Pharmaceuticals



New Oral Anticoagulants provide improved efficacy and safety in treatment of patients with Atrial Fibrillation and Acute Coronary Syndrome


 

By Callan Emery

Middle East Health was invited to a media roundtable organised by Bayer at the European Society of Cardiology (ESC) Congress in Amsterdam in September. Titled – From Trials to Practice: Management of Arterial Thrombosis – the session saw several of the world’s leading experts in the field, discuss arterial thrombosis, its epidemiology and look at the history of treatment with a focus on a set of new medications which has shown a marked improvement in efficacy and safety – specifically in the treatment of patients with Atrial Fibrillation and Acute Coronary Syndrome.

Venous and arterial thromboembolism (VAT) occurs when some or all of a blood clot becomes loose and is moved by the blood stream to block a vein or artery which can result in stroke, heart attack, pulmonary embolism (PE), or in some cases can cause death. In fact, more people die from blood clots than from AIDS, breast cancer, prostate cancer and road traffic accidents combined.

VAT encompasses two serious conditions - VTE (venous thromboembolism), which includes pulmonary embolism and deep vein thrombosis (DVT); and Arterial Thromboembolism, which includes stroke and heart attack.

Speaking at the roundtable, Professor The Lord Kakkar of the Thrombosis Research Institute in London, UK, explained that of the 57 million deaths each year 13% were due to Coronary Artery Disease, 12% Cancer and 10% stroke. “So nearly a quarter of all deaths are due to thromboembolism,” he emphasised.

He said that thrombosis can be either acute or chronic and pointed out that after the first acute event, the patient is at a high risk of recurrent VTE.

“The European Union has a population of 454 million people. We can expect about 500,000 deaths from VTE per year,” he stated. “Even with current management techniques, up to 20% of patients will suffer another event within three years.”

He noted that people with atrial fibrillation are at greater risk of a thromboembolism. “Research shows that 25% of people over 40 years of age will get Atrial Fibrillation. People with Atrial Fibrillation have a five times greater risk of suffering a thromboembolic event, such as stroke.”

He pointed out a couple of examples of the huge economic burden of VAT, saying that in the United States, some $1.5 billion is spent on DVT alone. In the EU, the annual cost of stroke is Euro 38 billion. The panel explored the importance of delivering optimal management in two specific populations at high risk of arterial thrombosis – patients with Atrial Fibrillation and patients with Acute Coronary Syndrome.

Patients with Atrial Fibrillation

Patients with AF need protection from stroke as they are at much greater risk of having a stroke. Long-term stroke protection includes: 1. Lifestyle modification, such as correct diet, stopping smoking and exercise; 2. Pharmaceuticals, such as aspirin and warfarin; Interventions, such as cardioversion and catheter ablation.

Looking specifically at the pharmaceuticals, people at risk of stroke or patients who have suffered a thromboembolic event, have traditionally been treated with Vitamin K antagonists (VKAs) such as warfarin, which have been around since the 1950s, however there is now a new class of drugs on the market called Oral Anticoagulants or OACs, such as rivaroxaban, that have been shown in several recent trials to offer better efficacy, safety and patient convenience / compliance.

Speaking at the session, Professor Alexander Turpie of McMaster University in Hamilton, Ontario, Canada, supported this, saying: “Traditional therapy with VKAs makes effective anticoagulation harder than it needs to be and can often leave the patient unprotected. Recent data from the GARFIELD real-life registry supports this, showing that only 24.5% of those patients treated with VKAs were well-controlled and 40% of those patients eligible for anticoagulation were not receiving treatment.”

For most AF patients, VKAs are no longer the recommended option for stroke prevention. ESC Guidelines for the management of atrial fibrillation (updated August 2012) recommend rivaroxaban and other novel OACs as broadly preferable to VKAs in the vast majority of patients with non-valvular AF, stating that novel OACs offer better efficacy, safety and convenience. VKAs are associated with significant drawbacks that challenge optimal patient treatment, including the slow onset of action, need for routine coagulation monitoring and frequent dose adjustments, and many food and drug interactions.

For people with AF, once-daily rivaroxaban offers highly effective protection against stroke without the need for routine coagulation monitoring. In general, a oncedaily dosing regimen has been shown to be preferred by patients and is associated with improved patient adherence compared to regimens with higher dosing frequency.

