The drug that could save tens of thousands of lives - if only doctors could be told about it

The clotting drug tranexamic acid has already been included in the White House Medical Unit treatment protocols for President Obama. But until more people know about it, thousands of trauma victims all over the world will die needlessly without it.

Nothing could have saved President Lincoln. Kennedy might have survived the bullet in his back but not the one in his head. Garfield and McKinley, shot in the abdomen, died from massive internal bleeding. With four out of forty-four incumbents assassinated, and many more failed attempts, the job of US President is among the world’s more hazardous occupations.

However, the recent inclusion of the drug tranexamic acid into White House Medical Unit treatment protocols will increase the chance that Obama and future presidents will survive their terms. Being Commander in Chief means that presidential medical care is a military matter. The White House Medical Unit is in the White House Military Unit. Obama’s doctor is a Navy Captain.

In March 2010, results from the largest clinical trial ever conducted in trauma patients were reported in medical journal the Lancet. The CRASH-2 trial had randomly allocated over 20,200 bleeding victims of accidents or violence to receive either an injection of a drug called tranexamic acid or a matching placebo.1,2 Tranexamic acid had been used for decades to treat heavy monthly bleeding in women, but could it help in life threatening bleeding say from a knife in the ribs or bullet in the groin?

The results were spectacular. There were 160 fewer deaths in the tranexamic acid treated group. If given soon after injury, tranexamic acid reduced the risk of bleeding to death by about one third and without any side effects. Two weeks later, the British Army were using tranexamic acid to treat combat casualties in Afghanistan.

US military medics were not convinced. They had only recently burned their fingers on a new blood clotting drug called activated Factor VII. Seduced by industry hype and dubious expert advice, they had started using activated Factor VII to treat bleeding American soldiers even before results from randomised controlled trials were available. When the trials eventually reported they showed no evidence of benefit but significant side effects from unwanted clotting, with more heart attacks, strokes and gangrene.3 Lawyers smelled blood. And so even though there was a truckload of controlled trial evidence for tranexamic acid, they still wanted more data. The Taliban were more than happy to provide it.

Between January 2009 and December 2010, around 900 seriously wounded soldiers were treated by military medics at Camp Bastion in the Helmand province of Afghanistan. Improvised explosive devices had wreaked bloody havoc and double, triple, even quadruple amputees were not uncommon. One military surgeon described how he had worked on three soldiers wounded in the same explosion who had only two remaining testicles between them.

Of the 900 wounded, one third had been treated with tranexamic acid. Although the treated third were more severely injured than the untreated group, they were significantly less likely to die (17 per cent dead with tranexamic acid versus 25 per cent dead without). After statistical adjustment, the treatment benefit was even more dramatic.4 Although results from a randomised controlled trial with more than 20,000 participants should pack much greater scientific clout than the Helmand data, the experience of seeing a treatment effect in their own data was a powerful one and on 11 August 2011 US Tactical Combat Casualty Care Guidelines (pdf) were revised to include tranexamic acid.

A flag draped over a military coffin is politically inflammable. In large numbers, they can even smoke a president out of the White House. It takes the precise choreography of an Arlington funeral to get the corpse safely underground. Much less pomp and political risk surrounds the routine urban slaughter of young black Americans even though the number of deaths is considerably higher. A recent study estimated that the use of tranexamic acid to treat bleeding trauma patients in US hospitals could prevent more than 3,500 premature deaths each year.5 It was with these deaths in mind that the CRASH-2 investigators sent the entire clinical trial dataset to the US Food and Drug Administration (FDA) in March 2011 in the hope that the FDA would scrutinise the data and consider amending the licensing indications for tranexamic acid so that it could be marketed for use in trauma. Until this happens, any pharmaceutical company that promotes the use of tranexamic acid in trauma risks large fines.

Sadly, saving lives is not as easy as that. According to Dr Susan Shurin acting Director of the US Department of Health and Human Services, the FDA does not approve drugs unless the marketing company requests it and the marketing company will only request it if there is a demand. So we have a drug that could save a lot of lives if doctors knew about it but no one can tell them about it until it is licensed and it cannot be licensed until doctors know about it.

In an attempt to break this vicious circle, the trial investigators have had to take over the role of a pharmaceutical marketing department. Art students have been are enlisted to create informational cartoons that might go viral but might not.6 Doctors and university professors have had to lobby drug companies, to persuade them to take more interest in one of their own drugs, which is now generic and so not particularly profitable. If we do manage to raise the profile of this lifesaving treatment, the drug company will pay the FDA the license application fee, the FDA might give them permission to tell US doctors about tranexamic acid, the company will make some money and a few thousand Americans will not die.

It is absolutely right that those who risk their lives in the service of the President deserve the same standard of emergency medical care as the president. But so do the many tens of thousands of victims of violence and accidents who die needlessly every year around the world.

