Bare-metal stent superior safety debunked in DAPT analysis

CHICAGO – Drug-eluting stents were associated with significantly lower risks of both stent thrombosis and major adverse cardio- and cerebrovascular events, compared with bare-metal stents in a prespecified secondary analysis of the landmark Dual Antiplatelet Therapy (DAPT) trial.

“What I’ve learned from this is the myth of the safety of the bare-metal stent: It is not safer. So the concept that we still see in practice every day, where colleagues put in bare-metal stents because they perceive them to be safer and they perceive the optimal duration of dual antiplatelet therapy to be shorter, I’m not sure that’s the right thought process,” Dr. Dean J. Kereiakes said in presenting the study findings at the American Heart Association scientific sessions.

Another eye-opening finding in the secondary analysis was that when it comes to the duration of DAPT after stent placement, be it a drug-eluting stent (DES) or bare-metal stent (BMS), longer appears to be better. A surprising proportion of cases of stent thrombosis in both groups occurred after they stopped DAPT at the 12-month mark.

“Patients who don’t bleed on DAPT should be left on it a long time. I have evolved my thought process such that I’m thinking of this like a statin,” said Dr. Kereiakes, medical director of the Christ Hospital Heart and Vascular Center in Cincinnati.

The DAPT trial included 9,961 patients who underwent percutaneous coronary intervention with one of four types of drug-eluting stent (DES) and 1,687 who got a bare-metal stent (BMS), all of whom received 12 months of DAPT and then were randomized to blinded placebo or an additional 18 months of DAPT. The primary outcome was presented earlier at the AHA meeting and simultaneously published online (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1409312]).

The secondary analysis addressed two key questions: Do the risks of stent thrombosis and major adverse cardio- and cerebrovascular events (MACCE) differ between DES and BMS? And does the optimal duration of DAPT differ between the two stent platforms?

Dr. Kereiakes presented a propensity-matched analysis that included 8,308 patients with DES and 1,178 with BMS. The key finding here was that the rate of stent thrombosis was significantly lower in the DES group. This was the case both through the first 12 months of DAPT, where the stent thrombosis rates were 0.7% and 1.7% in the DES and BMS groups, respectively, and at 33 months, where the cumulative stent thrombosis rates were 1.7% and 2.6%.

The MACCE rate – defined as death, MI, or stroke – at 12 months was also significantly lower in the DES group: 5.1%, compared with 6.8% with BMS. The same was true at 33 months, when the rate was 11.4% in the DES group, compared with 13.4% in patients with a BMS. However, because of the smaller sample size of the BMS propensity-matched comparison group, this absolute 2% difference in MACCE at 33 months was sufficient to show DES were noninferior to BMS on this endpoint, but not superior to BMS, the cardiologist continued.

The advantage for DES over BMS in terms of MACCE appeared to be similar across all four DES types utilized in the trial: everolimus-, sirolimus-, paclitaxel-, and zotarolimus-eluting stents. While paclitaxel-eluting stents weren’t significantly better than BMS in terms of stent thrombosis rates, the other three DES types were, and to a comparable degree.

The hazard ratio for stent thrombosis with 30 months of DAPT as compared to 12 months was 0.29 in the DES group and 0.49 in BMS recipients.

“The magnitude of reduction in stent thrombosis risk with the longer, 30-month duration thienopyridine therapy appears consistent for both bare-metal stents and drug-eluting stents,” Dr. Kereiakes said.

There was no significant difference between DES and BMS in the rate of moderate to severe bleeding through 33 months: 4.04% with DES and 3.67% in the BMS group. Stroke rates were similar as well.

Dr. Kereiakes also presented another prespecified secondary analysis from the DAPT trial, this one a comparison of event rates in 1,687 BMS patients randomized to 12 versus 30 months of DAPT. At 33 months’ follow-up, the stent thrombosis rate was 0.5% in BMS patients who got 30 months of DAPT, compared with 1.1% in those who got 12 months of DAPT followed by aspirin plus placebo. The MACCE rate was 4.0% in BMS recipients who received 30 months of DAPT and 4.7% with 12 months.

