Of course, patients with ischaemic heart disease may be expected to feel a little down and anxious, but for this to be correlated with angina shows that these feelings are more than simply a personal emotional response, they have a physiological effect – and perhaps a physiological source as well. Therefore, treating these feelings at the same time could help treat the coronary symptoms and improve both physical and mental patient well-being.

There have been links found between these types of psychosocial feelings and other diseases. Depression has been shown to be linked with cognitive decline and physical impairment in Parkinson’s disease, for example.

However, this post is a triumverate of facts: hard to treat depression is one of the conditions that is being investigated at the Mayo clinic as susceptible to deep brain stimulation, originally a treatment for PD. What is interesting is that in some cases of DBS for PD where the electrodes have been malpositioned, the patient can experience severe bouts of depression and even voice suicidal thoughts, but only when the electrodes are turned on. The link is real and physical.

Thus the links between pathological disorders of the brain, physiological conditions of the heart, and the emotional response, are strengthening and will have to be addressed. This serves to emphasise the fact that, increasingly, physicians will have to take more of a holistic approach to medical management.

So far so what? Well, it is of course hugely disappointing when drugs fail in phase III, given how much money and time has been invested in them to get them that far. What is extra disappointing is that rolofylline – or KW-3902 as it was then known – was the jewel in the crown of Merck’s 2007 acquisition of NovaCardia. The only other compound that is regularly mentioned in connection with NovaCardia is K201 (JTV-519) for the treatment of atrial fibrillation, which Merck did not want and is now part of Sequel Pharmaceuticals – an aptly named company that seems to be aiming to exactly mimic NovaCardia’s feat.

So we are left with a multi-million dollar flop. Pharmaceutical pipelines are notoriously running dry, and the great biotech land-grab is seen by many as the best way forwards, but nothing is certain. Many thought that, given that NovaCardia already had preliminary results from a pilot phase III trial of rolofylline that “indicated a strong trend toward efficacy”, success and approval were a shoo-in. So what has Merck done in the two years since the acquisition, other than develop a new name for the drug?

I see parallels with the housing market, where prices were grossly inflated in a self-fulfilling prophetic circle of people desperate to buy and make money before prices rose further. People would window dress their properties – a quick lick of paint here, some plywood there, baking bread in the oven – to make them appear more attractive. Is Merck a similar sucker for a one-trick biotech company? Paying so much money for a company, to be left with one failed compound, is rather disasterous. As with first-time home buyers, I doubt that pharma can sustain this level of M&A activity for too long – particularly when the results are so disappointing. New types of deal or a whole new strategy would seem to be called for.

PCI procedures were initially introduced for coronary interventions where open surgery is much more difficult and risky. However, not satisfied with conquering the heart, interventional cardiologists have looked to expand their remit to other more peripheral vessels, starting with the carotid artery, much to the chagrin of neurologists and vascular surgeons. As one delegate at ESC 2009 remarked, “The Cardiology-Brain barrier is permeable”. Particularly in the US, the cardiologists appear to be gaining ground – but the data are not in their favour.

At ESC 2009, early safety results from the International Carotid Stenting Study (ICSS) were presented by Dr Brown, and made poor reading for any cardiologists present. The multicentre trial of 1713 patients used a wide variety of approved stents, with or without protection devices, compared to surgery. The rates of stroke, myocardial infarction (MI) and death within 30 days were examined; the primary outcome was roughly twice as common following CAS than CEA. “Stroke or death” was 72 cases (8.5%) with CAS compared to 39 cases (4.6%) with CEA (p=0.001). Brown concluded that there is “strong evidence” that CEA is the safer procedure.

Added to previous meta-analyses, the ICSS results cement the current conclusion that CAS simply does not live up to expectation. Part of the problem is that carotid atherosclerotic plaque is not a true surrogate for coronary plaque, and that the two plaques build up in a different way in the small vessels of the heart compared to the larger vessel in the neck.

It is unlikely that cardiologists will give up on their aim to percutaneously conquer the body, and by all accounts patients prefer the minimally invasive techniques, but until results improve the cardiologists are at least empirically losing the turf war.

The definition of overweight is a moveable feast itself. The most commonly used definition is body mass index (BMI), but this is rather crude and while it varies by race, it doesn’t take into account musculature and having big bones. Many rugby players are overweight or even obese by BMI standards. Other methods include measuring visceral fat or abdominal fat (using waist circumference), which are more tailored to the individual but have less evidence to support them.

The other major problem is that cardiovascular conditions are multi-multi-factoral, having many different causes both genetic and environmental. And while fat is a contributing factor, it is not the only corporeal or dietary factor that needs to be accounted for. Indeed, fundamentally, heart disease may well be a different condition in lean people than fat people.

I am tempted to look into the quality of the evidence for dietary fat/calorie intake and the success (or otherwise) of various weight loss diets and treatments, but that is a whole other post for another day.

In conventional pacemakers, radiofrequency energy can heat up the lead tip to around 80°C, enough to cause serious tissue damage. Moreover, alternative magnetic fields can induce current in the pacemaker, disrupting normal activity or even changing the settings of the device. MRI scans for patients with conventional pacemaker devices are strongly contraindicated, even for extremities.

The market for pacemakers is worth billions, and is increasing with improvements in technology and the ageing population. Ironically, it is often this population that most needs MRI scans. The first company to prove that its pacemaker technology can be safely used with MRI will gain a huge market advantage. With this news Medtronic will be hoping to outpace its rivals – including Biotronik, Boston Scientific, Sorin, St. Jude Medical, and Zoll Medical.

There is also evidence that folic acid supplementation can help with adult heart disease, stroke and cancer, amongst other diseases. So far so good, but what is the case against this wonder vitamin? Well folic acid is a synthetic form of the B vitamin folate, which has an odd and not quite equal relationship with vitamin B12. If people with vitamin B12 deficiency take folic acid, it can mask the underlying anaemia leading to damage tothe nervous system. Evidence is scanty and equivocal, however.

I can’t help but feel that what this boils down to is whether the risks of birth defects outweigh the risks to the elderly. There should not be fortification of foods until we are sure the risk is minimal or non-existent; they may be past the prime of their life but their quality of life should not be discounted.

I think I will stick with my regular intake of marmite.

The trial enrolled a substantial number of patients (18,624 in 43 countries), which is getting on for pretty standard in today’s competitive cardiovascular arena. The primary endpoint of PLATO is time to first occurrence of death from vascular causes, myocardial infarction, or stroke, and AZ said this endpoint was met. No figures were presented.

It is pretty standard for a company to announce the headline results before the paper is presented – and enjoying a 6% boost to share price in the process, but the proof of the pudding will not be eaten until the ESC meeting in August – with submission due late in 2009. And, as Eli Lilly found out with prasugrel, the way ahead may not be straightforward.

Moreover, even if ticagrelor makes it to market – with or without competition from prasugrel – there is no guarantee that it will eat much out of clopidogrel’s current $8+ billion market, as the patent on this drug has only two years left in the US. It would have to be a pretty astonishingly superior drug to maintain a price differential against a well-known and trusted – and now cheap – generic.