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CVD Webinar - Q&A Summary

Dr Sarah Davies - 13 Feb, 2020

On Wednesday the 29th January we ran the first in a series of three free evening CVD Webinars, with a view to getting into the real detail of cardiovascular disease management in primary care over the next few months. We were joined by a consultant cardiologist and it was great to discuss that interaction between primary and secondary care, particularly around secondary prevention. We know that this area is increasingly complex and truly risks the patient falling into a gap between primary and secondary care following a CV event.

We had a huge audience both live that evening and on catch up with lots of questions asked, which repeated on similar themes, some of which I will tackle in this blog.

What does CVD actually mean?

A good lesson for me was the reminder that cardiovascular disease refers to anything affecting the vascular system – so Mi/angina, CVA, peripheral arterial disease, microvascular disease and so on. Of course, atherosclerotic diseases share common risk factors and many patients will have disease in multiple vascular territories and are thus at particularly high risk.

What is the most up to date CV risk calculator?

A significant update on QRisk2 is the Qrisk3 10 year CV risk calculator. It contains a number of additional CV risk factors such as rheumatoid arthritis, CKD stage 3 (as well as 4 and 5), severe mental illness, migraine and erectile dysfunction. Although it has been around for a while it has not yet been incorporated into most GP computer systems. Watch this space…(hopefully)!

What is the role for ezetimibe?

Ezetimibe selectively blocks LDL (bad) cholesterol absorption. It has not been tested as an alternative to statins (unlike fibrates). In addition to statins, they reduce cholesterol a little more. We now have some outcome data to show improved CV outcomes for secondary prevention (patients post-ACS) where ezetimibe is added to simvastatin (IMPROVE-IT study) - Addition of ezetimibe to simvastatin reduced the relative risk of a CV event by 6% requiring treatment of 50 people to prevent 1 event. When the breakdown was analysed this was predominantly in people with diabetes such that we only need to treat 20 people with diabetes to prevent an event whereas close to 200 people to prevent 1 in those without diabetes. 

In summary - Not an alternative to statins. Consider in secondary prevention post-ACS in addition to statins for those with diabetes who do not reach targets (possibly if they have had a CV event on statins).

What are the PCSK9 inhibitors all about?

LDL receptors on the cell membrane are responsible for bringing LDL into the cells. Once in the cell, the PCSK9 molecule holds them in the cell and breaks them down. By blocking the PCSK9, the LDL receptors are free to return to the cell membrane and bring down the cholesterol further. Using biologics (synthetic antibody fragments) the PCSK9 molecule can be blocked over a long time period up to 3 months. 

In the very high risk, and those who’s cholesterol is not responsive to statins, these reduce risk of heart attacks and stroke a further 15-20%. Currently, these are expensive, however as technology develops they are becoming cheaper. They have the benefit over tablets in that 3 monthly injections have better adherence, the disadvantage is that they are injections and may need a day case treatment centre to give them. Use of these drugs will be through secondary care, but it is important to bear them in mind as an option for patients with familial hypercholesterolaemia who do not reach their target cholesterol level with high intensity statins +/- ezetimibe - if you are in an area without access to a specialist lipid clinic consider referral to your local cardiologist for consideration if you have patients in this situation. 

What is the up to date evidence on aspirin in primary prevention?

We have known for a while that aspirin is not advised in primary prevention and most recent evidence supports this. A number of trials over the last few years including ASCEND in people with diabetes and ASPREE in older people have reinforced that the risk of bleeding outweighs any benefits in primary prevention. In terms of the numbers, a large metanalysis in 2016 showed a relative risk reduction in MI of 22% but a 59% increase in GI bleeding and a 33% increase in haemorrhagic stroke 

What are the anti-platelets advised for each type of CVD?

Anti-platelet and anti-coagulation strategies in secondary prevention of CVD is an area where regimens have become increasingly complex. The risk stratification and evidence base vary between different type of CV disease, meaning that patients end up on very different regimens both in terms of content and duration. The take-home message for me is that we are moving to an age of personalised medicine where individual risk needs to be taken into account when selecting strategies. 

