Christine Kilgore

Major Finding: At 2 years, treatment with the everolimus-eluting Xience V stent rather than the paclitaxel-eluting Taxus stent resulted in a 30% relative reduction in target lesion failure, a 34% relative reduction in ischemia-driven target lesion revascularization, and a 64% relative reduction in stent thrombosis. Between 1 and 2 years in the COMPARE trial, there was a 77% reduction in very late definite or probable stent thrombosis in favor of Xience V.

Data Source: SPIRIT IV: a randomized prospective study of 3,687 patients treated at 66 U.S. medical centers. COMPARE: a randomized single-center trial of 1,800 patients.

Disclosures: The SPIRIT IV trial is sponsored by Abbott Vascular; the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific.

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at the meeting.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We've seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there's a difference in the mechanistic response of diabetics versus nondiabetics … to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5–3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group, compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Liberté stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Liberté stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Liberté group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The lack of benefit of the Xience V stent in diabetics means there is a difference in their mechanistic response.

Source DR. STONE

Major Finding: At 2 years, treatment with the everolimus-eluting Xience V stent rather than the paclitaxel-eluting Taxus stent resulted in a 30% relative reduction in target lesion failure, a 34% relative reduction in ischemia-driven target lesion revascularization, and a 64% relative reduction in stent thrombosis. Between 1 and 2 years in the COMPARE trial, there was a 77% reduction in very late definite or probable stent thrombosis in favor of Xience V.

Data Source: SPIRIT IV: a randomized prospective study of 3,687 patients treated at 66 U.S. medical centers. COMPARE: a randomized single-center trial of 1,800 patients.

Disclosures: The SPIRIT IV trial is sponsored by Abbott Vascular; the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific.

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at the meeting.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We've seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there's a difference in the mechanistic response of diabetics versus nondiabetics … to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5–3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group, compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Liberté stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Liberté stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Liberté group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The lack of benefit of the Xience V stent in diabetics means there is a difference in their mechanistic response.

Source DR. STONE

Major Finding: At 2 years, treatment with the everolimus-eluting Xience V stent rather than the paclitaxel-eluting Taxus stent resulted in a 30% relative reduction in target lesion failure, a 34% relative reduction in ischemia-driven target lesion revascularization, and a 64% relative reduction in stent thrombosis. Between 1 and 2 years in the COMPARE trial, there was a 77% reduction in very late definite or probable stent thrombosis in favor of Xience V.

Data Source: SPIRIT IV: a randomized prospective study of 3,687 patients treated at 66 U.S. medical centers. COMPARE: a randomized single-center trial of 1,800 patients.

Disclosures: The SPIRIT IV trial is sponsored by Abbott Vascular; the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific.

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at the meeting.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We've seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there's a difference in the mechanistic response of diabetics versus nondiabetics … to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5–3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group, compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Liberté stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Liberté stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Liberté group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The lack of benefit of the Xience V stent in diabetics means there is a difference in their mechanistic response.

Source DR. STONE

Major Finding: At 9 months, the rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in 1,384 Cypher-treated patients in ISAR-TEST 4. At 2 years, target lesion revascularization was 16% with Xience and 18.8% with Cypher in SORT OUT 4.

Data Source: Two prospective, randomized industry-independent studies conducted in Europe: ISAR-TEST 4 and SORT OUT 4.

Disclosures: Dr. Jensen reported that she has a financial interest/arrangement or affiliation with Cordis, Johnson & Johnson, and Abbott. Dr. Byrne reported that he had no relevant disclosures.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team's SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Byrne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

Major Finding: At 9 months, the rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in 1,384 Cypher-treated patients in ISAR-TEST 4. At 2 years, target lesion revascularization was 16% with Xience and 18.8% with Cypher in SORT OUT 4.

Data Source: Two prospective, randomized industry-independent studies conducted in Europe: ISAR-TEST 4 and SORT OUT 4.

Disclosures: Dr. Jensen reported that she has a financial interest/arrangement or affiliation with Cordis, Johnson & Johnson, and Abbott. Dr. Byrne reported that he had no relevant disclosures.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team's SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Byrne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

Major Finding: At 9 months, the rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in 1,384 Cypher-treated patients in ISAR-TEST 4. At 2 years, target lesion revascularization was 16% with Xience and 18.8% with Cypher in SORT OUT 4.

Data Source: Two prospective, randomized industry-independent studies conducted in Europe: ISAR-TEST 4 and SORT OUT 4.

Disclosures: Dr. Jensen reported that she has a financial interest/arrangement or affiliation with Cordis, Johnson & Johnson, and Abbott. Dr. Byrne reported that he had no relevant disclosures.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team's SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Byrne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated. 

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated. 

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated. 

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated. 

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated. 

WASHINGTON – Treating symptomatic femoropopliteal artery disease with a paclitaxel-eluting peripheral stent beat both percutaneous transluminal angioplasty and provisional bare-metal stenting in achieving vessel patency rates at 12 months in a prospective, randomized trial.

With the increasing development of dedicated devices for peripheral lesions, more interventional cardiologists have become interested in peripheral interventions. Other drug-eluting stents that were tested in previous trials failed, however, to show significant differences in outcome, compared with those of bare-metal stenting.

This trial was different. In one major finding of the multitiered study, patency rates at 12 months were 83.1% with Cook Medical Inc.’s paclitaxel-eluting Zilver stent and 67% with “standard” care (angioplasty with provisional bare-metal stenting). And in a head-to-head comparison of provisional stenting, the patency rate was 89.9% with the Zilver PTX stent and 73% with the bare-metal stent.

“This is the largest randomized trial ever performed for the endovascular management of peripheral artery disease,” said principal investigator Dr. Michael D. Dake, who presented the results of the industry-sponsored Zilver PTX trial at the Transcatheter Cardiovascular Therapeutics 2010.

“I think it’s a signal that it’s possible to improve the results of current therapies for PAD with a combination of both drugs and mechanical devices,” he said in a press conference.

The trial enrolled 479 patients at 55 sites in the United States, Germany, and Japan. Patients had symptomatic disease of the above-the-knee femoropopliteal artery (most were moderately to severely symptomatic), as well as lesions up to 14 cm. The average lesion length was 6.6 cm, and vessel diameter was 4-9 mm.

In the first of two randomization protocols, patients were randomized to treatment with either conventional percutaneous transluminal angioplasty (PTA) or with the Zilver PTX stent, a self-expanding nitinol stent with a polymer-free paclitaxel coating. After 1 year, 83.1% of the vessels that were treated with the paclitaxel-eluting stent were still patent, compared with 32.8% of the vessels in the PTA-treated group.

Patency was defined as peak systolic velocity ratio less than 2.0 as measured by duplex ultrasonography, or diameter stenosis less than 50% as determined by angiography.

