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Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents

Prevention of Premature Discontinuation of Dual Antiplatelet Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents. A Science Therapy in Patients With Coronary Artery Stents. A Science Advisory From the American Heart Association, American Advisory From the American Heart Association, American

College of Cardiology, Society for Cardiovascular Angiography College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American and Interventions, American College of Surgeons, and American

Dental Association, With Representation From the American Dental Association, With Representation From the American College of PhysiciansCollege of Physicians

Cindy L. Grines; Robert O. Bonow; Donald E. Casey, Jr.; Cindy L. Grines; Robert O. Bonow; Donald E. Casey, Jr.;

Timothy J. Gardner; Peter B. Lockhart; David J. Moliterno; Patrick O’Gara; Timothy J. Gardner; Peter B. Lockhart; David J. Moliterno; Patrick O’Gara;

and Patrick Whitlowand Patrick Whitlow

Published in Circulation Published in Circulation

January 15, 2007January 15, 2007

Prevention of Premature Discontinuation of Dual Antiplatelet Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents. A Science Therapy in Patients With Coronary Artery Stents. A Science Advisory From the American Heart Association, American Advisory From the American Heart Association, American

College of Cardiology, Society for Cardiovascular Angiography College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American and Interventions, American College of Surgeons, and American

Dental Association, With Representation From the American Dental Association, With Representation From the American College of PhysiciansCollege of Physicians

Cindy L. Grines; Robert O. Bonow; Donald E. Casey, Jr.; Cindy L. Grines; Robert O. Bonow; Donald E. Casey, Jr.;

Timothy J. Gardner; Peter B. Lockhart; David J. Moliterno; Patrick O’Gara; Timothy J. Gardner; Peter B. Lockhart; David J. Moliterno; Patrick O’Gara;

and Patrick Whitlowand Patrick Whitlow

Published in Circulation Published in Circulation

January 15, 2007January 15, 2007


• The combination of thienopyridine and aspirin The combination of thienopyridine and aspirin therapy have been shown to dramatically reduce therapy have been shown to dramatically reduce the incidence of early major adverse cardiac the incidence of early major adverse cardiac events after bare metal stent (BMS) placement events after bare metal stent (BMS) placement compared with aspirin (ASA) alone or in compared with aspirin (ASA) alone or in combination with warfarin.combination with warfarin.

• It is known that thienopyridine therapy plus ASA It is known that thienopyridine therapy plus ASA for up to 1 year after non-ST-segment elevation for up to 1 year after non-ST-segment elevation ACS decreases the incidence of ischemic ACS decreases the incidence of ischemic cardiovascular events. cardiovascular events.

• The combination of thienopyridine and aspirin The combination of thienopyridine and aspirin therapy have been shown to dramatically reduce therapy have been shown to dramatically reduce the incidence of early major adverse cardiac the incidence of early major adverse cardiac events after bare metal stent (BMS) placement events after bare metal stent (BMS) placement compared with aspirin (ASA) alone or in compared with aspirin (ASA) alone or in combination with warfarin.combination with warfarin.

• It is known that thienopyridine therapy plus ASA It is known that thienopyridine therapy plus ASA for up to 1 year after non-ST-segment elevation for up to 1 year after non-ST-segment elevation ACS decreases the incidence of ischemic ACS decreases the incidence of ischemic cardiovascular events. cardiovascular events.

Grines CL, et al. Circulation. 2007 Jan:1-6. Grines CL, et al. Circulation. 2007 Jan:1-6.

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: BackgroundPrevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Background


• Thienopyridine treatment in combination with ASA Thienopyridine treatment in combination with ASA therapy is recommended by the ACC/AHA practice therapy is recommended by the ACC/AHA practice guidelines for the treatment of patients undergoing guidelines for the treatment of patients undergoing PCI and for the medical treatment of patients with PCI and for the medical treatment of patients with non-ST segment elevation ACS. non-ST segment elevation ACS.

• The leading adverse event associated with early The leading adverse event associated with early antiplatelet discontinuation is stent thrombosis, antiplatelet discontinuation is stent thrombosis, and the majority of these events lead to acute MI and the majority of these events lead to acute MI or death.or death.

• Thienopyridine treatment in combination with ASA Thienopyridine treatment in combination with ASA therapy is recommended by the ACC/AHA practice therapy is recommended by the ACC/AHA practice guidelines for the treatment of patients undergoing guidelines for the treatment of patients undergoing PCI and for the medical treatment of patients with PCI and for the medical treatment of patients with non-ST segment elevation ACS. non-ST segment elevation ACS.

