After a heart attack: a ‘Goldilocks’ path to recovery

Philosophers speak of a midpoint between two extremes as a ‘golden mean’. Public-policy-makers call an economy that is neither overheated nor undercooled a ‘Goldilocks’ scenario. The school-of-life teaches that a good approach to most situations is moderation.

So it is with people who have suffered a heart attack, and are now on anti-aggregant medication. They clearly want to avoid one extreme – the repeated formation of arterial blood clots – that triggered the heart attack in the first place. At the same time, they also want to avoid the other extreme that also can be life-threatening, uncontrolled bleeding.

As with so many things, finding the golden mean is easier said than done.

To keep blood at its ‘just-so’ level of clotting, doctors today have two main medicinal options, both with pros and cons. One is to prescribe an anti-platelet drug, called clopidogrel, that is proven, relatively low-cost, but fails to work effectively in some patients. The other is to dispense another platelet inhibitor, called prasugrel, that is more expensive and in some cases can work too well, causing patients to bleed more excessively, even fatally so.

So doctors are faced with a tricky decision. There probably is no perfect answer, but a blood-test solution from Roche promises to make their choice more informed.

An instrument called the Multiplate analyzer can, in a blood test that takes only ten minutes, deliver an assessment of a patient’s cellular clotting capability, mediated via blood platelets. Using a sample of ordinary blood (not centrifuged or processed), this diagnostic device (about the size of a typical desktop computer) can guide the doctor’s decision about whether to go with clopidogrel or prasugrel.

Don't use a sledgehammer to crack a walnut

In the event of heart attack, technically known as a myocardial infarction, one or more vessels supplying blood to the heart muscle itself are blocked, usually by a blood clot. After the clot is cleared, one standard medical practice is to insert a stent to reopen and stabilize the calcified coronary artery. Ironically, the stent itself poses potential hazard. As a hard, foreign object, it can set off clotting of the stented vessel segment. To suppress this, stented patients usually are given anti-clotting drugs to inhibit arterial blood clotting.

Clopidogrel has long been the medicine of choice. It subdues platelet activation and clotting, and because it went off patent a few years ago, is now available as a relatively low-priced generic drug. However, clopidogrel does not work for all people. The drug needs to be activated within the liver by certain enzymes – which some people have mutations thereof. About one-quarter of Europeans have an enzyme mutation slowing down activation of clopidogrel, with the effect of platelets being insufficiently inhibited. Adherence to therapy is another important factor which can be checked by testing. Noncompliance to therapy is a major risk for recurrent thrombotic events in an aged multi-morbid patient population usually being on multiple drug treatments. To the rescue came another drug that is chemically similar to clopidogrel, called prasugrel. It costs more, and acts more potently because of its simplified liver-activation not influenced by the patient’s genetic predisposition However, long-term use of prasugrel can be harmful, says Dirk Sibbing, MD, principal investigator and cardiologist at the Department of Cardiology at Ludwig-Maximilians University Hospital in Munich, Germany. Prasugrel poses an increased risk of excessive bleeding, including fatal intra-cranial bleeding.

So, the best answer for post-heart-attack blood thinning just might be: use clopidogrel if it does its job, use prasugrel if not.

This hypothesis is being tested thoroughly in a year-long clinical trial being run by Sibbing and colleagues. The Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet treatment for Acute Coronary Syndromes, or TROPICAL-ACS study, involves 2,600 coronary patients who now have stents.

Half of them are receiving standard treatment with prasugrel over the year. The other half takes prasugrel in the first week after their stent was implanted, followed by clopidogrel in the second week. Then they are tested with Roche’s Multiplate analyzer, to see if they respond properly to the clopidogrel. If yes, they will continue on clopidogrel for the rest of the year. If no, they are getting switched back to prasugrel.

The results, to be delivered in 2016, will suggest which approach is better.Tailoring anti-platelet therapy to the patients’ needs could support cost-effective decision-making of healthcare professionals to improve benefits and safety, says Professor Christian Zaugg, Global Medical Leader at Roche Professional Diagnostics. Our support for this investigator-initiated study reinforces Roche’s strong commitment to Personalized Healthcare, and is part of our ambition to bring medical value to patients.