ManY tHanKs - as tHrIVe MoVes Into Its FInaL pHase

FINAL ISSUE Spring 2012

HPS2-THRIVE is a remarkable study aiming to improve heart health – and it is now coming to a close.

THRIVE has followed the health of more than 25,000 people in six countries to study the effects of raising good cholesterol on the prevention of heart attacks and strokes. Thank you for being a part of it, and making this research possible.

We expect to report our findings in the early part of 2013 both at a medical conference and in a medical journal. Where possible we will also send you a summary of the results. But you will also be able to see the summary results on our website www.thrivestudy.org A clear result showing

that extended release niacin prevents heart attacks and strokes could change treatment practices, and save many lives.

However, such a result is by no means certain, which is why we need big studies like THRIVE to discover even modest treatment benefits. When these are applied to the large numbers of people at risk, they might have a significant impact on the numbers having a heart attack or stroke.

Thank you, once again, for your help. Without it we would not be able to make important advances in the treatment and care of people at risk of strokes and heart attacks.

THRIVE participant Tom Borthwick, doesn’t let much stand

in the way of an exciting time – and not least his age, or the

thought of tumbling out of an aeroplane. This 81 year-old

undertook a parachute jump aged just 80 (despite concerns

raised by the rest of his family!) and thoroughly enjoyed the

adrenalin-pumping experience. Since

then, Tom has abseiled down the Souter

Lighthouse, an iconic cliff top beacon

near where he lives, and is planning to

cross a major UK river on a zip-line. What

next, one wonders? Tom joined THRIVE

in June 2008. He had a stroke almost ten

years ago, having previously had a heart

attack and bypass operation. We caught

up with him on his 81st birthday at the

Peterlee Airfield, where he undertook

his jump. He used to work perched on

the top of high buildings as a lead work

plumber, so he has a head and stomach for heights. In the

1960s he also parachuted from a plane with the Royal

Dragoon Guards. We were delighted when he agreed to join

THRIVE to help others at risk of heart attack and stroke.

Thanks Tom!

THRIVE participant

Tom Borthwick

toM’s HIgH LIFe

THRIVE has followed the

health of more than 25,000

people in six countries.

THRIVE study organisers are grateful to everyone who has participated and hope people have enjoyed taking part .

Maintaining low ‘bad’ cholesterol levels and having high levels of ‘good’ cholesterol is key to keeping healthy. Fortunately, as well as taking tablets, there are a number of other things we can do to reduce our levels of bad cholesterol - and the great thing is that it involves eating plenty of tasty food that can be easy to prepare.

Saturated fats do most damage to your heart because eating them raises your ‘bad’ cholesterol levels. A good rule of thumb is to avoid those fats that are solid at room temperature (like lamb

and bacon fat), though don’t ditch the healthier spreads – especially those containing olive oil.

Do keep an eye out for healthier unsaturated and – better still –

polyunsaturated fats.

Daily helpings of fruits and vegetables also provide

a good addition to any cholesterol-lowering regime, as is that all

important regular exercise.

Fresh, tinned, frozen and dried fruits and vegetables all count towards a healthier diet. It can be handy to keep some ready-chopped in the fridge to snack upon instead of reaching for the biscuit tin.

Steaming, grilling and boiling are

generally better than frying and roasting. Creating your own dishes can be cheaper (and quicker!) than buying a ready meal.

Oily fish once or twice a week – such as sardines, salmon, trout and mackerel –is a great treat, and good heart-health food as well.

FINAL ISSUE SPRING 2012

Your FInaL appoIntMentWe will be starting to see patients for their final visits from May, so your final follow-up appointment will be due soon. It is important that you come to the visit if you are able to do so, even if you are not still taking study treatment or if your most recent follow-up has been by telephone.

A final appointment will allow THRIVE nurses and doctors to ensure your records are complete – making the results of the study more reliable.

Please note that the appointment will take a little longer than earlier ones. This is because we would like to ask you a few more questions, and staff will take some extra tubes of blood for additional tests. They will also ask you for a urine sample.

