Note: This is a multi-article spread containing a shared commentary. Please scroll down for the other article(s).
Therapeutics
Review: After coronary DES placement, shorter vs longer dual-antiplatelet therapy reduces mortality Clinical impact ratings:
多多多多多多夞
Palmerini T, Benedetto U, Bacchi-Reggiani L, et al. Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials. Lancet. 2015;Mar 13. Epub ahead of print.
多多多多多多夞
Question
Review methods
After coronary drug-eluting stent (DES) implantation, what are the efficacy and safety of different durations of dual-antiplatelet therapy (DAPT)?
MEDLINE, EMBASE/Excerpta Medica, Cochrane databases, www.clinicaltrials.gov, www.tctmd.com, www.clinicaltrialresults.org, www.cardiosource.com, and proceedings from major cardiovascular meetings were searched for randomized controlled Review scope trials (RCTs). 10 RCTs (n = 31 666, mean age 62 to 68 y, 63% Included studies compared different durations (≤ 6 mo vs 1 y vs to 81% men, follow-up 9 to 24 mo) published between Dec > 1 y) of DAPT after DES implantation. Primary outcome was all2011 and Nov 2014 met the inclusion criteria and had sufficause mortality. Other outcomes were cardiac mortality, noncarcient data for analysis. 2 RCTs compared DAPT for 3 vs 12 diac mortality, myocardial infarction (MI), stroke, stent thrombomonths, 3 for 6 vs 12 months, 2 for 6 vs 24 months, and 3 for sis (definite or probable), any bleeding, and major bleeding. 12 vs 18 to 36 months. Type of stent used varied across studies. All 10 RCTs blinded outcome adjudicators and had adequate allocation concealShorter vs longer DAPT after coronary drug-eluting stent placement* ment and follow-up data, 2 were described as double-blind, and 9 used intention-to-treat Outcomes Number of Weighted At 9 to 24 mo† analysis. trials (n) event rates Shorter Longer DAPT DAPT All-cause mortality
10 (31 666)
1.48%
1.80%
Cardiac mortality
8 (26 407)
1.05%
1.13%
Noncardiac mortality
8 (26 407)
0.60%
0.90%
Any bleeding Major bleeding
RRR (95% CI) 18% (2 to 31)
NNT (CI) 311 (181 to 2803)
7% (⫺17 to 27) 33% (11 to 49)
Not significant 338 (228 to 1015)
9 (26 621)
1.66%
2.95%
44% (34 to 52)
78 (66 to 101)
10 (31 666)
0.81%
1.39%
42% (28 to 53)
172 (137 to 259)
RRI (CI) Myocardial infarction Stroke Definite or probable stent thrombosis‡
10 (31 666)
2.00%
1.50%
10‡ (31 666)
0.67%
0.65%
9 (26 621)
0.66%
0.37%
NNH (CI)
34% (7 to 68)
199 (98 to 961)
3% (⫺22 to 36) 79% (6 to 202)
Not significant 344 (134 to 4514)
*DAPT = dual-antiplatelet therapy; other abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from hazard ratios and longer DAPT event rates in article using a random-effects model. DAPT duration comparisons were ≤ 6 mo vs 1 y, 6 mo vs > 1 y, and 1 y vs > 1 y.
Main results Compared with longer DAPT, shorter DAPT reduced all-cause mortality, noncardiac mortality, and major or any bleeding; increased MI and stent thrombosis; and did not differ for cardiac mortality or stroke (Table).
Conclusion After coronary drug-eluting stent placement, shorter-duration dual-antiplatelet therapy reduces all-cause mortality compared with longer-duration therapy. Source of funding: No external funding. For correspondence: Dr. Gregg W. Stone, Columbia University Medical Center, New York, NY, USA. E-mail [email protected].
†Results were similar using a fixed-effect model and Bayesian analysis with noninformative priors. ‡Revised data provided by author.
