NHS EVIDENCE

Antiplatelet dosage for PCI
Overview: Percutaneous coronary intervention (PCI) is an important advance in the treatment of patients with acute coronary syndromes, with or without ST segment elevation. Despite the capacity of PCI to reduce major cardiovascular events, the risk of thrombotic complications remains an important concern. Hence, attention is being focused on the development of fast-acting anti-platelet regimens that achieve high levels of platelet inhibition.

Current advice: Aspirin, in combination with clopidogrel – a thienopyridine adenosine diphosphate receptor antagonist – prevents major thrombotic events in patients undergoing PCI and has been the standard of care for more than a decade.NICE guidance on the early management of unstable angina and non ST segment elevation myocardial infarction recommends offering a single loading dose of 300 mg aspirin and continuing aspirin indefinitely.For patients with no contraindications, who may undergo PCI within 24 hours of admission to hospital, NICE recommends offering a 300 mg loading dose of clopidogrel. The guidance states that there is emerging evidence about the use of a 600 mg loading dose of clopidogrel for patients undergoing PCI within 24 hours of admission. However, NICE was not able to formally review all the evidence and was therefore unable to recommend this at the time of guidance publication (March 2010).
New evidence: The CURRENT-OASIS 7 trial (The Lancet Volume 376, Issue 9748) assessed whether doubling of the loading and maintenance dose of clopidogrel for 7 days was better than the standard dose and if high dose aspirin was better than low dose aspirin in patients undergoing PCI.A 7 day double dose clopidogrel regimen (600 mg on day 1, 150 mg on days 2 to 7, then 75 mg daily) was associated with a reduction in cardiovascular events and stent thrombosis compared to the standard dose (300 mg on day 1 then 75 mg daily). The analysis suggests a clear benefit in the 17,236 patients who underwent a PCI procedure.
Using the CURRENT/OASIS 7 trial definition, major bleeding was more common with double than standard dose clopidogrel. Before PCI, rates of ischaemic events or major bleeding did not differ between the groups.The researchers conclude that a double-dose clopidogrel regimen (600 mg loading dose) can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI.Efficacy and safety did not differ between high dose (300 to 325 mg daily) and low dose (75 to 100mg daily) aspirin. However, since the dose comparison was for only 30 days, use of low-dose aspirin is still thought to be reasonable for long-term therapy.

Commentary:"CURRENT-OASIS 7 is the latest in a long list of trials that tests the impact of dual anti-platelet therapy on efficacy, and since most trials look at the effect of increased therapy to prevent stent thrombosis (or its surrogate acute myocardial infarction/death), also importantly bleeding. A number of studies and retrospective analyses of large trials have shown the benefit of 600 mg over 300 mg.
"I see two problems with this study. First, two things were changed at once (so we don't really know which change, aspirin or clopidogrel, was beneficial in this study) and secondly, increasing the loading dose of clopidogrel to 150 mg with maintenance of 150 mg, if this is thought to be of value (and the trial suggests it might be), was associated with extra bleeding risk.
"So how should we use this study as applied to UK practice? In patients presenting with acute coronary syndrome who are at a low risk of bleeding (i.e. normal renal function, body weight of more than 60kg and no evidence of GI tract disease), it might be reasonable to give 600 mg clopidogrel loading but then to increase the maintenance clopidogrel dose to 150 mg for one week (only) and to maintain the patient on 75 mg aspirin and 75 mg clopidogrel." - Tony Gershlick, Professor of Interventional Cardiology, University of Leicester.

For more evidence relating to cardiovascular health visit NHS Evidence - Cardiovascular.
NICE guidance on the early management of unstable angina and non ST segment elevation myocardial infarction is due to be updated in March 2013.

Eyes on Evidence helps contextualise significant new evidence, highlighting areas that could signal a change in clinical practice. It does not constitute formal NICE guidance. The commentaries included are the opinions of contributors and do not necessarily reflect the views of NICE.

