Dr. Joseph Mills

Introduction

As evidenced by this month’s Point/Counterpoint article by Dr. William Jordan and Dr. Joseph Mills, there is still debate as to the benefit of antiplatelet agents in patients with peripheral artery disease. Currently, dual antiplatelet agents refer to aspirin and clopidogrel, but over the last year or two, ticagrelor and vorapaxar are also being prescribed for patients with peripheral atherosclerosis. The addition of these medications will probably only add to our confusion! Why don’t you weigh in on this discussion by voting on our online poll at www.vascularspecialistonline.com? ­

Dr. Russell Samson is the medical editor of Vascular Specialist.

Definitely, maybe.

William D. Jordan, M.D.

First, primary prevention must be considered, as few patients with no prior intervention require dual antiplatelet therapy. It seems that we only have some scant data on the prevention of first-time events in at-risk patients when they are treated with aspirin alone.

While lipid management seems to be the most recent focus for primary prevention, single antiplatelet therapy seems appropriate for many patients who have higher risk due to atherosclerotic disease. A recent study from the University of Alabama at Birmingham found that asymptomatic carotid artery stenosis patients treated with dual antiplatelet therapy actually had higher bleed rates, higher mortality, and lower neurologic event rates, compared with those treated with aspirin alone.

While this study examined only a select group of patients treated for carotid artery disease, these vascular patients had worse outcomes when treated with aspirin and clopidogrel. Thus, caution should be considered before adding too many medical therapies.

Now, consider the short-term outlook for patients – specifically those who undergo some type of vascular intervention. The very nature of vascular intervention is disruptive to the arterial endothelium. Of course, most of the arteries that we enter have some underlying pathology; thus the intimal layer is not normal. The pathologic process is already, at least, partly underway. The concept of antiplatelet therapy is focused on limiting the platelet adhesions that might exaggerate the response to injury that creates a hyperplastic reaction within the vessels. We abhor the excessive response to injury due to the potential failure of the arterial reconstruction. Paradoxically, the same platelet inhibition can also cause excessive bleeding that may complicate the vascular repair. In the current medical climate, most of us tolerate the aggravation of diminished platelet function during open reconstruction in order to protect the target repair site and to avoid the dreaded “troponin leak” that may get classified as a myocardial infarction.

Some of our nonvascular colleagues avoid intervention (e.g., axial anesthesia, endoscopic biopsy) if stronger antiplatelet medication is present.

Now, to borrow some insight from other specialties, we should consider the extensive cardiology literature that shows the value of dual platelet inhibition after percutaneous coronary intervention or a recent cardiac event. While this strategy has shown improvement in PCI results, probably due to the great risk of thrombosis when disrupting the endothelial layer of a 2- to 3-mm coronary artery, the bleeding complications, including access-site hematomas, pseudoaneurysms, or retroperitoneal bleeding, are not analyzed as extensively. The preponderance of literature supports aggressive inhibition, but the long term needs to be considered – both expense and bleeding risk.

Currently, we use short-term dual treatment when the arterial endothelium is intentionally disrupted such as after an endarterectomy, angioplasty, with or without a stent, or atherectomy. Specifically, we add short-term IV dextran to oral agents for patients undergoing a carotid endarterectomy, but most are discharged on a single oral agent unless there is another indication for dual therapy.

Patients undergoing lower-extremity, catheter-based interventions are given dual therapy for the first 30 days, which is then adjusted according to the clinical response, duplex findings and other medical conditions. Bypass graft patients (yes, we still do some) are usually given a single agent unless the graft or patient has exhibited some concern for early failure.

In summary, I suspect that dual therapy is overused in our “pill-driven” population, but there still seem to be areas for its application. On each encounter with patients, I would encourage all vascular specialists to review the indications for antiplatelet therapy to consider removing a medication, improving compliance, and limiting bleeding risk.

Dr. Jordan is the director of the division of vascular surgery at the University of Alabama Birmingham School of Medicine. He has no relevant conflicts.