When you attend the study clinic for your final visit please bring with you any study tablets that you haven’t taken, as the staff need to collect all of them back.

portIon DIstortIonIf you do decide to treat yourself, beware of portion distortion. So many biscuits, cakes and muffins are extra-sized to make you feel like you are getting a bargain. But who needs a giant-sized cookie when one half the size will satisfy that desire? Don’t be embarrassed to leave over-sized portions, or share a cake with a friend – which cuts the cholesterol and the cost of that well-deserved treat.

KeepIng HeaLtHY

A final appointment will allow

THRIVE nurses and doctors to

ensure your records are complete

DIsappoIntIng neWs FroM aCross tHe oCeanAnother study which looked at the value of niacin to prevent heart attacks and strokes recently stopped early because the results were unlikely to provide a clear answer. The AIM-HIGH study had some similarities to THRIVE, but also some important differences. About 3400 people from the USA and Canada took part. After about 3 years there was no difference in the risk of heart attacks or strokes among those people who took active niacin compared to a dummy pill. Fortunately, it did not show any particular problems with niacin either. THRIVE is about 8 times larger than AIM-HIGH and has been designed to be able to detect moderate benefits of niacin if they exist. If AIM-HIGH had been larger it might have been able to show effects but we will have to wait for the results of THRIVE before we will know whether ER niacin/laropiprant is a useful drug for heart attack and stroke prevention.

FINAL ISSUE SPRING 2012

some tablets increase the risk of muscle problemsa note about myopathyVery rarely, statins can cause unexplained muscle pain or weakness. This is called ‘myopathy’ when it is accompanied by a significant increase in the muscle blood test called ’creatine kinase’ (or, for short, ’CK’). That is why volunteers in THRIVE are asked to report any new or unexplained muscle pain at each clinic visit, and a sample of blood is taken to measure muscle blood markers. Some other treatments can increase the risk of myopathy when taken with simvastatin or some other statins. These are listed on the right. So, if any of these medications are started by THRIVE participants, we recommend that you call the study clinic. It may be necessary to stop one or other of the study treatments. At all times you need to report via the Freefone number or to your local clinic any unusual or unexplained muscle pain or weakness as soon as possible. The large tablets may also sometimes cause rashes. Please also contact your study clinic or call the Freefone number if you develop an unexplained rash.

Drugs that can increase the risk of myopathy substantially and so should not be taken with the study simvastatin tabletsFor kidney and heart transplants:u Ciclosporin (Neoral, Sandimmum, SangCya)For heart irregularities (arrhthymias):u Amiodarone (Cordarone, Cordarone X, Amidox)u Dronaderone (Multaq)u Verapamil (Berkatens, Cordilox, Securon, Univer, Tarka, Verapress, Vertab, Zolvera)For lowering cholesterol:u “Fibrates”: Bezafibrate (Bezalip, Bezalip Mono, Bezagen XL, Zimbacol XL)

Ciprofibrate (Modalim)Fenofibrate (Lipantil, Lipantil Micro)Gemfibrozil (Lopid)

For infections:u Erythromycin (also sold as Arpimycin, Erycen, Erymax, Erymin, Erythrocin, Erythroped A,

Erythrolar, Erythromid, Ilosone, Ilotycin, Retcin, Rommix)u Clarithromycin (Klaricid, Helimet, Heliclear)For fungal infections (only if these drugs are given by mouth or injection, ointments or lotions are fine to use):u Fluconazole: (Diflucan)u Itraconazole: (Sporanox)u Ketoconazale: (Nizoral)u Miconazole: (Daktarin)

If you are prescribed any of these drugs please contact your study nurse or doctor or ring the Freefone service on 0800 585323 for further advice. Sometimes this advice will involve an extra clinic visit to measure CK levels in the blood. In other cases, for example with certain short courses of antibiotics, you may be advised to stop the study simvastatin temporarily until the other treatment has been completed.

BIg stuDIes: BeautIFuL resuLtsHPS2-THRIVE has been run by scientists at Oxford University’s Clinical Trial Service Unit (CTSU) – a world-leader in big studies to test new approaches to prevention and treatment of disease.

The Unit was where the late Professor Sir Richard Doll followed the lives of 40,000 British doctors over 50 years to reveal just how damaging smoking is to health.

Today, one of the Unit’s co-directors, Professor Rory Collins, leads UK Biobank – a pioneering study following the health of 500,000 people over the next 30 years.

