TCT 2011

SAN FRANCISCO – Prasugrel can overcome a lack of platelet response to clopidogrel in patients undergoing elective, noncomplicated percutaneous coronary intervention. But the rate of cardiovascular events in this group of clopidogrel nonresponders is low no matter which agent they receive – so low, in fact, that it prompted early closure of a randomized trial comparing the two.

Trial results, reported at Transcatheter Cardiovascular Therapeutics 2011, showed that merely 1 of the 236 patients having 6 months of follow-up experienced a myocardial infarction and none died of cardiovascular causes, with no significant difference between those who continued on clopidogrel and those who switched to prasugrel. Rates of major bleeding were also low and similar.

"Given the low event rate in elective percutaneous coronary intervention [PCI] patients without periprocedural complications, it was not possible to assess the risk-benefit ratio with prasugrel treatment. Therefore, the study was terminated prematurely for futility," lead investigator Dietmar Trenk, Ph.D., explained in a press conference. He presented results on behalf of the TRIGGER-PCI investigators.

Discussant Dr. Matthew J. Price, director of the Cardiac Catheterization Laboratory at the Scripps Clinic in La Jolla, Calif., agreed that the trial population had very low risk to begin with, and not just from a procedural perspective. For example, the patients on average had relatively large stented vessel diameters and received shorter stents.

"Also, this trial shows the challenges of performing a randomized clinical trial looking at individualized antiplatelet therapy, because about one-third of the patients who were identified as having high on-treatment platelet reactivity withdrew from the study because they did not want to participate," he commented. "So I think this shows that doing these trials, it’s very hard not to get selection bias for the lowest-risk patients, and that’s a challenge that we will have going forward in designing these randomized clinical trials."

"I do think it’s consistent [across trials] that in these low-risk patients, who have low-risk clinical scenarios and low [anatomical risk], the event rates are incredibly low, and although the hazard associated with on-treatment [platelet] reactivity may be substantial, ...the absolute event rates in these very low risk patients may mean that changing therapy may not provide net clinical benefit," Dr. Price maintained.

Patients were eligible for the trial, which was sponsored by Eli Lilly and Daiichi Sankyo Co., if they underwent successful PCI with implantation of drug-eluting stents, did not have any major complications, and did not receive any glycoprotein IIb/IIIa inhibitors, according to Dr. Trenk, who is a professor at the Herz-Zentrum Bad Krozingen (Germany).

All had received standard-of-care clopidogrel in the periprocedural period and were found to be clopidogrel nonresponders because they had a result of more than 208 platelet reactive units on the VerifyNow P2Y12 assay (Accumetrics) on the day after the procedure.

The patients were randomized in nearly equal numbers to either continue clopidogrel (Plavix; 75-mg daily maintenance dose) or switch to prasugrel (Effient; a one-time 60-mg loading dose and a 10-mg daily maintenance dose), with matching placebos.

When the trial was stopped, 423 patients had been enrolled and had data for clinical outcomes, Dr. Trenk reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Analyses showed that the patients who switched to prasugrel indeed had lower platelet reactivity than did their counterparts who stayed on clopidogrel, both at 90 days (P less than .001) and at 176 days (P less than .001).

"Platelet reactivity in patients randomized to clopidogrel remained fairly constant, with a high rate of more than 70% of patients being hyporesponsive to the drug," Dr. Trenk pointed out. On the other hand, "prasugrel consistently decreased platelet reactivity, and only 5% of patients remained hyporesponsive at 3 months’ follow-up and at 6 months’ follow-up."

Despite this difference in platelet reactivity, the prasugrel and clopidogrel groups had similarly low 6-month rates of the primary composite efficacy end point of cardiovascular death and MI (0% and 0.5%), and secondary end points such as rehospitalization for cardiac ischemic events (0.9% and 1.9%), urgent target vessel revascularization (0.9% and 0.5%), and stroke (0% and 0.5%). There were no cases of definite or probably stent thrombosis.

Additionally, the prasugrel and clopidogrel groups had similarly low rates of the key safety end point of non–CABG-related TIMI (Thrombolysis in Myocardial Infarction) major bleeding (1.4% and 0.5%).

Dr. Trenk reported that he receives honoraria and advisory board fees from Daiichi-Sankyo, Eli Lilly, AstraZeneca, and Sanofi-Aventis. Dr. Price reported that he receives grant or research support from Bristol-Myers Squibb and Sanofi-Aventis, and that he is a consultant to, receives honoraria from, or is a speaker for Abiomed, AstraZeneca, Boston Scientific, Medtronic, Terumo Medical, Bristol-Myers Squibb, Daiichi-Sankyo/Eli Lilly, Sanofi-Aventis, and W.L. Gore & Associates.

SAN FRANCISCO – Prasugrel can overcome a lack of platelet response to clopidogrel in patients undergoing elective, noncomplicated percutaneous coronary intervention. But the rate of cardiovascular events in this group of clopidogrel nonresponders is low no matter which agent they receive – so low, in fact, that it prompted early closure of a randomized trial comparing the two.

Trial results, reported at Transcatheter Cardiovascular Therapeutics 2011, showed that merely 1 of the 236 patients having 6 months of follow-up experienced a myocardial infarction and none died of cardiovascular causes, with no significant difference between those who continued on clopidogrel and those who switched to prasugrel. Rates of major bleeding were also low and similar.

"Given the low event rate in elective percutaneous coronary intervention [PCI] patients without periprocedural complications, it was not possible to assess the risk-benefit ratio with prasugrel treatment. Therefore, the study was terminated prematurely for futility," lead investigator Dietmar Trenk, Ph.D., explained in a press conference. He presented results on behalf of the TRIGGER-PCI investigators.

Discussant Dr. Matthew J. Price, director of the Cardiac Catheterization Laboratory at the Scripps Clinic in La Jolla, Calif., agreed that the trial population had very low risk to begin with, and not just from a procedural perspective. For example, the patients on average had relatively large stented vessel diameters and received shorter stents.