Dueling over dual antiplatelet therapy

Joseph L. Mills Sr., M.D.

Amidst a background of constant clamoring for data-driven and evidence-based medical decision-making, the practice of vascular medicine and surgery remains mired in the anecdotal. If a little is good, more must be better, seems the rationale for dual antiplatelet therapy. There may be small, as yet unclearly defined subsets of patients for whom dual therapy is actually beneficial, but an unbiased review of the current literature leads to the inescapable conclusion that more patients would be harmed by injudicious application of the more-is-better principle as concerns antiplatelet therapy for patients with carotid artery and peripheral artery disease (PAD).

The best evidence for antiplatelet therapy in patients with carotid disease suggests that aspirin as a single agent in doses ranging from 75 to 150 mg daily is preferred, and at least two meta-analyses and systematic reviews were unable to support the use of dual antiplatelet therapy.¹ At least in symptomatic patients, combination or dual antiplatelet therapy may increase the short-term risk of hemorrhagic complications in patients with acute ischemic stroke caused by large-artery disease.² Long-term dual therapy for secondary stroke prevention with aspirin and clopidogrel has been associated with four times the bleeding risk of monotherapy.³ These bleeds are often intracranial or gastrointestinal and are serious.

With respect to asymptomatic patients, while the CHARISMA trial did demonstrate a modest reduction in subsequent thrombotic events in a subset analysis of patients with stable, preexisting vascular disease, the bottom line was that dual antiplatelet therapy was associated with a 4% risk of moderate to severe bleeding and that there were strong correlations between moderate bleeding and all cause mortality (hazard ratio, 2.55), myocardial infarction (HR, 2.92) and stroke (HR, 4.2).⁴ The bleeding risk of dual antiplatelet therapy thus seems to outweigh the benefits.

Other data muddy the situation, but only a little. While at least two small studies (one a randomized controlled trial – CARESS [Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis])⁵ have suggested that the combination of aspirin and clopidogrel may reduce the frequency of perioperative microembolic signals detected early after carotid endarterectomy compared with monotherapy, it is not established that this surrogate measure would translate into long-term clinical benefit and would outweigh the established bleeding risk of dual therapy.

At present, the vascular surgeon should urge his patients to stop smoking, prescribe a statin, control blood pressure (but not necessarily with a beta-blocker), control diabetes, and prescribe a single antiplatelet agent, most often baby aspirin, for most of his or her patients. More good than harm will result.

References

Dr. Mills is professor of surgery and chief, division of vascular and endovascular surgery, University of Arizona Health Sciences Center, Tucson, and an associate medical editor for Vascular Specialist. He has no relevant conflicts.

Introduction

As evidenced by this month’s Point/Counterpoint article by Dr. William Jordan and Dr. Joseph Mills, there is still debate as to the benefit of antiplatelet agents in patients with peripheral artery disease. Currently, dual antiplatelet agents refer to aspirin and clopidogrel, but over the last year or two, ticagrelor and vorapaxar are also being prescribed for patients with peripheral atherosclerosis. The addition of these medications will probably only add to our confusion! Why don’t you weigh in on this discussion by voting on our online poll at www.vascularspecialistonline.com? ­

Dr. Russell Samson is the medical editor of Vascular Specialist.

Definitely, maybe.

William D. Jordan, M.D.

First, primary prevention must be considered, as few patients with no prior intervention require dual antiplatelet therapy. It seems that we only have some scant data on the prevention of first-time events in at-risk patients when they are treated with aspirin alone.

While lipid management seems to be the most recent focus for primary prevention, single antiplatelet therapy seems appropriate for many patients who have higher risk due to atherosclerotic disease. A recent study from the University of Alabama at Birmingham found that asymptomatic carotid artery stenosis patients treated with dual antiplatelet therapy actually had higher bleed rates, higher mortality, and lower neurologic event rates, compared with those treated with aspirin alone.