Ian Roberts is Professor of Epidemiology & Public Heath and Director of the WHO Centre for Injury and Violence Prevention at the London School of Hygiene & Tropical Medicine

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1CRASH-2 Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376:23-32.

2The CRASH-2 collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. The Lancet 2011;377:1096-101.

3Levi M, Levy J, Andersen H, Trulof D. Safety of recombinant factor VII in randomized clinical trials.  N Engl J Med 2010;363:1791–1800.

4Morrison J, Dubose J, Rasmussen T, Midwinter M. Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147:113-119.

5Ker K, Kiriya J, Perel P, Edwards P, Shakur H, Roberts I. Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial. BMC Emergency Medicine 2012, 12:3 doi:10.1186/1471-227X-12-3

6The Lancet. CRASH-2 goes viral. The Lancet 2011;378:1758

 

The inclusion of tranexamic acid in White House treatment protocols will increase the chance that Obama and future presidents will survive their terms. Photo: Getty

Ian Roberts is Professor of Epidemiology & Public Heath at the London School of Hygiene & Tropical Medicine

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French presidential election: Macron and Le Pen projected to reach run-off

The centrist former economy minister and the far-right leader are set to contest the run-off on 7 May.

Emmanuel Macron and Marine Le Pen will contest the run-off of the French presidential election, according to the first official projection of the first-round result.

Macron, the maverick former economy minister, running under the banner of his centrist En Marche! movement, is projected to finish first with an estimated 23.7 per cent of the vote, putting him marginally ahead of Le Pen. The leader of the far-right Front National is estimated to have won 21.7 per cent, with the scandal-hit Républicain François Fillon and the left-winger Jean-Luc Mélenchon tied for third on an estimated 19.5 per cent each. Benoît Hamon, of the governing Socialist Party, is set to finish a distant fourth on just 6.2 per cent. Pollsters Ifop project a turnout of around 81 per cent, slightly up on 2012.

Macron and Le Pen will now likely advance to the run-off on 7 May. Recent polling has consistently indicated that Macron, who at 39 would be the youngest candidate ever to win the French presidency, would probably beat Le Pen with roughly 60 per cent of the vote to her 40. In the immediate aftermath of the announcement, he told Agence France Presse that his En Marche! was "turning a page in French political history", and went on to say his candidacy has fundamentally realigned French politics. "To all those who have accompanied me since April 2016, in founding and bringing En Marche! to life, I would like to say this," he told supporters. " 'In the space of a year, we have changed the face of French political life.' "

Le Pen similarly hailed a "historic" result. In a speech peppered with anti-establishment rhetoric, she said: "The first step that should lead the French people to the Élysée has been taken. This is a historic result.

"It is also an act of French pride, the act of a people lifting their heads. It will have escaped no one that the system tried by every means possible to stifle the great political debate that must now take place. The French people now have a very simple choice: either we continue on the path to complete deregulation, or you choose France.

"You now have the chance to choose real change. This is what I propose: real change. It is time to liberate the French nation from arrogant elites who want to dictate how it must behave. Because yes, I am the candidate of the people."

The projected result means the run-off will be contested by two candidates from outside France's establishment left and right parties for the first time in French political history. Should Le Pen advance to the second round as projected, it will mark only the second time a candidate from her party has reached the run-off. Her father, Jean-Marie Le Pen, reached the second round in 2002, but was decisively beaten by Jacques Chirac after left-wingers and other mainstream voters coalesced in a so-called front républicain to defeat the far right.

Fillon has conceded defeat and backed Macron, as have Hamon and the French prime minister, Bernard Cazeneuve. "We have to choose what is best for our country," Fillon said. "Abstention is not in my genes, above all when an extremist party is close to power. The Front National is well known for its violence and its intolerance, and its programme would lead our country to bankruptcy and Europe into chaos.

"Extremism can can only bring unhappiness and division to France. There is no other choice than to vote against the far right. I will vote for Emmanuel Macron. I consider it my duty to tell you this frankly. It is up to you to reflect on what is best for your country, and for your children."

Though Hamon acknowledged that the favourite a former investment banker – was no left-winger, he said: "I make a distinction between a political adversary and an enemy of the Republic."

Mélenchon, however, has refused to endorse Macron, and urged voters to consult their own consciences ahead of next month's run-off.

The announcement sparked ugly scenes in Paris in the Place de la Bastille, where riot police have deployed tear gas on crowds gathered to protest Le Pen's second-place finish. Reaction from the markets was decidedly warmer: the euro hit a five-month high after the projection was announced.

Now read Pauline Bock on the candidate most likely to win, and the NS'profiles of Macron and Le Pen.

 

Patrick Maguire writes about politics and is the 2016 winner of the Anthony Howard Award.

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