agents, and if GPs do not feel they have the expertise or resources to do this properly, they have a duty to refer to someone who can.’

He adds: ‘Commissioners need to predict this activity and may want to commission a service specifically for this, which is more cost-effective than a traditional outpatient referral.’

Dr Matthew Fay, a GP in Shipley, Yorkshire, and a member of the NICE AF guidelines development group, concedes practices may need extra help.

He says: ‘If GPs feel uncomfortable with [managing anticoagulation] then they should be approaching the CCG executive to say, “we need a service to provide expert support for this”. The CCG may choose to come up with an enhanced service.’

What the new AF guidance says

• GPs should use the CHA2DS2-VASc score to assess stroke risk in patients with atrial fibrillation and offer anticoagulation to men with a score above 0, and women with a score above 1.

• Offer anticoagulation therapy with warfarin, another vitamin K antagonist or one of the new oral anticoagulants – dabigatran, rivaroxaban or apixaban.

• Aspirin should no longer be offered solely for stroke prevention. Only continue aspirin if a patient is on it for another reason, such as occlusive vascular disease and is at low risk of stroke, does not want to start on anticoagulation, or is advised to continue on aspirin as well as anticoagulation by a cardiologist –for example as part of dual or triple antithrombotic therapy following coronary stenting.

• GPs should also use the HAS-BLED score to assess patients’ bleeding risk and then monitor and correct risk factors for bleeding, including high blood pressure, poor INR control and harmful alcohol consumption.

• Patients on warfarin should now have their time in therapeutic range calculated at each visit, with dosing adjusted accordingly. If poor anticoagulation control cannot be improved, discuss an alternative anticoagulant with the patient.

Source: NICE 2014. The management of atrial fibrillation. CG180. guidance.nice.org.uk/CG180

Opportunistic review

CCG leads acknowledge they may see more referrals into secondary care, but have said GPs should be able to manage the transition with the support of networks in primary care.

Dr Chris Arden, NHS West Hampshire CCG’s lead on cardiology and a GP in Southampton, says: ‘I do think GPs may refer on to other colleagues in the community or secondary care, which is going to be something we will need to try to manage.

‘It is a real concern if everyone reacts quickly on it and you could see patients pushed into secondary care – but I don’t think that’s necessarily appropriate. I think there are colleagues within the CCG and within practices who can advise.’

Dr Fay adds that GPs can look at reviewing patients opportunistically.

He says: ‘I think that’s perfectly acceptable. A lot of these patients who are at risk in this situation we will be reviewing because of their hypertension and other comorbidities, and those patients on aspirin should have that discussed at the next presentation.’

Others insist CCGs need to take a more proactive approach if the work is to be prioritised. Dr John Robson, a GP in Tower Hamlets and University College London Partners primary care lead for cardiovascular disease, recently led a programme in Tower Hamlets, east London, that saw practices raise the proportion of atrial fibrillation patients on anticoagulation by 10% over two years.

Education

The programme provided practices with software to identify patients on aspirin who would be suitable for anticoagulation, arranged educational sessions with local cardiologists and haematologists and also involved publishing individual practices’ performance to encourage bench-marking relative to peers.

Although the improvements in Tower Hamlets were made without financial incentives, the CCG has since introduced an enhanced service and Dr Robson says CCGs do need to set aside resources to identify patients proactively and educate GPs about the new recommendations, including the use of the newer oral anticoagulants.

Dr Robson says: ‘It does require some resource, because somebody has to organise the educational meetings and put the software tools onto practices’ computer systems. We need to make it easy for practices to do it.’

In the meantime, GPs without such support will need to take responsibility for reviewing and updating patients.

According to medicolegal advisors, practices should take steps to ensure patients are identified and reviewed, whether opportunistically or more proactively, or risk being in breach of their duty of care.

Dr Pallivi Bradshaw, a medicolegal advisor at the Medical Protection Society, says: ‘If it was found such steps had not been taken, and a patient slipped through the system, the practice could be criticised if the person went on to have a stroke. You might be able to establish there was a breach in the duty of care. That could also be the case if an individual doctor had been informed the guidance had changed and perhaps forgot to change it.’