While this study examined only a select group of patients treated for carotid artery disease, these vascular patients had worse outcomes when treated with aspirin and clopidogrel. Thus, caution should be considered before adding too many medical therapies.

Now, consider the short-term outlook for patients – specifically those who undergo some type of vascular intervention. The very nature of vascular intervention is disruptive to the arterial endothelium. Of course, most of the arteries that we enter have some underlying pathology; thus the intimal layer is not normal. The pathologic process is already, at least, partly underway. The concept of antiplatelet therapy is focused on limiting the platelet adhesions that might exaggerate the response to injury that creates a hyperplastic reaction within the vessels. We abhor the excessive response to injury due to the potential failure of the arterial reconstruction. Paradoxically, the same platelet inhibition can also cause excessive bleeding that may complicate the vascular repair. In the current medical climate, most of us tolerate the aggravation of diminished platelet function during open reconstruction in order to protect the target repair site and to avoid the dreaded “troponin leak” that may get classified as a myocardial infarction.

Some of our nonvascular colleagues avoid intervention (e.g., axial anesthesia, endoscopic biopsy) if stronger antiplatelet medication is present.

Now, to borrow some insight from other specialties, we should consider the extensive cardiology literature that shows the value of dual platelet inhibition after percutaneous coronary intervention or a recent cardiac event. While this strategy has shown improvement in PCI results, probably due to the great risk of thrombosis when disrupting the endothelial layer of a 2- to 3-mm coronary artery, the bleeding complications, including access-site hematomas, pseudoaneurysms, or retroperitoneal bleeding, are not analyzed as extensively. The preponderance of literature supports aggressive inhibition, but the long term needs to be considered – both expense and bleeding risk.

Currently, we use short-term dual treatment when the arterial endothelium is intentionally disrupted such as after an endarterectomy, angioplasty, with or without a stent, or atherectomy. Specifically, we add short-term IV dextran to oral agents for patients undergoing a carotid endarterectomy, but most are discharged on a single oral agent unless there is another indication for dual therapy.

Patients undergoing lower-extremity, catheter-based interventions are given dual therapy for the first 30 days, which is then adjusted according to the clinical response, duplex findings and other medical conditions. Bypass graft patients (yes, we still do some) are usually given a single agent unless the graft or patient has exhibited some concern for early failure.

In summary, I suspect that dual therapy is overused in our “pill-driven” population, but there still seem to be areas for its application. On each encounter with patients, I would encourage all vascular specialists to review the indications for antiplatelet therapy to consider removing a medication, improving compliance, and limiting bleeding risk.

Dr. Jordan is the director of the division of vascular surgery at the University of Alabama Birmingham School of Medicine. He has no relevant conflicts.

Dueling over dual antiplatelet therapy

Joseph L. Mills Sr., M.D.

Amidst a background of constant clamoring for data-driven and evidence-based medical decision-making, the practice of vascular medicine and surgery remains mired in the anecdotal. If a little is good, more must be better, seems the rationale for dual antiplatelet therapy. There may be small, as yet unclearly defined subsets of patients for whom dual therapy is actually beneficial, but an unbiased review of the current literature leads to the inescapable conclusion that more patients would be harmed by injudicious application of the more-is-better principle as concerns antiplatelet therapy for patients with carotid artery and peripheral artery disease (PAD).

The best evidence for antiplatelet therapy in patients with carotid disease suggests that aspirin as a single agent in doses ranging from 75 to 150 mg daily is preferred, and at least two meta-analyses and systematic reviews were unable to support the use of dual antiplatelet therapy.¹ At least in symptomatic patients, combination or dual antiplatelet therapy may increase the short-term risk of hemorrhagic complications in patients with acute ischemic stroke caused by large-artery disease.² Long-term dual therapy for secondary stroke prevention with aspirin and clopidogrel has been associated with four times the bleeding risk of monotherapy.³ These bleeds are often intracranial or gastrointestinal and are serious.