Prof Kakkar said: “Many doctors are still prescribing warfarin, although the new OACs are safer, more effective and easier. “Novel OACs are a better tool, but doctors need to be thorough when administering the drug and switching patients from the older medication to this novel medication. “With the novel OAC there is considerably less bleeding, particularly bleeding into the brain. Studies show a reduction by up to 50%. So the new drug is particularly good for older patients when bleeding into the brain is more dangerous,” he said.

Patients with Acute Coronary Syndrome

Speaking at the Media Roundtable, Professor Robert C. Welsh of Mazankowski Alberta Heart Institute University of Alberta, Edmonton, Alberta, Canada explained: “Acute Coronary Syndrome (ACS) is a common and life-threatening condition which occurs when a coronary artery is blocked by a blood clot reducing blood supply to the heart, thereby causing a heart attack.”

ACS is common in adults, more frequently occurring in people over the age of 50 years. Typically, it occurs in people who are overweight with high blood pressure and diabetes mellitus. As with Atrial Fibrillation, ACS becomes more common with increasing age.

“There are 2.5 million ACS cases diagnosed annually,” Prof Welsh noted. “It is the most common cause of death in the EU, with 741,000 deaths annually.” Studies show that following an ACS, one in 10 patients will have another major atherothrombotic event, such as heart attack or stroke, within a year. “The majority (68-97%) of deaths related to ACS occur after hospital discharge,” Prof Welsh pointed out. The current standard of care for longterm secondary prevention of ACS is antiplatelet therapy alone, as well as lifestyle modification such as exercise, weight loss and smoking cessation. However, improved protection is seen with dual treatment – when rivaroxaban is used in combination with standard antiplatelet therapy.

Complementary modes of action of antiplatelets and anticoagulants is found to provide more complete protection in long-term ACS clot formation. – (Hamm CW et al. Eur Heart J. 2011;32:2999- 3054).

In May this year the European Medicines Agency approved rivaroxaban 2.5 mg twice daily in combination with standard antiplatelet therapy as the only novel OAC available for the secondary prevention of ACS in patients with elevated cardiac biomarkers. Prof Welsh noted that the approval is based on the positive efficacy and safety profile of rivaroxaban 2.5 mg twice daily in combination with standard antiplatelet demonstrated in the pivotal, Phase III ATLAS ACS 2-TIMI 51 study. (N Engl J Med 2012; 366:9-19. Jan 5, 2012. doi: 10.1056/ NEJMoa1112277).

Also, ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation (August 2012) recommend the use of rivaroxaban 2.5 mg twice daily in specific STEMI patients. (Steg G, et al. Eur Heart J. 2012. doi: 10.1093/eurheartj/ehs215).

A paradigm shift in treatment

Prof Samuel Z. Goldhaber, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA, pointed out that this novel OAC is a “major landmark advance” in treatment for stroke prevention in patients with AF and for patients with ACS.

He noted that up until four years ago there had only been one anticoagulant – warfarin - introduced in the 1950s. In the past four years, four new anticoagulants have been introduced. “There now exists a major new treatment to prevent CAD and CVD like never before.”

He stressed it is now important for doctors and patients to be aware that there are alternatives to warfarin. He noted that rivaroxaban has multiple indications: l Stroke Prevention in AF l DVT Acute Treatment l PE Acute Treatment l DVT Extended Treatment l PE Extended Treatment l ACS: Decrease Recurrent MI, Stroke, Death l Prevention of VTE: Hip/Knee Surgery And has multiple advantages: l Does not require preceding parenteral anticoagulation therapy such as LMWH l Once daily in AF stroke prevention and short-term VTE prevention after orthopaedic surgery l The shortest half life of all novel OACs, thereby enhancing safety l Fixed doses by treatment indication l Liberates the patient from dietary restrictions imposed by using warfarin l Liberates the patient from spending time getting INR tested and waiting for the Anticoagulation Management Service to phone with INR result and dose adjustment l Cuts in half the chance of ICH l Streamlines educational process for clinicians re: pharmacology, metabolism, bleeding risk l Allows hospital formularies to choose one NOAC for all thrombosis indications l A patient may be prescribed rivaroxaban to treat or prevent one thrombotic disorder, and subsequently may require rivaroxaban for a different thrombotic disorder – enhanced familiarity with drug.

 Date of upload: 20th Nov 2013

 

                                  
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