CTSU has just embarked on another major international study called REVEAL, which will bring together 30,000 people in the UK, US, China, Canada, Scandinavia, Germany, Italy and Japan.

The study will see if a new drug which not only reduces bad “LDL” cholesterol, but substantially increases good “HDL” cholesterol can reduce heart attacks and strokes in vulnerable patients. You might be invited to participate in this study once you have finished THRIVE. More information is available by contacting the REVEAL team on 0800 585323 .

tHanK You FroM Jane & MartIn When we are presented with a question about whether or not a new treatment works, the only way to find out is to test it by comparing people who take it with similar people who do not. Often such trials of new treatments need to take place over several years – to be sure the treatment is safe and that clear improvements can be detected.

But ultimately, success is only possible if people are prepared to go out of their way and help. We have tried not to forget that our participants – you – are all volunteers and that it is your time and commitment that allows us to make advances.

So thank you very much for taking part in THRIVE. We will be analysing the results in the coming months and hope, very much, that we have a positive finding that will improve the lives of millions of people at risk of a devastating heart attack or stroke.

Very best wishes

Jane Armitage & Martin Landray

(THRIVE Principal Investigators, University of Oxford)

HPS2-THRIVE Coordinating CentreCTSU , Richard Doll Building, Old Road Campus, Oxford University, Roosevelt Drive, Oxford OX3 7LF

24-hour Freefone service: 0800 585323www.thrivestudy.org

Do I need to let my doctor know that the study is finishing?Yes. You will need to ask your own doctor to supply your statin treatment after the study ends. We recommend that you contact the doctor responsible for your routine care to let them know that your involvement in THRIVE is coming to an end, and that you would require your statin treatment prescribed, to begin after the final follow-up visit. We will also write to your GP to inform them. We want to ensure that your statin supply is not interrupted. BUT, please keep taking your THRIVE simvastatin or ezetimibe/simvastatin until your final visit so that your final blood samples are taken when you are still on the study.

Will the doctor know what treatment I received during the study? After the results of the study have been reported to the public, it will be possible to find out what treatment (active or dummy) you were allocated during the study. This can be done by phoning the freefone number 0800 585323.

Will I need to take any special precautions when I stop taking the study treatment?No. Your study treatment was either a tablet containing active ER-niacin/laropirant or a matching dummy tablet. There are no recognised withdrawal symptoms when people stop taking these tablets. However, if you are taking warfarin tablets you should arrange an INR blood test about one week after stopping the study treatments, in case your warfarin requirements have changed.

What about my simvastatin?After the study, your own doctor will be responsible for prescribing your statin and ezetimibe treatment. You will need to make sure you have a supply to take after your final visit. If you find this difficult and are without statin treatment for a few days or weeks this is very unlikely to be dangerous for you, but we would recommend that you restart as soon as possible.

I feel that I have benefited from the study treatment. Can I now get it from my doctor?The ER niacin/laropiprant tablets can be prescribed by doctors in the UK and Scandinavia. However, until we know the results of THRIVE we don’t know whether it will be beneficial to you and whether it is appropriate for your doctor to prescribe it. It is unlikely that they will be willing to prescribe it for you until this information is available.

How can I find out the results of the study?The results are expected to be presented for the first time at a medical conference in early 2013. They will also appear on the study website www.thrivestudy.org. We will send you and your GP a summary of the results. The final results will also be published in a medical journal.

How can I find out more information?As well as a summary of the main results, there will be background and other material available on the study website.

Visit the THRIVE website at www.thrivestudy.org

WHat Happens next?It will take several months for the THRIVE results to undergo detailed analysis. Scientists will compare results from people who took the active tablet (extended release niacin and laropiprant) with those who took a dummy version of the tablet. Even those people who stopped taking the

tablets will be included.

Scientists will want to see if there is a difference in the number of people having a heart attack or stroke between the two groups.

The results will be published in a health journal for all other scientists and doctors to see. Before it is published,

the work will be reviewed by other experts, to ensure that nothing has been overlooked or misinterpreted.

The THRIVE team will also talk about the findings at conferences around the world, where specialist doctors and scientists will be able to ask questions and find out more.

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