• The leading adverse event associated with early The leading adverse event associated with early antiplatelet discontinuation is stent thrombosis, antiplatelet discontinuation is stent thrombosis, and the majority of these events lead to acute MI and the majority of these events lead to acute MI or death.or death.




• The AHA working with the ACC, the Society for The AHA working with the ACC, the Society for Cardiovascular Angiography and Interventions Cardiovascular Angiography and Interventions (SCAI), the American College of Physicians, the (SCAI), the American College of Physicians, the American College of Surgeons, and the American American College of Surgeons, and the American Dental Association, commissioned this advisory to Dental Association, commissioned this advisory to emphasize the potential complications of emphasize the potential complications of premature discontinuation of thienopyridine premature discontinuation of thienopyridine therapy and to address potential strategies to therapy and to address potential strategies to minimize this occurrence.minimize this occurrence.

• The AHA working with the ACC, the Society for The AHA working with the ACC, the Society for Cardiovascular Angiography and Interventions Cardiovascular Angiography and Interventions (SCAI), the American College of Physicians, the (SCAI), the American College of Physicians, the American College of Surgeons, and the American American College of Surgeons, and the American Dental Association, commissioned this advisory to Dental Association, commissioned this advisory to emphasize the potential complications of emphasize the potential complications of premature discontinuation of thienopyridine premature discontinuation of thienopyridine therapy and to address potential strategies to therapy and to address potential strategies to minimize this occurrence.minimize this occurrence.




MACE,%*MACE,%*

StudyStudy # Pts # Pts StudiedStudied

# Pts # Pts TreatedTreated

ASA ASA ThienopyridineThienopyridine

ASA ASA WarfarinWarfarin

ASA ASA AloneAlone PP

ISARISAR3232 517517 626626 1.61.6 6.26.2 …… 0.010.01

FANTASTICFANTASTIC33

33 473473 485485 5.75.7†† 8.68.6†† …… 0.370.37

STARSSTARS3434 16531653 19651965 0.50.5 2.72.7 3.63.6 0.00010.0001

MATTISMATTIS3535 350350 350350 5.65.6 11.011.0 …… 0.070.07

Hall et alHall et al3636 226226 358358 0.80.8 …… 3.93.9 0.10.1



After BMS Placement, ASA Plus Thienopyridine Reduces Cardiac Events Compared with ASA Alone or with Oral AntithrombinsAfter BMS Placement, ASA Plus Thienopyridine Reduces Cardiac Events Compared with ASA Alone or with Oral Antithrombins

MACE indicates major adverse cardiovascular events; Pts, patients; ASA, aspirin; ISAR, Intracoronary Stenting and Antithrombotic Regimen trial; FANTASTIC, Full ANTicoagulation versus Aspirin TIClopidine after stent implantation; STARS, STent Anticoagulation Regimen Study; and MATTIS, Multicenter Aspirin and Ticlopidine Trial after Intracoronary Stenting.

*Cardiac death, acute MI, or repeat TVR at 30 days (except for the FANTASTIC study).††Death, MI, or stent occlusion at 6 weeks.Adapted from ten Berg et al.

MACE indicates major adverse cardiovascular events; Pts, patients; ASA, aspirin; ISAR, Intracoronary Stenting and Antithrombotic Regimen trial; FANTASTIC, Full ANTicoagulation versus Aspirin TIClopidine after stent implantation; STARS, STent Anticoagulation Regimen Study; and MATTIS, Multicenter Aspirin and Ticlopidine Trial after Intracoronary Stenting.

*Cardiac death, acute MI, or repeat TVR at 30 days (except for the FANTASTIC study).††Death, MI, or stent occlusion at 6 weeks.Adapted from ten Berg et al.


• The current ACC/AHA/SCAI recommendations for the The current ACC/AHA/SCAI recommendations for the prevention of stent thrombosis after coronary stent prevention of stent thrombosis after coronary stent implantation state:implantation state:

– At the minimum, patients should be treated with At the minimum, patients should be treated with 75 mg clopidogrel and ASA 325mg for 1 month 75 mg clopidogrel and ASA 325mg for 1 month after BMS implantation, 3 months after sirolimus after BMS implantation, 3 months after sirolimus DES implantation, 6 months after paclitaxel DES DES implantation, 6 months after paclitaxel DES implantation, and ideally, up to 12 months if they implantation, and ideally, up to 12 months if they are not at a high-risk for bleeding.are not at a high-risk for bleeding.