"Also, this trial shows the challenges of performing a randomized clinical trial looking at individualized antiplatelet therapy, because about one-third of the patients who were identified as having high on-treatment platelet reactivity withdrew from the study because they did not want to participate," he commented. "So I think this shows that doing these trials, it’s very hard not to get selection bias for the lowest-risk patients, and that’s a challenge that we will have going forward in designing these randomized clinical trials."

"I do think it’s consistent [across trials] that in these low-risk patients, who have low-risk clinical scenarios and low [anatomical risk], the event rates are incredibly low, and although the hazard associated with on-treatment [platelet] reactivity may be substantial, ...the absolute event rates in these very low risk patients may mean that changing therapy may not provide net clinical benefit," Dr. Price maintained.

Patients were eligible for the trial, which was sponsored by Eli Lilly and Daiichi Sankyo Co., if they underwent successful PCI with implantation of drug-eluting stents, did not have any major complications, and did not receive any glycoprotein IIb/IIIa inhibitors, according to Dr. Trenk, who is a professor at the Herz-Zentrum Bad Krozingen (Germany).

All had received standard-of-care clopidogrel in the periprocedural period and were found to be clopidogrel nonresponders because they had a result of more than 208 platelet reactive units on the VerifyNow P2Y12 assay (Accumetrics) on the day after the procedure.

The patients were randomized in nearly equal numbers to either continue clopidogrel (Plavix; 75-mg daily maintenance dose) or switch to prasugrel (Effient; a one-time 60-mg loading dose and a 10-mg daily maintenance dose), with matching placebos.

When the trial was stopped, 423 patients had been enrolled and had data for clinical outcomes, Dr. Trenk reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Analyses showed that the patients who switched to prasugrel indeed had lower platelet reactivity than did their counterparts who stayed on clopidogrel, both at 90 days (P less than .001) and at 176 days (P less than .001).

"Platelet reactivity in patients randomized to clopidogrel remained fairly constant, with a high rate of more than 70% of patients being hyporesponsive to the drug," Dr. Trenk pointed out. On the other hand, "prasugrel consistently decreased platelet reactivity, and only 5% of patients remained hyporesponsive at 3 months’ follow-up and at 6 months’ follow-up."

Despite this difference in platelet reactivity, the prasugrel and clopidogrel groups had similarly low 6-month rates of the primary composite efficacy end point of cardiovascular death and MI (0% and 0.5%), and secondary end points such as rehospitalization for cardiac ischemic events (0.9% and 1.9%), urgent target vessel revascularization (0.9% and 0.5%), and stroke (0% and 0.5%). There were no cases of definite or probably stent thrombosis.

Additionally, the prasugrel and clopidogrel groups had similarly low rates of the key safety end point of non–CABG-related TIMI (Thrombolysis in Myocardial Infarction) major bleeding (1.4% and 0.5%).

Dr. Trenk reported that he receives honoraria and advisory board fees from Daiichi-Sankyo, Eli Lilly, AstraZeneca, and Sanofi-Aventis. Dr. Price reported that he receives grant or research support from Bristol-Myers Squibb and Sanofi-Aventis, and that he is a consultant to, receives honoraria from, or is a speaker for Abiomed, AstraZeneca, Boston Scientific, Medtronic, Terumo Medical, Bristol-Myers Squibb, Daiichi-Sankyo/Eli Lilly, Sanofi-Aventis, and W.L. Gore & Associates.

SAN FRANCISCO – Prasugrel can overcome a lack of platelet response to clopidogrel in patients undergoing elective, noncomplicated percutaneous coronary intervention. But the rate of cardiovascular events in this group of clopidogrel nonresponders is low no matter which agent they receive – so low, in fact, that it prompted early closure of a randomized trial comparing the two.

Trial results, reported at Transcatheter Cardiovascular Therapeutics 2011, showed that merely 1 of the 236 patients having 6 months of follow-up experienced a myocardial infarction and none died of cardiovascular causes, with no significant difference between those who continued on clopidogrel and those who switched to prasugrel. Rates of major bleeding were also low and similar.

"Given the low event rate in elective percutaneous coronary intervention [PCI] patients without periprocedural complications, it was not possible to assess the risk-benefit ratio with prasugrel treatment. Therefore, the study was terminated prematurely for futility," lead investigator Dietmar Trenk, Ph.D., explained in a press conference. He presented results on behalf of the TRIGGER-PCI investigators.

Discussant Dr. Matthew J. Price, director of the Cardiac Catheterization Laboratory at the Scripps Clinic in La Jolla, Calif., agreed that the trial population had very low risk to begin with, and not just from a procedural perspective. For example, the patients on average had relatively large stented vessel diameters and received shorter stents.

"Also, this trial shows the challenges of performing a randomized clinical trial looking at individualized antiplatelet therapy, because about one-third of the patients who were identified as having high on-treatment platelet reactivity withdrew from the study because they did not want to participate," he commented. "So I think this shows that doing these trials, it’s very hard not to get selection bias for the lowest-risk patients, and that’s a challenge that we will have going forward in designing these randomized clinical trials."

"I do think it’s consistent [across trials] that in these low-risk patients, who have low-risk clinical scenarios and low [anatomical risk], the event rates are incredibly low, and although the hazard associated with on-treatment [platelet] reactivity may be substantial, ...the absolute event rates in these very low risk patients may mean that changing therapy may not provide net clinical benefit," Dr. Price maintained.

Patients were eligible for the trial, which was sponsored by Eli Lilly and Daiichi Sankyo Co., if they underwent successful PCI with implantation of drug-eluting stents, did not have any major complications, and did not receive any glycoprotein IIb/IIIa inhibitors, according to Dr. Trenk, who is a professor at the Herz-Zentrum Bad Krozingen (Germany).

