Clopidogrel and rationing in the NHS

Photo:Trounce/Wikimedia Commons

Last year I was at a clinical update day for GPs and one of the topics covered was the current guidance for anti-platelet treatment. Clopidogrel has now replaced aspirin in several areas. For instance, it is now the anti-platelet of choice after stroke. The king is dead, long live the king.

I’ve no problem with that – but I was a little shocked to discover that the evidence for its superiority has been known since 1996. Seventeen years? I know it takes a while but this seems a little beyond even the usual delay from research into practice. The key factor that has now changed is that clopidogrel is out of license – so it is a darn sight cheaper than it was. It was purely a cost-effectiveness decision to keep aspirin. Actually, even in terms of pure effectiveness, the difference between clopidogrel and aspirin is quite small – and the confidence intervals cross so it may not be real in any case. But clopidogrel does appear to have the edge and hence the recent change.

(Just as an aside. Do you say CLOPPY-DOG-rel or CLOH-pidogrel? I’m fairly sure the latter is ‘right’ but the first always sounds more fun and less Pharma.)

It is clear that this was a case of rationing. I don’t have a problem with that either – it’s hard to envisage a sustainable health service that doesn’t ration in some form, at some point. However, the public health approach can jar at the individual level. For instance, and this is just a little thought, if you had a bit of spare money would you have been prepared to spend it on clopidogrel rather than aspirin? An upgrade if you like. If I’d had a stroke I’d be pretty enthusiastic about doing what I can to reduce my chance of another. Should people have the option? Or perhaps it’s the price we have to pay for the NHS – we won’t always get access to the absolutely leading edge of healthcare but all of us, without exception, will receive something that is pretty darn good. It’s a deeply political argument and you can apply it to all areas of medicine. Heck, you can have the same debate about schooling.

We shouldn’t be under any illusions though, the NHS doesn’t provide perfect treatment every time. It never could. The clear downside of allowing any sort of ‘top-up care’ is that it will worsen health inequalities and encourage a two-tier system. That is, in my view, highly undesirable and I’d pick the NHS above other healthcare systems because I value the total inclusion it provides. Yet, when sat with a patient it’s awkward as we’ve withheld information from people who’ve had strokes about the best possible treatment. The real differences may not have been great but it still feels a little uncomfortable.

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Heavy alcohol use and the treatment gap

SMMGP Blog: Heavy alcohol use and the treatment gap

I wrote the blogpost (link above) after putting together the last SMMGP Clinical Update. I’m sure we’re going to see a lot more of these harm reduction medications targeting alcohol use coming through in the next few years.

You can read the Aug-Sep 2013 Clinical Update here. I’m busy writing another one – due out next week.

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The SMMGP Clinical Update – Oct/Nov 2012

This is my 20th Clinical Update – you can access them all here. Or jump to the bottom to learn about SMMGP.

The papers covered this time are:

A record-linkage study of drug-related death and suicide after hospital discharge among drug-treatment clients in Scotland, 1996-2006. Merrall ELC, Bird SM, Hutchinson SJ. Addiction 2012. Published online ahead of print. 

This study showed that there is an increased risk of death in folk who have recently been in hospital and are also registered with substance misuse services in Scotland. Even those who hadn’t stayed overnight showed an increased risk of death.

Opioid dependence during pregnancy: relationships of anxiety and depression symptoms to treatment outcomes. Benningfield MM, Dietrich MS, Jones HE, et al. Addiction 2012;107 Suppl 1:74–82

This was a secondary analysis from the excellent MOTHER study. Women who had just anxiety were more likely to drop out. Women who were just depressed were less likely to leave treatment.

Jones HE, Heil SH, Baewert A, et al. Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review. Addiction 2012;107 Suppl 1:5–27.

This was a huge review that lays out all the most recent evidence for buprenorphine treatment.

‘Subutex is safe’: Perceptions of risk in using illicit drugs during pregnancy. Leppo A. Int J Drug Policy 2012;23:365–73.

This qualitative study highlights some of the wider issues in women who use during pregnancy: far too often health care professionals get stuck in the ‘biomedical discourse’ without considering other areas.

Heroin users’ experiences of depression: a qualitative study. Cornford CS, Umeh K, Manshani N. Fam Pract 2012;29:586–92.

Another qualitative study from the remarkable Fulcrum Medical Practice in Middlesborough.

Depression and prescription opioid misuse among chronic opioid therapy recipients with no history of substance abuse. Grattan A, Sullivan MD, Saunders KW, et al. Ann Fam Med 2012;10:304–11.

Development of dependence following treatment with opioid analgesics for pain relief: a systematic review. Minozzi S, Amato L, Davoli M. Addiction 2012. Published online ahead of print. 

These two papers look at different aspects around the problems of prescription opioid misuse.

The challenges of reducing tobacco use among prisoners. Richmond RL, Butler TG, Indig D, et al. Drug Alcohol Rev 2012;31:625–30.

