Point/Counter

Should anticoagulation for cancer-associated thrombosis extend beyond 6 months?

Click here to read the Cover Story, “Prospective trials, society guidelines offer new insights into cancer-associated thrombosis.”

Point

Yes.

However, this depends on a case-by-case basis, and it also could depend on the type of anticoagulant used.

Marc Carrier
After 6 months of anticoagulation, if there is still an underlying cancer or if the patient is still undergoing anticancer treatment, then anticoagulation needs to continue to prevent a second clot.

However, in order for physicians to decide if they should extend prophylaxis beyond 6 months, the risk for VTE recurrence needs to be higher than the potential risk of the intervention.

Patients are at increased risk for bleeding if they continue anticoagulation. VTE among patients with cancer is associated with high morbidity, which is why we want to continue some form of anticoagulation to prevent VTE recurrence. The majority of VTE cases occur among patients with advanced cancer and metastatic disease; thus, these patients certainly will need to continue anticoagulation beyond 6 months to prevent recurrent VTE.

Of note, guidelines for anticoagulation for patients who do not have cancer but previously had a clot recommend long-term use of anticoagulation for those who are not at increased risk for bleeds. This also applies to the cancer population, because there is an ongoing risk factor.

There is a very small percentage of patients for whom we can certainly stop anticoagulation: those who will have their tumor removed during surgery and who stop cancer treatment. However, this represents such a small fraction of patients, so a significant majority will need to continue anticoagulants long term.

It is debatable whether the anticoagulant should be low-molecular-weight heparin injections or the newer direct anticoagulant oral tablets. There is no right answer, because there are very little data comparing the injectable form of blood thinners with oral tablets. This is a matter of sitting down with each patient and discussing their best option with them. Still, a majority of patients will need to continue anticoagulation past 6 months. Only a small percentage can stop prophylaxis after 6 months.

Marc Carrier, MD, MSc, is senior scientist in the clinical epidemiology program at The Ottawa Hospital Research Institute. He can be reached at mcarrier@toh.ca. Disclosure: Carrier reports no relevant financial disclosures.

Counter

No.

Although the treatment of cancer-associated thrombosis in the first 6 months is based on meta-analysis of several randomized controlled trials, the data beyond this time point are considerably lacking.

Simon Noble
In the presence of ongoing active cancer, the thrombotic risk is arguably ongoing and indefinite anticoagulation seems justified. Clinical guidelines are consistent in their recommendations, acknowledging the limited data and suggesting a decision needs to be made on an individual patient basis, taking into consideration patient preference and bleeding risk.

However, the data on VTE recurrence with or without continued anticoagulation are limited, and it is impossible to advise whether a patient’s risk for VTE exceeds the bleeding risk of ongoing anticoagulation. Further, there are even less data supporting any particular anticoagulant of choice.

At a time in medicine when targeted oncology treatments may be so precise that anticancer therapies are offered according to the presence or absence of molecular biomarkers, it seems ludicrous that we have yet to identify definitive data to inform the management of cancer-associated thrombosis beyond 6 months. However, three well-designed randomized controlled trials with differing interventions have failed to recruit sufficient patients to answer this important question.

This leaves clinicians with little to guide them beyond observational studies, registry data and their own heuristic laden, clinical experience. The best decision tools and algorithms are only as good as the extrapolated data and clinical conjecture they contain and, in the unselected prospective comparative data, we are, to some degree, treating our patients blind — or, in the very least, myopically.

Historically, the outcomes of decision-making at the 6-month point were of little clinical or economic consequence. Patients rarely lived a further 6 months. Now, patients are living longer with metastatic disease, and they may continue to receive chemotherapy and targeted anticancer therapies long after the initial cancer-associated thrombosis episode.

A blanket policy supporting indefinite anticoagulation fails to adequately consider the very real risk of major hemorrhage so long as the patient with cancer remains on such drugs.

In preselected populations, 3% to 4% of patients with cancer-associated thrombosis experience major bleeding over months 6 to 12, with increased bleeding as the cancer progresses.

For now, at least, we should take a break from producing clinical guidance in areas of data drought and concentrate our efforts on fertilizing the field with new information, no matter what the challenges may be.

Simon Noble, MBBS, PGCE, DipPalMed, MD, FRCP, is clinical reader in palliative medicine at Cardiff University in the United Kingdom. He can be reached at noblesi1@cardiff.ac.uk. Disclosure: Noble reports no relevant financial disclosures.