However, PTA failed to restore primary patency in approximately half of the patients in the PTA group – a rate seen in other trials. When the Zilver PTX stent was compared with “optimal” PTA (only those who achieved optimal results after primary PTA), the Zilver stent still performed significantly better, at 83.1% vs. 65.3%.

In the secondary randomization, the “suboptimal” PTA group (those who failed primary PTA) was randomized again to receive either a bare-metal Zilver stent or the paclitaxel-eluting version. In this comparison of provisional stenting, 12-month patency rates were 89.9% in the Zilver PTX group and 73% in the bare-metal stent group.

In other words, the 12-month restenosis rates were 10.1% with the Zilver PTX stent and 27% with the bare-metal stent, said Dr. Dake of Stanford (Calif.) University.

In another analysis crossing both tiers, the investigators compared primary use of the paclitaxel-eluting stent with the “real-world standard of care” in a group that comprised patients whose PTA treatment was optimal as well as those who received bare-metal stents after their PTA had failed. This “standard of care” group had a patency rate of 67%, significantly less than the 83.1% patency rate of the primary Zilver PTX group.

The primary safety end point was 12-month, event-free survival, which included freedom from amputation, target lesion revascularization, and significant worsening of claudication. Event-free survival was 90.4% in the patients who were initially randomized for treatment with the Zilver PTX stent and 82.6% in the PTA group.

There was “only a 0.9% stent fracture rate through 12 months,” and none of the four stent fractures that occurred had any clinical sequelae, said Dr. Dake.

Moreover, subgroup studies with intravascular ultrasound and angiography showed “no evidence of untoward effects [of the drug] or complications of the device,” and there were no cases of acute stent thrombosis, he reported. Patients in the trial were on a dual antiplatelet regimen for at least 2 months. At 12 months, “61% of patients had remained on it,” Dr. Dake said.

Dr. John Laird of the University of California, Davis, Medical Center said that longer-term results are critical since “there’s potential for late restenosis” resulting from the “chronic injury and chronic irritation” caused by stents. “The big difference here is that there’s no polymer on the stent to be a source of irritation as well,” he said.

It is also uncertain whether the patency results can be replicated with the longer lesions that are typically seen in PAD in the “real world,” panelists said.

(Investigators in the current randomized trial were limited, per the Food and Drug Administration–approved study protocol, to treat lesions that were no longer than 14 cm, Dr. Dake said.)

Dr. Hans Krankenberg of the cardiovascular center at the University of Hamburg (Germany) said that an ongoing international Zilver PTX registry is showing, thus far, that “the findings from this trial can be transferred to almost all [other lesions].”

Patients in the randomized trial had an average age of 68 years, and almost half had diabetes.

Clinical outcomes, which will be presented later, mirror the patency findings, Dr. Dake said. There will be ongoing follow-up through 5 years.

Dr. William A. Gray, director of endovascular services at Columbia University Medical Center, New York, who moderated a discussion of the study at the meeting, noted that the Zilver PTX trial followed both the SIROCCO trial, which tested a sirolimus-eluting, durable polymer–coated SMART stent against a bare-metal stent in patients with femoropopliteal disease, and the STRIDES trial, which tested an everolimus-eluting, durable polymer–coated ABSOLUTE stent. Both studies failed to show any real efficacy at reducing restenosis.

The Zilver PTX stent lacks a durable polymer and delivers paclitaxel rather than a limus drug, which raises questions about the causal mechanisms for its unprecedented success, Dr. Gray said. There are also questions about how its effectiveness in the shorter lesions in this trial can be extrapolated to real-world lesion lengths of 20 cm and even 30 cm. Nevertheless, he noted, this positive trial is a critically important proof of concept, and potentially groundbreaking in the way superficial femoral artery disease and popliteal treatment will be viewed from now on.

The Zilver PTX stent is currently available in Europe. In the United States, Cook Medical has submitted a premarket approval application to the FDA, a company spokesperson said.

The trial was sponsored by Cook Medical, which manufactures the Zilver PTX stent. Dr. Dake disclosed that he had clinical trial support from Cook Medical, consulting fees/honoraria from W.L. Gore and Abbott Vascular, and equity interest/stock options in various device companies. Dr. Gray is a consultant for Cook Medical, which manufactures the Zilver PTX stent, as well as Abbott Vascular and Cordis/Johnson and Johnson.

* Correction, Oct. 20, 2010: The original version of this article incorrectly referred to Zilver PTX as Zenith PTX on several references. This version has been updated. 

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We’ve seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there’s a difference in the mechanistic response of diabetics versus nondiabetics ... to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5-3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

At a press conference, Dr. Dean Kereiakes said in his presentation of the 2-year SPIRIT IV findings that for every 1 million patients treated with the everolimus-eluting stent, there would be 24,000 fewer repeat revascularization procedures.

“And for every 1 million patients treated (with Xience V), there would be more than 8,000 stent thromboses prevented,” said Dr. Kereiakes of the Christ Hospital Ohio Heart and Vascular Center in Cincinnati.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Libert? stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Libert? stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Libert? group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The SPIRIT IV trial is sponsored by Abbott Vascular, and the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific. Dr. Kereiakes disclosed that he has received honoraria and grant support from both Abbott Vascular and Boston Scientific.

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We’ve seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there’s a difference in the mechanistic response of diabetics versus nondiabetics ... to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5-3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

At a press conference, Dr. Dean Kereiakes said in his presentation of the 2-year SPIRIT IV findings that for every 1 million patients treated with the everolimus-eluting stent, there would be 24,000 fewer repeat revascularization procedures.

“And for every 1 million patients treated (with Xience V), there would be more than 8,000 stent thromboses prevented,” said Dr. Kereiakes of the Christ Hospital Ohio Heart and Vascular Center in Cincinnati.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Libert? stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Libert? stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Libert? group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The SPIRIT IV trial is sponsored by Abbott Vascular, and the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific. Dr. Kereiakes disclosed that he has received honoraria and grant support from both Abbott Vascular and Boston Scientific.

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We’ve seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there’s a difference in the mechanistic response of diabetics versus nondiabetics ... to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5-3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

At a press conference, Dr. Dean Kereiakes said in his presentation of the 2-year SPIRIT IV findings that for every 1 million patients treated with the everolimus-eluting stent, there would be 24,000 fewer repeat revascularization procedures.

“And for every 1 million patients treated (with Xience V), there would be more than 8,000 stent thromboses prevented,” said Dr. Kereiakes of the Christ Hospital Ohio Heart and Vascular Center in Cincinnati.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Libert? stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Libert? stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Libert? group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The SPIRIT IV trial is sponsored by Abbott Vascular, and the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific. Dr. Kereiakes disclosed that he has received honoraria and grant support from both Abbott Vascular and Boston Scientific.

