FDA Advisory Panel Gives Tepid Support To New Daiichi Sankyo Drug Reply

On Thursday the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-1 in favor of approval for Daiichi Sankyo’s edoxaban(Savaysa), but the outcome will likely result in a drug that will be on the market but that few physicians will prescribe until further studies are performed.

Click here to read the full post on Forbes.

Warfarin Benefits Extended To Patients with Chronic Kidney Disease Reply

Anticoagulation is a cornerstone of therapy for atrial fibrillation because it lowers the heightened risk for stroke in this population. People with chronic kidney disease are also at increased risk for stroke, but the benefits of anticoagulation are less clear in this group, and anticoagulation is used less often in AF patients who have CKD. Now, a large observational study offers some reassurance that anticoagulation in AF patients with CKD may be beneficial.

Researchers in Sweden analyzed data from more than 24,000 survivors of acute myocardial infarction who had AF….

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Problems Persist Despite Gains In Oral Anticoagulant Use Reply

Although significant progress has been made in recent years, a new survey from the European Society of Cardiology finds that there are still too many atrial fibrillation patients who are not taking the best medications to reduce their elevated risk of stroke. Many elderly patients are not receiving oral anticoagulants and overall too many patients are still taking aspirin, despite the fact that it is not recommended for this group of patients.

In a paper published in the American Journal of Medicine, Gregory YH Lip and colleagues analyzed data from more than 3,100 patients surveyed in the Euro Observational Research Programme on Atrial Fibrillation from February 2012 to March 2013.

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Atrial Fibrillation: Radiofrequency Catheter Ablation And Antiarrhythmic Drug Therapy Compared Reply

A trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drug therapy (AAD) as initial therapy for atrial fibrillation (AF) found no difference in the overall burden of AF between the groups. But the trial also turned up evidence supporting the use of RFA as an initial treatment strategy in some patients.

In a paper published in the New England Journal of Medicine, European investigators report on 294 patients with paroxysmal AF with no previous use of AADs who were randomized in the MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) trial. Patients– under 70 years of age and with no other major heart disease– were healthier than the general AF population.

The investigators found no significant differences in the cumulative burden of AF or the burden at  3, 6, 12, or 18 months. However, at 2 years the AF burden was significantly reduced in the RFA group compared with the AAD group (90th percentile of AF burden: 9% for RFA versus 18% for AAD, p=0.007). In addition, the percentage of patients with no AF and no symptomatic AF was higher in the RFA group than in the AAD group (85% vs. 71%, p=0.004; 93% vs. 84%, p=0.01, respectively). In the RFA group, there were three cases of cardiac tamponade in addition to one death after a procedure-related stroke. In the AAD group 36% of the patients received supplementary RFA.

The overall results, write the authors, “support the current guidelines recommending antiarrhythmic drugs as first-line treatment in most patients with paroxysmal atrial fibrillation.” However, the positive findings for RFA, as well as the high number of crossovers from AAD to RFA, suggest that “a substantial minority of patients” treated with AAD “may eventually require ablation for adequate rhythm control.”

In an accompanying editorial, William Stevenson and Christine Albert mention the “substantial procedural risks” associated with RFA and warn that the results should not be extrapolated to different patient populations, since the MANTRA-PAF population was younger and healthier than the general AF population. They express hope that the much larger CABANA (Catheter Ablation versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation) trial will provide more definitive evidence about RFA. RFA, they conclude, is “a reasonable option for patients with symptomatic paroxysmal atrial fibrillation before therapy with an antiarrhythmic drug.”

High Rate Of Warfarin Discontinuation Observed In Study Reply

One of the many potential problems with warfarin-based anticoagulant therapy is the poor rate of adherence and persistence among patients who are prescribed the drug. Now a new observational study published in Archives of Internal Medicine raises the possibility that the problem may be even worse than many may have previously suspected, as discontinuation rates in clinical trials appear to be much lower than in the real world.

Tara Gomes and colleagues analyzed data from more than 125,000 new users of warfarin in Ontario, Canada and found very high rates of discontinuation over time:

  • 8.9% never filled a second prescription
  • 31.8% discontinued warfarin within 1 year
  • 43.2% discontinued warfarin with 2 years
  • 61.3% discontinued warfarin within 5 years

People at higher risk for stroke, as assessed by the CHADS2 score, were more likely to continue taking warfarin over the course of the study.

In an invited commentary, Whitney Maxwell and Charles Bennett write that the results are consistent with previous observational studies but that warfarin discontinuation can be appropriate and is often initiated by the physician. “Appropriateness of anticoagulation discontinuation is perhaps a more important outcome to evaluate rather than absolute discontinuation rates,” they write. An additional plausible explanation for the study finding is that few patients in Canada were treated at anticoagulation clinics.

Maxwell and Bennett write that any potential problem with anticoagulation discontinuation is not limited to warfarin. In the RE-LY trial, they note, more patients discontinued therapy in the dabigatran arm than in the warfarin arm, and a similar trend was observed with rivaroxaban in ROCKET AF.

FDA Sets New Decision Date For Eliquis (Apixaban) Reply

The FDA will decide the fate of apixaban (Eliquis) by March 17, 2013. The new Prescription Drug User Fee Act (PDUFA) goal date was announced yesterday by the drug’s manufacturers, Pfizer and BristolMyers Squibb.

The new drug application (NDA) for stroke prevention in atrial fibrillation has been delayed twice. Although the pivotal ARISTOTLE trial was highly praised when it was first published, the FDA first extended its review by three months and then issued a complete response letter (CRL) on June 25 requesting “additional information on data management and verification from the ARISTOTLE trial.” According to Pfizer and BristolMyers Squibb, the FDA has now accepted for evaluation their response to the CRL.

In Europe last week the Committee for Medicinal Products for Human Use (CHMP) recommended approval for apixaban for the same indication.

Click here to read the press release from Pfizer and BMS…

In AF, Women Have A Bigger Risk Of Stroke Than Men Reply

When compared to elderly men with atrial fibrillation, elderly women with AF have a significantly elevated risk for stroke. This increased risk occurs regardless of warfarin use, according to a new study published in JAMA.

Meytal Avgil Tsadok and colleagues reviewed data from Quebec, Canada on more than 80,000 AF patients at least 65 years of age. Much of the increased risk occurred in women over the age of 75.

Overall crude stroke incidence:

  • Women versus men: 2.02 versus 1.61 per 100 person-years, p<0.001

The risk for stroke among women remained elevated after adjustment for baseline risk factors, individual components of the CHADS2 score, and warfarin treatment:

  • Adjusted hazard ratio: 1.14, CI 1.07-1.22, p<0.001

The authors wrote that “women older than 75 years represent the most important target population for stroke prevention in patients with AF, and the effectiveness of novel anticoagulants in this population in real-world practice will need to be closely monitored.”
Click here for the press release from JAMA…

Study Explores Role of Periprocedural Dabigatran in AF Ablation 1

Updated with a comment from John Mandrola– As dabigatran becomes more widely used in atrial fibrillation (AF) patients, electrophysiologists are now trying to figure out how to handle anticoagulation in patients taking dabigatran (Pradaxa) for whom AF ablation is planned. In a new study published in the Journal of the American College of Cardiology, Dhanunjaya Lakkireddy and colleagues report on a multicenter, observational study of 290 patients who underwent an AF ablation procedure. Half the patients were taking periprocedural dabigatran and half were matched controls taking warfarin.

There were significantly more thromboembolic  and bleeding complications in the dabigatran group than in the warfarin group:
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