All had received standard-of-care clopidogrel in the periprocedural period and were found to be clopidogrel nonresponders because they had a result of more than 208 platelet reactive units on the VerifyNow P2Y12 assay (Accumetrics) on the day after the procedure.

The patients were randomized in nearly equal numbers to either continue clopidogrel (Plavix; 75-mg daily maintenance dose) or switch to prasugrel (Effient; a one-time 60-mg loading dose and a 10-mg daily maintenance dose), with matching placebos.

When the trial was stopped, 423 patients had been enrolled and had data for clinical outcomes, Dr. Trenk reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Analyses showed that the patients who switched to prasugrel indeed had lower platelet reactivity than did their counterparts who stayed on clopidogrel, both at 90 days (P less than .001) and at 176 days (P less than .001).

"Platelet reactivity in patients randomized to clopidogrel remained fairly constant, with a high rate of more than 70% of patients being hyporesponsive to the drug," Dr. Trenk pointed out. On the other hand, "prasugrel consistently decreased platelet reactivity, and only 5% of patients remained hyporesponsive at 3 months’ follow-up and at 6 months’ follow-up."

Despite this difference in platelet reactivity, the prasugrel and clopidogrel groups had similarly low 6-month rates of the primary composite efficacy end point of cardiovascular death and MI (0% and 0.5%), and secondary end points such as rehospitalization for cardiac ischemic events (0.9% and 1.9%), urgent target vessel revascularization (0.9% and 0.5%), and stroke (0% and 0.5%). There were no cases of definite or probably stent thrombosis.

Additionally, the prasugrel and clopidogrel groups had similarly low rates of the key safety end point of non–CABG-related TIMI (Thrombolysis in Myocardial Infarction) major bleeding (1.4% and 0.5%).

Dr. Trenk reported that he receives honoraria and advisory board fees from Daiichi-Sankyo, Eli Lilly, AstraZeneca, and Sanofi-Aventis. Dr. Price reported that he receives grant or research support from Bristol-Myers Squibb and Sanofi-Aventis, and that he is a consultant to, receives honoraria from, or is a speaker for Abiomed, AstraZeneca, Boston Scientific, Medtronic, Terumo Medical, Bristol-Myers Squibb, Daiichi-Sankyo/Eli Lilly, Sanofi-Aventis, and W.L. Gore & Associates.

SAN FRANCISCO – Platelet inhibition in response to adenosine diphosphate antagonists strongly predicted stent thrombosis within 30 days of implanting a drug-eluting stent in 8,575 patients on dual-antiplatelet therapy after percutaneous coronary intervention.

Both absolute and relative levels of platelet inhibition to ADP antagonists, as measured by the VerifyNow P2712 test, independently predicted early stent thrombosis, with a significant proportion of the thromboses associated with poor platelet response to clopidogrel, which inhibits the P2Y12 receptor, Dr. Gregg W. Stone and his associates reported.

The study assessed platelet function after dual-antiplatelet therapy loading using a suite of VerifyNow branded tests, and the findings may not be applicable to other tests. The tests assessed platelet reactivity to aspirin (VerifyNow Aspirin) and clopidogrel (VerifyNow P2Y12), and assessed overall platelet responsiveness (VerifyNow IIb/IIa).

The risk for stent thrombosis tripled in patients with P2Y12 reaction units (PRU) measuring greater than 208, which accounted for 50% of stent thromboses in a multivariable analysis, he said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The risk nearly tripled with a PRU of 230 or greater or with 11% or less inhibition of PY12, which accounted for 41% and 33% of stent thromboses, respectively.

Factors that were not predictive of 30-day risk of stent thrombosis included the baseline level of platelet P2Y12 response, platelet responsiveness to aspirin, and overall platelet responsiveness after dual-antiplatelet therapy loading, he said.

Giving agents that are more effective at inhibiting ADP-induced platelet activation to large patient populations should reduce the risk of 30-day stent thrombosis based on these findings, said Dr. Stone, director of cardiovascular research and education at New York-Presbyterian Hospital and professor of medicine at Columbia University, New York.

In that sense, the results of the ADAPT-DES study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) support the results of two previous studies, the TRITON-TIMI (Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction) 38 trial (N. Engl. J. Med. 2007;357:2001-15) and the PLATO (Platelet Inhibition and Patient Outcomes) study (N. Engl. J. Med. 2009;361:1045-57), he said.

On the other hand, the low rate of stent thrombosis – 0.46%, or only 39 in 30 days – and the modest sensitivity and specificity of platelet function testing suggest that testing platelet responsiveness to ADP antagonists probably isn’t helpful for clinical decision-making about preventing 30-day stent thrombosis in most patients, although the findings may be helpful on a population level.

Testing for a PRU greater than 208 was 74% sensitive and 57% specific, for an accuracy of 58%. Testing for a PRU of 230 or greater was 64% sensitive and 65% specific, for an accuracy of 65%. Testing for P2Y12 inhibition of 11% or less was 51% sensitive and 80% specific, for an accuracy of 80%.

Measuring platelet responsiveness to ADP antagonists was predictive in both diabetic and nondiabetic patients and in patients with acute coronary syndromes, but not in patients with stable coronary artery disease.

Thirty of the 39 stent thromboses occurred in the 4,347 patients with acute coronary syndromes. In this subgroup, a PRU greater than 208 or P2Y12 inhibition of 11% or less predicted a fourfold increased risk for 30-day stent thrombosis, and a PRU of 230 or greater predicted a tripling in risk. These tests flagged 60%, 44%, and 41% of 30-day stent thromboses, respectively, in patients with acute coronary syndromes.

In patients without acute coronary syndromes, the tests were not significantly associated with 30-day risk for stent thrombosis.