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We’ve seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there’s a difference in the mechanistic response of diabetics versus nondiabetics ... to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5-3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

At a press conference, Dr. Dean Kereiakes said in his presentation of the 2-year SPIRIT IV findings that for every 1 million patients treated with the everolimus-eluting stent, there would be 24,000 fewer repeat revascularization procedures.

“And for every 1 million patients treated (with Xience V), there would be more than 8,000 stent thromboses prevented,” said Dr. Kereiakes of the Christ Hospital Ohio Heart and Vascular Center in Cincinnati.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Libert? stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Libert? stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Libert? group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The SPIRIT IV trial is sponsored by Abbott Vascular, and the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific. Dr. Kereiakes disclosed that he has received honoraria and grant support from both Abbott Vascular and Boston Scientific.

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We’ve seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there’s a difference in the mechanistic response of diabetics versus nondiabetics ... to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5-3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

At a press conference, Dr. Dean Kereiakes said in his presentation of the 2-year SPIRIT IV findings that for every 1 million patients treated with the everolimus-eluting stent, there would be 24,000 fewer repeat revascularization procedures.

“And for every 1 million patients treated (with Xience V), there would be more than 8,000 stent thromboses prevented,” said Dr. Kereiakes of the Christ Hospital Ohio Heart and Vascular Center in Cincinnati.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Libert? stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Libert? stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Libert? group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The SPIRIT IV trial is sponsored by Abbott Vascular, and the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific. Dr. Kereiakes disclosed that he has received honoraria and grant support from both Abbott Vascular and Boston Scientific.

WASHINGTON – The benefits seen 1 year after percutaneous coronary intervention with the everolimus-eluting Xience V stent compared with the paclitaxel-eluting Taxus stent were sustained at 2 years of follow-up in two very different types of randomized studies.

And in the case of stent thrombosis in particular, the benefits of the everolimus-eluting stent appear to have intensified at 2 years, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

The new 2-year findings from both the SPIRIT IV trial, a large study involving 66 U.S. sites, and the COMPARE trial, a small, single-center, “all-comers” trial in Europe, confirm the superiority of the everolimus-eluting stent in patients – except in patients with diabetes, the investigators and other discussants said.

In patients with diabetes, no significant differences in the risk of major adverse cardiac events (MACE) were observed with either stent in either trial at 1 or 2 years after PCI, a finding that led experts at the meeting to surmise that diabetic patients may fare equally well with both stents.

“We’ve seen this now in almost every trial” comparing these drug-eluting stents. “There is no difference in MACE rates,” Dr. Gregg W. Stone of Columbia University College of Physicians and Surgeons, New York, said in a session announcing the new SPIRIT IV findings.

“In my mind, this lack of benefit [to the Xience V stent] in diabetics means without any doubt that there’s a difference in the mechanistic response of diabetics versus nondiabetics ... to these types of drugs,” he said. Dr. Stone is principal investigator for Spirit IV and codirector of medical research and education at the Cardiovascular Research Foundation, which sponsored the TCT meeting.

The 3,687 patients in the industry-sponsored SPIRIT IV trial, including 1,185 with diabetes, were randomized in 2:1 fashion to receive either the everolimus-eluting Xience V stent (Abbott Vascular) or the first-generation paclitaxel-eluting Taxus Express stent (Boston Scientific). The patients had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5-3.75 mm.

At 2 years, treatment with Xience V resulted in a relative 30% reduction (and a 3% absolute decline) in target lesion failure compared with treatment with the Taxus stent, with target lesion failure occurring in about 6.9% and 9.9% of the patients, respectively. (The rates of this primary end point after 1 year were 4.0% and 6.9%, respectively.)

The relative reduction in target lesion failure was 39% in patients without diabetes, but in diabetic patients there was little difference between the two groups. Target lesion failure is a composite end point reflecting cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization.

Ischemia-driven target lesion revascularization, a secondary end point, occurred at a rate of 4.5% at 2 years in the Xience group compared with 6.9% in the Taxus group, for an absolute reduction of 2.4% and a relative reduction of 34%. The rates of this secondary outcome after 1 year were 2.4% compared with 4.6%.

While there were no mortality differences, target-vessel MI also occurred at a significantly reduced rate in the Xience group at both 1 and 2 years (2.3% v. 3.5% at 2 years), said Dr. Stone.

At a press conference, Dr. Dean Kereiakes said in his presentation of the 2-year SPIRIT IV findings that for every 1 million patients treated with the everolimus-eluting stent, there would be 24,000 fewer repeat revascularization procedures.

“And for every 1 million patients treated (with Xience V), there would be more than 8,000 stent thromboses prevented,” said Dr. Kereiakes of the Christ Hospital Ohio Heart and Vascular Center in Cincinnati.

The rates in stent thrombosis in both studies, in fact, drew significant attention at the meeting. At 2 years after intervention in SPIRIT IV, 1.2% in the Taxus group had developed definite/probable stent thrombosis according to definitions of the Academic Research Consortium (ARC), compared with 0.4% in the Xience arm.

This translates into a 64% relative risk reduction for stent thrombosis (a 0.8% absolute reduction) that occurred during each period – early (the first 30 days), late (31 days to 1 year) and very late period (over 1 year).

The 2-year reductions in stent thrombosis reported from the COMPARE trial were even more striking, discussants said at the meeting.

In this trial, 1,800 consecutive patients undergoing PCI at one center in Rotterdam, the Netherlands, were randomly assigned in 1:1 fashion to treatment with the Xience V stent or the Taxus Libert? stent, a second-generation paclitaxel-eluting stent.

(The Taxus Express stent used in SPIRIT IV is no longer commercially available, according to a spokesperson for Boston Scientific. The Taxus Libert? stent, which uses the same polymer but a different stent platform, is currently available in the United States and in Europe, he said.)

The rate of definite/probable stent thrombosis (again, by ARC definition) at 2 years in the COMPARE trial was 0.9% in the Xience V group and 3.9% in the Taxus group – higher rates than found in SPIRIT IV. Most notable, however, was a 77% reduction in very late definite/probable stent thrombosis in the Xience V arm. The rate of this outcome was 0.3% in the Xience V group and 1.5% in the Taxus Libert? group, reported Dr. Peter Smits of Maasstad Ziekenhuis.

This difference is especially notable because the vast majority of patients were no longer taking dual antiplatelet therapy at 2 years, said Dr. Smits, principal investigator of COMPARE. In contrast, more than 70% of patients in each arm of the SPIRIT IV trial remained on dual antiplatelet therapy at 2 years.

Unlike the SPIRIT design, the COMPARE trial was designed to be an “all-comer, real-world study” without exclusions for complex patients. At 2 years, the superiority of the Xience V stent for the primary end point – a composite of all mortality, nonfatal MI, and target vessel revascularization (MACE) – was maintained, with larger absolute differences between the stents than at 12 months.

