Latest Canadian AF Guidelines Encourage New Oral Anticoagulants

March 22, 2012

March 21, 2012 (London, Ontario, Canada) — The Canadian Cardiovascular Society has updated its guidelines on atrial fibrillation to reflect some major new findings that have been reported during the past year or so [1].

The new update, published in the March 2012 issue of the Canadian Journal of Cardiology, adds to the most recent version of the Canadian AF guidelines published in 2010. Lead author of the new update, Dr Allan Skanes (University of Western Ontario, London), told heartwire that the guidelines committee felt an update was needed, as so much had happened in 2011, including new trials with the new oral anticoagulants rivaroxaban and apixaban and the PALLAS study with dronedarone.

Support for the new drugs

Notable in the new update is support for the oral anticoagulant drugs, which are said to be "preferable" to warfarin for most patients. Skanes said this may be one step further than many other national guidelines, which have simply said the new drugs can be considered as alternatives to warfarin.

The update states: "When oral anticoagulant therapy is indicated, most patients should receive dabigatran, rivaroxaban, or apixaban (once approved by Health Canada), in preference to warfarin (conditional recommendation, high-quality evidence)."

Skanes commented to heartwire : "The 2010 guidelines made a soft recommendation for dabigatran over warfarin, and we have now extended this to rivaroxaban and apixaban." Even though apixaban is not yet available in Canada for this indication, Skanes said the guidelines committee felt it would be approved fairly soon, and they didn't want to have to make a further update.

He added: "We are nudging toward the new agents. This is because two of them have been shown superior to warfarin in reducing stroke, and across the board they all reduce intracranial hemorrhage, which is the worst problem with warfarin."

But the guidelines temper their enthusiasm somewhat for the new agents in patients managing well on warfarin. They state: "The preference for one of the new oral anticoagulants over warfarin is less marked among patients already receiving warfarin with stable INRs and no bleeding complications."

Caution in elderly and renal dysfunction

The update also advises on dose reductions in the elderly, saying: "Among patients over 75 years and certainly those over 80 years, dose reduction of the new oral anticoagulants, especially dabigatran, should be considered."

Skanes commented: "We have done our best to highlight when to reduce the dose by using a 'practical tip' rather than a recommendation, as the data are not strong enough for a full recommendation."

Similarly, for patients with reduced renal function, the guidelines suggest that while patients with mild to moderate kidney dysfunction — glomerular filtration rate (GFR) of 30 to 50 mL/min — can be treated with normal doses of the new oral anticoagulants, they need more frequent measures of kidney function and may need dose reductions with conditions that may transiently reduce GFR. This is especially true in the elderly (age older than 75 years), as bleeding risk increases with age.

For patients with more severe renal dysfunction (GFR 15-30 mL/min), the guidelines suggest warfarin would be the preferred agent. About this group, Skanes said: "There are very little data on the new drugs in this group, and so we would prefer physicians to stick with warfarin, which they are more familiar with."

For patients with a GFR < 15 who would be on dialysis, the guidelines do not recommend any routine antithrombotic therapy.

Stick to warfarin where there are few data on new drugs

For ACS patients, no firm recommendations are made on the use of the new anticoagulants. Skanes commented: "This is a very challenging area for the use of any anticoagulation, as the patients will already be on dual antiplatelet therapy. Many physicians will start on triple therapy and then stop aspirin, but we have little data on this. We don't even know how to use warfarin in this situation, never mind the new drugs."

He noted that although there were some new data now on rivaroxaban in ACS patients (from ATLAS), this had not yet been incorporated into the guidelines. He added: "I would say that if physicians are comfortable using warfarin in these patients, they should stick to warfarin for the time being."

Some CHA2DS2-VASc factors considered for risk prediction

Another section of the update deals with the prediction of stroke risk for the decision on which patents need anticoagulation.

Skanes explained that the last Canadian guidelines used the CHADS2 score, while the latest European guidelines have started to recommend the newer CHA2DS2-VASc score.

"We stopped short of going wholeheartedly for the CHA2DS2-VASc score, but we have incorporated some of its features. We were more impressed with increasing age as a risk factor, but not so much with female sex."

The end result is that oral anticoagulation is recommended for all patients at high or intermediate risk (CHADS2 score ≥1), but the guidelines have made some changes regarding the low-risk patients (CHADS2 risk score of 0). Skanes said: "We advise that those at highest risk within this low-risk category (age greater than age 65 or the combination of female sex and vascular disease) should get oral anticoagulation; female patients or those with vascular disease should receive aspirin; and those without any of these risks factors do not need any antithrombotic therapy."

New dronedarone advice from PALLAS

The final major highlight of the new update is new advice on dronedarone following the PALLAS trial. This recommends against using the drug in AF patients with permanent AF or for the sole purpose of rate control or in patients with a history of CHF or a left ventricular ejection fraction below 40%. It also cautions on use of dronedarone with digoxin.

Skanes commented: "We really don't know what drove the adverse events in PALLAS, so they have been attributed to differences in the patient population between PALLAS and ATHENA (which showed better results)."