Dr Bradshaw adds that GPs should document any decisions that depart from the NICE guidance, particularly as discussions with patients who have been on aspirin for a long time may be tricky.

She says: ‘Patients may not understand or even be scared if they are suddenly going from aspirin to an anticoagulant. GPs might need to get a second opinion from a specialist for the patient, or have a discussion with the consultant.’

How we moved most of our patients with atrial fibrillation onto anticoagulation:

1. Stroke risk assessment
We took a pragmatic approach and continued to use the CHADS2 tool for routine assessment, as a score of 1 or greater is equivalent to a CHA2DS2-VASc score of 2 or greater. Only in cases where the patient had a CHADS2 score of 0 did we consider using the CHA2DS2-VASc score, to determine if the patient was trulylow risk and did not require anticoagulation.

2. Bleeding risk

To assess bleeding risk, we used the SPARC tool (www.sparctool.com), or the HAS-BLED score, the use of which is now recommended in the updated NICE guidance. Bleeding risk was a great concern for GPs, and to a lesser extent patients, but even if the risk on HAS-BLED is high (a score greater than 3), if the CHA2DS2-VASc score is above 1 then the net clinical benefit is always in favour of an anticoagulant.

3. Choice of intervention
We used material produced by the Atrial Fibrillation Association extensively to assess the risks and benefits of intervention with an oral anticoagulant or no intervention, and referred patients to the association for further information and support.

4. Offering NOACs

Since NICE approved the use of non-vitamin K antagonist oral anticoagulants (NOACs) in 2011, we have widened the discussion with patients who are being initiated on anticoagulation so that, as well as offering either clinic-monitored warfarin or self-testing and self-managed warfarin. We also discuss the option of taking a NOAC.

Some patients who have struggled to achieve a stable therapeutic dose of warfarin, resulting in either very frequent visits to the practice-based clinic or poor time in therapeutic range (<65%), have been offered the option of changing to a NOAC.

Clinicians were supported in NOAC dosing by a locally developed prescribing guide, and currently 18% of our anticoagulated patients are on a NOAC.

Dr Matthew Fay is a GP in Shipley and NICE advisor on the atrial fibrillation guidelines. He is also a medical advisor to the Arrhythmia Alliance, the Atrial Fibrillation Association and Anticoagulation Europe.

References:

Holt TA et al. Risk of stroke and oral anticoagulant use in atrial fibrillation: a cross-sectional survey.
Br J Gen Pr 2012; 62: e710-17
Murphy NF et al. A national survey of the prevalence, incidence, primary care burden and treatment of atrial fibrillation in Scotland. Heart 2007; 93: 606–612
NICE personal communication, based on IMS disease Analyzer 2012/12 and GRASP-AF database. April 2014
Estimates by CCG leads
Aguilar MI et al. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 2007; 3: CD006186
Mant J et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493– 503
Petersen P et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet 1989; 1 :175-179
Sato H et al. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke 2006; 37: 447-451
Robson J et al. Improving anticoagulation in atrial fibrillation: observational study in three primary care trusts. Br J Gen Pr 2014; 64: e275-e281

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About jeanne hambleton

Journalist-wordsmith, former reporter, columnist, film critic, editor, Town Clerk and then fibromite and eventer with 5 conferences done and dusted. Interested in all health and well being issues, passionate about research to find a cure and cause for fibromyalgia. Member LinkedIn. Worked for 4 years with FMA UK as Regional Coordinator for SW and SE,and Chair for FMS SAS the Sussex and Surrey FM umbrella charity and Chair Folly Pogs Fibromyalgia Research UK - finding funding for our "cause for a cure" and President and co ordinator of National FM Conferences. Just finished last national annual Fibromyalgia Conference Weekend. This was another success with speakers from the States . Next year's conference in Chichester Park Hotel, West Sussex, will be April 24/27 2015 and bookings are coming in from those who raved about the event every year. I am very busy but happy to produce articles for publication. News Editor of FMS Global News on line but a bit behind due to conference. A workaholic beyond redemption! The future - who knows? Open to offers with payment. Versatile and looking for a regular paid column - you call the tune and I will play the pipes.
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