Combination treatment for myocardial infarction shows no added benefit compared to ASA monotherapy

The drug ticagrelor has been approved since February 2016 for adults who had a myocardial infarction a year or more ago and are at a high risk of a new myocardial infarction or stroke. Ticagrelor is used together with low-dose acetylsalicylic acid (ASA). In its dossier assessment published in early July 2016, the German Institute for Quality and Efficiency in Health Care (IQWiG) determined an indication of a minor added benefit of ticagrelor in comparison with the administration of ASA alone.

 acetylsalicylic acid(ASA)   Ticagrelor

On the inclusion of additional analyses that the drug manufacturer provided in the commenting procedure conducted by the Federal Joint Committee (G-BA), the Institute now came to a different conclusion, however: An added benefit is not proven because positive effects are called into question by negative effects.

Non-severe bleeding notably more common

The dossier had only contained data on severe bleeding. There were no data on non-severe bleeding that are clinically relevant. The results of the analyses subsequently submitted by the manufacturer were to the disadvantage of ticagrelor: Since these bleeding events were notably more common than under ASA monotherapy, IQWiG determined proof of greater harm with the extent "considerable".

No data on quality of life

In addition, there were no data on quality of life. Particularly in coronary heart disease (CHD), this is a very important outcome criterion however, which is even more important in view of side effects such as dyspnoea. "Disease-related quality of life" is the first treatment goal listed in the recently published revised version of the National Care Guideline for Coronary Heart Disease.

Since, on the one hand, greater harm was proven for an additional outcome, and, on the other, no data on quality of life were available, the positive effects, including the ones regarding mortality and late complications, were called into question by the negative effects. In the overall consideration, no added benefit of ticagrelor plus ASA in comparison with ASA monotherapy could be derived from the data.

Ticagrelor drug shows minor added benefit for patients with history of myocardial infarction

The German Institute for Quality and Efficiency in Health Care (IQWiG) assessed the added benefit of ticagrelor for patients with acute coronary syndrome already in 2011 in its very first dossier assessment, just after the Act on the Reform of the Market for Medicinal Products (AMNOG) had come into force. It was shown then that the drug provided considerable added benefit to patients with mild myocardial infarction without the typical changes in the ECG or with unstable angina pectoris. There was no corresponding proof for severe myocardial infarction.

The approval has now been expanded: Ticagrelor is approved for co-administration with low-dose acetylsalicylic acid (ASA) for prevention of atherothrombotic events after an initial one-year treatment also in specific patients whose myocardial infarction occurred at least one year ago. IQWiG investigated whether the drug has advantages in comparison with the appropriate comparator therapy also for this therapeutic indication. According to the findings, there is an indication of an added benefit with the extent "minor".

Myocardial infarction must have occurred one to three years ago

The expansion of approval applies to adults with a high risk of developing another atherothrombotic event whose myocardial infarction occurred one to three years ago. Risk factors are the following: age of at least 65 years, diabetes mellitus requiring medication, more than one previous myocardial infarction, multivessel coronary heart disease, or chronic renal impairment.

Ticagrelor at a dose of 60 mg is co-administered with ASA for prevention, whereas dosage of the initial treatment (myocardial infarction less than one year ago) is 90 mg. The Federal Joint Committee (G-BA) specified ASA monotherapy under continued basic therapy of the myocardial infarction and measures to achieve an adequate lifestyle as appropriate comparator therapy.

Benefit assessment on the basis of the PEGASUS study

The assessment was conducted based on the three-arm randomized study PEGASUS-TIMI 54. All patients received unblinded ASA as basic therapy and, blinded, ticagrelor in dosages of 60 mg or 90 mg or placebo. Data from the 60 mg arm and the placebo arm were compared for the benefit assessment. About three quarters of these patients complied with the approval, thus constituting the subpopulation relevant for the assessment.

Advantages in mortality and morbidity, but also disadvantages

An indication of an added benefit of the combination in comparison with ASA monotherapy was shown in all-cause mortality. There were also indications of an added benefit in the morbidity outcomes "cardiovascular mortality, nonfatal myocardial infarction and nonfatal stroke" as well as "myocardial infarction".

