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An entire year of dual-antiplatelet therapy may be no better at limiting ischemic events or death than a shorter course for patients who have undergone percutaneous coronary intervention with a drug-eluting stent.
The two trials, which tested dual-antiplatelet therapy (DAPT) regimens of 3 months and 1 month, are also noteworthy for giving a P2Y12 inhibitor after DAPT instead of aspirin monotherapy, which is a more common approach. Each randomized about 3,000 patients.
According to lead author Joo-Yong Hahn, MD, of Sungkyunkwan University in Seoul, South Korea, and colleagues, who conducted the first trial (SMART-CHOICE), both shorter and longer DAPT regimens with aspirin have been associated with shortcomings.
Specifically, shorter duration DAPT with subsequent aspirin monotherapy carries increased risks of MI and stent thrombosis, the investigators wrote. “Conversely, prolonged DAPT increases the risk of bleeding, which offsets the benefit from reducing recurrent ischemic events. Therefore, neither prolonged DAPT nor short-duration DAPT followed by aspirin monotherapy is fully satisfactory.” Because of these shortcomings, the investigators suggested that developing novel strategies “is of paramount importance.”
SMART-CHOICE
The multicenter trial by Dr. Hahn and colleagues, conducted in South Korea, involved 2,993 patients undergoing percutaneous coronary intervention with drug-eluting stents. Patients were randomized to receive either standard DAPT with aspirin and a P2Y12 inhibitor for 12 months, or aspirin plus a P2Y12 inhibitor for 3 months followed by 9 months of P2Y12 monotherapy. Patients were stratified by enrolling center, clinical presentation, type of stent, and type of P2Y12 therapy. Stents were limited to those eluting cobalt-chromium everolimus (Xience Prime, Xience Expedition, or Xience Alpine; Abbott Vascular), platinum-chromium everolimus (Promus Element, Promus Premier, or SYNERGY; Boston Scientific), or sirolimus (Orsiro; Biotronik). Acceptable P2Y12 therapies were clopidogrel, ticagrelor, and prasugrel. The primary endpoint was a composite of major adverse cerebrovascular and cardiac events, including stroke, MI, or all-cause death, at 12 months after percutaneous coronary intervention. A number of secondary endpoints were also evaluated, such as bleeding rate, stent thrombosis, and the individual components of the primary endpoint.
Almost all patients (95%) in the DAPT group adhered to the study protocol, while a smaller proportion (79%) followed P2Y12 monotherapy as described. Still, for both groups, more than 97% of patients completed 1-year follow-up. Primary endpoint analysis showed that the cumulative rate of major adverse cerebrovascular and cardiac events was similar between both groups, at 2.9% in the P2Y12 group versus 2.5% in the DAPT group, which was statistically significant for noninferiority (P = .007). Per-protocol analysis supported this finding.
Similarly, the components of the primary endpoint – stroke, MI, or all-cause death – did not vary significantly between groups. No significant difference was detected for the risk of stent thrombosis. Although the major bleeding rate was comparable between groups, the overall bleeding rate was significantly lower in the P2Y12 inhibitor group than the DAPT group (2.0% vs. 3.4%; P = .02); this finding also was supported by per-protocol analysis (1.8% vs. 3.1%; P = .04).
The investigators proposed several explanations for the results. “First, aspirin might provide little additional inhibition of platelet aggregation in the presence of a P2Y12 inhibitor. … Second, the risk of bleeding was significantly lower with P2Y12 inhibitor monotherapy than with DAPT in the present study.”
They noted that second-generation drug-eluting stents were used, which have been shown to significantly reduce MI and stent thrombosis, compared with first-generation products.
STOPDAPT-2
This study, led by Hirotoshi Watanabe, MD, of Kyoto University, and colleagues, followed a similar design, but with an even shorter duration of DAPT in the treatment arm, at 1 month, and stricter criteria for the stent, which was limited to one cobalt-chromium everolimus-eluting model (Xience Series; Abbott Vascular). During the first month of the trial, all patients received aspirin plus either clopidogrel or prasugrel; thereafter, patients in the 12-month group received aspirin and clopidogrel while the 1-month group was given clopidogrel alone.
The primary endpoint was a composite of cardiovascular and bleeding events, including MI, stent thrombosis, cardiovascular death, stroke, and major or minor bleeding. Secondary endpoints included these components individually, as well as a list of other cardiovascular and bleeding measures.