• The current ACC/AHA/SCAI recommendations for the The current ACC/AHA/SCAI recommendations for the prevention of stent thrombosis after coronary stent prevention of stent thrombosis after coronary stent implantation state:implantation state:

– At the minimum, patients should be treated with At the minimum, patients should be treated with 75 mg clopidogrel and ASA 325mg for 1 month 75 mg clopidogrel and ASA 325mg for 1 month after BMS implantation, 3 months after sirolimus after BMS implantation, 3 months after sirolimus DES implantation, 6 months after paclitaxel DES DES implantation, 6 months after paclitaxel DES implantation, and ideally, up to 12 months if they implantation, and ideally, up to 12 months if they are not at a high-risk for bleeding.are not at a high-risk for bleeding.

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Current

Recommendations


Recommendations



• The current recommendations were based on the The current recommendations were based on the antiplatelet regimen used in trials that were conducted antiplatelet regimen used in trials that were conducted to obtain U.S. Food and Drug Administration approval to obtain U.S. Food and Drug Administration approval (low-risk lesions in low-risk patients) and the (low-risk lesions in low-risk patients) and the anticipated time it takes for the metal stent struts to anticipated time it takes for the metal stent struts to become adequately endothelialized to reduce the risk become adequately endothelialized to reduce the risk of stent thrombosis.of stent thrombosis.

• The current recommendations were based on the The current recommendations were based on the antiplatelet regimen used in trials that were conducted antiplatelet regimen used in trials that were conducted to obtain U.S. Food and Drug Administration approval to obtain U.S. Food and Drug Administration approval (low-risk lesions in low-risk patients) and the (low-risk lesions in low-risk patients) and the anticipated time it takes for the metal stent struts to anticipated time it takes for the metal stent struts to become adequately endothelialized to reduce the risk become adequately endothelialized to reduce the risk of stent thrombosis.of stent thrombosis.


Recommendations (cont.)


Recommendations (cont.)



• However, DESs are now being used in high-risk However, DESs are now being used in high-risk lesions, and reports have suggested that they may lesions, and reports have suggested that they may be associated with delayed (or absent) be associated with delayed (or absent) endothelialization, localized hypersensitivity endothelialization, localized hypersensitivity reactions, and late stent thrombosis.reactions, and late stent thrombosis.

• However, DESs are now being used in high-risk However, DESs are now being used in high-risk lesions, and reports have suggested that they may lesions, and reports have suggested that they may be associated with delayed (or absent) be associated with delayed (or absent) endothelialization, localized hypersensitivity endothelialization, localized hypersensitivity reactions, and late stent thrombosis.reactions, and late stent thrombosis.

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Need For

New Recommendations

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Need For

New Recommendations



• Stent thrombosis most commonly occurs in the first Stent thrombosis most commonly occurs in the first month after stent implantation and referred to as month after stent implantation and referred to as “subacute stent thrombosis”“subacute stent thrombosis”

• Many cases of “late-stent thrombosis”, occurring Many cases of “late-stent thrombosis”, occurring months or years after stent implantation, have been months or years after stent implantation, have been reported – especially in patients treated with DESreported – especially in patients treated with DES

• Stent thrombosis often results in life-threatening Stent thrombosis often results in life-threatening complicationscomplications

• Stent thrombosis most commonly occurs in the first Stent thrombosis most commonly occurs in the first month after stent implantation and referred to as month after stent implantation and referred to as “subacute stent thrombosis”“subacute stent thrombosis”

• Many cases of “late-stent thrombosis”, occurring Many cases of “late-stent thrombosis”, occurring months or years after stent implantation, have been months or years after stent implantation, have been reported – especially in patients treated with DESreported – especially in patients treated with DES

• Stent thrombosis often results in life-threatening Stent thrombosis often results in life-threatening complicationscomplications

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Stent

Thrombosis


Thrombosis



• The incidence of death or MI associated with The incidence of death or MI associated with angiographically documented stent thrombosis was angiographically documented stent thrombosis was 64.4% in a pooled analysis of 6 trials and registries 64.4% in a pooled analysis of 6 trials and registries from the 1990s.from the 1990s.

• Mortality rates due to presumed or documented stent Mortality rates due to presumed or documented stent thrombosis range from 20% to 45%.thrombosis range from 20% to 45%.

• The incidence of death or MI associated with The incidence of death or MI associated with angiographically documented stent thrombosis was angiographically documented stent thrombosis was 64.4% in a pooled analysis of 6 trials and registries 64.4% in a pooled analysis of 6 trials and registries from the 1990s.from the 1990s.