Discussant Dr. Daniel B. Mark said these secondary analyses of the DAPT trial have brought home for him several key points: First, BMS are not safer than DES from the patient’s viewpoint; second, the risk of stent thrombosis continues after 12 months for both stent platforms; and third, current DAPT regimens can decrease but certainly don’t eliminate either stent thrombosis or non–stent related cardiovascular events.

The late occurrence of stent thromboses between 12 and 30 months in both study arms “really makes us think of this issue of DAPT in a different way than we have in the past,” added Dr. Mark, professor of medicine at Duke University and director of outcomes research at the Duke Clinical Research Institute in Durham, N.C.

He observed that “a perfect storm” of observational evidence arose beginning in 2006 which convinced physicians that BMS were safer – wrongly, as it now turns out.

The conventional wisdom was that BMS had a restenosis problem seen as “a benign nuisance requiring repeat revascularization procedures but having no discernible effect on death or MI,” Dr. Marks said, “while the DES were extremely effective at reducing restenosis but had this stent thrombosis problem” that was viewed in hyperbolic terms in the literature. The DAPT trial has gone a long way towards correcting those misperceptions, he said.

He wondered, however, just how confident Dr. Kereiakes is in the validity of his propensity matching.

“The matching was based on 55 different variables,” Dr. Kereiakes replied. “With all the limitations inherent in propensity-matched analysis, I think this is about as good as it gets.”

Dr. Mark noted that while cardiologists ponder the fine points between DES and BMS, it’s important not to lose sight of the big picture as highlighted in a recent study by Dr. Mark A. Hlatky of Stanford (Calif.) University and coinvestigators. Their analysis of Medicare beneficiaries who underwent either multivessel coronary artery bypass surgery or multivessel percutaneous coronary intervention concluded that the introduction of DES didn’t alter the comparative effectiveness of CABG and PCI. The 5-year survival rate following CABG has been about 10% better than with PCI both in the pre-DES era of BMS and in the DES era. Moreover, the 5-year rate of freedom from MI has been about 18% better with multivessel CABG than multivessel PCI in both stent platform eras (Am. Heart J. 2014;169:149-54).

The DAPT study was supported by more than half a dozen pharmaceutical and medical device companies as well as the U.S. Department of Health and Human Services. Dr. Kereiakes reported receiving payments as an advisor to Boston Scientific and Abbott Vascular. Dr. Marks reported receiving research grants from the National Institutes of Health and serving as a consultant to Somahlution, Milestone, Medtronic, and CardioDx.

[email protected]

CHICAGO – Drug-eluting stents were associated with significantly lower risks of both stent thrombosis and major adverse cardio- and cerebrovascular events, compared with bare-metal stents in a prespecified secondary analysis of the landmark Dual Antiplatelet Therapy (DAPT) trial.

“What I’ve learned from this is the myth of the safety of the bare-metal stent: It is not safer. So the concept that we still see in practice every day, where colleagues put in bare-metal stents because they perceive them to be safer and they perceive the optimal duration of dual antiplatelet therapy to be shorter, I’m not sure that’s the right thought process,” Dr. Dean J. Kereiakes said in presenting the study findings at the American Heart Association scientific sessions.

Another eye-opening finding in the secondary analysis was that when it comes to the duration of DAPT after stent placement, be it a drug-eluting stent (DES) or bare-metal stent (BMS), longer appears to be better. A surprising proportion of cases of stent thrombosis in both groups occurred after they stopped DAPT at the 12-month mark.

“Patients who don’t bleed on DAPT should be left on it a long time. I have evolved my thought process such that I’m thinking of this like a statin,” said Dr. Kereiakes, medical director of the Christ Hospital Heart and Vascular Center in Cincinnati.

