From rags to riches: the atrial fibrillation story

Suddenly, irregular heart beat in general and atrial fibrillation in particular is everywhere. The past fortnight alone has seen “heart rhythm week,” organised by the Arrythmia Alliance (patron: Tony Blair), and the National Institute for Health and Clinical Excellence recommend rivaroxaban as stroke prophylaxis for some patients with atrial fibrillation. Although we can’t be sure which cardiac rhythm the footballer Fabrice Muamba collapsed with in March, his “death” and “resurrection” have turned the beatifically smiling footballer into the patron saint of arrhythmias, with his doctors not far behind.

But to return to atrial fibrillation and its humble back story. Not so long ago the main treatment option for the condition was digoxin, one of the active ingredients of a traditional folk remedy for dropsy. Introduced in the 1930s, the drug costs the NHS about £0.04 (€0.05; $0.06) a patient for a daily dose. Costing much the same is warfarin, used to reduce the risk of embolic stroke.

In the past few years, however, new drugs have been crowding in for consideration: dronedarone (for persistent or paroxysmal atrial fibrillation) and angiotensin receptor blockers (for preventing new onset atrial fibrillation). The device industry has pitched in with pacemakers and ablation kits.

If medical conditions were listed on the stock exchange like companies, atrial fibrillation would clearly have been one of the top performers these past five years. A marker of this: during this time BMJ mentions of the condition have risen by a third over the previous five years.

The real action has been on antistroke prophylaxis for patients with atrial fibrillation. While warfarin has been used for this purpose for decades, it entailed fiddly titration of dose at anticoagulant clinics and sometimes life threatening undertreatment and overtreatment. The new drugs hit the coagulation cascade at different points from warfarin: dabigatran inhibits thrombin mediated conversion of fibrinogen to fibrin, and rivaroxaban and apixaban block the conversion of prothrombin to thrombin, by inhibiting factor Xa. With less risk of bleeding than warfarin, there’s no need for the frequent follow-up at coagulation clinics—the bane of patients’ lives. However, the irreversibility of their anticoagulant effects spooks some doctors.

Financial analysts have estimated that the annual market for this new class of drugs is $14bn to $20bn, and business writers have got caught up in the excitement. “For the past few years cardiology . . . has been a drug development wasteland, filled with dead drugs that were too unsafe to market . . . and zombie medicines that made it to market but just didn’t sell,” wrote the Forbes journalist Matthew Herper, whose byline reads: “I cover science and medicine, and believe this is biology’s century.”1

But no longer. Here is “a lucrative, mass-market opportunity for drug companies,” said Herper. “Next up, expect these companies to market like it’s 1999. Even before a panel of Food and Drug Administration experts met to look at Pradaxa [dabigatran], Boehringer was pitching reporters on a meeting with soap actress Susan Lucci and her husband, who has atrial fibrillation . . . Before Pradaxa was approved, advertisements were running on TV telling patients to ask their doctors about atrial fibrillation. This is going to be a crowded area, and the companies are going to need to get patients to come out of the woodwork.”

Who could decry the attention that atrial fibrillation is suddenly attracting? As Carmelo Lafuente-Lafuente and colleagues point out in their review,2 the condition is the commonest sustained cardiac arrhythmia, with an estimated prevalence in the United Kingdom of 10% in patients aged 75 or over and an associated fivefold increase in the risk of ischaemic stroke. By common consent the condition is poorly diagnosed and treated; if all patients with atrial fibrillation were managed according to guidelines there would be at least 10 000 fewer strokes each year in the UK. So we’re not talking here of overdiagnosis or the sort of disease mongering of which compilers of the next edition of the Diagnostic and Statistical Manual of Mental Disorders are being accused.3 4

Nevertheless, I’m left feeling queasy that the explosion of interest in atrial fibrillation has occurred only now that big profits are in the offing. No one worked themselves into a lather over how the condition was managed 10 or 20 years ago.

With all the new initiatives, it seems that an expanded market is being assembled—wittingly or unwittingly—for ultimate delivery to the manufacturers of these expensive new products. The closest analogy comes from a David Attenborough documentary, in which one species rounds up another, before gorging themselves on their catch. Think dolphins and sardines, or African hunting dogs and impala.

Attenborough called them “bait balls,” and they’re forming all over the place. In 2009 the British Heart Foundation’s billboard campaign exhorted the public to check their pulses for irregularity.

In March this year a consensus conference organised by the Royal College of Physicians of Edinburgh called for a national programme to screen over 65s for atrial fibrillation but—bucking the trend—backed warfarin over the newer anticoagulants in uncomplicated patients.5 (In October 2010 the latest European guidelines on atrial fibrillation had recommended dabigatran ahead of its regulatory approval in Europe 6). April saw the launch of the latest phase of the “1 million 1 mission” campaign at the World Cardiology Congress in Dubai. Supported by the Atrial Fibrillation Association, the campaign hopes “to secure 1 million pledges from around the globe in a bid to prevent AF-related stroke.”

Patients with AF should do well out of this recent flurry of activity—and so will drug and device manufacturers. These companies stand to make billions; whether those who pick up the bill get their money’s worth remains to be seen.