• Mortality rates due to presumed or documented stent Mortality rates due to presumed or documented stent thrombosis range from 20% to 45%.thrombosis range from 20% to 45%.


Thrombosis (cont.)


Thrombosis (cont.)



• The average reported occurrence of subacute stent The average reported occurrence of subacute stent thrombosis is 1% and the timing of thrombosis seems thrombosis is 1% and the timing of thrombosis seems to be delayed in DES.to be delayed in DES.

• Late stent thrombosis was not readily apparent in Late stent thrombosis was not readily apparent in BMS but was reported to occur in 0.19% of patients in BMS but was reported to occur in 0.19% of patients in a large DES registry.a large DES registry.

• The average reported occurrence of subacute stent The average reported occurrence of subacute stent thrombosis is 1% and the timing of thrombosis seems thrombosis is 1% and the timing of thrombosis seems to be delayed in DES.to be delayed in DES.

• Late stent thrombosis was not readily apparent in Late stent thrombosis was not readily apparent in BMS but was reported to occur in 0.19% of patients in BMS but was reported to occur in 0.19% of patients in a large DES registry.a large DES registry.


Thrombosis in DES


Thrombosis in DES



ClinicalClinical AngiographicAngiographic

Advanced AgeAdvanced Age Long StentsLong Stents

ACSACS Multiple LesionsMultiple Lesions

DiabetesDiabetes Overlapping stentsOverlapping stents

Low Ejection FractionLow Ejection Fraction Ostial or bifurcation lesionsOstial or bifurcation lesions

Prior brachytherapyPrior brachytherapy Small vesselsSmall vessels

Renal failureRenal failure Suboptimal stent resultsSuboptimal stent results

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents:

Need for New Recommendations


Need for New Recommendations

Reference/Presentation LocationReference/Presentation Location

Predictors of DES Thrombosis: Considerations for Predictors of DES Thrombosis: Considerations for Prolonged Dual Antiplatelet Therapy Prolonged Dual Antiplatelet Therapy


• A panel convened by the FDA concluded that there A panel convened by the FDA concluded that there appears to be an excess of late stent thrombosis appears to be an excess of late stent thrombosis with DES; however, the magnitude is uncertain and with DES; however, the magnitude is uncertain and the off-label use of DES, as with BMS, is associated the off-label use of DES, as with BMS, is associated with increased risk when compared with on-label with increased risk when compared with on-label use.use.

• A panel convened by the FDA concluded that there A panel convened by the FDA concluded that there appears to be an excess of late stent thrombosis appears to be an excess of late stent thrombosis with DES; however, the magnitude is uncertain and with DES; however, the magnitude is uncertain and the off-label use of DES, as with BMS, is associated the off-label use of DES, as with BMS, is associated with increased risk when compared with on-label with increased risk when compared with on-label use.use.

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: FDA

Advisory Panel Meeting


Advisory Panel Meeting



• In the future, DES studies should have:In the future, DES studies should have:

– Longer follow-upLonger follow-up

– Greater number of patients enrolledGreater number of patients enrolled

– Stent thrombosis as study endpointStent thrombosis as study endpoint

• Concurred with joint clinical practice guideline Concurred with joint clinical practice guideline recommendation: 12 months of antiplatelet therapy recommendation: 12 months of antiplatelet therapy after placement of DES in patients who are not at after placement of DES in patients who are not at high risk for bleeding.high risk for bleeding.

• In the future, DES studies should have:In the future, DES studies should have:

– Longer follow-upLonger follow-up

– Greater number of patients enrolledGreater number of patients enrolled

– Stent thrombosis as study endpointStent thrombosis as study endpoint

• Concurred with joint clinical practice guideline Concurred with joint clinical practice guideline recommendation: 12 months of antiplatelet therapy recommendation: 12 months of antiplatelet therapy after placement of DES in patients who are not at after placement of DES in patients who are not at high risk for bleeding.high risk for bleeding.


Advisory Panel Meeting (cont.)





• The panel also agreed that a large randomized The panel also agreed that a large randomized clinical trial looking specifically at appropriate duration clinical trial looking specifically at appropriate duration of dual antiplatelet therapy is needed.of dual antiplatelet therapy is needed.

• The panel also agreed that a large randomized The panel also agreed that a large randomized clinical trial looking specifically at appropriate duration clinical trial looking specifically at appropriate duration of dual antiplatelet therapy is needed.of dual antiplatelet therapy is needed.