Commentary Compared with bare-metal stents (BMSs), DESs decrease risk for in-stent restenosis and repeated revascularization of the target lesion by inhibiting the intimal hyperplasia response to arterial injury associated with stent implantation. However, a major limitation of delayed vascular healing with DESs is the risk for stent thrombosis before reendothelialization internalizes the stent struts in the vascular wall. DAPT with aspirin and a P2Y12 inhibitor is usually recommended for ≥ 1 month after BMS implantation (1). In contrast, the initial recommendation of 3 to 6 months of DAPT after implantation of first-generation DESs was later increased to ≥ 12 months after early observational reports warned that patients with DESs had an ongoing annual risk for stent thrombosis, MI, and mortality (2). A more complete evaluation of subsequent clinical data suggested that DES implantation did not increase risk for death, presumably because the small increased risk for MI from stent thrombosis was balanced by a decreased risk for MI from restenosis (3). Still, the recommendations for longer DAPT after DES implantation persist. Newer-generation DESs seem to be associated with better healing and lower risk for stent thrombosis (4), so the optimal duration of DAPT is being reevaluated. 10 RCTs evaluating DAPT duration have been published. Palmerini and colleagues did a study-level meta-analysis of all 10 tri-
姝 2015 American College of Physicians
JC2
als comparing shorter- and longer-duration DAPT. DAPT for > 12 months decreased stent thrombosis and MI but was associated with increased bleeding and noncardiac death, with no difference in cardiovascular death. The increased noncardiac mortality risk is unexplained, with no signal suggesting a causal relation to bleeding. In another review, Palmerini and colleagues did a patient-level meta-analysis of 4 of these trials comparing DAPT for 3 to 6 months vs 12 months and found no differences in death, MI, stent thrombosis, or repeated revascularization. Rates of any bleeding were lower with shorterduration DAPT. Decreasing the duration of DAPT was supported, but not proved, because the confidence intervals were wide due to low event rates. Compared with 12 months of DAPT after elective implantation of newer-generation DESs, shorter-duration DAPT seems to be safe in patients with low risk for stent thrombosis, whereas longer-duration DAPT decreases MI and stent thrombosis but increases bleeding. Therefore, it seems reasonable to treat most stable patients after elective DES implantation with 6 months of DAPT. Longer-duration therapy may be desirable in patients who have increased clinical or angiographic risk for very late stent thrombosis or MI but have not had bleeding complications when using DAPT, depending on their estimated risk for future bleeding. Unfortunately, it will be difficult to construct a clinical (continued on page JC3)
ACP Journal Club
Annals of Internal Medicine
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/934240/ by a Uppsala Universitetsbibliotek User on 07/11/2017
21 Jul 2015
Note: This is a multi-article spread containing a shared commentary. Please scroll down for the other article(s).
Therapeutics
Review: After coronary DES placement, ≤ 6 mo and 1 y of dual-antiplatelet therapy do not differ for cardiac events Clinical impact ratings:
多多多多多夞夞
Palmerini T, Sangiorgi D, Valgimigli M, et al. Short- versus long-term dual antiplatelet therapy after drug-eluting stent implantation: an individual patient data pairwise and network meta-analysis. J Am Coll Cardiol. 2015;65:1092-102.
多多多多多多夞
Question
Review methods
After coronary drug-eluting stent (DES) implantation, what are the efficacy and safety of ≤ 6 months vs 1 year of dual-antiplatelet therapy (DAPT)?
MEDLINE, EMBASE/Excerpta Medica, Cochrane databases, www.clinicaltrials.gov, www.tctmd.com, www.clinicaltrialresults.org, www.cardiosource.com, and proceedings from major cardiovascular meetings were searched for randomized controlled trials (RCTs). Investigators were contacted for original data. 4 RCTs (n = 8180; mean age 63 y; 66% men; 63% with zotarolimuseluting stents, 22% with everolimus-eluting stents, and 15% with other types of stents) met the inclusion criteria and had individual patient data available for analysis. 2 RCTs compared DAPT for 3 vs 12 months, 1 for 6 vs 12 months, and 1 for 6 vs 24 months. Data for the last RCT were censored at 12 months for analysis. All RCTs had adequate allocation concealment, blinded outcome adjudicators, and used intention-to-treat analysis.
Review scope Included studies compared DAPT for 3 or 6 months vs ≥ 1 year after DES implantation. Primary outcome was a composite of major adverse cardiac events (MACE), including cardiac mortality, myocardial infarction, and definite or probable stent thrombosis. Other prespecified outcomes included components of the composite outcome, all-cause mortality, stroke, minor and major bleeding, and target vessel revascularization.