With respect to asymptomatic patients, while the CHARISMA trial did demonstrate a modest reduction in subsequent thrombotic events in a subset analysis of patients with stable, preexisting vascular disease, the bottom line was that dual antiplatelet therapy was associated with a 4% risk of moderate to severe bleeding and that there were strong correlations between moderate bleeding and all cause mortality (hazard ratio, 2.55), myocardial infarction (HR, 2.92) and stroke (HR, 4.2).⁴ The bleeding risk of dual antiplatelet therapy thus seems to outweigh the benefits.

Other data muddy the situation, but only a little. While at least two small studies (one a randomized controlled trial – CARESS [Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis])⁵ have suggested that the combination of aspirin and clopidogrel may reduce the frequency of perioperative microembolic signals detected early after carotid endarterectomy compared with monotherapy, it is not established that this surrogate measure would translate into long-term clinical benefit and would outweigh the established bleeding risk of dual therapy.

At present, the vascular surgeon should urge his patients to stop smoking, prescribe a statin, control blood pressure (but not necessarily with a beta-blocker), control diabetes, and prescribe a single antiplatelet agent, most often baby aspirin, for most of his or her patients. More good than harm will result.

References

Dr. Mills is professor of surgery and chief, division of vascular and endovascular surgery, University of Arizona Health Sciences Center, Tucson, and an associate medical editor for Vascular Specialist. He has no relevant conflicts.

Introduction

As evidenced by this month’s Point/Counterpoint article by Dr. William Jordan and Dr. Joseph Mills, there is still debate as to the benefit of antiplatelet agents in patients with peripheral artery disease. Currently, dual antiplatelet agents refer to aspirin and clopidogrel, but over the last year or two, ticagrelor and vorapaxar are also being prescribed for patients with peripheral atherosclerosis. The addition of these medications will probably only add to our confusion! Why don’t you weigh in on this discussion by voting on our online poll at www.vascularspecialistonline.com? ­

Dr. Russell Samson is the medical editor of Vascular Specialist.

Definitely, maybe.

William D. Jordan, M.D.

First, primary prevention must be considered, as few patients with no prior intervention require dual antiplatelet therapy. It seems that we only have some scant data on the prevention of first-time events in at-risk patients when they are treated with aspirin alone.

While lipid management seems to be the most recent focus for primary prevention, single antiplatelet therapy seems appropriate for many patients who have higher risk due to atherosclerotic disease. A recent study from the University of Alabama at Birmingham found that asymptomatic carotid artery stenosis patients treated with dual antiplatelet therapy actually had higher bleed rates, higher mortality, and lower neurologic event rates, compared with those treated with aspirin alone.

While this study examined only a select group of patients treated for carotid artery disease, these vascular patients had worse outcomes when treated with aspirin and clopidogrel. Thus, caution should be considered before adding too many medical therapies.

Now, consider the short-term outlook for patients – specifically those who undergo some type of vascular intervention. The very nature of vascular intervention is disruptive to the arterial endothelium. Of course, most of the arteries that we enter have some underlying pathology; thus the intimal layer is not normal. The pathologic process is already, at least, partly underway. The concept of antiplatelet therapy is focused on limiting the platelet adhesions that might exaggerate the response to injury that creates a hyperplastic reaction within the vessels. We abhor the excessive response to injury due to the potential failure of the arterial reconstruction. Paradoxically, the same platelet inhibition can also cause excessive bleeding that may complicate the vascular repair. In the current medical climate, most of us tolerate the aggravation of diminished platelet function during open reconstruction in order to protect the target repair site and to avoid the dreaded “troponin leak” that may get classified as a myocardial infarction.

Some of our nonvascular colleagues avoid intervention (e.g., axial anesthesia, endoscopic biopsy) if stronger antiplatelet medication is present.