SNIPPETS FROM JOURNAL WATCH

Lancet 19 Jun 2010 Vol 375
2161 Golly - here's something you don't often see in The Lancet: a trial puffing a new drug for angina which costs about £20 per year. Nor is it subsidised and ghost-written by the drug's manufacturers, who have probably long ago lost interest in it. Because the drug is our old friend allopurinol, at 600mg daily, used to improve exercise tolerance in ischaemic heart disease as opposed to preventing gout. It's a very small short-term trial, but there seems to be no reason not to give the drug a go - and quite a few reasons to believe that it may be a good thing for the strained myocardium (see editorial on p.2126).
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60391-1/abstract

JAMA 9 Jun 2010 Vol 303
2280 "Does This Patient Have a Haemorrhagic Stroke?" asks the latest in The Rational Clinical Examination Series. "How should I know, I haven't seen the scan" might be the usual answer, and it also turns out to be the correct one. Features like coma, headache, neck stiffness and high blood pressure all make haemorrhage a bit more likely, but the only way to know with sufficient certainty is by putting the patient through a CT scanner, preferably within the window for thrombolysis if the stroke turns out to be ischaemic. This is confirmed by 19 prospectively studies, meticulously analysed here.
http://jama.ama-assn.org/cgi/content/abstract/303/22/2280

NEJM 10 Jun 2010 Vol 362
2155 This study is based on the Kaiser Permanente insured population of California and it tells a pretty amazing tale - ST elevation myocardial infarction has fallen by 62% in the last decade. Interestingly the incidence of non-ST elevation MI went up between 2002 and 2004 as troponin assays became widely adopted as the diagnostic gold standard, but even taking this into account, the incidence of any MI has gone down by a third. During this time, Californians became a bit fatter, did slightly more exercise, were banned from smoking in public places, and were prescribed more statins, beta-blockers and ACE inhibitors. We are not told if they drank more of their sometimes passable wines.
http://content.nejm.org/cgi/content/abstract/362/23/2155

Lancet 12 Jun 2010 Vol 375
2073 From the point of view of someone fixated on the cardiovascular system, the body consists of a central pump supplying blood to various tufts - lung-tufts to oxygenate it, gut-tufts to feed it and kidney tufts to get rid of waste products, and so on. I can see that for some the kidney is an interesting organ, but it's essentially a dangling footnote to the business of assessing cardiovascular risk, and delicious when prepared correctly. Now assessing risk (or prognosis) is itself of little importance unless you can use it to guide interventions to reduce risk. All of which makes it very frustrating to wade through a paper like this which pools data from 14 studies (over 100 000 individuals) to derive risk tables for all-cause and cardiovascular mortality graded by eGFR and albuminuria, independently of blood pressure, cholesterol and smoking. There seems to be a definite association which, surprisingly, is slightly U-shaped when you combine the two factors. So was QOF right to make us identify and check out everyone with an eGFR under 60? That's another question entirely, which depends on how much these factors contribute to total CV risk, and what we can do about it.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60674-5/abstract

JAMA 2 Jun 2010 Vol 303
2141 Acute heart failure is regarded by most members of the public as synonymous with death, and indeed a proportion of patients admitted to hospital with HF do die within 30 days, but this stands at barely more than one in ten, and has hardly changed between 1993 and 2006, dropping from 12.8% to 10.7%. During that time, nearly 7 million Americans covered by Medicare have been to hospital with acute HF, and very little else has changed either: they get discharged a bit sooner, and readmitted slightly more often. A huge, meticulous, well-described outcomes study of this kind inevitably has one looking for Harlan Krumholz; yes, there he is.
http://jama.ama-assn.org/cgi/content/abstract/303/21/2141

2148 The heart failure figures are rather disappointing, whichever way you spin them; but one definite way to reduce HF is to save myocardium by timely reperfusion therapy for acute myocardial infarction. We know this from many interventional trials, of course, but given the immense organisational effort that has gone into providing access to immediate percutaneous intervention for MI, it is nice to have observational evidence from a large population too. Voici QuÃÆ'Ã" '©bec. In 2006-7, nearly 80% of quÃÆ'Ã" '©bÃÆ'Ã" '©cois with ST elevation MI received PCI, but in 68% of cases this occurred after more than 90 minutes. If you look at a map of Canada, you will see why: the province is more than twice the size of France and stretches up and beyond the Arctic Circle. Of those who received thrombolysis, 54% got it later than the ideal 30 minutes. The mortality figures following the two modes of treatment are remarkably similar, but outcomes such as recurrent MI and the need for bypass grafting favour PCI. By contrast, the treatment within the ideal window halves your chance of death within 30 days.
http://jama.ama-assn.org/cgi/content/abstract/303/21/2148

BMJ 5 Jun 2010 Vol 340
1231 The star of this week's BMJ is Julia Hippisley-Cox, professor of primary care in Nottingham, who has used the EMIS database of British general practices to derive an improved cardiovascular risk score (QRISK) and has also (see below) worked out from it what the true risks and benefits of statins are in UK primary care. We are lucky to have such studies to refine our practice, since they apply directly to the population we treat. As she has been working on the two versions of QRISK, Gary Collins and Doug Altman have been dogging her footsteps, and here they publish an independent and external validation of QRISK2. Use it with confidence in British general practice - you won't get a better Good Housekeeping Seal of Approval than this.
http://www.bmj.com/cgi/content/full/340/may13_2/c2442