At 1 year, this primary end point had occurred in 6.2% and 9.1% in the Xience V and Taxus groups, respectively, for an absolute difference of 2.9%. At 2 years, these rates rose to 9.0% and 13.7%, for an absolute difference of 4.7%. There were similar reductions in secondary end points. As in SPIRIT IV, there were no benefits of the Xience V stent for diabetic patients.

Both studies are still ongoing and will conclude with 5-year analyses.

The SPIRIT IV trial is sponsored by Abbott Vascular, and the COMPARE trial is funded by Abbott Vascular and Boston Scientific. Dr. Stone disclosed that he sits on the advisory boards for, and receives honoraria from, Abbott Vascular and Boston Scientific. Dr. Smits disclosed that he received a speaking fee from Abbott Vascular and that his cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific. Dr. Kereiakes disclosed that he has received honoraria and grant support from both Abbott Vascular and Boston Scientific.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team’s SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Bryne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne, who reported no disclosures. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The ISAR-TEST 4 study is powered for noninferiority and included patients with de novo coronary artery stenosis of at least 50% and symptoms or objective evidence of ischemia. Patients with left main stem disease and patients with cardiogenic shock were excluded.

In a press conference announcing the findings, Dr. David Cohen of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., who was not involved in either study, said the studies were the first “reasonably sized comparisons” between a first-generation sirolimus-eluting stent and a second-generation everolimus-eluting stent.

Asked whether physicians should be using the so-called first-generation stents at this point in time, Dr. Cohen said he believes that the question about how the everolimus-eluting stent compares with the paclitaxel-eluting stent “has been pretty well answered through several large studies,” including SPIRIT IV and COMPARE, but that larger studies are still needed to compare the everolimus-eluting stent with the older sirolimus-eluting stent. In the meantime, he added, “more and more data [are] showing that the everolimus-eluting stent is a very safe stent.”

Dr. Jensen disclosed that she has a financial interest/arrangement or affiliation with Cordis, Johnson and Johnson, and Abbott.

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team’s SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Bryne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne, who reported no disclosures. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The ISAR-TEST 4 study is powered for noninferiority and included patients with de novo coronary artery stenosis of at least 50% and symptoms or objective evidence of ischemia. Patients with left main stem disease and patients with cardiogenic shock were excluded.

In a press conference announcing the findings, Dr. David Cohen of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., who was not involved in either study, said the studies were the first “reasonably sized comparisons” between a first-generation sirolimus-eluting stent and a second-generation everolimus-eluting stent.

Asked whether physicians should be using the so-called first-generation stents at this point in time, Dr. Cohen said he believes that the question about how the everolimus-eluting stent compares with the paclitaxel-eluting stent “has been pretty well answered through several large studies,” including SPIRIT IV and COMPARE, but that larger studies are still needed to compare the everolimus-eluting stent with the older sirolimus-eluting stent. In the meantime, he added, “more and more data [are] showing that the everolimus-eluting stent is a very safe stent.”

Dr. Jensen disclosed that she has a financial interest/arrangement or affiliation with Cordis, Johnson and Johnson, and Abbott.

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team’s SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Bryne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne, who reported no disclosures. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The ISAR-TEST 4 study is powered for noninferiority and included patients with de novo coronary artery stenosis of at least 50% and symptoms or objective evidence of ischemia. Patients with left main stem disease and patients with cardiogenic shock were excluded.

In a press conference announcing the findings, Dr. David Cohen of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., who was not involved in either study, said the studies were the first “reasonably sized comparisons” between a first-generation sirolimus-eluting stent and a second-generation everolimus-eluting stent.

Asked whether physicians should be using the so-called first-generation stents at this point in time, Dr. Cohen said he believes that the question about how the everolimus-eluting stent compares with the paclitaxel-eluting stent “has been pretty well answered through several large studies,” including SPIRIT IV and COMPARE, but that larger studies are still needed to compare the everolimus-eluting stent with the older sirolimus-eluting stent. In the meantime, he added, “more and more data [are] showing that the everolimus-eluting stent is a very safe stent.”

Dr. Jensen disclosed that she has a financial interest/arrangement or affiliation with Cordis, Johnson and Johnson, and Abbott.

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team’s SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Bryne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne, who reported no disclosures. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The ISAR-TEST 4 study is powered for noninferiority and included patients with de novo coronary artery stenosis of at least 50% and symptoms or objective evidence of ischemia. Patients with left main stem disease and patients with cardiogenic shock were excluded.

In a press conference announcing the findings, Dr. David Cohen of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., who was not involved in either study, said the studies were the first “reasonably sized comparisons” between a first-generation sirolimus-eluting stent and a second-generation everolimus-eluting stent.

Asked whether physicians should be using the so-called first-generation stents at this point in time, Dr. Cohen said he believes that the question about how the everolimus-eluting stent compares with the paclitaxel-eluting stent “has been pretty well answered through several large studies,” including SPIRIT IV and COMPARE, but that larger studies are still needed to compare the everolimus-eluting stent with the older sirolimus-eluting stent. In the meantime, he added, “more and more data [are] showing that the everolimus-eluting stent is a very safe stent.”

Dr. Jensen disclosed that she has a financial interest/arrangement or affiliation with Cordis, Johnson and Johnson, and Abbott.

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team’s SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Bryne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne, who reported no disclosures. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The ISAR-TEST 4 study is powered for noninferiority and included patients with de novo coronary artery stenosis of at least 50% and symptoms or objective evidence of ischemia. Patients with left main stem disease and patients with cardiogenic shock were excluded.

In a press conference announcing the findings, Dr. David Cohen of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., who was not involved in either study, said the studies were the first “reasonably sized comparisons” between a first-generation sirolimus-eluting stent and a second-generation everolimus-eluting stent.

Asked whether physicians should be using the so-called first-generation stents at this point in time, Dr. Cohen said he believes that the question about how the everolimus-eluting stent compares with the paclitaxel-eluting stent “has been pretty well answered through several large studies,” including SPIRIT IV and COMPARE, but that larger studies are still needed to compare the everolimus-eluting stent with the older sirolimus-eluting stent. In the meantime, he added, “more and more data [are] showing that the everolimus-eluting stent is a very safe stent.”

Dr. Jensen disclosed that she has a financial interest/arrangement or affiliation with Cordis, Johnson and Johnson, and Abbott.

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

WASHINGTON – Two European head-to-head comparisons of the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent have failed to detect any significant clinical differences between the two stents in patients with coronary artery disease, investigators reported at Transcatheter Cardiovascular Therapeutics 2010.

“The sirolimus-eluting stent demonstrated the least amount of late lumen loss among previously released first-generation drug-eluting stents, but its efficacy and safety have not [previously] been compared head-to-head with the second-generation everolimus-eluting stent,” Dr. Lisette Okkels Jensen said in describing the rationale for her team’s SORT OUT IV trial.