• The leading independent predictor for stent The leading independent predictor for stent thrombosis in multivariate analyses is premature thrombosis in multivariate analyses is premature discontinuation of thienopyridine therapydiscontinuation of thienopyridine therapy

• In a large observational cohort study of patients In a large observational cohort study of patients treated with DES, stent thrombosis occurred in treated with DES, stent thrombosis occurred in 29% of patients in whom antiplatelet therapy was 29% of patients in whom antiplatelet therapy was discontinued prematurely.discontinued prematurely.

• The leading independent predictor for stent The leading independent predictor for stent thrombosis in multivariate analyses is premature thrombosis in multivariate analyses is premature discontinuation of thienopyridine therapydiscontinuation of thienopyridine therapy

• In a large observational cohort study of patients In a large observational cohort study of patients treated with DES, stent thrombosis occurred in treated with DES, stent thrombosis occurred in 29% of patients in whom antiplatelet therapy was 29% of patients in whom antiplatelet therapy was discontinued prematurely.discontinued prematurely.

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Premature

Thienopyridine Discontinuation and Stent Thrombosis

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Premature

Thienopyridine Discontinuation and Stent Thrombosis



• Several reports have described incidents of stent Several reports have described incidents of stent thrombosis that occurred after the discontinuation thrombosis that occurred after the discontinuation of antiplatelet therapy for noncardiac surgery of antiplatelet therapy for noncardiac surgery among patients recently treated with coronary among patients recently treated with coronary stents.stents.

• Kaluza et al reported on 40 patients treated with Kaluza et al reported on 40 patients treated with BMS who underwent noncardiac surgery within 6 BMS who underwent noncardiac surgery within 6 weeks of stent implantation. Seven patients had an weeks of stent implantation. Seven patients had an MI, of which 6 were fatal.MI, of which 6 were fatal.

• Several reports have described incidents of stent Several reports have described incidents of stent thrombosis that occurred after the discontinuation thrombosis that occurred after the discontinuation of antiplatelet therapy for noncardiac surgery of antiplatelet therapy for noncardiac surgery among patients recently treated with coronary among patients recently treated with coronary stents.stents.

• Kaluza et al reported on 40 patients treated with Kaluza et al reported on 40 patients treated with BMS who underwent noncardiac surgery within 6 BMS who underwent noncardiac surgery within 6 weeks of stent implantation. Seven patients had an weeks of stent implantation. Seven patients had an MI, of which 6 were fatal.MI, of which 6 were fatal.


Thrombosis After Noncardiac Surgery





• Stent thrombosis was presumed to be the cause Stent thrombosis was presumed to be the cause of all MIs and in 5 of the 7 cases thienopyridine of all MIs and in 5 of the 7 cases thienopyridine therapy was withheld before surgery.therapy was withheld before surgery.

• In a similar analysis of 47 patients who In a similar analysis of 47 patients who underwent noncardiac surgery within 90 days of underwent noncardiac surgery within 90 days of BMS implantation, 6 of the 7 patients in whom BMS implantation, 6 of the 7 patients in whom thienopyridine therapy was discontinued died, thienopyridine therapy was discontinued died, likely due to stent thrombosis.likely due to stent thrombosis.

• Stent thrombosis was presumed to be the cause Stent thrombosis was presumed to be the cause of all MIs and in 5 of the 7 cases thienopyridine of all MIs and in 5 of the 7 cases thienopyridine therapy was withheld before surgery.therapy was withheld before surgery.

• In a similar analysis of 47 patients who In a similar analysis of 47 patients who underwent noncardiac surgery within 90 days of underwent noncardiac surgery within 90 days of BMS implantation, 6 of the 7 patients in whom BMS implantation, 6 of the 7 patients in whom thienopyridine therapy was discontinued died, thienopyridine therapy was discontinued died, likely due to stent thrombosis.likely due to stent thrombosis.