DAPT for ≤ 6 mo vs 1 y after coronary drug-eluting stent placement* Outcomes
Events per 1000 patient-y
At 1 y
< 6-mo DAPT (n ⴝ 4095)
1-y DAPT (n ⴝ 4085)
Major adverse cardiac event†
31
28
1.11 (0.85 to 1.43)
All-cause mortality
20
22
0.89 (0.66 to 1.20)
Stroke
4.5
Minor bleeding
9.1
Major bleeding Target vessel revascularization
4.5 42
5.6 12 7.9 36
Hazard ratio (95% CI)
0.82 (0.55 to 1.52) 0.76 (0.50 to 1.18) 0.58 (0.32 to 1.03)‡ 1.14 (0.91 to 1.43)
*DAPT = dual-antiplatelet therapy; other abbreviations defined in Glossary. Results were similar using Bayesian network meta-analysis unless otherwise indicated. †Cardiac mortality (P = 0.47), myocardial infarction (P = 0.52), or definite or probable stent thrombosis (P = 0.57).
Main results DAPT for ≤ 6 months vs 1 year did not differ for any outcomes (Table). Prespecified subgroup analyses found that DAPT duration did not differ for MACE by sex; age; the acute coronary syndrome vs stable angina; or presence or absence of diabetes, multivessel disease, or left anterior descending coronary artery disease.
Conclusion After coronary drug-eluting stent placement, ≤ 6 months of dual-antiplatelet therapy does not differ from 1 year of therapy for major adverse cardiac events. Source of funding: Not stated. For correspondence: Dr. Gregg W. Stone, Columbia University Medical Center, New York, NY, USA. E-mail [email protected].
‡Network meta-analysis odds ratio 0.52, 95% credible interval 0.30 to 0.93.
Commentary (continued from page JC2)
References
risk prediction tool to assist in that decision because the variables that predict ischemic risk also predict bleeding risk. In patients with acute coronary syndromes, ≥ 12 months of DAPT is still recommended, regardless of whether a DES was implanted. Eric R. Bates, MD University of Michigan Ann Arbor, Michigan, USA
1. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44-122. 2. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007;115:813-8. 3. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007;356:998-1008. 4. Baber U, Mehran R, Sharma SK, et al. Impact of the everolimus-eluting stent on stent thrombosis: a meta-analysis of 13 randomized trials. J Am Coll Cardiol. 2011;58:1569-77.
21 Jul 2015
Annals of Internal Medicine
ACP Journal Club
JC3
姝 2015 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/934240/ by a Uppsala Universitetsbibliotek User on 07/11/2017
Therapeutics
Review: After coronary DES placement, shorter vs longer dual-antiplatelet therapy reduces mortality Clinical impact ratings:
多多多多多多夞
Palmerini T, Benedetto U, Bacchi-Reggiani L, et al. Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials. Lancet. 2015;Mar 13. Epub ahead of print.
多多多多多多夞
Question
Review methods
After coronary drug-eluting stent (DES) implantation, what are the efficacy and safety of different durations of dual-antiplatelet therapy (DAPT)?