Data on health-related quality of life were not recorded in the study. In the outcome category of side effects, there was an indication of greater harm from ticagrelor regarding both discontinuation due to adverse events (including bleeding) and severe bleeding, and proof of greater harm from ticagrelor regarding dyspnoea.

These disadvantages did not completely outweigh the advantages, particularly in all-cause mortality. In summary, there is an indication of a minor added benefit of ticagrelor in combination with ASA in comparison with ASA monotherapy for the prevention of atherothrombotic events in patients at risk and a history of myocardial infarction.

Brintellix (vortioxetine) Renamed Trintellix (vortioxetine) in U.S. to Avoid Name Confusion

In continuation of my update on vortioxetine

Takeda Pharmaceuticals U.S.A., Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502) (collectively “Takeda”), and Lundbeck announced today that Brintellix(vortioxetine) will be marketed in the United States under the new name Trintellix(vortioxetine) starting in June of 2016. The vortioxetine product is a prescription medicine approved to treat Major Depressive Disorder (MDD) in adults. The formulation, indication and dosages of Trintellix remain the same as that of Brintellix.

This name change comes after receiving reports of name confusion in the marketplace between Brintellix and the anti-blood clotting therapy Brilinta® (ticagrelor). In response, Takeda and Lundbeck, in coordination with the U.S. Food and Drug Administration (FDA), determined that a name change would be the best way to minimize future product name confusion by patients and providers.

“Though the original name was fully screened prior to launch, after learning about name confusion issues with Brintellix and Brilinta, we quickly took action to educate healthcare professionals and pharmacies about the potential for name confusion,” said Thomas Harris, Vice President Global Regulatory Affairs at Takeda. “Takeda and Lundbeck then proactively worked with the FDA and decided to change the name of our product as we believe this action will help minimize future risk of patients inadvertently receiving the incorrect medication.”

“Even though the name of the product is changing, together with Takeda, we will work to ensure providers and patients are aware that the vortioxetine product itself has not changed. It’s still the same medication, dosing and expected outcomes,” said Gregg Pratt, Vice President, U.S. Regulatory Affairs at Lundbeck.

“Patient safety is our utmost priority at Takeda and Lundbeck,” said Ramona Sequeira, President, U.S. Business Unit at Takeda. “Together, with our partners at Lundbeck, we will initiate a robust communication campaign and actively work to ensure that patients, healthcare professionals and pharmacies have uninterrupted access to this important medication. We believe these actions speak to our goals of building our business around patients, trust and reputation.”

During the transition period this summer, healthcare providers can still prescribe, and patients will still have access to, the product under its current brand name. The newly named Trintellix will be available in June 2016. Additionally, markings on the Trintellix tablets will be identical to the markings on tablets prior to the name change. Trintellix will have new National Drug Code (NDC) numbers associated with the product. Individuals and healthcare professionals who have questions about Brintellix, Trintellix and/or the name change, should contact Takeda at 1-877-TAKEDA-7.

Errors involving Brintellix/Trintellix or any other products should be reported to the FDA MedWatch program online at www.fda.gov/medwatch.

About Brintellix (vortioxetine), now known as Trintellix (vortioxetine), in the United States

Brintellix (vortioxetine) Renamed Trintellix (vortioxetine) in U.S. to Avoid Name Confusion

Ticagrelor drug may reduce risk of dying following heart attack

In continuation of my update on ticagrelor 

Scientists from the University of Sheffield have discovered ground breaking clues as to how the pioneering heart drug ticagrelor might reduce the risk of dying following a heart attack, in comparison to previous standard treatments.

The new findings, published in Platelets, show that ticagrelor (see left structure above) may reduce the risk of dying as a result of a lung infection after suffering a heart attack compared to patients treated with the drug clopidogrel (see right structure below).

The analysis, which was led by researchers from the University of Sheffield and Uppsala University Sweden, is the latest to come from the PLATO study which originally included over 18,000 patients worldwide. 