The DAPT trial included 9,961 patients who underwent percutaneous coronary intervention with one of four types of drug-eluting stent (DES) and 1,687 who got a bare-metal stent (BMS), all of whom received 12 months of DAPT and then were randomized to blinded placebo or an additional 18 months of DAPT. The primary outcome was presented earlier at the AHA meeting and simultaneously published online (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1409312]).

The secondary analysis addressed two key questions: Do the risks of stent thrombosis and major adverse cardio- and cerebrovascular events (MACCE) differ between DES and BMS? And does the optimal duration of DAPT differ between the two stent platforms?

Dr. Kereiakes presented a propensity-matched analysis that included 8,308 patients with DES and 1,178 with BMS. The key finding here was that the rate of stent thrombosis was significantly lower in the DES group. This was the case both through the first 12 months of DAPT, where the stent thrombosis rates were 0.7% and 1.7% in the DES and BMS groups, respectively, and at 33 months, where the cumulative stent thrombosis rates were 1.7% and 2.6%.

The MACCE rate – defined as death, MI, or stroke – at 12 months was also significantly lower in the DES group: 5.1%, compared with 6.8% with BMS. The same was true at 33 months, when the rate was 11.4% in the DES group, compared with 13.4% in patients with a BMS. However, because of the smaller sample size of the BMS propensity-matched comparison group, this absolute 2% difference in MACCE at 33 months was sufficient to show DES were noninferior to BMS on this endpoint, but not superior to BMS, the cardiologist continued.

The advantage for DES over BMS in terms of MACCE appeared to be similar across all four DES types utilized in the trial: everolimus-, sirolimus-, paclitaxel-, and zotarolimus-eluting stents. While paclitaxel-eluting stents weren’t significantly better than BMS in terms of stent thrombosis rates, the other three DES types were, and to a comparable degree.

The hazard ratio for stent thrombosis with 30 months of DAPT as compared to 12 months was 0.29 in the DES group and 0.49 in BMS recipients.

“The magnitude of reduction in stent thrombosis risk with the longer, 30-month duration thienopyridine therapy appears consistent for both bare-metal stents and drug-eluting stents,” Dr. Kereiakes said.

There was no significant difference between DES and BMS in the rate of moderate to severe bleeding through 33 months: 4.04% with DES and 3.67% in the BMS group. Stroke rates were similar as well.

Dr. Kereiakes also presented another prespecified secondary analysis from the DAPT trial, this one a comparison of event rates in 1,687 BMS patients randomized to 12 versus 30 months of DAPT. At 33 months’ follow-up, the stent thrombosis rate was 0.5% in BMS patients who got 30 months of DAPT, compared with 1.1% in those who got 12 months of DAPT followed by aspirin plus placebo. The MACCE rate was 4.0% in BMS recipients who received 30 months of DAPT and 4.7% with 12 months.

Discussant Dr. Daniel B. Mark said these secondary analyses of the DAPT trial have brought home for him several key points: First, BMS are not safer than DES from the patient’s viewpoint; second, the risk of stent thrombosis continues after 12 months for both stent platforms; and third, current DAPT regimens can decrease but certainly don’t eliminate either stent thrombosis or non–stent related cardiovascular events.

The late occurrence of stent thromboses between 12 and 30 months in both study arms “really makes us think of this issue of DAPT in a different way than we have in the past,” added Dr. Mark, professor of medicine at Duke University and director of outcomes research at the Duke Clinical Research Institute in Durham, N.C.

He observed that “a perfect storm” of observational evidence arose beginning in 2006 which convinced physicians that BMS were safer – wrongly, as it now turns out.

The conventional wisdom was that BMS had a restenosis problem seen as “a benign nuisance requiring repeat revascularization procedures but having no discernible effect on death or MI,” Dr. Marks said, “while the DES were extremely effective at reducing restenosis but had this stent thrombosis problem” that was viewed in hyperbolic terms in the literature. The DAPT trial has gone a long way towards correcting those misperceptions, he said.