• Premature discontinuation of antiplatelet therapy Premature discontinuation of antiplatelet therapy may occur for many reasons:may occur for many reasons:– Cost of clopidogrel may discourage prescription renewal (~$4 Cost of clopidogrel may discourage prescription renewal (~$4 daily)daily)

– Older ageOlder age

– Not referred for cardiac rehabilitationNot referred for cardiac rehabilitation

– Did not finish high school Did not finish high school

– Not seeking health care due to costNot seeking health care due to cost

– Not receiving discharge instructions for medication useNot receiving discharge instructions for medication use

– Greater likelihood of having preexistent CV disease or anemiaGreater likelihood of having preexistent CV disease or anemia

– Not being marriedNot being married

• Premature discontinuation of antiplatelet therapy Premature discontinuation of antiplatelet therapy may occur for many reasons:may occur for many reasons:– Cost of clopidogrel may discourage prescription renewal (~$4 Cost of clopidogrel may discourage prescription renewal (~$4 daily)daily)

– Older ageOlder age

– Not referred for cardiac rehabilitationNot referred for cardiac rehabilitation

– Did not finish high school Did not finish high school

– Not seeking health care due to costNot seeking health care due to cost

– Not receiving discharge instructions for medication useNot receiving discharge instructions for medication use

– Greater likelihood of having preexistent CV disease or anemiaGreater likelihood of having preexistent CV disease or anemia

– Not being marriedNot being married

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Factors

Related to Premature Cessation of Thienopyridine Therapy

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Factors

Related to Premature Cessation of Thienopyridine Therapy



• Antiplatelet therapy may be stopped at the instruction of Antiplatelet therapy may be stopped at the instruction of physicians, dentists, and other healthcare providers who physicians, dentists, and other healthcare providers who are to perform an invasive or surgical procedure on the are to perform an invasive or surgical procedure on the patient because of misguided concerns about excessive patient because of misguided concerns about excessive procedure-related bleeding.procedure-related bleeding.

• Many of these procedures (e.g., minor surgery, teeth Many of these procedures (e.g., minor surgery, teeth cleaning, and tooth extraction) can likely be performed at cleaning, and tooth extraction) can likely be performed at no or only minor risk of bleeding or could be delayed no or only minor risk of bleeding or could be delayed until the prescribed antiplatelet regimen is completed.until the prescribed antiplatelet regimen is completed.

• Antiplatelet therapy may be stopped at the instruction of Antiplatelet therapy may be stopped at the instruction of physicians, dentists, and other healthcare providers who physicians, dentists, and other healthcare providers who are to perform an invasive or surgical procedure on the are to perform an invasive or surgical procedure on the patient because of misguided concerns about excessive patient because of misguided concerns about excessive procedure-related bleeding.procedure-related bleeding.

• Many of these procedures (e.g., minor surgery, teeth Many of these procedures (e.g., minor surgery, teeth cleaning, and tooth extraction) can likely be performed at cleaning, and tooth extraction) can likely be performed at no or only minor risk of bleeding or could be delayed no or only minor risk of bleeding or could be delayed until the prescribed antiplatelet regimen is completed.until the prescribed antiplatelet regimen is completed.

Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Factors Related to Premature

Cessation of Thienopyridine Therapy (cont.)





• Although there is a long standing concern on the Although there is a long standing concern on the part of dental practitioners about the possibility of part of dental practitioners about the possibility of prolonged bleeding during and after invasive dental prolonged bleeding during and after invasive dental procedures on patients receiving antiplatelet procedures on patients receiving antiplatelet therapy, a recent prospective study of single tooth therapy, a recent prospective study of single tooth extractions on patients randomized to ASA versus a extractions on patients randomized to ASA versus a placebo failed to show a statistically significant placebo failed to show a statistically significant difference in postoperative bleeding.difference in postoperative bleeding.

• Although there is a long standing concern on the Although there is a long standing concern on the part of dental practitioners about the possibility of part of dental practitioners about the possibility of prolonged bleeding during and after invasive dental prolonged bleeding during and after invasive dental procedures on patients receiving antiplatelet procedures on patients receiving antiplatelet therapy, a recent prospective study of single tooth therapy, a recent prospective study of single tooth extractions on patients randomized to ASA versus a extractions on patients randomized to ASA versus a placebo failed to show a statistically significant placebo failed to show a statistically significant difference in postoperative bleeding.difference in postoperative bleeding.








Need for New Recommendations: Summary


Need for New Recommendations: Summary

• Thienopyridine therapy in combination with aspirin Thienopyridine therapy in combination with aspirin has become the mainstay antiplatelet treatment has become the mainstay antiplatelet treatment strategy for the prevention of stent thrombosis. strategy for the prevention of stent thrombosis.

• Premature discontinuation of antiplatelet therapy Premature discontinuation of antiplatelet therapy markedly increases the risk of stent thrombosis, a markedly increases the risk of stent thrombosis, a catastrophic event that frequently leads to MI catastrophic event that frequently leads to MI and/or death.and/or death.

