Thrombosis Guidelines Provide Weak Recommendation of Aspirin

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Thrombosis Guidelines Provide Weak Recommendation of Aspirin

CLINICAL CONTEXT
The ninth edition of the Antithrombotic Therapy and Prevention of Thrombosis: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines is based, in part, on a systematic review of patients' values and preferences regarding antithrombotic therapy. Each guideline section was written by clinicians expert in methodology and interpretation of the evidence, rather than by world experts in the field of antithrombotics as in previous years.

The latest recommendations also acknowledge the limitations of using asymptomatic thrombosis as a surrogate outcome, and they incorporate strategies to estimate reductions in symptomatic deep vein thrombosis and pulmonary embolism with antithrombotic prophylaxis. Other new features include an article on diagnosing patients with symptoms and signs suggesting deep vein thrombosis, an increased range of described interventions, and many tables summarizing the findings.

STUDY SYNOPSIS AND PERSPECTIVE
New thrombosis guidelines from the American College of Chest Physicians have come down in favor of aspirin use for primary prevention in adults over 50 years old [1].

Lead author of the coronary artery disease chapter of the guidelines, Dr Per Vandvik (Gjøvik Hospital, Oslo, Norway), noted that these are thought to be the first major guidelines to come out after the studies suggesting a reduction in cancer risk and mortality with aspirin were reported, and "incorporating these data pushed us to give aspirin a weak recommendation in primary prevention."

Vandvik added: "I would say the cardiovascular benefit and the bleeding risk is pretty much well balanced, but the suggestion of a benefit in mortality may just swing the balance over to taking aspirin." But he stressed that this was not a blanket recommendation. "Doctors need to talk to their patients about it, and it is something they might want to consider."

The ninth edition of the Antithrombotic Therapy and Prevention of Thrombosis Guidelines, published in the February 2012 issue of Chest, states: "People who are averse to taking medication over a prolonged time period for very small benefits will be disinclined to use aspirin for primary prophylaxis. Individuals who value preventing an MI [myocardial infarction] substantially higher than avoiding a GI [gastrointestinal] bleed will be, if they are in the moderate or high cardiovascular risk group, more likely to choose aspirin."

Head of the guidelines committee, Dr Gordon Guyatt (McMaster University, Hamilton, ON), added: "We agonized over this recommendation endlessly, with some heated discussions. Some people thought we should recommend aspirin for everyone; others were adamant that no primary-prevention patient should take it. The right message is that there are trade-offs to be made and a lot of uncertainty. In this situation, it is inevitable that individual patient values and preferences will bear in the decision."

He noted that this approach of collaborating with the patient in making the decision to take antithrombotic therapy or not was a big feature throughout these guidelines. "In many cases, the trade-offs between benefit and risk are very small, so we need to ask the patient more questions, really push for information to make the decision as to whether antithrombotic treatment is the right way to go."

Opinion Leaders Less Involved Than Before

Guyatt also explained that there were big process changes in the way the guidelines were formulated this time. In particular, instead of having world experts in the field of antithrombotics in charge of each guideline section, it was decided this year to choose instead clinicians who were experts in methodology and interpretation of the evidence. "It was felt that the experts in the field were maybe a little too close to the information, and they often have intellectual and/or financial conflicts. While thrombosis experts were still included on the panel, they did not have the same weight as in previous occasions."

Vandvik added: "If you performed the study that we were referring to you could not participate in the final discussions of what recommendations should be made."

Asked what the antithrombotics experts on the panel thought of the new system, Guyatt said, "We made a lot of converts because our approach was so rigorous. Most acknowledged that it was a superior process. Some, however, were still a little grumpy!" Vandvik added: "This is somewhat an experiment, in terms of the academic conflict of interest, but I think it will catch on."

Less Strong Recommendations

Not surprisingly, this new process has resulted in a set of guidelines that recommends antithrombotic treatment less often and less strongly than before. "The guidelines panel felt that the strength of the evidence in favor of antithrombotic therapy was less than has been thought in the past. Consequently, our recommendations tend to be weaker than in previous guidelines," Guyatt says. "There is recognition that not everyone in the hospital needs antithrombotic therapy, and we need to individualize such therapy more.

"From an outside view, it appears that antithrombotics may have been used a little too much in North America, although the situation is very variable," he adds. "In many cases, the risk of thrombosis is very small, and this has to be balanced by the risk of bleeding, the cost, and the inconvenience," Guyatt noted.

He explained that in making this trade-off, one stroke was thought to be equal to three bleeds. He gave the example of an atrial fibrillation (AF) patient at a low risk of stroke. If a patient has a 1% risk of stroke over a year, and this risk is halved by antithrombotic treatment, 200 patients would need to be treated to prevent one stroke. But if the bleeding risk was 3%, that would mean six bleeds in the 200 patients, with the balance of six bleeds vs one stroke going against antithrombotic treatment.

However, in another patient with a 6% risk of stroke and a 3% risk of bleeding, this would translate into six strokes vs three bleeds, so antithrombotic therapy would be the right option in this case.

"We have got to be much more quantitative than we have been in the past. We may not have the greatest ways of assessing stroke and bleeding risk, but we have to offer clinicians something," Guyatt says. The guidelines have opted for the congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, prior stroke or transient ischemic attack (CHADS2) score for stroke, rather than the CHA2DS2-VASc score as the first choice. "We also need to consider the values and preferences of the patient. Some people are more stroke averse; others are more bleeding averse. Some will be better than others at managing warfarin."

The guidelines do not advise passengers on long-haul flights to take antithrombotic prophylaxis unless they have known risk factors. Guyatt says: "The risk is very small. If your risk of [venous thromboembolism] VTE is one in 1000 and a long-haul flight doubles this risk, then your risk is still very low. But if your baseline risk is one in 100, then it would become one in 50, and then you start to worry."

Dabigatran Recommended for AF

But the guidelines do appear to welcome the new oral anticoagulants as an alternative to warfarin. For patients with atrial fibrillation in whom oral anticoagulants are indicated (CHADS2 score of >1), they recommend dabigatran rather than warfarin as long as the patient does not have severe renal impairment.

Ticagrelor Preferred Over Clopidogrel in ACS

The guidelines also include a recommendation for the use of ticagrelor (Brilinta, AstraZeneca) in place of clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) for patients in the first year after an acute coronary syndrome (ACS) who have been treated with or without percutaneous coronary intervention. AstraZeneca issued a press release on this highlighting the fact that this is the first time that clinical-treatment guidelines in the US have specifically suggested the use of ticagrelor over clopidogrel.

The latest European Society of Cardiology guidelines on ACS, released last September, also favor the newer antiplatelet agents over clopidogrel but include prasugrel (Effient, Lilly) as well as ticagrelor as preferable options.

Related Link

The US Preventive Services Task force guideline on Aspirin for the Prevention of Cardiovascular Disease is available online.

References

Guyatt GH, Akl EA, Crowther M, et al. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141(2)(Suppl):7S–47S.