We have emerging evidence of advantages from adding low dose DOACs to anti-platelets, namely rivaroxaban (NICE approved Oct 2019). The evidence in stable coronary artery disease comes from the COMPASS trial which showed small but significant benefits in the highest risk patients i.e. those with multiple sites of CVD and multiple risk factors. Of course, benefits need to be closely balanced with bleeding risks.

We have also seen emerging evidence in TIA and CVA management from a systematic review published in the BMJ which was triggered by the publication of the large POINT trial. This review showed benefits of dual antiplatelet treatment for the first 10 to 21 days after a TIA or minor CVA over and above aspirin alone.

So, fascinating emerging evidence in this area. But are these more complex regimens all for secondary care to decide and commence? What about our patients with stable coronary artery or peripheral artery disease under primary care? Of course, we asked our secondary care colleague where the decisions and prescribing should lie – and interestingly he felt in future this would lie mainly with primary care once national guidelines are updated, further evidence emerges and clinical confidence increases. An interesting area for further discussion…

See my simplified table below with the most recent evidence currently available. The key is individualised choice according to patient risk vs benefit profile, a highly informed discussion is vital.

Screenshot 2020-02-12 at 14.10.29.png

Join us for the next instalment on 23rd April when we will focus mainly on Primary Prevention of CVD – a case based discussion about how best to do prevent CV disease, how to optimise treatment and improve compliance.

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Step away from the needle…and keep walking

Dr Rob Walker - 27 Feb, 2020

Rebecca is 68 and has proven OA of the knee. She otherwise has no significant past medical history and has been managing her knee pain reasonably well, but has been wary of ‘overdoing it’. She comes to see you to ask for a steroid injection as a friend of hers had one recently and said it was ‘wonderful’.

As a GP registrar (a good 10 plus years ago) it felt, rightly or wrongly, that the general consensus was to stick a needle, usually loaded with some steroid, into any musculoskeletal problem we could find. This was certainly the prevailing impression having recently come out of a six month rheumatology job which involved sessions in the injection clinic, where I focussed more on injection technique than the evidence base to support the procedure. Shoulders - ‘certainly Sir, would you like the anterior, lateral or posterior approach?’ Tennis elbow - ‘yes Madam, shall we try the perpendicular or fan technique?’ Plantar fasciitis - ‘this will hurt you more than me’…and what about knees? The satisfaction of draining a few 20ml syringes of synovial fluid out of an inflammatory effusion followed by an 80mg kenalog chaser was fairly substantial for both patient and clinician!

But times have changed and so has the evidence base, with increasing evidence that corticosteroid injections give, at best, only short term benefits for many musculoskeletal conditions, and in some cases worse longer term outcomes. But should we consider a corticosteroid injection for Rebecca for her knee OA? The evidence is equivocal but there seems to be an increasing ‘signal’ that we need to think twice before diving in with this intervention, at least as a ‘routine’ procedure. Corticosteroid injection for knee OA was the subject of a good review in the BMJ ‘uncertainties’ section in January 2020 (BMJ 2020;368:l6923). The latest Cochrane review from 2015 cited low quality evidence that corticosteroid injection may improve pain and function compared to placebo in the short term (up to 6 weeks), but there was no evidence to show improvement beyond 6 months. Subsequently a placebo controlled RCT in JAMA 2017 showed no clinical difference in those having steroid injections every 3 months over a 2 year period, compared to placebo. Worryingly this study also showed a small but statistically significant deterioration in cartilage depth on imaging in the steroid injection group - this is obviously only a surrogate marker and does not necessarily correlate to a deterioration in pain or function, but the BMJ article also cited some observational data suggesting worsening pain, stiffness and function in those having repeated steroid injections.

What about other options for knee OA? It is such a common presentation in General Practice and it feels like treatment options are increasingly being taken away from us. Paracetamol? Unlikely to help according to the latest Cochrane review in 2019 which cites high quality evidence that paracetamol does not give any meaningful benefits to pain or function in knee or hip OA. Opiates? NICE recommend them as an option, but given the latest Cochrane review in 2019 tramadol is another one off the list, with results showing overall minimal benefits and significant increased side effects in those taking tramadol. Topical NSAIDS can be effective but we are all too aware of the GI, CV and renal risks of oral NSAIDS. Knee replacements can be a highly effective intervention for those with more severe OA, but even that is not a panacea - we will all have many patients that have had fantastic outcomes from this procedure, but likewise a number who had significant complications or simply wish they had never had the operation in the first place.