‘Do more, smoke less!’ Harm reduction in action for smokers with mental health/substance use problems who cannot or will not quit. Baker AL, Callister R, Kelly PJ, et al. Drug Alcohol Rev 2012;31:714–7.

These two papers draw together papers on smoking cessation in some very challenging groups who have high rates of smoking.

Widening access to treatment for alcohol misuse: description and formative evaluation of an innovative web-based service in one primary care trust. Murray E, Linke S, Harwood E, et al. Alcohol Alcohol 2012;47:697–701.

A web-based service that helps address alcohol may seem like a good wheeze but, in practice, there are many problems and barriers to overcome.

Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. MacArthur GJ, Minozzi S, Martin N, et al. BMJ 2012;345:e5945–5.

A solid BMJ systematic review that makes it clear that opiate substitution therapy remains a key intervention to prevent HIV transmission. Yet, globally, only around 6-12% of people who inject drugs will receive it.

Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS). Gallacher J, Elwood P, Pickering J, et al. J Epidemiol Community Health 2012;66:869–73

A UK based cohort that shows that there is a clear association between benzos and dementia. Some aspects of the paper seem to rule out reverse causation but there wasn’t a dose-dependent relationship – so whether benzos are causal is not yet clear.

The SMMGP Clinical Update is a summary of some of the key clinical papers on substance misuse relevant to primary care. Generally, it’s around 3000 words long and I might cover anything from seven to ten papers in that. There is a summary of the methodology and findings of the paper and I make an attempt to put it all into some sort of appropriate context. The team at SMMGP read it through, make helpful comments, and try to filter out any blatant libels. It’s available at under the ‘Resource Library’ heading.

If you’ve any interest in substance misuse in primary care then you should join SMMGP – it’s free.


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The SMMGP Clinical Update

I’m continuing to write the SMMGP Clinical Update on a bi-monthly basis. It’s a summary of some of the key clinical papers on substance misuse relevant to primary care. Generally, it’s around 3000 words long and I might cover anything from seven to ten papers in that. There is a summary of the methodology and findings of the paper and I make an attempt to put it all into some sort of appropriate context. The team at SMMGP read it through, make helpful comments, and try to filter out any blatant libels. It’s available at under the ‘Resource Library’ heading. If you’ve an interest in substance misuse in primary care then you should join SMMGP – it’s free.

I’ve been writing this every couple of months since August 2009 so I’ve now racked up quite a few of these – my next one will be my 20th Clinical Update.

The last one was the Aug-Sep 2012 version and covered the following papers:

Prevalence of common chronic respiratory diseases in drug misusers: a cohort study. Palmer F, Jaffray M, Moffat MA, et al. Primary Care Respiratory Journal. Published online: 8 August 2012.

An interesting retrospective study from Scotland looking at this sorely neglected area. And there are few surprises in the findings – even without smoking (and smoking is pretty terrible in this group) respiratory diseases are much more likely.

Persistent cannabis users show neuropsychological decline from childhood to midlife. Meier MH, Caspi A, Ambler A, et al. Proc Natl Acad Sci USA Published online: 27 August 2012.

This is a deeply impressive study based on the New Zealand Dunedin cohort. It goes a long way to settling a fair few questions around harms from cannabis – and adolescents looks particularly vulnerable.

Substance misuse of gabapentin. Smith BH, Higgins C, Baldacchino A, et al. Br J Gen Pract 2012;62:406–7.

A brief report/letter in the BJGP highlights an issue that won’t come as a surprise to many folk working in substance misuse (or particularly prisons). Gabapentin is highly abusable and this report points out some of the issues.

Retrospective accounts of injection initiation in intimate partnerships. Simmons J, Rajan S, McMahon JM. Int J Drug Policy 2012;23:303–11.

This qualitative study does what a good qualitative study should – it’ll really make you step back and consider some of your attitudes. Recommended.

Brief case finding tools for anxiety disorders: Validation of GAD-7 and GAD-2 in addictions treatment. Delgadillo J, Payne S, Gilbody S, et al. Drug Alcohol Depend 2012;125:37–42.

This UK study studied whether or now GAD-7 is actually of any value in an addiction setting.

Involvement of general practitioners in managing alcohol problems: a randomized controlled trial of a tailored improvement programme. van Beurden I, Anderson P, Akkermans RP, et al. Addiction 2012;107:1601–11.

This Dutch study had a bit of a torrid time as they struggled with poor recruitment and not very impressive participation. Some good lessons on how we might go about improving the management of alcohol problems in general practice.

Buprenorphine/naloxone and dental caries: a case report. Suzuki J, Park EM. Am J Addict 2012;21:494–5.

This was just a short case that reported on a woman who developed marked dental caries while on buprenorphine/naloxone. It’s a good opportunity to reflect on the dire state of oral health in many of those with substance misuse issues.