Nine-month data from this prospective randomized study, which involved patients in a population-based health care setting and was powered to detect noninferiority, show that the everolimus-eluting Xience V stent (Abbott Vascular) was noninferior to the sirolimus-eluting Cypher Select Plus stent (Cordis) when it came to the primary end point of major adverse cardiac events (MACE) – a composite of cardiac death, myocardial infarction, definite stent thrombosis, and target vessel revascularization.

The rate of MACE was 4.9% in the 1,390 Xience-treated patients and 5.2% in the 1,384 Cypher-treated patients, reported Dr. Jensen of Odense (Denmark) University.

Approximately 55% of the patients in each arm had stable angina, and almost 33% in each arm had NSTEMI/unstable angina. In most of the remaining patients, STEMI drove the need for percutaneous coronary intervention.

The other head-to-head drug-eluting stent comparison was part of the larger randomized, two-center ISAR-TEST 4 trial designed to compare a biodegradable polymer DES with permanent polymer stents. Within the permanent polymer arm of 1,304 subjects, patients were randomized 1:1 to receive either the Xience or Cypher stent.

At 2 years – a longer follow-up period than in SORT OUT I – there were no significant differences in the combined primary end point of cardiac death, target-vessel–related myocardial infarction, and target lesion revascularization (16% in Xience-treated patients and 18.8% in Cypher-treated patients), reported Dr. Robert A. Bryne of Deutsches Herzzentrum in Munich.

The rates of definite or probable stent thrombosis at 2 years – the secondary, safety end point of the study – were also similar (1.4% in those who received the everolimus-eluting stent and 1.9% in patients treated with the sirolimus-eluting stent).

There was a trend toward superior antirestenotic efficacy with the Xience stent, but “specifically powered studies are needed to evaluate the clinical significance of this finding,” said Dr. Byrne, who reported no disclosures. (Target lesion revascularization occurred in 9.9% of Xience-treated patients and 13.5% of the Cypher-treated patients.)

The ISAR-TEST 4 study is powered for noninferiority and included patients with de novo coronary artery stenosis of at least 50% and symptoms or objective evidence of ischemia. Patients with left main stem disease and patients with cardiogenic shock were excluded.

In a press conference announcing the findings, Dr. David Cohen of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., who was not involved in either study, said the studies were the first “reasonably sized comparisons” between a first-generation sirolimus-eluting stent and a second-generation everolimus-eluting stent.

Asked whether physicians should be using the so-called first-generation stents at this point in time, Dr. Cohen said he believes that the question about how the everolimus-eluting stent compares with the paclitaxel-eluting stent “has been pretty well answered through several large studies,” including SPIRIT IV and COMPARE, but that larger studies are still needed to compare the everolimus-eluting stent with the older sirolimus-eluting stent. In the meantime, he added, “more and more data [are] showing that the everolimus-eluting stent is a very safe stent.”

Dr. Jensen disclosed that she has a financial interest/arrangement or affiliation with Cordis, Johnson and Johnson, and Abbott.

The Cypher Select Plus sirolimus-eluting stent that was used in the SORT OUT IV trial is a version of the Cypher stent that is not commercially available in the United States. U.S. physicians who discussed the trial said they have no reason to believe results would be different with other Cypher stent products.

WASHINGTON – Treatment with the investigational antiplatelet agent atopaxar did not significantly increase bleeding in patients with acute coronary syndromes in a randomized trial, making protease-activated receptor-1 blockade “a promising target” for ACS treatment, the trial’s lead investigator reported.

Drugs that inhibit platelet activation, such as aspirin and P2Y12 inhibitors (clopidogrel, for instance), are the mainstay of therapy for patients with ACS, but these drugs do not inhibit the thrombin receptor as atopaxar does. “Thrombin is known to be the most potent platelet agonist,” explained Dr. Michelle O’Donoghue of Brigham and Women’s Hospital in Boston.

Thrombin acts primarily via the PAR-1 receptor, which has led investigators to wonder whether PAR-1 receptor blockage – in addition to the current antiplatelet therapy – can move clinicians closer to the goal of reducing major adverse cardiac events without increasing the incidence of clinically significant bleeding.

Results from the LANCELOT ACS trial show that the PAR-1 antagonist atopaxar “achieves potent and rapid platelet inhibition ... without a significant increase in bleeding in patients with ACS,” Dr. O’Donoghue reported at the Transcatheter Cardiovascular Therapeutics 2010 meeting, which was sponsored by the Cardiovascular Research Foundation.

In the multicenter, double-blind study, 603 patients with unstable angina or non–ST-elevation myocardial infarction (NSTEMI) were randomized within 72 hours of symptom onset to receive either placebo or a 400-mg loading dose of atopaxar followed by a daily maintenance dose of 50 mg, 100 mg, or 200 mg for 12 weeks. The patients were followed for 4 weeks and, with few exceptions, were treated with aspirin or dual antiplatelet therapy in addition to atopaxar or the placebo drug.

The average rate of bleeding across the three atopaxar groups was 3.1% according to the CURE bleeding classification (1.8% CURE major and 1.3% CURE minor), compared with 2.2% in placebo group (all CURE minor). There was “no evidence of any dose-dependent trend,” Dr. O’Donoghue said.

The study, funded by Eisai Inc., was not powered for efficacy – the primary objective was to establish safety and tolerability – but “numerically, there was a lower incidence of cardiovascular death, MI, or stroke in the active combined group as compared with placebo,” Dr. O’Donoghue said. This difference was not statistically significant, but it shows “favorable trends for efficacy,” she said.

The incidence of Holter-detected ischemia at 48 hours following a 400-mg loading dose also was significantly lower in the atopaxar groups, compared with placebo.

“There was a significant 33% relative risk reduction [in the atopaxar groups combined],” she said. “This is the first time an oral antiplatelet drug was shown to reduce Holter-detected ischemia.”

Overall, the drug was well tolerated, but dose-dependent transaminitis and relative QTc prolongation were observed with the higher doses of atopaxar.

A platelet function substudy showed there was significant inhibition of platelet aggregation 1-3 hours after the loading dose. Platelet inhibition increased further at 3-6 hours to levels that were maintained until the first maintenance dose. Once maintenance doses began, “there was some evidence of a dose-dependent trend, with greater inhibition of platelet aggregation at the higher doses,” said Dr. O’Donoghue.

Dr. David J. Moliterno, who moderated a discussion of the trial, said that atopaxar is “only the second drug to be studied in this class in a phase II fashion.”

“Should we be concerned by the increase [in the rate of major bleeds], from 0 to 1.8%?” said Dr. Moliterno, chief of cardiology at the University of Kentucky, Lexington. “I don’t think we should be discouraged. ... It was a small trial ... and there was no clear dose effect.”