So what, I hear you cry, can we do to help Rebecca? Well, we should not forget the importance of an honest and empathetic discussion about her condition and the importance of self management. There were some excellent insights in a 2018 Cochrane review looking at exercise interventions in patients with OA knee and hip. The quantitative data was inevitably of lowish quality, but there was enough data to suggest exercise interventions do improve pain, physical function and depression. Possibly of more importance was the review of the qualitative data which strongly suggests that challenging inappropriate health beliefs (e.g. that exercise will worsen joint damage) is a crucial barrier we can remove for patients by giving better information about the safety and value of exercise in OA.

So are steroid injections for knee OA off the menu? No, but I do think we need to be honest about the uncertainty of the evidence and any potential benefits; there will clearly still be situations where this might be a beneficial intervention - the younger patient that needs some improvement in symptoms to allow them to pursue exercise therapy and/or weight loss, or the frail patient that is not fit for surgery who might benefit from an injection to improve pain and function and reduce falls risk. As always there are no right answers in General Practice, but we do need to inform patients that knee steroid injections will only give short term relief and may possibly increase the risk of disease progression if repeatedly done, and that in the longer term it may be better to step away from the needle and focus more on exercise.

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Sit less, move more - a simple message for 2020

Rob Walker - 19 Feb, 2020

We are well into February and we’ve had storms and floods but at least we have got rid of the worst of those dreadful dark mornings! Alongside the short days the other thing that is often fizzling out by the time we get to this stage of February are the New Year resolutions, which is a pity as for many people and ‘getting fit’ is likely to be high on the list of priorities. Indeed the YouGov stats for last year showed that exercising more was the commonest New Year resolution in Britain, with almost 50% of those surveyed saying this was their main goal. Gym memberships will have been re-instated and new trainers bought, but for some this New Year burst is either unmanageable or unsustainable. We all know physical activity improves multiple outcomes - back in 2015 the Academy of Royal Colleges published an evidence based review of exercise titled ‘The Miracle Cure’, which reviewed the plethora of proven benefits of exercise. But how much exercise is enough? I personally love running and get a huge amount of mental and physical benefit from it, but does everyone have to be doing moderate to vigorous levels of exercise to get any benefits? I’m sure we’ve all had the situation where we have discussed with patients the NHS recommended activity levels of 150 minutes of moderate intensity activity per week, and they’ve looked back at you like you’re off your rocker - How on earth am I supposed to manage that doc? So what about less intense levels of activity - does walking your 10,000 steps per day help? Or even just spending less time sitting down….

A new meta-analysis from August 2019 (BMJ 2019;366:l4570) has helped moved this debate on, giving important new data on what level of exercise intensity gives mortality benefits, and also whether sedentary behaviour plays a part. This study was important as it used objective measurements of physical activity. Historically exercise studies have used self reported levels of exercise, and as discussed in the attached editorial (BMJ 2019;366:l5051) self reports are notoriously inaccurate, often underestimating low levels of activity and overestimating more vigorous activity. With the advent of body sensor devices we can now more accurately assess physical activity levels, and this meta-analysis reviewed the data using such devices.

Using high quality studies the authors reviewed more than 36,000 middle aged and older adults (mean age ~60 years old), with a median follow-up of 5.8 years, and reviewed all-cause mortality rates based on both the intensity of activity and length of time spent active, as well as sedentary time. The results show a substantial and steep reduction in mortality as total volume of activity increases, even with light physical activity (equivalent to normal walking pace). The difference from previous studies is the effect size seen with light physical activity - this study shows substantially larger benefits for light physical activity, quite possibly due to under-reporting of lighter activity in previous self-reported studies. Importantly the study also confirms that sedentary time is directly linked to mortality - more than 9.5 hours (excluding sleep) of sedentary time/day is associated with a statistically significant increase in mortality. Whether the increased mortality with increased sedentary time is simply the flip side of those doing less physical activity, or whether sedentary time is an independent risk factor, as has been suggested, we don’t yet know.