Now, to borrow some insight from other specialties, we should consider the extensive cardiology literature that shows the value of dual platelet inhibition after percutaneous coronary intervention or a recent cardiac event. While this strategy has shown improvement in PCI results, probably due to the great risk of thrombosis when disrupting the endothelial layer of a 2- to 3-mm coronary artery, the bleeding complications, including access-site hematomas, pseudoaneurysms, or retroperitoneal bleeding, are not analyzed as extensively. The preponderance of literature supports aggressive inhibition, but the long term needs to be considered – both expense and bleeding risk.

Currently, we use short-term dual treatment when the arterial endothelium is intentionally disrupted such as after an endarterectomy, angioplasty, with or without a stent, or atherectomy. Specifically, we add short-term IV dextran to oral agents for patients undergoing a carotid endarterectomy, but most are discharged on a single oral agent unless there is another indication for dual therapy.

Patients undergoing lower-extremity, catheter-based interventions are given dual therapy for the first 30 days, which is then adjusted according to the clinical response, duplex findings and other medical conditions. Bypass graft patients (yes, we still do some) are usually given a single agent unless the graft or patient has exhibited some concern for early failure.

In summary, I suspect that dual therapy is overused in our “pill-driven” population, but there still seem to be areas for its application. On each encounter with patients, I would encourage all vascular specialists to review the indications for antiplatelet therapy to consider removing a medication, improving compliance, and limiting bleeding risk.

Dr. Jordan is the director of the division of vascular surgery at the University of Alabama Birmingham School of Medicine. He has no relevant conflicts.

Dueling over dual antiplatelet therapy

Joseph L. Mills Sr., M.D.

Amidst a background of constant clamoring for data-driven and evidence-based medical decision-making, the practice of vascular medicine and surgery remains mired in the anecdotal. If a little is good, more must be better, seems the rationale for dual antiplatelet therapy. There may be small, as yet unclearly defined subsets of patients for whom dual therapy is actually beneficial, but an unbiased review of the current literature leads to the inescapable conclusion that more patients would be harmed by injudicious application of the more-is-better principle as concerns antiplatelet therapy for patients with carotid artery and peripheral artery disease (PAD).

The best evidence for antiplatelet therapy in patients with carotid disease suggests that aspirin as a single agent in doses ranging from 75 to 150 mg daily is preferred, and at least two meta-analyses and systematic reviews were unable to support the use of dual antiplatelet therapy.¹ At least in symptomatic patients, combination or dual antiplatelet therapy may increase the short-term risk of hemorrhagic complications in patients with acute ischemic stroke caused by large-artery disease.² Long-term dual therapy for secondary stroke prevention with aspirin and clopidogrel has been associated with four times the bleeding risk of monotherapy.³ These bleeds are often intracranial or gastrointestinal and are serious.

With respect to asymptomatic patients, while the CHARISMA trial did demonstrate a modest reduction in subsequent thrombotic events in a subset analysis of patients with stable, preexisting vascular disease, the bottom line was that dual antiplatelet therapy was associated with a 4% risk of moderate to severe bleeding and that there were strong correlations between moderate bleeding and all cause mortality (hazard ratio, 2.55), myocardial infarction (HR, 2.92) and stroke (HR, 4.2).⁴ The bleeding risk of dual antiplatelet therapy thus seems to outweigh the benefits.

Other data muddy the situation, but only a little. While at least two small studies (one a randomized controlled trial – CARESS [Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis])⁵ have suggested that the combination of aspirin and clopidogrel may reduce the frequency of perioperative microembolic signals detected early after carotid endarterectomy compared with monotherapy, it is not established that this surrogate measure would translate into long-term clinical benefit and would outweigh the established bleeding risk of dual therapy.

At present, the vascular surgeon should urge his patients to stop smoking, prescribe a statin, control blood pressure (but not necessarily with a beta-blocker), control diabetes, and prescribe a single antiplatelet agent, most often baby aspirin, for most of his or her patients. More good than harm will result.

References

Dr. Mills is professor of surgery and chief, division of vascular and endovascular surgery, University of Arizona Health Sciences Center, Tucson, and an associate medical editor for Vascular Specialist. He has no relevant conflicts.