Similar outcomes of treatment with the new agent were reported this year for the J-LANCELOT trial, which tested atopaxar in patients with ACS and high-risk coronary artery disease in Japan (Eur. Heart J. 2010 [doi:10.1093/eurheartj/ehq320]).

The study was funded by Eisai Inc. Dr. O’Donoghue disclosed that she has received research support from Eisai and GlaxoSmithKline, and that she is a consultant for Eli Lilly & Co. and Daiichi Sankyo.

WASHINGTON – Treatment with the investigational antiplatelet agent atopaxar did not significantly increase bleeding in patients with acute coronary syndromes in a randomized trial, making protease-activated receptor-1 blockade “a promising target” for ACS treatment, the trial’s lead investigator reported.

Drugs that inhibit platelet activation, such as aspirin and P2Y12 inhibitors (clopidogrel, for instance), are the mainstay of therapy for patients with ACS, but these drugs do not inhibit the thrombin receptor as atopaxar does. “Thrombin is known to be the most potent platelet agonist,” explained Dr. Michelle O’Donoghue of Brigham and Women’s Hospital in Boston.

Thrombin acts primarily via the PAR-1 receptor, which has led investigators to wonder whether PAR-1 receptor blockage – in addition to the current antiplatelet therapy – can move clinicians closer to the goal of reducing major adverse cardiac events without increasing the incidence of clinically significant bleeding.

Results from the LANCELOT ACS trial show that the PAR-1 antagonist atopaxar “achieves potent and rapid platelet inhibition ... without a significant increase in bleeding in patients with ACS,” Dr. O’Donoghue reported at the Transcatheter Cardiovascular Therapeutics 2010 meeting, which was sponsored by the Cardiovascular Research Foundation.

In the multicenter, double-blind study, 603 patients with unstable angina or non–ST-elevation myocardial infarction (NSTEMI) were randomized within 72 hours of symptom onset to receive either placebo or a 400-mg loading dose of atopaxar followed by a daily maintenance dose of 50 mg, 100 mg, or 200 mg for 12 weeks. The patients were followed for 4 weeks and, with few exceptions, were treated with aspirin or dual antiplatelet therapy in addition to atopaxar or the placebo drug.

The average rate of bleeding across the three atopaxar groups was 3.1% according to the CURE bleeding classification (1.8% CURE major and 1.3% CURE minor), compared with 2.2% in placebo group (all CURE minor). There was “no evidence of any dose-dependent trend,” Dr. O’Donoghue said.

The study, funded by Eisai Inc., was not powered for efficacy – the primary objective was to establish safety and tolerability – but “numerically, there was a lower incidence of cardiovascular death, MI, or stroke in the active combined group as compared with placebo,” Dr. O’Donoghue said. This difference was not statistically significant, but it shows “favorable trends for efficacy,” she said.

The incidence of Holter-detected ischemia at 48 hours following a 400-mg loading dose also was significantly lower in the atopaxar groups, compared with placebo.

“There was a significant 33% relative risk reduction [in the atopaxar groups combined],” she said. “This is the first time an oral antiplatelet drug was shown to reduce Holter-detected ischemia.”

Overall, the drug was well tolerated, but dose-dependent transaminitis and relative QTc prolongation were observed with the higher doses of atopaxar.

A platelet function substudy showed there was significant inhibition of platelet aggregation 1-3 hours after the loading dose. Platelet inhibition increased further at 3-6 hours to levels that were maintained until the first maintenance dose. Once maintenance doses began, “there was some evidence of a dose-dependent trend, with greater inhibition of platelet aggregation at the higher doses,” said Dr. O’Donoghue.

Dr. David J. Moliterno, who moderated a discussion of the trial, said that atopaxar is “only the second drug to be studied in this class in a phase II fashion.”

“Should we be concerned by the increase [in the rate of major bleeds], from 0 to 1.8%?” said Dr. Moliterno, chief of cardiology at the University of Kentucky, Lexington. “I don’t think we should be discouraged. ... It was a small trial ... and there was no clear dose effect.”

Similar outcomes of treatment with the new agent were reported this year for the J-LANCELOT trial, which tested atopaxar in patients with ACS and high-risk coronary artery disease in Japan (Eur. Heart J. 2010 [doi:10.1093/eurheartj/ehq320]).

The study was funded by Eisai Inc. Dr. O’Donoghue disclosed that she has received research support from Eisai and GlaxoSmithKline, and that she is a consultant for Eli Lilly & Co. and Daiichi Sankyo.

WASHINGTON – Treatment with the investigational antiplatelet agent atopaxar did not significantly increase bleeding in patients with acute coronary syndromes in a randomized trial, making protease-activated receptor-1 blockade “a promising target” for ACS treatment, the trial’s lead investigator reported.

Drugs that inhibit platelet activation, such as aspirin and P2Y12 inhibitors (clopidogrel, for instance), are the mainstay of therapy for patients with ACS, but these drugs do not inhibit the thrombin receptor as atopaxar does. “Thrombin is known to be the most potent platelet agonist,” explained Dr. Michelle O’Donoghue of Brigham and Women’s Hospital in Boston.

Thrombin acts primarily via the PAR-1 receptor, which has led investigators to wonder whether PAR-1 receptor blockage – in addition to the current antiplatelet therapy – can move clinicians closer to the goal of reducing major adverse cardiac events without increasing the incidence of clinically significant bleeding.

Results from the LANCELOT ACS trial show that the PAR-1 antagonist atopaxar “achieves potent and rapid platelet inhibition ... without a significant increase in bleeding in patients with ACS,” Dr. O’Donoghue reported at the Transcatheter Cardiovascular Therapeutics 2010 meeting, which was sponsored by the Cardiovascular Research Foundation.

In the multicenter, double-blind study, 603 patients with unstable angina or non–ST-elevation myocardial infarction (NSTEMI) were randomized within 72 hours of symptom onset to receive either placebo or a 400-mg loading dose of atopaxar followed by a daily maintenance dose of 50 mg, 100 mg, or 200 mg for 12 weeks. The patients were followed for 4 weeks and, with few exceptions, were treated with aspirin or dual antiplatelet therapy in addition to atopaxar or the placebo drug.

The average rate of bleeding across the three atopaxar groups was 3.1% according to the CURE bleeding classification (1.8% CURE major and 1.3% CURE minor), compared with 2.2% in placebo group (all CURE minor). There was “no evidence of any dose-dependent trend,” Dr. O’Donoghue said.

The study, funded by Eisai Inc., was not powered for efficacy – the primary objective was to establish safety and tolerability – but “numerically, there was a lower incidence of cardiovascular death, MI, or stroke in the active combined group as compared with placebo,” Dr. O’Donoghue said. This difference was not statistically significant, but it shows “favorable trends for efficacy,” she said.