Dr. Stone suggested that the poor prognostic accuracy in patients without acute coronary syndromes and the low rate of stent thrombosis in this subgroup (only 9 of the 39 thromboses that occurred) may explain the negative results in two previous trials involving clopidogrel and platelet reactivity, the GRAVITAS (Gauging Responsiveness with A VerifyNow assay–Impact on Thrombosis And Safety) study (JAMA 2011;305:1097-1105) and the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study.

Although ADAPT-DES was a registry, "we tried to run it more like a randomized trial," Dr. Stone said. Eleven sites in the United States and Germany enrolled patients between January 2008 and September 2011 who underwent successful and uncomplicated PCI with an approved drug-eluting stent.

The ADAPT-DES study plans a 2-year follow-up to assess associations between platelet responsiveness testing and the risk of late or very late stent thrombosis.

The study was funded by the Cardiovascular Research Foundation, Accumetrics (which makes the VerifyNow tests), Boston Scientific, Abbott Vascular, Cordis, Biosensors, The Medicines Company, Daiichi Sankyo, Eli Lilly, and Volcano. Dr. Stone has received consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo, and Eli Lilly.

SAN FRANCISCO – Platelet inhibition in response to adenosine diphosphate antagonists strongly predicted stent thrombosis within 30 days of implanting a drug-eluting stent in 8,575 patients on dual-antiplatelet therapy after percutaneous coronary intervention.

Both absolute and relative levels of platelet inhibition to ADP antagonists, as measured by the VerifyNow P2712 test, independently predicted early stent thrombosis, with a significant proportion of the thromboses associated with poor platelet response to clopidogrel, which inhibits the P2Y12 receptor, Dr. Gregg W. Stone and his associates reported.

The study assessed platelet function after dual-antiplatelet therapy loading using a suite of VerifyNow branded tests, and the findings may not be applicable to other tests. The tests assessed platelet reactivity to aspirin (VerifyNow Aspirin) and clopidogrel (VerifyNow P2Y12), and assessed overall platelet responsiveness (VerifyNow IIb/IIa).

The risk for stent thrombosis tripled in patients with P2Y12 reaction units (PRU) measuring greater than 208, which accounted for 50% of stent thromboses in a multivariable analysis, he said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The risk nearly tripled with a PRU of 230 or greater or with 11% or less inhibition of PY12, which accounted for 41% and 33% of stent thromboses, respectively.

Factors that were not predictive of 30-day risk of stent thrombosis included the baseline level of platelet P2Y12 response, platelet responsiveness to aspirin, and overall platelet responsiveness after dual-antiplatelet therapy loading, he said.

Giving agents that are more effective at inhibiting ADP-induced platelet activation to large patient populations should reduce the risk of 30-day stent thrombosis based on these findings, said Dr. Stone, director of cardiovascular research and education at New York-Presbyterian Hospital and professor of medicine at Columbia University, New York.

In that sense, the results of the ADAPT-DES study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) support the results of two previous studies, the TRITON-TIMI (Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction) 38 trial (N. Engl. J. Med. 2007;357:2001-15) and the PLATO (Platelet Inhibition and Patient Outcomes) study (N. Engl. J. Med. 2009;361:1045-57), he said.

On the other hand, the low rate of stent thrombosis – 0.46%, or only 39 in 30 days – and the modest sensitivity and specificity of platelet function testing suggest that testing platelet responsiveness to ADP antagonists probably isn’t helpful for clinical decision-making about preventing 30-day stent thrombosis in most patients, although the findings may be helpful on a population level.

Testing for a PRU greater than 208 was 74% sensitive and 57% specific, for an accuracy of 58%. Testing for a PRU of 230 or greater was 64% sensitive and 65% specific, for an accuracy of 65%. Testing for P2Y12 inhibition of 11% or less was 51% sensitive and 80% specific, for an accuracy of 80%.

Measuring platelet responsiveness to ADP antagonists was predictive in both diabetic and nondiabetic patients and in patients with acute coronary syndromes, but not in patients with stable coronary artery disease.

Thirty of the 39 stent thromboses occurred in the 4,347 patients with acute coronary syndromes. In this subgroup, a PRU greater than 208 or P2Y12 inhibition of 11% or less predicted a fourfold increased risk for 30-day stent thrombosis, and a PRU of 230 or greater predicted a tripling in risk. These tests flagged 60%, 44%, and 41% of 30-day stent thromboses, respectively, in patients with acute coronary syndromes.

In patients without acute coronary syndromes, the tests were not significantly associated with 30-day risk for stent thrombosis.

Dr. Stone suggested that the poor prognostic accuracy in patients without acute coronary syndromes and the low rate of stent thrombosis in this subgroup (only 9 of the 39 thromboses that occurred) may explain the negative results in two previous trials involving clopidogrel and platelet reactivity, the GRAVITAS (Gauging Responsiveness with A VerifyNow assay–Impact on Thrombosis And Safety) study (JAMA 2011;305:1097-1105) and the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study.

Although ADAPT-DES was a registry, "we tried to run it more like a randomized trial," Dr. Stone said. Eleven sites in the United States and Germany enrolled patients between January 2008 and September 2011 who underwent successful and uncomplicated PCI with an approved drug-eluting stent.

The ADAPT-DES study plans a 2-year follow-up to assess associations between platelet responsiveness testing and the risk of late or very late stent thrombosis.

The study was funded by the Cardiovascular Research Foundation, Accumetrics (which makes the VerifyNow tests), Boston Scientific, Abbott Vascular, Cordis, Biosensors, The Medicines Company, Daiichi Sankyo, Eli Lilly, and Volcano. Dr. Stone has received consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo, and Eli Lilly.

SAN FRANCISCO – Platelet inhibition in response to adenosine diphosphate antagonists strongly predicted stent thrombosis within 30 days of implanting a drug-eluting stent in 8,575 patients on dual-antiplatelet therapy after percutaneous coronary intervention.