MEDLINE, EMBASE/Excerpta Medica, Cochrane databases, www.clinicaltrials.gov, www.tctmd.com, www.clinicaltrialresults.org, www.cardiosource.com, and proceedings from major cardiovascular meetings were searched for randomized controlled Review scope trials (RCTs). 10 RCTs (n = 31 666, mean age 62 to 68 y, 63% Included studies compared different durations (≤ 6 mo vs 1 y vs to 81% men, follow-up 9 to 24 mo) published between Dec > 1 y) of DAPT after DES implantation. Primary outcome was all2011 and Nov 2014 met the inclusion criteria and had sufficause mortality. Other outcomes were cardiac mortality, noncarcient data for analysis. 2 RCTs compared DAPT for 3 vs 12 diac mortality, myocardial infarction (MI), stroke, stent thrombomonths, 3 for 6 vs 12 months, 2 for 6 vs 24 months, and 3 for sis (definite or probable), any bleeding, and major bleeding. 12 vs 18 to 36 months. Type of stent used varied across studies. All 10 RCTs blinded outcome adjudicators and had adequate allocation concealShorter vs longer DAPT after coronary drug-eluting stent placement* ment and follow-up data, 2 were described as double-blind, and 9 used intention-to-treat Outcomes Number of Weighted At 9 to 24 mo† analysis. trials (n) event rates Shorter Longer DAPT DAPT All-cause mortality
10 (31 666)
1.48%
1.80%
Cardiac mortality
8 (26 407)
1.05%
1.13%
Noncardiac mortality
8 (26 407)
0.60%
0.90%
Any bleeding Major bleeding
RRR (95% CI) 18% (2 to 31)
NNT (CI) 311 (181 to 2803)
7% (⫺17 to 27) 33% (11 to 49)
Not significant 338 (228 to 1015)
9 (26 621)
1.66%
2.95%
44% (34 to 52)
78 (66 to 101)
10 (31 666)
0.81%
1.39%
42% (28 to 53)
172 (137 to 259)
RRI (CI) Myocardial infarction Stroke Definite or probable stent thrombosis‡
10 (31 666)
2.00%
1.50%
10‡ (31 666)
0.67%
0.65%
9 (26 621)
0.66%
0.37%
NNH (CI)
34% (7 to 68)
199 (98 to 961)
3% (⫺22 to 36) 79% (6 to 202)
Not significant 344 (134 to 4514)
*DAPT = dual-antiplatelet therapy; other abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from hazard ratios and longer DAPT event rates in article using a random-effects model. DAPT duration comparisons were ≤ 6 mo vs 1 y, 6 mo vs > 1 y, and 1 y vs > 1 y.
Main results Compared with longer DAPT, shorter DAPT reduced all-cause mortality, noncardiac mortality, and major or any bleeding; increased MI and stent thrombosis; and did not differ for cardiac mortality or stroke (Table).
Conclusion After coronary drug-eluting stent placement, shorter-duration dual-antiplatelet therapy reduces all-cause mortality compared with longer-duration therapy. Source of funding: No external funding. For correspondence: Dr. Gregg W. Stone, Columbia University Medical Center, New York, NY, USA. E-mail [email protected].
†Results were similar using a fixed-effect model and Bayesian analysis with noninformative priors. ‡Revised data provided by author.
Commentary Compared with bare-metal stents (BMSs), DESs decrease risk for in-stent restenosis and repeated revascularization of the target lesion by inhibiting the intimal hyperplasia response to arterial injury associated with stent implantation. However, a major limitation of delayed vascular healing with DESs is the risk for stent thrombosis before reendothelialization internalizes the stent struts in the vascular wall. DAPT with aspirin and a P2Y12 inhibitor is usually recommended for ≥ 1 month after BMS implantation (1). In contrast, the initial recommendation of 3 to 6 months of DAPT after implantation of first-generation DESs was later increased to ≥ 12 months after early observational reports warned that patients with DESs had an ongoing annual risk for stent thrombosis, MI, and mortality (2). A more complete evaluation of subsequent clinical data suggested that DES implantation did not increase risk for death, presumably because the small increased risk for MI from stent thrombosis was balanced by a decreased risk for MI from restenosis (3). Still, the recommendations for longer DAPT after DES implantation persist. Newer-generation DESs seem to be associated with better healing and lower risk for stent thrombosis (4), so the optimal duration of DAPT is being reevaluated. 10 RCTs evaluating DAPT duration have been published. Palmerini and colleagues did a study-level meta-analysis of all 10 tri-
姝 2015 American College of Physicians
JC2
als comparing shorter- and longer-duration DAPT. DAPT for > 12 months decreased stent thrombosis and MI but was associated with increased bleeding and noncardiac death, with no difference in cardiovascular death. The increased noncardiac mortality risk is unexplained, with no signal suggesting a causal relation to bleeding. In another review, Palmerini and colleagues did a patient-level meta-analysis of 4 of these trials comparing DAPT for 3 to 6 months vs 12 months and found no differences in death, MI, stent thrombosis, or repeated revascularization. Rates of any bleeding were lower with shorterduration DAPT. Decreasing the duration of DAPT was supported, but not proved, because the confidence intervals were wide due to low event rates. Compared with 12 months of DAPT after elective implantation of newer-generation DESs, shorter-duration DAPT seems to be safe in patients with low risk for stent thrombosis, whereas longer-duration DAPT decreases MI and stent thrombosis but increases bleeding. Therefore, it seems reasonable to treat most stable patients after elective DES implantation with 6 months of DAPT. Longer-duration therapy may be desirable in patients who have increased clinical or angiographic risk for very late stent thrombosis or MI but have not had bleeding complications when using DAPT, depending on their estimated risk for future bleeding. Unfortunately, it will be difficult to construct a clinical (continued on page JC3)
ACP Journal Club
Annals of Internal Medicine
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/934240/ by a Uppsala Universitetsbibliotek User on 07/11/2017
21 Jul 2015
Note: This is a multi-article spread containing a shared commentary. Please scroll down for the other article(s).