The incidence of Holter-detected ischemia at 48 hours following a 400-mg loading dose also was significantly lower in the atopaxar groups, compared with placebo.

“There was a significant 33% relative risk reduction [in the atopaxar groups combined],” she said. “This is the first time an oral antiplatelet drug was shown to reduce Holter-detected ischemia.”

Overall, the drug was well tolerated, but dose-dependent transaminitis and relative QTc prolongation were observed with the higher doses of atopaxar.

A platelet function substudy showed there was significant inhibition of platelet aggregation 1-3 hours after the loading dose. Platelet inhibition increased further at 3-6 hours to levels that were maintained until the first maintenance dose. Once maintenance doses began, “there was some evidence of a dose-dependent trend, with greater inhibition of platelet aggregation at the higher doses,” said Dr. O’Donoghue.

Dr. David J. Moliterno, who moderated a discussion of the trial, said that atopaxar is “only the second drug to be studied in this class in a phase II fashion.”

“Should we be concerned by the increase [in the rate of major bleeds], from 0 to 1.8%?” said Dr. Moliterno, chief of cardiology at the University of Kentucky, Lexington. “I don’t think we should be discouraged. ... It was a small trial ... and there was no clear dose effect.”

Similar outcomes of treatment with the new agent were reported this year for the J-LANCELOT trial, which tested atopaxar in patients with ACS and high-risk coronary artery disease in Japan (Eur. Heart J. 2010 [doi:10.1093/eurheartj/ehq320]).

The study was funded by Eisai Inc. Dr. O’Donoghue disclosed that she has received research support from Eisai and GlaxoSmithKline, and that she is a consultant for Eli Lilly & Co. and Daiichi Sankyo.

WASHINGTON – Treatment with the investigational antiplatelet agent atopaxar did not significantly increase bleeding in patients with acute coronary syndromes in a randomized trial, making protease-activated receptor-1 blockade “a promising target” for ACS treatment, the trial’s lead investigator reported.

Drugs that inhibit platelet activation, such as aspirin and P2Y12 inhibitors (clopidogrel, for instance), are the mainstay of therapy for patients with ACS, but these drugs do not inhibit the thrombin receptor as atopaxar does. “Thrombin is known to be the most potent platelet agonist,” explained Dr. Michelle O’Donoghue of Brigham and Women’s Hospital in Boston.

Thrombin acts primarily via the PAR-1 receptor, which has led investigators to wonder whether PAR-1 receptor blockage – in addition to the current antiplatelet therapy – can move clinicians closer to the goal of reducing major adverse cardiac events without increasing the incidence of clinically significant bleeding.

Results from the LANCELOT ACS trial show that the PAR-1 antagonist atopaxar “achieves potent and rapid platelet inhibition ... without a significant increase in bleeding in patients with ACS,” Dr. O’Donoghue reported at the Transcatheter Cardiovascular Therapeutics 2010 meeting, which was sponsored by the Cardiovascular Research Foundation.

In the multicenter, double-blind study, 603 patients with unstable angina or non–ST-elevation myocardial infarction (NSTEMI) were randomized within 72 hours of symptom onset to receive either placebo or a 400-mg loading dose of atopaxar followed by a daily maintenance dose of 50 mg, 100 mg, or 200 mg for 12 weeks. The patients were followed for 4 weeks and, with few exceptions, were treated with aspirin or dual antiplatelet therapy in addition to atopaxar or the placebo drug.

The average rate of bleeding across the three atopaxar groups was 3.1% according to the CURE bleeding classification (1.8% CURE major and 1.3% CURE minor), compared with 2.2% in placebo group (all CURE minor). There was “no evidence of any dose-dependent trend,” Dr. O’Donoghue said.

The study, funded by Eisai Inc., was not powered for efficacy – the primary objective was to establish safety and tolerability – but “numerically, there was a lower incidence of cardiovascular death, MI, or stroke in the active combined group as compared with placebo,” Dr. O’Donoghue said. This difference was not statistically significant, but it shows “favorable trends for efficacy,” she said.

The incidence of Holter-detected ischemia at 48 hours following a 400-mg loading dose also was significantly lower in the atopaxar groups, compared with placebo.

“There was a significant 33% relative risk reduction [in the atopaxar groups combined],” she said. “This is the first time an oral antiplatelet drug was shown to reduce Holter-detected ischemia.”

Overall, the drug was well tolerated, but dose-dependent transaminitis and relative QTc prolongation were observed with the higher doses of atopaxar.

A platelet function substudy showed there was significant inhibition of platelet aggregation 1-3 hours after the loading dose. Platelet inhibition increased further at 3-6 hours to levels that were maintained until the first maintenance dose. Once maintenance doses began, “there was some evidence of a dose-dependent trend, with greater inhibition of platelet aggregation at the higher doses,” said Dr. O’Donoghue.

Dr. David J. Moliterno, who moderated a discussion of the trial, said that atopaxar is “only the second drug to be studied in this class in a phase II fashion.”

“Should we be concerned by the increase [in the rate of major bleeds], from 0 to 1.8%?” said Dr. Moliterno, chief of cardiology at the University of Kentucky, Lexington. “I don’t think we should be discouraged. ... It was a small trial ... and there was no clear dose effect.”

Similar outcomes of treatment with the new agent were reported this year for the J-LANCELOT trial, which tested atopaxar in patients with ACS and high-risk coronary artery disease in Japan (Eur. Heart J. 2010 [doi:10.1093/eurheartj/ehq320]).

The study was funded by Eisai Inc. Dr. O’Donoghue disclosed that she has received research support from Eisai and GlaxoSmithKline, and that she is a consultant for Eli Lilly & Co. and Daiichi Sankyo.

WASHINGTON – Treatment with the investigational antiplatelet agent atopaxar did not significantly increase bleeding in patients with acute coronary syndromes in a randomized trial, making protease-activated receptor-1 blockade “a promising target” for ACS treatment, the trial’s lead investigator reported.

Drugs that inhibit platelet activation, such as aspirin and P2Y12 inhibitors (clopidogrel, for instance), are the mainstay of therapy for patients with ACS, but these drugs do not inhibit the thrombin receptor as atopaxar does. “Thrombin is known to be the most potent platelet agonist,” explained Dr. Michelle O’Donoghue of Brigham and Women’s Hospital in Boston.

Thrombin acts primarily via the PAR-1 receptor, which has led investigators to wonder whether PAR-1 receptor blockage – in addition to the current antiplatelet therapy – can move clinicians closer to the goal of reducing major adverse cardiac events without increasing the incidence of clinically significant bleeding.

Results from the LANCELOT ACS trial show that the PAR-1 antagonist atopaxar “achieves potent and rapid platelet inhibition ... without a significant increase in bleeding in patients with ACS,” Dr. O’Donoghue reported at the Transcatheter Cardiovascular Therapeutics 2010 meeting, which was sponsored by the Cardiovascular Research Foundation.