Similarly to the first trial, Dr. Watanabe and colleagues found that the shorter DAPT protocol was noninferior to standard DAPT and associated with a lower rate of bleeding events. The primary endpoint occurred in 2.4% of the 1-month DAPT group, compared with 3.7% of the 12-month DAPT group, thereby meeting noninferiority criteria (P less than .001). This finding was confirmed in the per-protocol population. The 1-month DAPT regimen was significantly associated with fewer major bleeding events than the 12-month protocol (0.41% vs. 1.54%), demonstrating superiority (P = .004). In addition, seven other measures of bleeding frequency were lower in the 1-month DAPT group than the standard DAPT group, including Bleeding Academic Research Consortium type 3 or 5 criteria, and Global Use of Strategies to Open Occluded Arteries moderate or severe criteria.
Dr. Watanabe and colleagues provided some insight into these findings and described clinical implications. “The benefit [of the 1-month DAPT regimen] was driven by a significant reduction of bleeding events without an increase in cardiovascular events,” they wrote. “Therefore, the very short DAPT duration of 1 month would be a potential option even in patients without high bleeding risk. Given the very low rates of stent thrombosis in studies using contemporary drug-eluting stents, avoiding bleeding with de-escalation of antiplatelet therapy may be more important than attempting further reduction of stent thrombosis with intensive antiplatelet therapy.”
SMART-CHOICE was funded by the Korean Society of Interventional Cardiology, Biotronik, Abbott Vascular, and Boston Scientific. Dr. Hahn and colleagues reported receiving additional financial relationships with AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, and others. STOPDAPT-2 was funded by Abbott Vascular. Dr. Watanabe and colleagues reported receiving additional funding from Daiichi Sankyo, Otsuka Pharmaceutical, Kowa Pharmaceuticals, and others.
SOURCES: Watanabe H et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8145; Hahn J-Y et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8146.
These two studies evaluated shorter-duration dual-antiplatelet therapy (DAPT) with a novel variation: Instead of discontinuing the P2Y12 inhibitor, which is a more common approach, the regimens discontinued aspirin. Although the studies had slightly different 1-year endpoints, both found that shorter DAPT with continued P2Y12 monotherapy reduced bleeding complications without increasing risk of ischemic events or death.
Based on these findings, and those from other trials, shorter DAPT will likely gain support, particularly when used with atherosclerosis risk factor reduction, newer implantation techniques, and contemporary stents. However, clinicians considering shorter DAPT for their patients should do so in light of baseline ischemic complication risk and clinical presentation. Furthermore, it remains unclear whether P2Y12 or aspirin monotherapy should be given after shorter DAPT. Until more evidence is available, it is too soon to abandon aspirin monotherapy or traditional DAPT.
Khaled M. Ziada, MD, and David J. Moliterno, MD, are with the department of cardiovascular medicine at the University of Kentucky, Lexington. Dr. Moliterno has received grants from AstraZeneca. No other disclosures were reported. Their remarks are adapted from an accompanying editorial (JAMA. 2019 June 25. doi: 10.1001/jama.2019.7025).
These two studies evaluated shorter-duration dual-antiplatelet therapy (DAPT) with a novel variation: Instead of discontinuing the P2Y12 inhibitor, which is a more common approach, the regimens discontinued aspirin. Although the studies had slightly different 1-year endpoints, both found that shorter DAPT with continued P2Y12 monotherapy reduced bleeding complications without increasing risk of ischemic events or death.
Based on these findings, and those from other trials, shorter DAPT will likely gain support, particularly when used with atherosclerosis risk factor reduction, newer implantation techniques, and contemporary stents. However, clinicians considering shorter DAPT for their patients should do so in light of baseline ischemic complication risk and clinical presentation. Furthermore, it remains unclear whether P2Y12 or aspirin monotherapy should be given after shorter DAPT. Until more evidence is available, it is too soon to abandon aspirin monotherapy or traditional DAPT.
Khaled M. Ziada, MD, and David J. Moliterno, MD, are with the department of cardiovascular medicine at the University of Kentucky, Lexington. Dr. Moliterno has received grants from AstraZeneca. No other disclosures were reported. Their remarks are adapted from an accompanying editorial (JAMA. 2019 June 25. doi: 10.1001/jama.2019.7025).
These two studies evaluated shorter-duration dual-antiplatelet therapy (DAPT) with a novel variation: Instead of discontinuing the P2Y12 inhibitor, which is a more common approach, the regimens discontinued aspirin. Although the studies had slightly different 1-year endpoints, both found that shorter DAPT with continued P2Y12 monotherapy reduced bleeding complications without increasing risk of ischemic events or death.