• Premature cessation of thienopyridine therapy Premature cessation of thienopyridine therapy should be eliminated.should be eliminated.

• Thienopyridine therapy in combination with aspirin Thienopyridine therapy in combination with aspirin has become the mainstay antiplatelet treatment has become the mainstay antiplatelet treatment strategy for the prevention of stent thrombosis. strategy for the prevention of stent thrombosis.

• Premature discontinuation of antiplatelet therapy Premature discontinuation of antiplatelet therapy markedly increases the risk of stent thrombosis, a markedly increases the risk of stent thrombosis, a catastrophic event that frequently leads to MI catastrophic event that frequently leads to MI and/or death.and/or death.

• Premature cessation of thienopyridine therapy Premature cessation of thienopyridine therapy should be eliminated.should be eliminated.



Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents: Need for New

Recommendations: Advisory Group’s Recommendations



1.1. Physicians should discuss thienopyridine therapy with Physicians should discuss thienopyridine therapy with patients before stent implantation. In patients not patients before stent implantation. In patients not expected to comply with 12 months of treatment, strong expected to comply with 12 months of treatment, strong consideration should be given to avoiding DES.consideration should be given to avoiding DES.

2.2. In patients preparing for PCI and likely to require invasive In patients preparing for PCI and likely to require invasive or surgical procedures within 12 months, consideration or surgical procedures within 12 months, consideration should be given to BMS or balloon angioplasty instead of should be given to BMS or balloon angioplasty instead of DES.DES.

1.1. Physicians should discuss thienopyridine therapy with Physicians should discuss thienopyridine therapy with patients before stent implantation. In patients not patients before stent implantation. In patients not expected to comply with 12 months of treatment, strong expected to comply with 12 months of treatment, strong consideration should be given to avoiding DES.consideration should be given to avoiding DES.

2.2. In patients preparing for PCI and likely to require invasive In patients preparing for PCI and likely to require invasive or surgical procedures within 12 months, consideration or surgical procedures within 12 months, consideration should be given to BMS or balloon angioplasty instead of should be given to BMS or balloon angioplasty instead of DES.DES.







3.3. Before patient discharge, more effort towards the Before patient discharge, more effort towards the education of patients about thienopyridines and education of patients about thienopyridines and associated risks should be made by healthcare associated risks should be made by healthcare professionals.professionals.

4.4. Before patient discharge, patients should be Before patient discharge, patients should be specifically instructed to contact their treating specifically instructed to contact their treating cardiologist before stopping any antiplatelet cardiologist before stopping any antiplatelet therapy. therapy.

3.3. Before patient discharge, more effort towards the Before patient discharge, more effort towards the education of patients about thienopyridines and education of patients about thienopyridines and associated risks should be made by healthcare associated risks should be made by healthcare professionals.professionals.

4.4. Before patient discharge, patients should be Before patient discharge, patients should be specifically instructed to contact their treating specifically instructed to contact their treating cardiologist before stopping any antiplatelet cardiologist before stopping any antiplatelet therapy. therapy.







5.5. Healthcare providers who perform invasive or Healthcare providers who perform invasive or surgical procedures with risk of peri- and post-surgical procedures with risk of peri- and post-procedural bleeding must be made aware of the procedural bleeding must be made aware of the dangers of premature therapy discontinuation. dangers of premature therapy discontinuation. These providers should contact the patient’s These providers should contact the patient’s cardiologist if issues are unclear.cardiologist if issues are unclear.

6.6. Elective procedures for which there is significant Elective procedures for which there is significant risk of peri- or post-operative bleeding should be risk of peri- or post-operative bleeding should be deferred until patients have completed an deferred until patients have completed an appropriate course of thienopyridine therapy.appropriate course of thienopyridine therapy.

5.5. Healthcare providers who perform invasive or Healthcare providers who perform invasive or surgical procedures with risk of peri- and post-surgical procedures with risk of peri- and post-procedural bleeding must be made aware of the procedural bleeding must be made aware of the dangers of premature therapy discontinuation. dangers of premature therapy discontinuation. These providers should contact the patient’s These providers should contact the patient’s cardiologist if issues are unclear.cardiologist if issues are unclear.

6.6. Elective procedures for which there is significant Elective procedures for which there is significant risk of peri- or post-operative bleeding should be risk of peri- or post-operative bleeding should be deferred until patients have completed an deferred until patients have completed an appropriate course of thienopyridine therapy.appropriate course of thienopyridine therapy.