Click here to read the Cover Story, “Prospective trials, society guidelines offer new insights into cancer-associated thrombosis.”

Point

Yes.

However, this depends on a case-by-case basis, and it also could depend on the type of anticoagulant used.

Marc Carrier
After 6 months of anticoagulation, if there is still an underlying cancer or if the patient is still undergoing anticancer treatment, then anticoagulation needs to continue to prevent a second clot.

However, in order for physicians to decide if they should extend prophylaxis beyond 6 months, the risk for VTE recurrence needs to be higher than the potential risk of the intervention.

Patients are at increased risk for bleeding if they continue anticoagulation. VTE among patients with cancer is associated with high morbidity, which is why we want to continue some form of anticoagulation to prevent VTE recurrence. The majority of VTE cases occur among patients with advanced cancer and metastatic disease; thus, these patients certainly will need to continue anticoagulation beyond 6 months to prevent recurrent VTE.

Of note, guidelines for anticoagulation for patients who do not have cancer but previously had a clot recommend long-term use of anticoagulation for those who are not at increased risk for bleeds. This also applies to the cancer population, because there is an ongoing risk factor.

There is a very small percentage of patients for whom we can certainly stop anticoagulation: those who will have their tumor removed during surgery and who stop cancer treatment. However, this represents such a small fraction of patients, so a significant majority will need to continue anticoagulants long term.

It is debatable whether the anticoagulant should be low-molecular-weight heparin injections or the newer direct anticoagulant oral tablets. There is no right answer, because there are very little data comparing the injectable form of blood thinners with oral tablets. This is a matter of sitting down with each patient and discussing their best option with them. Still, a majority of patients will need to continue anticoagulation past 6 months. Only a small percentage can stop prophylaxis after 6 months.

Marc Carrier, MD, MSc, is senior scientist in the clinical epidemiology program at The Ottawa Hospital Research Institute. He can be reached at mcarrier@toh.ca. Disclosure: Carrier reports no relevant financial disclosures.

Counter

No.

Although the treatment of cancer-associated thrombosis in the first 6 months is based on meta-analysis of several randomized controlled trials, the data beyond this time point are considerably lacking.

Simon Noble
In the presence of ongoing active cancer, the thrombotic risk is arguably ongoing and indefinite anticoagulation seems justified. Clinical guidelines are consistent in their recommendations, acknowledging the limited data and suggesting a decision needs to be made on an individual patient basis, taking into consideration patient preference and bleeding risk.
PAGE BREAK

However, the data on VTE recurrence with or without continued anticoagulation are limited, and it is impossible to advise whether a patient’s risk for VTE exceeds the bleeding risk of ongoing anticoagulation. Further, there are even less data supporting any particular anticoagulant of choice.

At a time in medicine when targeted oncology treatments may be so precise that anticancer therapies are offered according to the presence or absence of molecular biomarkers, it seems ludicrous that we have yet to identify definitive data to inform the management of cancer-associated thrombosis beyond 6 months. However, three well-designed randomized controlled trials with differing interventions have failed to recruit sufficient patients to answer this important question.

This leaves clinicians with little to guide them beyond observational studies, registry data and their own heuristic laden, clinical experience. The best decision tools and algorithms are only as good as the extrapolated data and clinical conjecture they contain and, in the unselected prospective comparative data, we are, to some degree, treating our patients blind — or, in the very least, myopically.

Historically, the outcomes of decision-making at the 6-month point were of little clinical or economic consequence. Patients rarely lived a further 6 months. Now, patients are living longer with metastatic disease, and they may continue to receive chemotherapy and targeted anticancer therapies long after the initial cancer-associated thrombosis episode.

A blanket policy supporting indefinite anticoagulation fails to adequately consider the very real risk of major hemorrhage so long as the patient with cancer remains on such drugs.

In preselected populations, 3% to 4% of patients with cancer-associated thrombosis experience major bleeding over months 6 to 12, with increased bleeding as the cancer progresses.

For now, at least, we should take a break from producing clinical guidance in areas of data drought and concentrate our efforts on fertilizing the field with new information, no matter what the challenges may be.

PAGE BREAK

Simon Noble, MBBS, PGCE, DipPalMed, MD, FRCP, is clinical reader in palliative medicine at Cardiff University in the United Kingdom. He can be reached at noblesi1@cardiff.ac.uk. Disclosure: Noble reports no relevant financial disclosures.