This new drug does not require regular monitoring, frequent dose adjustments and has no diet restrictions. Ng Wan Ching reports

A new anti-clotting drug has been shown to better prevent strokes in people who have atrial fibrillation - a heart rhythm disorder which can cause strokes - than the current standard drug, warfarin.

Pradaxa, made by German pharmaceutical company Boehringer Ingelheim, is the world's first anti-coagulant drug to receive the US Food and Drug Administration's (FDA) approval in 60 years as a viable alternative to warfarin, say doctors.

The Health Sciences Authority approved it for use in Singapore on March 31. When it becomes available depends on whether it has passed through individual hospitals' drug approval committees.

The National Heart Centre Singapore's (NHCS) committee has approved the drug, which should be available this month, said Associate Professor Tan Ru San, senior consultant at the department of cardiology.

The new drug's other benefits over warfarin are that it does not need regular monitoring and frequent dose adjustments to maintain normal coagulation levels.

There are also no diet restrictions and concerns with multiple drug interactions, unlike with warfarin.

Up to 50,000 patients a year here develop atrial fibrillation, in which the heart's two upper chambers beat erratically, causing uneven and inefficient pumping of blood. As a result, blood can pool and clot in the chambers. If the clot travels to the brain, it can cause a stroke.

Patients who develop atrial fibrillation have five times the risk of stroke - the fourth leading cause of death here - over those whose heart rhythms are normal.

The effect of warfarin to thin blood can be used in medicine or exploited for pest control where high doses cause death through bleeding. It has been prescribed to prevent strokes since the 1950s. But it is often unpopular with patients, who need regular tests to ensure they do not accidentally overdose on it.

Professor Tan said: 'Frequent testing can be troublesome and time consuming as patients and their caregivers keep having to come to the hospital.'

On starting warfarin, patients need to be seen at least every week. It takes three to four days for the dose to reach equilibrium, he said.

Once a stable dose has been arrived at, patients should still have the anti-coagulant effect of the drug regularly monitored, as it can fluctuate due to multiple factors, such as drug and food interactions.

Ideally patients should be seen once a month, though most patients generally come once every two months, said Prof Tan, who is also the director of clinical trials at NHCS.

Unlike warfarin, Pradaxa takes effect rapidly, has very few and negligible interactions with other drugs, and does not require patients to be monitored, said Professor Michael Ezekowitz, professor of medicine at Thomas Jefferson School of Medicine in the United States.

But it does still have side effects, including bleeding, which can be serious and sometimes lead to death. It can also cause indigestion, stomach upset or burning, and stomach pain.


The advantages of the new drug were shown by the largest published atrial fibrillation trial of more than 18,000 patients from 44 countries.

Among them were 65 patients from the NHCS and Tan Tock Seng Hospital.

Prof Ezekowitz was a co-principal investigator of the 2009 trial published in the New England Journal of Medicine, while Prof Tan was a steering committee member and national coordinator of the trial in Singapore.

Patients were either given warfarin, or 110mg or 150mg of Pradaxa. The trial found that Pradaxa's 150mg pill reduced the risk of stroke and blood clots by 35 per cent more when compared to warfarin.

The 150mg dose also reduced the most serious complication - bleeding into the brain - by 59 per cent more when compared to warfarin.

Prof Tan said: 'This may be due to the greater stability of dose behaviour of the drug or that it spares the brain for some unexplained reason.'


Patients with prosthetic heart valves, who are pregnant or have severe renal failure (near dialysis) cannot be on Pradaxa.

For the rest with atrial fibrillation, the trial showed that a 150mg dose of Pradaxa is a superior drug to warfarin, said Prof Tan.

Pradaxa is also approved here for prevention of deep vein thrombosis and pulmonary embolism in patients undergoing hip and knee surgery.

'These patients are typically on short-term anti-coagulation, not with warfarin, but shorter-acting drugs such as heparin and low-molecular weight heparin, that are given by subcutaneous injections,' said Prof Tan.

But a stumbling block could be the cost of the new drug, which has yet to be set here. 'There is no doubt that Pradaxa will cost more than warfarin,' said Prof Tan.

He hopes that Boehringer Ingelheim will price the drug at a level that puts it within reach of most patients.

Recent British press reports say that Pradaxa is likely to cost a patient $5 a day. One warfarin pill costs 12 cents at NHCS.

Nonetheless, the costs of warfarin are not just how much patients pay for the drug alone.

Prof Tan said: 'We should also consider how much a patient has to pay for anti-coagulation management, which involves monitoring and travel to and from the hospital. And if a stroke occurs, we have to calculate the cost of hospitalisation, stroke rehabilitation, time off work for patient and caregivers, death and permanent productivity loss.'

Atrial fibrillation

It is the most common heart rhythm condition, affecting nearly one in four people over the age of 40 or 1 per cent of the world's population.

It occurs more frequently with age. The incidence rises to 10 per cent of those aged 80 and above.

People with this condition are more likely to experience blood clots. These clots tend to get trapped at major branches of the brain circulation.

While they may be small, the blockage will affect a large area that is dependent on the blood supply. Hence, strokes caused by atrial fibrillation strokes are larger, cause more disability, and are more likely to be lethal.

Other types of strokes tend to be more localised and smaller in size.

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