In the multicenter, double-blind study, 603 patients with unstable angina or non–ST-elevation myocardial infarction (NSTEMI) were randomized within 72 hours of symptom onset to receive either placebo or a 400-mg loading dose of atopaxar followed by a daily maintenance dose of 50 mg, 100 mg, or 200 mg for 12 weeks. The patients were followed for 4 weeks and, with few exceptions, were treated with aspirin or dual antiplatelet therapy in addition to atopaxar or the placebo drug.

The average rate of bleeding across the three atopaxar groups was 3.1% according to the CURE bleeding classification (1.8% CURE major and 1.3% CURE minor), compared with 2.2% in placebo group (all CURE minor). There was “no evidence of any dose-dependent trend,” Dr. O’Donoghue said.

The study, funded by Eisai Inc., was not powered for efficacy – the primary objective was to establish safety and tolerability – but “numerically, there was a lower incidence of cardiovascular death, MI, or stroke in the active combined group as compared with placebo,” Dr. O’Donoghue said. This difference was not statistically significant, but it shows “favorable trends for efficacy,” she said.

The incidence of Holter-detected ischemia at 48 hours following a 400-mg loading dose also was significantly lower in the atopaxar groups, compared with placebo.

“There was a significant 33% relative risk reduction [in the atopaxar groups combined],” she said. “This is the first time an oral antiplatelet drug was shown to reduce Holter-detected ischemia.”

Overall, the drug was well tolerated, but dose-dependent transaminitis and relative QTc prolongation were observed with the higher doses of atopaxar.

A platelet function substudy showed there was significant inhibition of platelet aggregation 1-3 hours after the loading dose. Platelet inhibition increased further at 3-6 hours to levels that were maintained until the first maintenance dose. Once maintenance doses began, “there was some evidence of a dose-dependent trend, with greater inhibition of platelet aggregation at the higher doses,” said Dr. O’Donoghue.

Dr. David J. Moliterno, who moderated a discussion of the trial, said that atopaxar is “only the second drug to be studied in this class in a phase II fashion.”

“Should we be concerned by the increase [in the rate of major bleeds], from 0 to 1.8%?” said Dr. Moliterno, chief of cardiology at the University of Kentucky, Lexington. “I don’t think we should be discouraged. ... It was a small trial ... and there was no clear dose effect.”

Similar outcomes of treatment with the new agent were reported this year for the J-LANCELOT trial, which tested atopaxar in patients with ACS and high-risk coronary artery disease in Japan (Eur. Heart J. 2010 [doi:10.1093/eurheartj/ehq320]).

The study was funded by Eisai Inc. Dr. O’Donoghue disclosed that she has received research support from Eisai and GlaxoSmithKline, and that she is a consultant for Eli Lilly & Co. and Daiichi Sankyo.

WASHINGTON – Treatment with the investigational antiplatelet agent atopaxar did not significantly increase bleeding in patients with acute coronary syndromes in a randomized trial, making protease-activated receptor-1 blockade “a promising target” for ACS treatment, the trial’s lead investigator reported.

Drugs that inhibit platelet activation, such as aspirin and P2Y12 inhibitors (clopidogrel, for instance), are the mainstay of therapy for patients with ACS, but these drugs do not inhibit the thrombin receptor as atopaxar does. “Thrombin is known to be the most potent platelet agonist,” explained Dr. Michelle O’Donoghue of Brigham and Women’s Hospital in Boston.

Thrombin acts primarily via the PAR-1 receptor, which has led investigators to wonder whether PAR-1 receptor blockage – in addition to the current antiplatelet therapy – can move clinicians closer to the goal of reducing major adverse cardiac events without increasing the incidence of clinically significant bleeding.

Results from the LANCELOT ACS trial show that the PAR-1 antagonist atopaxar “achieves potent and rapid platelet inhibition ... without a significant increase in bleeding in patients with ACS,” Dr. O’Donoghue reported at the Transcatheter Cardiovascular Therapeutics 2010 meeting, which was sponsored by the Cardiovascular Research Foundation.

In the multicenter, double-blind study, 603 patients with unstable angina or non–ST-elevation myocardial infarction (NSTEMI) were randomized within 72 hours of symptom onset to receive either placebo or a 400-mg loading dose of atopaxar followed by a daily maintenance dose of 50 mg, 100 mg, or 200 mg for 12 weeks. The patients were followed for 4 weeks and, with few exceptions, were treated with aspirin or dual antiplatelet therapy in addition to atopaxar or the placebo drug.

The average rate of bleeding across the three atopaxar groups was 3.1% according to the CURE bleeding classification (1.8% CURE major and 1.3% CURE minor), compared with 2.2% in placebo group (all CURE minor). There was “no evidence of any dose-dependent trend,” Dr. O’Donoghue said.

The study, funded by Eisai Inc., was not powered for efficacy – the primary objective was to establish safety and tolerability – but “numerically, there was a lower incidence of cardiovascular death, MI, or stroke in the active combined group as compared with placebo,” Dr. O’Donoghue said. This difference was not statistically significant, but it shows “favorable trends for efficacy,” she said.

The incidence of Holter-detected ischemia at 48 hours following a 400-mg loading dose also was significantly lower in the atopaxar groups, compared with placebo.

“There was a significant 33% relative risk reduction [in the atopaxar groups combined],” she said. “This is the first time an oral antiplatelet drug was shown to reduce Holter-detected ischemia.”

Overall, the drug was well tolerated, but dose-dependent transaminitis and relative QTc prolongation were observed with the higher doses of atopaxar.

A platelet function substudy showed there was significant inhibition of platelet aggregation 1-3 hours after the loading dose. Platelet inhibition increased further at 3-6 hours to levels that were maintained until the first maintenance dose. Once maintenance doses began, “there was some evidence of a dose-dependent trend, with greater inhibition of platelet aggregation at the higher doses,” said Dr. O’Donoghue.

Dr. David J. Moliterno, who moderated a discussion of the trial, said that atopaxar is “only the second drug to be studied in this class in a phase II fashion.”

“Should we be concerned by the increase [in the rate of major bleeds], from 0 to 1.8%?” said Dr. Moliterno, chief of cardiology at the University of Kentucky, Lexington. “I don’t think we should be discouraged. ... It was a small trial ... and there was no clear dose effect.”

Similar outcomes of treatment with the new agent were reported this year for the J-LANCELOT trial, which tested atopaxar in patients with ACS and high-risk coronary artery disease in Japan (Eur. Heart J. 2010 [doi:10.1093/eurheartj/ehq320]).

The study was funded by Eisai Inc. Dr. O’Donoghue disclosed that she has received research support from Eisai and GlaxoSmithKline, and that she is a consultant for Eli Lilly & Co. and Daiichi Sankyo.