In the initial PLATO study, the annual mortality rate for patients treated with clopidogrel was 5.9 per cent and this rate was significantly reduced to 4.5 per cent for patients treated with ticagrelor.

The extent of this reduced risk was unexpected, as previous similar trials had not been so successful in reducing mortality risk - prompting speculation as to the possible mechanisms for this benefit.

Professor Robert Storey said: "We have now shown that there were fewer deaths due to overwhelming bacterial infection (sepsis) in patients treated with ticagrelor, with lung infection accounting for the source of this sepsis in many cases.

"This is a surprising finding but does seem to provide a potential lead in explaining why ticagrelor saved so many lives in comparison to clopidogrel treatment.

"Ticagrelor not only has greater anticlotting activity compared to clopidogrel, which easily explains its greater effectiveness in preventing further heart attacks, but also has another property not possessed by clopidogrel that allows it to prevent adenosine from being cleared from the blood stream.

"Adenosine has many different effects in the body including influencing the activity of white blood cells that are involved in tackling pneumonia and other infections."

Ticagrelor drug may reduce risk of dying following heart attack

FDA approves AstraZeneca's anti-clotting drug Brilinta

 In continuation of my update on  Ticagrelor (Brilinta)......
FDA approves AstraZeneca's anti-clotting drug  Brilinta

New drug more effective than standard treatment to prevent heart-attack deaths

In continuation of my update on ticagrelor .....

Robert Storey, Professor of Cardiology at the University of Sheffield's Department of Cardiovascular Science, presented findings today that confirm one in five deaths in the year following a heart attack could be prevented if a new drug, ticagrelor (see structure), was used instead of the standard treatment, clopidogrel...

More...

Brilinta (Ticagrelor) better than Plavix. ?.......

W knew that, Astra-Zeneca,  in its PLATO clinical trial in mid-2009,  found that ticagrelor had better mortality rates than clopidogrel (9.8% vs. 11.7%, p<0.001) in treating patients with acute coronary syndrome. Patients given ticagrelor were less likely to die from vascular causes, heart attack, or stroke but had slightly greater chances of major bleeding which was non-significant (11.6 vs. 11.2, p=0.4). Like clopidogrel and ticlopidine, ticagrelor blocks ADP receptors of subtype P2Y₁₂. In contrast to the other antiplatelet drugs, the blockage is reversible. Moreover, it does not need hepatic activation, which could reduce the risk of drug interactions-which makes it special.

Now this has been further substantiated by Dr. Chris. Cannon, who claims that  clot-busting drug Ticagrelor (Brilinta), may soon take the place of Clopidogrel (Plavix) in treating patients with acute coronary syndrome, which includes angina and heart attack.

In a new trial (by Dr. Christopher Cannon, a cardiologist with Brigham and Women's Hospital and an associate professor of medicine at Harvard Medical School, both in Boston), the upstart drug ticagrelor (Brilinta) reduced the risk of second heart attacks and death without raising the risk of bleeding, as clopidogrel (Plavix) can do and the authors claim  that this is pretty compelling evidence from this trial that ticagrelor is better without any increased risk of bleeding. 

In this study (funded by AstraZeneca) of more than 13,000 patients with acute coronary syndrome, Brilinta, appears to be more potent than Plavix and has  emerged with several advantages over the old standby  claims the researchers.

Brilinta is s processed as soon as it's swallowed (meaning it doesn't have to go through the liver), and kicks in faster than Plavix, where as Plavix (usually in combination with aspirin) has its share of problems, namely a lag time between when it is administered and when it takes effect, and variability in how different individuals respond to it. And because of an increased risk of bleeding, Plavix must be discontinued before surgery. Overall the researchers, claim that Brilinta has a more reliable level of anti-clotting effect. There's less variability. At the dose, it has about twice the level of anti-clotting effect and hence the  benefit in preventing heart attacks and stent thrombosis. The authors attribute the reason for the superiority of the drug to its quicker reversblity (than Plavix) and patients could have surgery with a lower risk of bleeding. FDA is expected to approve the drug late this year and  hope the patients with thrombosis, angina and acute coronary syndrome will breathe a sigh of relief...

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2962191-7/fulltext