Based on these findings, and those from other trials, shorter DAPT will likely gain support, particularly when used with atherosclerosis risk factor reduction, newer implantation techniques, and contemporary stents. However, clinicians considering shorter DAPT for their patients should do so in light of baseline ischemic complication risk and clinical presentation. Furthermore, it remains unclear whether P2Y12 or aspirin monotherapy should be given after shorter DAPT. Until more evidence is available, it is too soon to abandon aspirin monotherapy or traditional DAPT.
Khaled M. Ziada, MD, and David J. Moliterno, MD, are with the department of cardiovascular medicine at the University of Kentucky, Lexington. Dr. Moliterno has received grants from AstraZeneca. No other disclosures were reported. Their remarks are adapted from an accompanying editorial (JAMA. 2019 June 25. doi: 10.1001/jama.2019.7025).
An entire year of dual-antiplatelet therapy may be no better at limiting ischemic events or death than a shorter course for patients who have undergone percutaneous coronary intervention with a drug-eluting stent.
The two trials, which tested dual-antiplatelet therapy (DAPT) regimens of 3 months and 1 month, are also noteworthy for giving a P2Y12 inhibitor after DAPT instead of aspirin monotherapy, which is a more common approach. Each randomized about 3,000 patients.
According to lead author Joo-Yong Hahn, MD, of Sungkyunkwan University in Seoul, South Korea, and colleagues, who conducted the first trial (SMART-CHOICE), both shorter and longer DAPT regimens with aspirin have been associated with shortcomings.
Specifically, shorter duration DAPT with subsequent aspirin monotherapy carries increased risks of MI and stent thrombosis, the investigators wrote. “Conversely, prolonged DAPT increases the risk of bleeding, which offsets the benefit from reducing recurrent ischemic events. Therefore, neither prolonged DAPT nor short-duration DAPT followed by aspirin monotherapy is fully satisfactory.” Because of these shortcomings, the investigators suggested that developing novel strategies “is of paramount importance.”
SMART-CHOICE
The multicenter trial by Dr. Hahn and colleagues, conducted in South Korea, involved 2,993 patients undergoing percutaneous coronary intervention with drug-eluting stents. Patients were randomized to receive either standard DAPT with aspirin and a P2Y12 inhibitor for 12 months, or aspirin plus a P2Y12 inhibitor for 3 months followed by 9 months of P2Y12 monotherapy. Patients were stratified by enrolling center, clinical presentation, type of stent, and type of P2Y12 therapy. Stents were limited to those eluting cobalt-chromium everolimus (Xience Prime, Xience Expedition, or Xience Alpine; Abbott Vascular), platinum-chromium everolimus (Promus Element, Promus Premier, or SYNERGY; Boston Scientific), or sirolimus (Orsiro; Biotronik). Acceptable P2Y12 therapies were clopidogrel, ticagrelor, and prasugrel. The primary endpoint was a composite of major adverse cerebrovascular and cardiac events, including stroke, MI, or all-cause death, at 12 months after percutaneous coronary intervention. A number of secondary endpoints were also evaluated, such as bleeding rate, stent thrombosis, and the individual components of the primary endpoint.
Almost all patients (95%) in the DAPT group adhered to the study protocol, while a smaller proportion (79%) followed P2Y12 monotherapy as described. Still, for both groups, more than 97% of patients completed 1-year follow-up. Primary endpoint analysis showed that the cumulative rate of major adverse cerebrovascular and cardiac events was similar between both groups, at 2.9% in the P2Y12 group versus 2.5% in the DAPT group, which was statistically significant for noninferiority (P = .007). Per-protocol analysis supported this finding.
Similarly, the components of the primary endpoint – stroke, MI, or all-cause death – did not vary significantly between groups. No significant difference was detected for the risk of stent thrombosis. Although the major bleeding rate was comparable between groups, the overall bleeding rate was significantly lower in the P2Y12 inhibitor group than the DAPT group (2.0% vs. 3.4%; P = .02); this finding also was supported by per-protocol analysis (1.8% vs. 3.1%; P = .04).
The investigators proposed several explanations for the results. “First, aspirin might provide little additional inhibition of platelet aggregation in the presence of a P2Y12 inhibitor. … Second, the risk of bleeding was significantly lower with P2Y12 inhibitor monotherapy than with DAPT in the present study.”
They noted that second-generation drug-eluting stents were used, which have been shown to significantly reduce MI and stent thrombosis, compared with first-generation products.