He wondered, however, just how confident Dr. Kereiakes is in the validity of his propensity matching.

“The matching was based on 55 different variables,” Dr. Kereiakes replied. “With all the limitations inherent in propensity-matched analysis, I think this is about as good as it gets.”

Dr. Mark noted that while cardiologists ponder the fine points between DES and BMS, it’s important not to lose sight of the big picture as highlighted in a recent study by Dr. Mark A. Hlatky of Stanford (Calif.) University and coinvestigators. Their analysis of Medicare beneficiaries who underwent either multivessel coronary artery bypass surgery or multivessel percutaneous coronary intervention concluded that the introduction of DES didn’t alter the comparative effectiveness of CABG and PCI. The 5-year survival rate following CABG has been about 10% better than with PCI both in the pre-DES era of BMS and in the DES era. Moreover, the 5-year rate of freedom from MI has been about 18% better with multivessel CABG than multivessel PCI in both stent platform eras (Am. Heart J. 2014;169:149-54).

The DAPT study was supported by more than half a dozen pharmaceutical and medical device companies as well as the U.S. Department of Health and Human Services. Dr. Kereiakes reported receiving payments as an advisor to Boston Scientific and Abbott Vascular. Dr. Marks reported receiving research grants from the National Institutes of Health and serving as a consultant to Somahlution, Milestone, Medtronic, and CardioDx.

[email protected]

CHICAGO – Drug-eluting stents were associated with significantly lower risks of both stent thrombosis and major adverse cardio- and cerebrovascular events, compared with bare-metal stents in a prespecified secondary analysis of the landmark Dual Antiplatelet Therapy (DAPT) trial.

“What I’ve learned from this is the myth of the safety of the bare-metal stent: It is not safer. So the concept that we still see in practice every day, where colleagues put in bare-metal stents because they perceive them to be safer and they perceive the optimal duration of dual antiplatelet therapy to be shorter, I’m not sure that’s the right thought process,” Dr. Dean J. Kereiakes said in presenting the study findings at the American Heart Association scientific sessions.

Another eye-opening finding in the secondary analysis was that when it comes to the duration of DAPT after stent placement, be it a drug-eluting stent (DES) or bare-metal stent (BMS), longer appears to be better. A surprising proportion of cases of stent thrombosis in both groups occurred after they stopped DAPT at the 12-month mark.

“Patients who don’t bleed on DAPT should be left on it a long time. I have evolved my thought process such that I’m thinking of this like a statin,” said Dr. Kereiakes, medical director of the Christ Hospital Heart and Vascular Center in Cincinnati.

The DAPT trial included 9,961 patients who underwent percutaneous coronary intervention with one of four types of drug-eluting stent (DES) and 1,687 who got a bare-metal stent (BMS), all of whom received 12 months of DAPT and then were randomized to blinded placebo or an additional 18 months of DAPT. The primary outcome was presented earlier at the AHA meeting and simultaneously published online (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1409312]).

The secondary analysis addressed two key questions: Do the risks of stent thrombosis and major adverse cardio- and cerebrovascular events (MACCE) differ between DES and BMS? And does the optimal duration of DAPT differ between the two stent platforms?

Dr. Kereiakes presented a propensity-matched analysis that included 8,308 patients with DES and 1,178 with BMS. The key finding here was that the rate of stent thrombosis was significantly lower in the DES group. This was the case both through the first 12 months of DAPT, where the stent thrombosis rates were 0.7% and 1.7% in the DES and BMS groups, respectively, and at 33 months, where the cumulative stent thrombosis rates were 1.7% and 2.6%.

The MACCE rate – defined as death, MI, or stroke – at 12 months was also significantly lower in the DES group: 5.1%, compared with 6.8% with BMS. The same was true at 33 months, when the rate was 11.4% in the DES group, compared with 13.4% in patients with a BMS. However, because of the smaller sample size of the BMS propensity-matched comparison group, this absolute 2% difference in MACCE at 33 months was sufficient to show DES were noninferior to BMS on this endpoint, but not superior to BMS, the cardiologist continued.

