First of Their Kind: Canadian Guidelines Specific to Antiplatelet Therapy

October 29, 2010

October 29, 2010 (Montreal, Quebec City) — The Canadian Cardiovascular Society (CCS) has issued guidelines, the first of their kind anywhere, specific to the use to antiplatelet therapy, including their use in multiple settings, such as primary and secondary prevention, as well as following PCI, CABG surgery, and in patients with peripheral arterial disease and diabetes.

The evidence-based document is intended for practical use and is designed to help healthcare professionals manage individuals who have or are at risk of developing vascular disease.

"We felt that although guidelines exist for the management of other cardiovascular risk factors, including hypertension, lipids, and diabetes, among others, in Canada there is really nothing to provide guidance to Canadian physicians on the use of antiplatelet therapy," Dr Alan Bell (University of Toronto, ON), the cochair of the antiplatelet-therapy guideline committee, told heartwire . "And it's really quite a confusing topic, with a number of drugs currently available on the market and new drugs approaching the market, so we felt it was important to provide guidance on the optimal use of these medications."

The new guidelines make recommendations on one of the more debated issues in interventional cardiology--namely, just how long an individual needs to take dual antiplatelet therapy. Following PCI with a bare-metal stent, the guideline committee recommends indefinite aspirin therapy, 75 to 162 mg daily, and clopidogrel 75 mg daily for at least one month and up to 12 months, in the absence of excessive bleeding risks. All patients who receive a drug-eluting stent should be prescribed clopidogrel 75 mg for 12 months in addition to indefinite aspirin therapy. Continuation of dual antiplatelet therapy beyond 12 months remains an option in acute coronary syndrome patients.

"In terms of coronary disease, we tried to define the duration of dual antiplatelet therapy post–acute coronary syndrome, with or without intervention," said Bell. "I think where we have stepped forward is stating clearly that dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor is appropriate to continue beyond one year in patients with a high thrombotic risk and low risk of bleeding. I think it provides license to physicians who would like to do that but who previously haven't seen guidelines suggesting it."

The new antiplatelet drug prasugrel is also given consideration, with the 10-mg daily dose recommended in addition to aspirin in patients with acute coronary syndrome who undergo stent implantation and who have an increased risk of stent thrombosis. The drug is to be avoided in certain patients, specifically in the elderly, lighter patients, those with an increased bleeding risk, and those with a history of stroke.

First Document of Its Kind

The new guidelines, cochaired by Dr Jean-Francois Tanguay (Montreal Heart Institute, QC), were presented this week at the Canadian Cardiovascular Congress 2010. Along with the antiplatelet guidelines, the CCS guideline committee also released new recommendations in the treatment of atrial fibrillation, reported by heartwire , and refractory angina.

Speaking with heartwire , Bell said that one important aspect of the new antiplatelet-therapy guidelines is that the writing committee recommends against the routine use of aspirin for primary prevention. The main rationale for not recommending routine aspirin use is the low event rate in primary prevention, said Bell.

"Data from a large number of studies tell us that the number needed to treat is extremely high and doesn't warrant therapy," he said. "In fact, in many patients, the risk of bleeding, although it is small, is of the same order as the reduction in cardiovascular events. So we agree that you do see impressive relative reductions in risk in primary prevention, but the absolute reductions are miniscule. We do allow an opening for physician discretion if they really feel the patient is at high risk because we don't have great data on these high-risk patients."

The new document provides guidance on the use of dual antiplatelet therapy in high-risk transient ischemic attack (TIA) patients or those with minor stroke. The committee recommends the daily use of aspirin 75 to 162 mg and clopidogrel 75 mg in the first month following TIA or minor ischemic stroke, stating the combination is superior to aspirin alone in patients not at high risk for bleeding.

The guidelines also outline how the antiplatelet medications should be used in patients who require surgery or other invasive procedures. For those receiving aspirin and undergoing a diagnostic test associated with a low risk of bleeding, aspirin can be continued without interruption, whereas it should be stopped seven to 10 days prior to noncardiac procedures that pose a higher risk for bleeds. For those on dual antiplatelet therapy, clopidogrel should also be stopped seven to 10 days prior if it can be done safely.

For patients who require elective surgery and who are being treated with clopidogrel and aspirin secondary to coronary stent implantation, the surgery should be put off for at least six weeks after a bare-metal-stent implantation and at least 12 months after a drug-eluting-stent implantation. If the surgery is urgent and within the six-week period following a bare-metal-stent implantation, clopidogrel and aspirin should be continued in the perioperative period, as they should be if the surgery falls within the first 12 months following a drug-eluting-stent implantation.

Role of COX-2 Inhibitors

In addition to these recommendations, the experts provide a road map for using antiplatelet therapies in patients with peripheral arterial disease, diabetes, heart failure, chronic kidney disease, and in women who are pregnant or breast-feeding. They also make recommendations on how to manage important drug interactions, such as between clopidogrel and proton-pump inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs).

According to Bell and the writing committee, there is evidence that in patients taking aspirin for cardiovascular prevention who require an anti-inflammatory drug, a COX-2 inhibitor might be a better choice over other NSAIDs. However, Bell noted that the recommendation is based mostly on secondary analyses, and not a1 evidence. "Some traditional anti-inflammatory drugs, such as ibuprofen, can block the effects of aspirin, where as COX-2 inhibitors do not."

Asked about the potential role of genetic testing for clopidogrel nonresponsiveness, Bell told heartwire that the writing committee chose not to make a specific statement because the new guidelines are meant to be a practical application for all physicians, many of whom are primary-care physicians and many of whom work in smaller communities. "Very few physicians have access to genetic testing," he said.

In addition, the evidence regarding genetic testing for cytochrome P450 loss-of-function alleles is weak and not a major determinant of clopidogrel action, said Bell. The writing group plans to comment on the role of platelet-function testing in the near future but is waiting for the results of the GRAVITAS trial as well as waiting for information about the availability of the platelet-function assay before doing so.

The guidelines are expected to be published in the Canadian Journal of Cardiology in the near future.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.