1233 Allan Struthers has done much of the basic work on BNP and the renin-angiotensin pathway. The end product of this pathway is aldosterone, and the Dundee-led RALES trial published in 1999 showed that by blocking it with spironolactone in patients with chronic heart failure, you could improve outcomes even if they were on other RAS-inhibiting treatments. So off I went and gave some to a few of my HF patients, noting that the RALES trial encountered few problems with hyperkalaemia. I duly checked the electrolytes of one patient a couple of weeks later and sent him straight to hospital with a potassium of 6.8. This alarming event proved to be common enough in Canada, too, according to a paper which appeared in the New England Journal in 2004. But here Allan Struthers et al rebut their critics with data from Tayside, proving that your canny Scots GP can use sprironolactone with perfect safety, laddie, aye perfect safety. As the great poet of the Tay might have put it :Physicians of England and Canada kill their patients with hyperkalaemia; But by the banks of the silvery Tay our doctors behave much more seemlier. W. McGonagall op posth.
http://www.bmj.com/cgi/content/full/340/may18_2/c1768

Heart death rates article from HSJ

Heart death rates show a nation of inequalities
Published: 17 January 2008 09:00 in HSJ
Author: Sally Gainsbury
More by this Author

Research by HSJ has revealed the huge inequalities between healthcare need and NHS spending throughout England.
An HSJ analysis of the latest data on coronary heart disease premature death rates and primary care trust heart disease spending shows that some of the PCTs with the greatest health need spend the least.
The data, published by the Department of Health's Information Centre, shows that the premature death rate for coronary heart disease - defined as deaths between the ages of one and 75 - ranges from 2.1 premature deaths per 10,000 population in Kensington and Chelsea to 8.5 premature deaths in Hartlepool.
HSJ compared these death rates with DH figures on PCT spending on heart disease in 2006-07 and found that spending per heart disease death ranged from £166,151 at Wakefield PCT to just £17,241 at Calderdale PCT. This is despite the fact that Wakefield's premature death rate from heart disease is 14 per cent higher than Calderdale's.
"There is quite a range of spend per death and the relationship between the two is not as strong as you would like"
The DH has made heart disease one of its priority areas for tackling health inequalities. Together with cancer and respiratory disease it accounts for two thirds of the life expectancy gap between PCTs in the poorest areas and the rest of England. The DH has set the NHS a target of a 10 per cent reduction in those life expectancy gaps by 2011, but the latest data shows that some PCTs could struggle to do that without radical changes to their programmes and spending.
NHS Alliance chief officer Michael Sobanja said: "PCTs will have to take great notice of data such as this and turn their attention to it. They must do something.
"Many health service contracts have been based on rolling forward what was spent in previous years and that is not necessarily related to the prevalence of disease."
It was only relatively recently that PCTs were able to compare disease-prevalence data such as premature death statistics with their budgets, Mr Sobanja added.
Now they had that information they needed to act on it, even if that meant areas that had traditionally been well resourced were disadvantaged in favour of poorer areas, he said.
King's Fund chief economist John Appleby said: "You would hope that spending reflected need, but the data does not show that. There is quite a range of spend per death and the relationship between the two is not as strong as you would like."
Because the figures on premature death rates do not include deaths over the age of 75 they could make more affluent areas with higher life expectancies appear to spend more per premature death.
However, the figures show that the majority of those spending the most per premature death also spent higher than average per head of population.
Even PCTs with similar rates of premature death spend hugely different amounts. Hastings and Rother PCT has a premature death rate from heart disease of 5.5 per 10,000 population and spent £114,534 per death in 2006-07. Medway teaching PCT's death rate is slightly lower at 5.1 per 10,000, but at £39,288 its heart disease spend per premature death is a third of Hastings and Medway's.
The data on premature deaths was published by the NHS Information Centre in late December. It shows, for each PCT area as well as each local authority, the actual numbers and rates of premature death due to a selection of diseases, including heart disease. The data also gives an assessment of the severity of premature death by measuring the years of life lost up to 75 years.
Measured on that scale, Blackpool has the highest rate of years of life lost at 100 per 10,000 population. Its spend per premature death was £49,262, well below the English average of £75,072.