The advantage for DES over BMS in terms of MACCE appeared to be similar across all four DES types utilized in the trial: everolimus-, sirolimus-, paclitaxel-, and zotarolimus-eluting stents. While paclitaxel-eluting stents weren’t significantly better than BMS in terms of stent thrombosis rates, the other three DES types were, and to a comparable degree.

The hazard ratio for stent thrombosis with 30 months of DAPT as compared to 12 months was 0.29 in the DES group and 0.49 in BMS recipients.

“The magnitude of reduction in stent thrombosis risk with the longer, 30-month duration thienopyridine therapy appears consistent for both bare-metal stents and drug-eluting stents,” Dr. Kereiakes said.

There was no significant difference between DES and BMS in the rate of moderate to severe bleeding through 33 months: 4.04% with DES and 3.67% in the BMS group. Stroke rates were similar as well.

Dr. Kereiakes also presented another prespecified secondary analysis from the DAPT trial, this one a comparison of event rates in 1,687 BMS patients randomized to 12 versus 30 months of DAPT. At 33 months’ follow-up, the stent thrombosis rate was 0.5% in BMS patients who got 30 months of DAPT, compared with 1.1% in those who got 12 months of DAPT followed by aspirin plus placebo. The MACCE rate was 4.0% in BMS recipients who received 30 months of DAPT and 4.7% with 12 months.

Discussant Dr. Daniel B. Mark said these secondary analyses of the DAPT trial have brought home for him several key points: First, BMS are not safer than DES from the patient’s viewpoint; second, the risk of stent thrombosis continues after 12 months for both stent platforms; and third, current DAPT regimens can decrease but certainly don’t eliminate either stent thrombosis or non–stent related cardiovascular events.

The late occurrence of stent thromboses between 12 and 30 months in both study arms “really makes us think of this issue of DAPT in a different way than we have in the past,” added Dr. Mark, professor of medicine at Duke University and director of outcomes research at the Duke Clinical Research Institute in Durham, N.C.

He observed that “a perfect storm” of observational evidence arose beginning in 2006 which convinced physicians that BMS were safer – wrongly, as it now turns out.

The conventional wisdom was that BMS had a restenosis problem seen as “a benign nuisance requiring repeat revascularization procedures but having no discernible effect on death or MI,” Dr. Marks said, “while the DES were extremely effective at reducing restenosis but had this stent thrombosis problem” that was viewed in hyperbolic terms in the literature. The DAPT trial has gone a long way towards correcting those misperceptions, he said.

He wondered, however, just how confident Dr. Kereiakes is in the validity of his propensity matching.

“The matching was based on 55 different variables,” Dr. Kereiakes replied. “With all the limitations inherent in propensity-matched analysis, I think this is about as good as it gets.”

Dr. Mark noted that while cardiologists ponder the fine points between DES and BMS, it’s important not to lose sight of the big picture as highlighted in a recent study by Dr. Mark A. Hlatky of Stanford (Calif.) University and coinvestigators. Their analysis of Medicare beneficiaries who underwent either multivessel coronary artery bypass surgery or multivessel percutaneous coronary intervention concluded that the introduction of DES didn’t alter the comparative effectiveness of CABG and PCI. The 5-year survival rate following CABG has been about 10% better than with PCI both in the pre-DES era of BMS and in the DES era. Moreover, the 5-year rate of freedom from MI has been about 18% better with multivessel CABG than multivessel PCI in both stent platform eras (Am. Heart J. 2014;169:149-54).

The DAPT study was supported by more than half a dozen pharmaceutical and medical device companies as well as the U.S. Department of Health and Human Services. Dr. Kereiakes reported receiving payments as an advisor to Boston Scientific and Abbott Vascular. Dr. Marks reported receiving research grants from the National Institutes of Health and serving as a consultant to Somahlution, Milestone, Medtronic, and CardioDx.

[email protected]