Archive

Tag Archives: Valves

Disappointing results here for novel anticoagulants in patients with mechanical heart valves

Old CardioBrief

Boehringer Ingelheim today announced that it had discontinued a phase 2 trial of its anticoagulant drug dabigatran (Pradaxa) in patients with mechanical heart valves. As reported here in October, the company had previously terminated one arm of the study after an interim review of the data by the trial’s Data Safety Monitoring Board

The RE-ALIGN trial was an open-label, 12-week randomized comparison of warfarin and dabigatran in 400 patients who received a mechanical valve. The first arm randomized patients during their initial hospital stay. The second arm randomized patients more than 3 months after their surgery.

Despite the recent advent of novel oral anticoagulants, the much-maligned warfarin remains the only current option available for patients who have received a mechanical valve. Now the first trial to explore this indication for one of the newer oral anticoagulants has been stopped.

In October Boehringer told members of its speakers bureau that the post-surgery arm of…

View original post 1,786 more words

A young physician scientist arrives for a visit to the laboratory of Willem Einthoven. It’s Leiden, around 1902…

Intern: Hey!

Einthoven: Ah yes, the intern. Sit quietly in the corner I’m busy.

After a few minutes the young physician can no longer contain either his enthusiasm nor his curiosity

I: What..is..that?

E: That? That is a string galvanometer.

I: A string what?

E: It’s a striiing gaaaalll-van-o-meter!

I: Cool!

E: Indeed!

I: What does it do?

E: Well it measures the electrical signal generated by the heart during the cardiac cycle.

I: Really? So the heart generates an electrical signal during the cardiac cycle.

E: Err, yes. That’s what I said.

Pause

I: Why would you want to measure that?

E: Well I’m not sure yet but I think it might tell us a lot about the normal heart structure, maybe function and I’ve got a feeling it might tell us something about when the heart gets injured.

I: That could be really useful. That could be used on hundreds of patients… maybe even thousands….

E: Now steady on…

I: There could even be a whole new branch of cardiology based on that sort of thing…

E: You’re getting carried away now… Anyway, that would be pretty dull.

I: Yeah, I guess so. But anyway, if it can detect injury to the heart  it could still be used on a lot of patients. Can you teach me how to run it.

E: Errr…No, everyone asks me that. No I won’t!

I: Why not?

E: Well it’s, it’s, it’s…. very difficult, very demanding. You could never learn.

I: But if you taught me. Anyway how hard can it be. How many did it take before you could do it well

E: Lots

I: How many?

E: Lots. Heaps and heaps…about 40…

I: Well I have a lot of time. I could do that.

E: Stop pestering me. I won’t show you how to do it. That’s final, It’s mine and only I can use it. If you carry on like this you’ll have to leave.

I: OK, OK, OK. Sorry…

Some more time passes

I: Don’t you think that people might miss out if you are the only person in Leiden able to use the string galvanometer?

E: The only person in the world actually.

Silence

I: How about I build my own, practice a lot and send you some results?

E: No, no you mustn’t do that!!

I: Why?

E: Well…well…it’s dangerous, that’s why.

I: Dangerous?

E: Erm, well, err…yes, really dangerous. So dangerous that you have to be in a really big hospital like this, or maybe even an institute. Otherwise the patient could die from the complications sustained by using the string galvanometer.

I: Crikey, how often does that happen?

E: Well, let’s see… about one in every 1000 cases.

I: That’s not many!

E: Well it’s enough, and when it happens you sure want the patient to be at the institute so their life can be saved. Your place is too far away…

I: That maybe, but that’s a lot of patients missing out while you wait for one to get a complication.

E: Well, that’s too bad! You’re too far away. You can’t do it. I won’t allow it.

I: OK. That’s a shame though….

Some time later…the young physicians enthusiasm has waned a little…

I: Well thanks Prof Einthoven I’ve learnt a lot today. I won’t forget about the string galvanometer – you know, I think it has a big future… I’ll keep in touch.

E: Sure, send me a telegram next time you’re around these parts.

I: OK I will. Actually I’ll send you an email. Bye.

The intern has left

E: Fine……wait a minute…an ‘e’ what??

I: (from halfway down the stairs) An email? Oh,  it’s just this new kind of message I’ve invented. No paper, delivered immediately…that kind of thing.

E: No paper? Immediate? Wait, wait! Come back, tell me more about this email….

….but the student has already disappeared off into the foggy evening…

Apologies to Willem Einthoven and his descendants. Einthoven received the 1924 Nobel Prize for Medicinefor his discovery of the mechanism of the electrocardiogram‘. Over a hundred years after his discovery the electrocardiogram remains the single investigation required in order to diagnose acute ST elevation myocardial infarction and initiate repercussion therapy.

Interestingly his biography on the Nobel website states that ‘The string galvanometer has led countless investigators to study the functions and diseases of the heart muscle. The laboratory at Leiden became a place of pilgrimage, visited by scientists from all over the world.’

You can read his Nobel lecture here

This post refers to

‘Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data’ by Carl Heneghan and others of The Self-Monitoring Trialist Collaboration  that was published in The Lancet – 28 January 2012, Vol. 379, Issue 9813, Pages 322-334 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61294-4/abstract?rss=yes

I never wanted this to be a medico-political blog but it has been difficult to avoid given the barbs that have fired at cardiologists over the last few weeks. I’m sure there will be more to come…

Anyway, for now at least, it’s nice to get back to reading some science.

One of my mentors as a medical student, in fact the senior physician on my first medical rotation at medical school, was the diabetes expert Prof. Robert Tattersall. Undoubtedly, Tattersall’s major contribution to medicine was his work promoting home blood glucose monitoring for people with diabetes. In his book, Diabetes: The Biography, he hands most of the credit to Dr Clara Lowy of St Thomas’s who allowed a pregnant diabetic patient to monitor her own blood sugar at home using a machine loaned by the hospital. This might not seem extraordinary now but at the time, as recently as 1975, this was seen as ‘irresponsible and dangerous’ by many colleagues. Tattersall is too modest about his part in this revolution, neglecting to mention that he led the ‘Nottingham Group’ that in 1978 published their experience alongside that of Lowy, in Issue 8067 of The Lancet.

So this meta-analysis concerning self-testing and management of anticoagulation from Oxford, caught my eye. The findings are particularly relevant to patients with mechanical artificial heart valves. Although the risk of thrombo-embolic complications is low with modern mechanical valves self-management of anticoagulation appears to have a fairly dramatic effect in reducing this risk further, without any increase in bleeding. This didn’t translate into a reduction in mortality although the trend was in favour.

Despite being available for some years self management of anticoagulation has never really caught on, probably for a variety of reasons. In Australia cost has been a significant hurdle. Nevertheless, inertia amongst the medical community, similar to that experienced by Tattersall and Lowy has probably also played its part.

Given the bad press surrounding the new oral anticoagulant dabigatran, and the lack of a defined role in patients with mechanical valves, it seems that warfarin still has some years to run. The Last Cardiologist will be taking another look at the whole place of self management of warfarin for his patients, and particularly those with mechanical valves.