Both absolute and relative levels of platelet inhibition to ADP antagonists, as measured by the VerifyNow P2712 test, independently predicted early stent thrombosis, with a significant proportion of the thromboses associated with poor platelet response to clopidogrel, which inhibits the P2Y12 receptor, Dr. Gregg W. Stone and his associates reported.

The study assessed platelet function after dual-antiplatelet therapy loading using a suite of VerifyNow branded tests, and the findings may not be applicable to other tests. The tests assessed platelet reactivity to aspirin (VerifyNow Aspirin) and clopidogrel (VerifyNow P2Y12), and assessed overall platelet responsiveness (VerifyNow IIb/IIa).

The risk for stent thrombosis tripled in patients with P2Y12 reaction units (PRU) measuring greater than 208, which accounted for 50% of stent thromboses in a multivariable analysis, he said at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.

The risk nearly tripled with a PRU of 230 or greater or with 11% or less inhibition of PY12, which accounted for 41% and 33% of stent thromboses, respectively.

Factors that were not predictive of 30-day risk of stent thrombosis included the baseline level of platelet P2Y12 response, platelet responsiveness to aspirin, and overall platelet responsiveness after dual-antiplatelet therapy loading, he said.

Giving agents that are more effective at inhibiting ADP-induced platelet activation to large patient populations should reduce the risk of 30-day stent thrombosis based on these findings, said Dr. Stone, director of cardiovascular research and education at New York-Presbyterian Hospital and professor of medicine at Columbia University, New York.

In that sense, the results of the ADAPT-DES study (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) support the results of two previous studies, the TRITON-TIMI (Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction) 38 trial (N. Engl. J. Med. 2007;357:2001-15) and the PLATO (Platelet Inhibition and Patient Outcomes) study (N. Engl. J. Med. 2009;361:1045-57), he said.

On the other hand, the low rate of stent thrombosis – 0.46%, or only 39 in 30 days – and the modest sensitivity and specificity of platelet function testing suggest that testing platelet responsiveness to ADP antagonists probably isn’t helpful for clinical decision-making about preventing 30-day stent thrombosis in most patients, although the findings may be helpful on a population level.

Testing for a PRU greater than 208 was 74% sensitive and 57% specific, for an accuracy of 58%. Testing for a PRU of 230 or greater was 64% sensitive and 65% specific, for an accuracy of 65%. Testing for P2Y12 inhibition of 11% or less was 51% sensitive and 80% specific, for an accuracy of 80%.

Measuring platelet responsiveness to ADP antagonists was predictive in both diabetic and nondiabetic patients and in patients with acute coronary syndromes, but not in patients with stable coronary artery disease.

Thirty of the 39 stent thromboses occurred in the 4,347 patients with acute coronary syndromes. In this subgroup, a PRU greater than 208 or P2Y12 inhibition of 11% or less predicted a fourfold increased risk for 30-day stent thrombosis, and a PRU of 230 or greater predicted a tripling in risk. These tests flagged 60%, 44%, and 41% of 30-day stent thromboses, respectively, in patients with acute coronary syndromes.

In patients without acute coronary syndromes, the tests were not significantly associated with 30-day risk for stent thrombosis.

Dr. Stone suggested that the poor prognostic accuracy in patients without acute coronary syndromes and the low rate of stent thrombosis in this subgroup (only 9 of the 39 thromboses that occurred) may explain the negative results in two previous trials involving clopidogrel and platelet reactivity, the GRAVITAS (Gauging Responsiveness with A VerifyNow assay–Impact on Thrombosis And Safety) study (JAMA 2011;305:1097-1105) and the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study.

Although ADAPT-DES was a registry, "we tried to run it more like a randomized trial," Dr. Stone said. Eleven sites in the United States and Germany enrolled patients between January 2008 and September 2011 who underwent successful and uncomplicated PCI with an approved drug-eluting stent.

The ADAPT-DES study plans a 2-year follow-up to assess associations between platelet responsiveness testing and the risk of late or very late stent thrombosis.

The study was funded by the Cardiovascular Research Foundation, Accumetrics (which makes the VerifyNow tests), Boston Scientific, Abbott Vascular, Cordis, Biosensors, The Medicines Company, Daiichi Sankyo, Eli Lilly, and Volcano. Dr. Stone has received consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo, and Eli Lilly.

SAN FRANCISCO – Using a rapid point-of-care test to identify patients likely to be poor metabolizers of clopidogrel and tailoring their antiplatelet therapy accordingly improves the biologic effectiveness of that therapy, concludes a trial reported at the annual Transcatheter Cardiovascular Therapeutics meeting.

Investigators conducted the open-label, randomized trial in 200 patients undergoing percutaneous coronary intervention with stenting, using a point-of-care test for the *2 allele of the CYP2C19 gene. The allele confers a loss of function of the CYP2C19 enzyme and thus reduced hepatic metabolic activation of clopidogrel and an increased risk of adverse cardiovascular events in this setting. Testing was performed by nurses at the bedside using buccal swabs and yielded results in about 1 hour.

Findings of the RAPID GENE (Reassessment of Antiplatelet Therapy Using an Individualized Strategy Based on Genetic Evaluation) trial showed that nearly a third of patients having the *2 allele had impaired platelet activity a week later if they had simply been given standard clopidogrel therapy. This compared with none of their counterparts who were instead given prasugrel, an agent that overcomes the problem of poor metabolism, on the basis of their point-of-care test results.

"What RAPID GENE has shown is that point-of-care genetic testing after stenting performed at the bedside by clinical nurses permits accurate identification of the *2 carrier status and facilitates a rapid, tailored approach to antiplatelet therapy," according to lead investigator Dr. Derek Y.F. So.

The findings are clinically important, given that up to one-fourth of the more than 2 million patients undergoing coronary stenting each year may have genetic variants increasing their risk of clopidogrel failure, he noted. "RAPID GENE is essentially a proof of concept that rapid genetic testing and adherence with tailored therapy is now feasible," he said at the meeting, which is sponsored by the Cardiovascular Research Foundation. "The other reason this is important is that this will be applicable to all other areas of medicine as well."