STOPDAPT-2
This study, led by Hirotoshi Watanabe, MD, of Kyoto University, and colleagues, followed a similar design, but with an even shorter duration of DAPT in the treatment arm, at 1 month, and stricter criteria for the stent, which was limited to one cobalt-chromium everolimus-eluting model (Xience Series; Abbott Vascular). During the first month of the trial, all patients received aspirin plus either clopidogrel or prasugrel; thereafter, patients in the 12-month group received aspirin and clopidogrel while the 1-month group was given clopidogrel alone.
The primary endpoint was a composite of cardiovascular and bleeding events, including MI, stent thrombosis, cardiovascular death, stroke, and major or minor bleeding. Secondary endpoints included these components individually, as well as a list of other cardiovascular and bleeding measures.
Similarly to the first trial, Dr. Watanabe and colleagues found that the shorter DAPT protocol was noninferior to standard DAPT and associated with a lower rate of bleeding events. The primary endpoint occurred in 2.4% of the 1-month DAPT group, compared with 3.7% of the 12-month DAPT group, thereby meeting noninferiority criteria (P less than .001). This finding was confirmed in the per-protocol population. The 1-month DAPT regimen was significantly associated with fewer major bleeding events than the 12-month protocol (0.41% vs. 1.54%), demonstrating superiority (P = .004). In addition, seven other measures of bleeding frequency were lower in the 1-month DAPT group than the standard DAPT group, including Bleeding Academic Research Consortium type 3 or 5 criteria, and Global Use of Strategies to Open Occluded Arteries moderate or severe criteria.
Dr. Watanabe and colleagues provided some insight into these findings and described clinical implications. “The benefit [of the 1-month DAPT regimen] was driven by a significant reduction of bleeding events without an increase in cardiovascular events,” they wrote. “Therefore, the very short DAPT duration of 1 month would be a potential option even in patients without high bleeding risk. Given the very low rates of stent thrombosis in studies using contemporary drug-eluting stents, avoiding bleeding with de-escalation of antiplatelet therapy may be more important than attempting further reduction of stent thrombosis with intensive antiplatelet therapy.”
SMART-CHOICE was funded by the Korean Society of Interventional Cardiology, Biotronik, Abbott Vascular, and Boston Scientific. Dr. Hahn and colleagues reported receiving additional financial relationships with AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, and others. STOPDAPT-2 was funded by Abbott Vascular. Dr. Watanabe and colleagues reported receiving additional funding from Daiichi Sankyo, Otsuka Pharmaceutical, Kowa Pharmaceuticals, and others.
SOURCES: Watanabe H et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8145; Hahn J-Y et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8146.
An entire year of dual-antiplatelet therapy may be no better at limiting ischemic events or death than a shorter course for patients who have undergone percutaneous coronary intervention with a drug-eluting stent.
The two trials, which tested dual-antiplatelet therapy (DAPT) regimens of 3 months and 1 month, are also noteworthy for giving a P2Y12 inhibitor after DAPT instead of aspirin monotherapy, which is a more common approach. Each randomized about 3,000 patients.
According to lead author Joo-Yong Hahn, MD, of Sungkyunkwan University in Seoul, South Korea, and colleagues, who conducted the first trial (SMART-CHOICE), both shorter and longer DAPT regimens with aspirin have been associated with shortcomings.
Specifically, shorter duration DAPT with subsequent aspirin monotherapy carries increased risks of MI and stent thrombosis, the investigators wrote. “Conversely, prolonged DAPT increases the risk of bleeding, which offsets the benefit from reducing recurrent ischemic events. Therefore, neither prolonged DAPT nor short-duration DAPT followed by aspirin monotherapy is fully satisfactory.” Because of these shortcomings, the investigators suggested that developing novel strategies “is of paramount importance.”
SMART-CHOICE
The multicenter trial by Dr. Hahn and colleagues, conducted in South Korea, involved 2,993 patients undergoing percutaneous coronary intervention with drug-eluting stents. Patients were randomized to receive either standard DAPT with aspirin and a P2Y12 inhibitor for 12 months, or aspirin plus a P2Y12 inhibitor for 3 months followed by 9 months of P2Y12 monotherapy. Patients were stratified by enrolling center, clinical presentation, type of stent, and type of P2Y12 therapy. Stents were limited to those eluting cobalt-chromium everolimus (Xience Prime, Xience Expedition, or Xience Alpine; Abbott Vascular), platinum-chromium everolimus (Promus Element, Promus Premier, or SYNERGY; Boston Scientific), or sirolimus (Orsiro; Biotronik). Acceptable P2Y12 therapies were clopidogrel, ticagrelor, and prasugrel. The primary endpoint was a composite of major adverse cerebrovascular and cardiac events, including stroke, MI, or all-cause death, at 12 months after percutaneous coronary intervention. A number of secondary endpoints were also evaluated, such as bleeding rate, stent thrombosis, and the individual components of the primary endpoint.