7.7. For DES patients who are to undergo For DES patients who are to undergo subsequent procedures that require subsequent procedures that require discontinuation of thienopyridine therapy, aspirin discontinuation of thienopyridine therapy, aspirin should be continued if at all possible and should be continued if at all possible and thienopyridine restarted as soon as possible.thienopyridine restarted as soon as possible.

8.8. The healthcare and pharmaceutical industries, The healthcare and pharmaceutical industries, insurers, and the US congress should ensure insurers, and the US congress should ensure that drug cost doesn’t cause patients to that drug cost doesn’t cause patients to discontinue antiplatelet therapy too soon, thus discontinue antiplatelet therapy too soon, thus incurring severe cardiovascular complications. incurring severe cardiovascular complications.

7.7. For DES patients who are to undergo For DES patients who are to undergo subsequent procedures that require subsequent procedures that require discontinuation of thienopyridine therapy, aspirin discontinuation of thienopyridine therapy, aspirin should be continued if at all possible and should be continued if at all possible and thienopyridine restarted as soon as possible.thienopyridine restarted as soon as possible.

8.8. The healthcare and pharmaceutical industries, The healthcare and pharmaceutical industries, insurers, and the US congress should ensure insurers, and the US congress should ensure that drug cost doesn’t cause patients to that drug cost doesn’t cause patients to discontinue antiplatelet therapy too soon, thus discontinue antiplatelet therapy too soon, thus incurring severe cardiovascular complications. incurring severe cardiovascular complications.



MemberMemberOrgan-Organ-izationization

Rsrch Rsrch GrantGrant

Other Other Rsrch Rsrch

SupportSupport

Speakers’ Speakers’ Bureau/Bureau/

HonorariaHonoraria

Owner-Owner-ShipShip

InterestInterest

Consul-Consul-tant/Adv tant/Adv

BoardBoardOtherOther

Cindy Cindy GrinesGrines AHAAHA NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

Robert Robert BonowBonow AHAAHA NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

Donald Donald Casey, Casey,

Jr.Jr.ACPACP NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

Timothy Timothy GardnerGardner ACSACS NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

Peter Peter LockhartLockhart ADAADA NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

David David MoliternoMoliterno SCAISCAI NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone


Need for New Recommendations: Disclosures



Writing Group DisclosuresWriting Group Disclosures



MemberMemberOrgan-Organ-izationization

Rsrch Rsrch GrantGrant

Other Other Rsrch Rsrch

SupportSupport


HonorariaHonoraria

Own-Own-ershipership

interestinterest



Patrick Patrick O’GaraO’Gara ACCACC NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

Patrick Patrick WhitlowWhitlow ACCACC NoneNone NoneNone NoneNone NoneNone

ICON ICON Intervention- Intervention- al systems,* al systems,* Medlogics*Medlogics*

NoneNone





Writing Group DisclosuresWriting Group Disclosures



ReviewerReviewer Rsrch GrantRsrch GrantOther Other Rsrch Rsrch

SupportSupport


HonorariaHonoraria

Owner-Owner-ShipShip

interestinterest



Elliott Elliott AntmanAntman Eli Lilly*Eli Lilly* NoneNone NoneNone NoneNone NoneNone NoneNone

Patrick Patrick DehmerDehmer NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

T. Bruce T. Bruce FurgusonFurguson NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

Raymond Raymond GibbonsGibbons

Radiant Radiant MedicalMedical††, KAI , KAI

Pharm. Pharm. ††, , TargeGen. TargeGen. ††, ,

TherOxTherOx††

NoneNone NoneNone NoneNoneHawaii Hawaii

Biotech,* Biotech,* TIMI 37A*TIMI 37A*

NoneNone

Arthur Arthur JeskeJeske NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone

Vincenza Vincenza SnowSnow NoneNone NoneNone NoneNone NoneNone NoneNone NoneNone





Reviewer DisclosuresReviewer Disclosures







•Table represents the relationships of reviewers that may be Table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. are required to complete and submit.

•A relationship is considered to be “significant” (†) if (1) the A relationship is considered to be “significant” (†) if (1) the person receives $10,000 or more during any 12-month period or person receives $10,000 or more during any 12-month period or 5% or more of the person’s gross income; or (2) the person owns 5% or more of the person’s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity or owns 5% or more of the voting stock or share of the entity or owns $10,000 or more of the fair market value of the entity.$10,000 or more of the fair market value of the entity.

•A relationship is considered to be “modest” (*) if it is less than A relationship is considered to be “modest” (*) if it is less than “significant” under this definition.“significant” under this definition.


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