However, added Dr. So, a cardiologist at the University of Ottawa Heart Institute, such testing remains more of a research tool at present. "I do think that it’s premature right now to say that this is going to be routinely implemented in hospitals. But ... this is going to be a game-changer in the sense that it allows us to design other prospective studies to evaluate this on a more detailed basis," he elaborated.

And this genetic information is merely one piece of a complex puzzle, he noted. "I don’t think using genetics alone is going to allow us to select out all the patients, but it’s going to be a combination of genetics in association with clinical risk factors, in association with platelet function. And I think that [*2 allelic information] will be a potential risk factor that will be incorporated in any future model."

Discussant Dr. Paul A. Gurbel, director of the Sinai Center for Thrombosis Research in Baltimore, expressed reservations about the trial, noting that a previous genome-wide associated study suggested that only 12.5% of the variability in platelet reactivity on clopidogrel can be attributed to the *2 allele, suggesting many genetic influences on the response to this drug. "So I have to say, this is a bit surprising – for any thienopyridine actually, there are so many influences on the response to thienopyridine therapies – to see absolutely no high platelet activity on prasugrel therapy in the *2 carriers," he said.

Furthermore, other studies in patients undergoing PCI suggest that the rate of high platelet reactivity on prasugrel is not zero. "So this [trial’s result] is discordant with data that’s already out there in the literature," Dr. Gurbel maintained.

He also sounded a note of caution about making decisions about clopidogrel therapy based solely on this allele. "There are many patients on clopidogrel who are *2 carriers who respond very nicely to the drug. So [by making] your decision based on *2, a lot of patients who would have responded nicely to clopidogrel are given another agent," he said.

In the trial, patients were randomized in balanced fashion to either standard therapy or genetically tailored therapy.

All patients in the former group received clopidogrel (Plavix) 75 mg daily. All patients in the latter group were started on clopidogrel but had point-of-care genotyping at the time of PCI to determine their *2 carrier status (Spartan RX, Spartan Bioscience); those found to carry the *2 allele were immediately switched to prasugrel 10 mg daily, whereas those found to be noncarriers continued on clopidogrel.

Platelet reactivity was assessed 1 week later with the VerifyNow P2Y12 assay (Accumetrics), and patients were defined as having high reactivity if their result exceeded 234 platelet reactive units. Additionally, *2 carrier status was assessed among patients in the standard therapy group at that time.

Trial results showed that *2 carriers were significantly less likely to have high platelet reactivity at 1 week if they received point-of-care testing plus prasugrel therapy than if they received standard clopidogrel therapy (0% vs. 30.4%).

Additional analyses showed that relative to the conventional laboratory genetic test, the rapid point-of-care test had 100% sensitivity and 99.4% specificity for identifying *2 carriers.

"There was no difference in clinical events between the two arms," Dr. So reported; however "there was a numerical increase in bleeding among patients on the rapid genotyping arm, compared to the standard therapy arm."

He acknowledged the numerous genetic influences on clopidogrel response and their interaction, and noted that the rapid point-of-care testing device is being improved in this regard. "There is a second study now of the three-SNP [single-nucleotide polymorphism] device, so we will be able to look at multiple SNPs at the same time in the future," he said.

Dr. So reported that he receives grant or research support from Spartan and is a consultant to, speaker for, or receives honoraria from Daiichi-Sankyo/Eli Lilly. Dr. Gurbel reported that he is a consultant to, speaker for, or receives honoraria from Merck/Schering Plough, Portola Pharmaceuticals, Bayer/Pozen, AstraZeneca, and Daiichi-Sankyo/Eli Lilly.

SAN FRANCISCO – Using a rapid point-of-care test to identify patients likely to be poor metabolizers of clopidogrel and tailoring their antiplatelet therapy accordingly improves the biologic effectiveness of that therapy, concludes a trial reported at the annual Transcatheter Cardiovascular Therapeutics meeting.

Investigators conducted the open-label, randomized trial in 200 patients undergoing percutaneous coronary intervention with stenting, using a point-of-care test for the *2 allele of the CYP2C19 gene. The allele confers a loss of function of the CYP2C19 enzyme and thus reduced hepatic metabolic activation of clopidogrel and an increased risk of adverse cardiovascular events in this setting. Testing was performed by nurses at the bedside using buccal swabs and yielded results in about 1 hour.

Findings of the RAPID GENE (Reassessment of Antiplatelet Therapy Using an Individualized Strategy Based on Genetic Evaluation) trial showed that nearly a third of patients having the *2 allele had impaired platelet activity a week later if they had simply been given standard clopidogrel therapy. This compared with none of their counterparts who were instead given prasugrel, an agent that overcomes the problem of poor metabolism, on the basis of their point-of-care test results.

"What RAPID GENE has shown is that point-of-care genetic testing after stenting performed at the bedside by clinical nurses permits accurate identification of the *2 carrier status and facilitates a rapid, tailored approach to antiplatelet therapy," according to lead investigator Dr. Derek Y.F. So.

The findings are clinically important, given that up to one-fourth of the more than 2 million patients undergoing coronary stenting each year may have genetic variants increasing their risk of clopidogrel failure, he noted. "RAPID GENE is essentially a proof of concept that rapid genetic testing and adherence with tailored therapy is now feasible," he said at the meeting, which is sponsored by the Cardiovascular Research Foundation. "The other reason this is important is that this will be applicable to all other areas of medicine as well."

However, added Dr. So, a cardiologist at the University of Ottawa Heart Institute, such testing remains more of a research tool at present. "I do think that it’s premature right now to say that this is going to be routinely implemented in hospitals. But ... this is going to be a game-changer in the sense that it allows us to design other prospective studies to evaluate this on a more detailed basis," he elaborated.