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Risk calculators in clinical practice

I haven’t had my blood pressure checked for a couple of years. I think the last time was for a life insurance medical so I wasn’t given much option. As with all investigations, it’s always worth having in mind what you plan to do with the result, and I’m pretty sure I wouldn’t be in any hurry to take blood pressure medication. We use QRISK in general practice (it is embedded in some of the GP computer systems) and I’ve been playing around with QRISK online. Here’s my QRISK score based on my current risk factors:


So, over the next 10 years that’s a risk of 0.8% (1 in 125) of a heart attack or stroke. Most of my risk is related to my age and my gender. Can’t do much about them.

Risk calculators can be a bit weird. You’ve got to be careful how you use them. Let’s assume that in fact I’ve got a slightly elevated BP – perhaps a systolic of 160mmHg, which according to NICE guidelines should be treated at that level. According to QRISK-2 (2011), my risk of a heart attack or stroke over the next 10 years is now 1.3%. That is, in my opinion, remains a fairly low risk (and just a 0.5% increase in absolute terms from having a normal blood pressure).

But, say I have a change of heart, my family insist, and I start on medication. I may then revisit the QRISK calculator a couple of months later. I pop in the same details but also check the box ‘on blood pressure treatment’. Even with a systolic BP of 120mmHg my risk is now 2% over 10 years.

It has gone up! That’s not very encouraging and is a good reminder of the limitations of these tools.

The QRISK information page does suggest the calculator can be used this way:

 Where patients are on antihypertensive treatment, should a pre-treatment blood pressure be used when calculating their risk?

No. QRISK®2 has been designed such that if a patient is taking antihypertensive medication then their current blood pressure on treatment can be used rather than a pre-treatment value.

I don’t have details of the algorithm used in QRISK. Presumably what is happening here is that either there is more harm than benefit from anti-hypertensives, or more likely, the sub-group ‘on blood pressure treatment’ has a lot of confounders which haven’t all been teased out. That means that being on blood pressure treatment is simply a marker of other medical issues that worsen risk when looked at on a population basis.

Risk calculators like this don’t offer some magical glimpse of the future for individuals – they are just playing with statistics and, as QRISK are at pains to point out, are best used with careful real world interpretation.

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Alcohol and breast cancer – some absolute numbers

This was a meta-analysis of data on light alcohol drinking and breast cancer. The authors reported that they looked at 113 papers which reported breast cancer risk estimates for light drinkers. Only 36% of the reported estimates were adjusted for the main risk factors (age, family history, parity, menopausal status, oral contraceptive/hormonal replacement therapy use). The findings reported in the abstract were:

 A significant increase of the order of 4% in the risk of breast cancer is already present at intakes of up to one alcoholic drink/day.

This fits with the random-effect summary relative risk (RR) of 1.04 (95% CI, 1.02 to 1.07) for the overall analysis. However, when pooling for the 36% of studies that had adjusted for the main risk factors the RR was 1.03 (95% CI, 1.00 to 1.07). Hmm, a 95% confidence interval that includes 1.0 – I’m starting to feel a little anxious about the numbers here.

These epidemiological studies can only show an association. However, alcohol as a causative agent in breast cancer doesn’t seem that unlikely. There is secure evidence that higher consumption of alcohol is associated with an increased risk of breast cancer. There is a plausible mechanism with alcohol affecting oestrogen levels and given that breasts are a highly oestrogen-sensitive tissue. The studies also seem to suggest a dose-response relationship – a further piece of evidence suggesting alcohol is causative.

So, seeing a small effect (and it is small) with light drinking is hardly surprising. On population terms the epidemiologists may be impressed but your average person may wonder at their real risk. It is notable that at no point in this paper, or the press release, or the Daily Telegraph article does anyone attempt to put it in absolute risk terms.

Telling people who drink heavily that they need to cut down isn’t controversial but how much can a woman who cuts down on her light drinking expect to benefit? Well, firstly, there is no guarantee that stopping or reducing drinking will reduce risk anyway- no one has ever done that study and they’re not likely too either. But we can do a very rough and ready calculation with the absolute numbers.

How about if we do something as simple as reduce the current age-related risks by 4%?

In women under 49 the absolute risk is estimated as 1 in 50 (2%). A reduction of 4% would put the risk at 1.92%.

That’s an absolute risk reduction of 0.08%.

In women under 39 the absolute risk is estimated as 1 in 215 (0.465%). A reduction of 4% would put the risk at 0.447%.

That’s an absolute risk reduction of 0.018%.

(Age-related risk data from Cancer Research UK.)

Of course, these numbers wouldn’t make quite such impressive headlines. But it’s a pity that the authors, the journal, or the newspaper haven’t made any referral to absolute risk at all.


ResearchBlogging.orgSeitz, H., Pelucchi, C., Bagnardi, V., & Vecchia, C. (2012). Epidemiology and Pathophysiology of Alcohol and Breast Cancer: Update 2012 Alcohol and Alcoholism DOI: 10.1093/alcalc/ags011

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