Almost all patients (95%) in the DAPT group adhered to the study protocol, while a smaller proportion (79%) followed P2Y12 monotherapy as described. Still, for both groups, more than 97% of patients completed 1-year follow-up. Primary endpoint analysis showed that the cumulative rate of major adverse cerebrovascular and cardiac events was similar between both groups, at 2.9% in the P2Y12 group versus 2.5% in the DAPT group, which was statistically significant for noninferiority (P = .007). Per-protocol analysis supported this finding.
Similarly, the components of the primary endpoint – stroke, MI, or all-cause death – did not vary significantly between groups. No significant difference was detected for the risk of stent thrombosis. Although the major bleeding rate was comparable between groups, the overall bleeding rate was significantly lower in the P2Y12 inhibitor group than the DAPT group (2.0% vs. 3.4%; P = .02); this finding also was supported by per-protocol analysis (1.8% vs. 3.1%; P = .04).
The investigators proposed several explanations for the results. “First, aspirin might provide little additional inhibition of platelet aggregation in the presence of a P2Y12 inhibitor. … Second, the risk of bleeding was significantly lower with P2Y12 inhibitor monotherapy than with DAPT in the present study.”
They noted that second-generation drug-eluting stents were used, which have been shown to significantly reduce MI and stent thrombosis, compared with first-generation products.
STOPDAPT-2
This study, led by Hirotoshi Watanabe, MD, of Kyoto University, and colleagues, followed a similar design, but with an even shorter duration of DAPT in the treatment arm, at 1 month, and stricter criteria for the stent, which was limited to one cobalt-chromium everolimus-eluting model (Xience Series; Abbott Vascular). During the first month of the trial, all patients received aspirin plus either clopidogrel or prasugrel; thereafter, patients in the 12-month group received aspirin and clopidogrel while the 1-month group was given clopidogrel alone.
The primary endpoint was a composite of cardiovascular and bleeding events, including MI, stent thrombosis, cardiovascular death, stroke, and major or minor bleeding. Secondary endpoints included these components individually, as well as a list of other cardiovascular and bleeding measures.
Similarly to the first trial, Dr. Watanabe and colleagues found that the shorter DAPT protocol was noninferior to standard DAPT and associated with a lower rate of bleeding events. The primary endpoint occurred in 2.4% of the 1-month DAPT group, compared with 3.7% of the 12-month DAPT group, thereby meeting noninferiority criteria (P less than .001). This finding was confirmed in the per-protocol population. The 1-month DAPT regimen was significantly associated with fewer major bleeding events than the 12-month protocol (0.41% vs. 1.54%), demonstrating superiority (P = .004). In addition, seven other measures of bleeding frequency were lower in the 1-month DAPT group than the standard DAPT group, including Bleeding Academic Research Consortium type 3 or 5 criteria, and Global Use of Strategies to Open Occluded Arteries moderate or severe criteria.
Dr. Watanabe and colleagues provided some insight into these findings and described clinical implications. “The benefit [of the 1-month DAPT regimen] was driven by a significant reduction of bleeding events without an increase in cardiovascular events,” they wrote. “Therefore, the very short DAPT duration of 1 month would be a potential option even in patients without high bleeding risk. Given the very low rates of stent thrombosis in studies using contemporary drug-eluting stents, avoiding bleeding with de-escalation of antiplatelet therapy may be more important than attempting further reduction of stent thrombosis with intensive antiplatelet therapy.”
SMART-CHOICE was funded by the Korean Society of Interventional Cardiology, Biotronik, Abbott Vascular, and Boston Scientific. Dr. Hahn and colleagues reported receiving additional financial relationships with AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, and others. STOPDAPT-2 was funded by Abbott Vascular. Dr. Watanabe and colleagues reported receiving additional funding from Daiichi Sankyo, Otsuka Pharmaceutical, Kowa Pharmaceuticals, and others.
SOURCES: Watanabe H et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8145; Hahn J-Y et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8146.
FROM JAMA