And this genetic information is merely one piece of a complex puzzle, he noted. "I don’t think using genetics alone is going to allow us to select out all the patients, but it’s going to be a combination of genetics in association with clinical risk factors, in association with platelet function. And I think that [*2 allelic information] will be a potential risk factor that will be incorporated in any future model."

Discussant Dr. Paul A. Gurbel, director of the Sinai Center for Thrombosis Research in Baltimore, expressed reservations about the trial, noting that a previous genome-wide associated study suggested that only 12.5% of the variability in platelet reactivity on clopidogrel can be attributed to the *2 allele, suggesting many genetic influences on the response to this drug. "So I have to say, this is a bit surprising – for any thienopyridine actually, there are so many influences on the response to thienopyridine therapies – to see absolutely no high platelet activity on prasugrel therapy in the *2 carriers," he said.

Furthermore, other studies in patients undergoing PCI suggest that the rate of high platelet reactivity on prasugrel is not zero. "So this [trial’s result] is discordant with data that’s already out there in the literature," Dr. Gurbel maintained.

He also sounded a note of caution about making decisions about clopidogrel therapy based solely on this allele. "There are many patients on clopidogrel who are *2 carriers who respond very nicely to the drug. So [by making] your decision based on *2, a lot of patients who would have responded nicely to clopidogrel are given another agent," he said.

In the trial, patients were randomized in balanced fashion to either standard therapy or genetically tailored therapy.

All patients in the former group received clopidogrel (Plavix) 75 mg daily. All patients in the latter group were started on clopidogrel but had point-of-care genotyping at the time of PCI to determine their *2 carrier status (Spartan RX, Spartan Bioscience); those found to carry the *2 allele were immediately switched to prasugrel 10 mg daily, whereas those found to be noncarriers continued on clopidogrel.

Platelet reactivity was assessed 1 week later with the VerifyNow P2Y12 assay (Accumetrics), and patients were defined as having high reactivity if their result exceeded 234 platelet reactive units. Additionally, *2 carrier status was assessed among patients in the standard therapy group at that time.

Trial results showed that *2 carriers were significantly less likely to have high platelet reactivity at 1 week if they received point-of-care testing plus prasugrel therapy than if they received standard clopidogrel therapy (0% vs. 30.4%).

Additional analyses showed that relative to the conventional laboratory genetic test, the rapid point-of-care test had 100% sensitivity and 99.4% specificity for identifying *2 carriers.

"There was no difference in clinical events between the two arms," Dr. So reported; however "there was a numerical increase in bleeding among patients on the rapid genotyping arm, compared to the standard therapy arm."

He acknowledged the numerous genetic influences on clopidogrel response and their interaction, and noted that the rapid point-of-care testing device is being improved in this regard. "There is a second study now of the three-SNP [single-nucleotide polymorphism] device, so we will be able to look at multiple SNPs at the same time in the future," he said.

Dr. So reported that he receives grant or research support from Spartan and is a consultant to, speaker for, or receives honoraria from Daiichi-Sankyo/Eli Lilly. Dr. Gurbel reported that he is a consultant to, speaker for, or receives honoraria from Merck/Schering Plough, Portola Pharmaceuticals, Bayer/Pozen, AstraZeneca, and Daiichi-Sankyo/Eli Lilly.

SAN FRANCISCO – Using a rapid point-of-care test to identify patients likely to be poor metabolizers of clopidogrel and tailoring their antiplatelet therapy accordingly improves the biologic effectiveness of that therapy, concludes a trial reported at the annual Transcatheter Cardiovascular Therapeutics meeting.

Investigators conducted the open-label, randomized trial in 200 patients undergoing percutaneous coronary intervention with stenting, using a point-of-care test for the *2 allele of the CYP2C19 gene. The allele confers a loss of function of the CYP2C19 enzyme and thus reduced hepatic metabolic activation of clopidogrel and an increased risk of adverse cardiovascular events in this setting. Testing was performed by nurses at the bedside using buccal swabs and yielded results in about 1 hour.

Findings of the RAPID GENE (Reassessment of Antiplatelet Therapy Using an Individualized Strategy Based on Genetic Evaluation) trial showed that nearly a third of patients having the *2 allele had impaired platelet activity a week later if they had simply been given standard clopidogrel therapy. This compared with none of their counterparts who were instead given prasugrel, an agent that overcomes the problem of poor metabolism, on the basis of their point-of-care test results.

"What RAPID GENE has shown is that point-of-care genetic testing after stenting performed at the bedside by clinical nurses permits accurate identification of the *2 carrier status and facilitates a rapid, tailored approach to antiplatelet therapy," according to lead investigator Dr. Derek Y.F. So.

The findings are clinically important, given that up to one-fourth of the more than 2 million patients undergoing coronary stenting each year may have genetic variants increasing their risk of clopidogrel failure, he noted. "RAPID GENE is essentially a proof of concept that rapid genetic testing and adherence with tailored therapy is now feasible," he said at the meeting, which is sponsored by the Cardiovascular Research Foundation. "The other reason this is important is that this will be applicable to all other areas of medicine as well."

However, added Dr. So, a cardiologist at the University of Ottawa Heart Institute, such testing remains more of a research tool at present. "I do think that it’s premature right now to say that this is going to be routinely implemented in hospitals. But ... this is going to be a game-changer in the sense that it allows us to design other prospective studies to evaluate this on a more detailed basis," he elaborated.

And this genetic information is merely one piece of a complex puzzle, he noted. "I don’t think using genetics alone is going to allow us to select out all the patients, but it’s going to be a combination of genetics in association with clinical risk factors, in association with platelet function. And I think that [*2 allelic information] will be a potential risk factor that will be incorporated in any future model."