However, the message for us in primary care, and for our patients is simple - moving more and sitting less, at any level of intensity can reap significant benefits.

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Improving early diagnosis of cancer: Goodbye tick boxes, Hello RDCs

Dr Simon Curtis - 11 Feb, 2020

Julie was 60 and presented with some cramping low abdominal pains and bloating. She had lost some weight and feels tired. She was a smoker. I did a CXR and some bloods. The CXR was fine, but she had a slight anaemia and raised platelets. I was worried that she may have cancer and wanted to urgently refer her, but to where? I referred her to colorectal, they did a colonoscopy and then referred her to upper GI. Nothing found. I then referred her to gynae and it was at this point, now about 6 weeks in from my original referral, that she started coughing up blood…Quick change of direction, and to respiratory she went where her lung cancer was diagnosed on CT scan. For poor Julie this was an avoidable delay in diagnosis. Recent data from the National Cancer Diagnosis Audit published in BJGP2018;68:e63 shows that a third of all avoidable diagnostic delays are not due to clinician or patient, but system related factors. We have all had patients like Julie, who as referrals have become pathway driven have fallen through the gaps between these pathways.

Improving early diagnosis of cancer has been a Hot Topic ever since the NICE NG12 suspected cancer guidance of 2015, and it has become more so as it is a key priority in the NHS Longterm Plan (LTP) published in 2019. At the moment in the UK, 50% of cancers are diagnosed at stage 1 or 2. The LTP has set an ambitious target to raise that figure to 75% over the next decade. They estimate this will lead to 50,000 more people each year surviving their cancer for more than 5 years. For GPs in England, NHSE have made early cancer diagnosis a major new QI domain in QOF for2020/21.

The NICE NG12 guideline is arguably the national guideline that has had most impact on clinical care and referral, and it is enshrined in most regions’ local urgent cancer referral pathways. It has many positive aspects and hopefully it will have led to many more patients having an early diagnosis of cancer, but it also re-enforces a tick-box pathway model and there are two fundamental problems with this. Firstly, as every GP knows, sometimes patients just don’t tick all the boxes and yet significant clinical concern remains. Secondly, patients like Julie may tick boxes on several different pathways but it is not clear where to refer her. This problem is compounded by the fact that we no longer refer to a clinician who will take clinical responsibility for the case, but to a nameless diagnostic pathway of an individual body system. Once cancer in that particular ‘silo’ has been ruled out, the patient is sent back to you and the process has to restart. Patients, like Julie, frequently fall then between the gaps and this can lead to significant diagnostic delays.

The NHS Longterm Plan (LTP) plans that there will be many more Rapid Diagnostic Centres (RDCs, sometimes called Multidisciplinary Centres or MDCs) across the country so that patients with possible cancer can be assessed and diagnosed in a single 'one stop shop' visit. These are now being rolled out (and already in place in some areas) to refer patients to who have non-specific symptoms that are concerning but do not 'fit' with a specific diagnosis. The longer-term plan however is for ALL suspected cancer referrals with suspected cancer to go through this single point of access to prevent patients falling through the gaps between different pathways.

 A recent pilot study , funded by CRUK and published in the BJGP January 2020 has just reported, looking at outcomes from a rapid diagnostic centre in Port Talbot, Wales. Patients were referred to the RDC if they did not fulfil criteria for a specific urgent cancer referral pathway, but had non-specific symptoms which their GP was worried may be due to cancer. They were matched with control patients not referred to the RDC. The RDC reduced mean time to diagnosis from 84 days in usual care to 6 days if a diagnosis was made in the RDC clinic, and if further investigations were needed from the initial RDC appointment the diagnostic delay was halved to 41 days.

These are very significant results and interestingly NICE have now announced that NG12 will not be updated, as we move towards a change in service delivery with RDCs at the centre of this (although outcomes from further pilot studies are awaited).

It’s too late for Julie, but hopefully over the next few years these changes will lead to fewer patients falling through the gaps and suffering avoidable delays in their cancer diagnosis. Ticking boxes may be helpful for to do lists and shopping, but for diagnosis of cancer we need a more subtle, flexible, thoughtful, clinical and above all holistic approach to diagnosis.

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