Discussant Dr. Paul A. Gurbel, director of the Sinai Center for Thrombosis Research in Baltimore, expressed reservations about the trial, noting that a previous genome-wide associated study suggested that only 12.5% of the variability in platelet reactivity on clopidogrel can be attributed to the *2 allele, suggesting many genetic influences on the response to this drug. "So I have to say, this is a bit surprising – for any thienopyridine actually, there are so many influences on the response to thienopyridine therapies – to see absolutely no high platelet activity on prasugrel therapy in the *2 carriers," he said.

Furthermore, other studies in patients undergoing PCI suggest that the rate of high platelet reactivity on prasugrel is not zero. "So this [trial’s result] is discordant with data that’s already out there in the literature," Dr. Gurbel maintained.

He also sounded a note of caution about making decisions about clopidogrel therapy based solely on this allele. "There are many patients on clopidogrel who are *2 carriers who respond very nicely to the drug. So [by making] your decision based on *2, a lot of patients who would have responded nicely to clopidogrel are given another agent," he said.

In the trial, patients were randomized in balanced fashion to either standard therapy or genetically tailored therapy.

All patients in the former group received clopidogrel (Plavix) 75 mg daily. All patients in the latter group were started on clopidogrel but had point-of-care genotyping at the time of PCI to determine their *2 carrier status (Spartan RX, Spartan Bioscience); those found to carry the *2 allele were immediately switched to prasugrel 10 mg daily, whereas those found to be noncarriers continued on clopidogrel.

Platelet reactivity was assessed 1 week later with the VerifyNow P2Y12 assay (Accumetrics), and patients were defined as having high reactivity if their result exceeded 234 platelet reactive units. Additionally, *2 carrier status was assessed among patients in the standard therapy group at that time.

Trial results showed that *2 carriers were significantly less likely to have high platelet reactivity at 1 week if they received point-of-care testing plus prasugrel therapy than if they received standard clopidogrel therapy (0% vs. 30.4%).

Additional analyses showed that relative to the conventional laboratory genetic test, the rapid point-of-care test had 100% sensitivity and 99.4% specificity for identifying *2 carriers.

"There was no difference in clinical events between the two arms," Dr. So reported; however "there was a numerical increase in bleeding among patients on the rapid genotyping arm, compared to the standard therapy arm."

He acknowledged the numerous genetic influences on clopidogrel response and their interaction, and noted that the rapid point-of-care testing device is being improved in this regard. "There is a second study now of the three-SNP [single-nucleotide polymorphism] device, so we will be able to look at multiple SNPs at the same time in the future," he said.

Dr. So reported that he receives grant or research support from Spartan and is a consultant to, speaker for, or receives honoraria from Daiichi-Sankyo/Eli Lilly. Dr. Gurbel reported that he is a consultant to, speaker for, or receives honoraria from Merck/Schering Plough, Portola Pharmaceuticals, Bayer/Pozen, AstraZeneca, and Daiichi-Sankyo/Eli Lilly.

Two competing devices for transcatheter aortic valve replacement produced good overall outcomes in a study of 305 patients from the Milan registry, Dr. Gill Louise Buchanan and associates reported at Transcatheter Cardiovascular Therapeutics 2011.

The combined 30-day mortality for the devices – Edwards Lifesciences’ Sapien valve (ESV) and Medtronic’s CoreValve ReValving System – was 4.7%. The myocardial infarction rate was 1.3% and the rate of stroke was 1.0%, said Dr. Buchanan of the interventional cardiology unit at San Raffaele Scientific Institute in Milan, and her associates.

"There was no difference in device success (92.5% overall), combined safety end point at 30 days (61.8%) or combined efficacy end point (72.0%) at 1-year follow-up," between the two valves, but there were significant differences in conduction disturbance and/or arrhythmia occurrence and the need for pacemaker (see graph, below), the investigators said.

Note: Based on data from 305 patients treated from November 2007 to April 2011.

Source: Dr. Gill Louise Buchanan and associates

Two competing devices for transcatheter aortic valve replacement produced good overall outcomes in a study of 305 patients from the Milan registry, Dr. Gill Louise Buchanan and associates reported at Transcatheter Cardiovascular Therapeutics 2011.

The combined 30-day mortality for the devices – Edwards Lifesciences’ Sapien valve (ESV) and Medtronic’s CoreValve ReValving System – was 4.7%. The myocardial infarction rate was 1.3% and the rate of stroke was 1.0%, said Dr. Buchanan of the interventional cardiology unit at San Raffaele Scientific Institute in Milan, and her associates.

"There was no difference in device success (92.5% overall), combined safety end point at 30 days (61.8%) or combined efficacy end point (72.0%) at 1-year follow-up," between the two valves, but there were significant differences in conduction disturbance and/or arrhythmia occurrence and the need for pacemaker (see graph, below), the investigators said.

Note: Based on data from 305 patients treated from November 2007 to April 2011.

Source: Dr. Gill Louise Buchanan and associates

Two competing devices for transcatheter aortic valve replacement produced good overall outcomes in a study of 305 patients from the Milan registry, Dr. Gill Louise Buchanan and associates reported at Transcatheter Cardiovascular Therapeutics 2011.

The combined 30-day mortality for the devices – Edwards Lifesciences’ Sapien valve (ESV) and Medtronic’s CoreValve ReValving System – was 4.7%. The myocardial infarction rate was 1.3% and the rate of stroke was 1.0%, said Dr. Buchanan of the interventional cardiology unit at San Raffaele Scientific Institute in Milan, and her associates.

"There was no difference in device success (92.5% overall), combined safety end point at 30 days (61.8%) or combined efficacy end point (72.0%) at 1-year follow-up," between the two valves, but there were significant differences in conduction disturbance and/or arrhythmia occurrence and the need for pacemaker (see graph, below), the investigators said.

Note: Based on data from 305 patients treated from November 2007 to April 2011.

Source: Dr. Gill Louise Buchanan and associates

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.