Therapeutics
Review: After coronary DES placement, ≤ 6 mo and 1 y of dual-antiplatelet therapy do not differ for cardiac events Clinical impact ratings:
多多多多多夞夞
Palmerini T, Sangiorgi D, Valgimigli M, et al. Short- versus long-term dual antiplatelet therapy after drug-eluting stent implantation: an individual patient data pairwise and network meta-analysis. J Am Coll Cardiol. 2015;65:1092-102.
多多多多多多夞
Question
Review methods
After coronary drug-eluting stent (DES) implantation, what are the efficacy and safety of ≤ 6 months vs 1 year of dual-antiplatelet therapy (DAPT)?
MEDLINE, EMBASE/Excerpta Medica, Cochrane databases, www.clinicaltrials.gov, www.tctmd.com, www.clinicaltrialresults.org, www.cardiosource.com, and proceedings from major cardiovascular meetings were searched for randomized controlled trials (RCTs). Investigators were contacted for original data. 4 RCTs (n = 8180; mean age 63 y; 66% men; 63% with zotarolimuseluting stents, 22% with everolimus-eluting stents, and 15% with other types of stents) met the inclusion criteria and had individual patient data available for analysis. 2 RCTs compared DAPT for 3 vs 12 months, 1 for 6 vs 12 months, and 1 for 6 vs 24 months. Data for the last RCT were censored at 12 months for analysis. All RCTs had adequate allocation concealment, blinded outcome adjudicators, and used intention-to-treat analysis.
Review scope Included studies compared DAPT for 3 or 6 months vs ≥ 1 year after DES implantation. Primary outcome was a composite of major adverse cardiac events (MACE), including cardiac mortality, myocardial infarction, and definite or probable stent thrombosis. Other prespecified outcomes included components of the composite outcome, all-cause mortality, stroke, minor and major bleeding, and target vessel revascularization.
DAPT for ≤ 6 mo vs 1 y after coronary drug-eluting stent placement* Outcomes
Events per 1000 patient-y
At 1 y
< 6-mo DAPT (n ⴝ 4095)
1-y DAPT (n ⴝ 4085)
Major adverse cardiac event†
31
28
1.11 (0.85 to 1.43)
All-cause mortality
20
22
0.89 (0.66 to 1.20)
Stroke
4.5
Minor bleeding
9.1
Major bleeding Target vessel revascularization
4.5 42
5.6 12 7.9 36
Hazard ratio (95% CI)
0.82 (0.55 to 1.52) 0.76 (0.50 to 1.18) 0.58 (0.32 to 1.03)‡ 1.14 (0.91 to 1.43)
*DAPT = dual-antiplatelet therapy; other abbreviations defined in Glossary. Results were similar using Bayesian network meta-analysis unless otherwise indicated. †Cardiac mortality (P = 0.47), myocardial infarction (P = 0.52), or definite or probable stent thrombosis (P = 0.57).
Main results DAPT for ≤ 6 months vs 1 year did not differ for any outcomes (Table). Prespecified subgroup analyses found that DAPT duration did not differ for MACE by sex; age; the acute coronary syndrome vs stable angina; or presence or absence of diabetes, multivessel disease, or left anterior descending coronary artery disease.
Conclusion After coronary drug-eluting stent placement, ≤ 6 months of dual-antiplatelet therapy does not differ from 1 year of therapy for major adverse cardiac events. Source of funding: Not stated. For correspondence: Dr. Gregg W. Stone, Columbia University Medical Center, New York, NY, USA. E-mail [email protected].
‡Network meta-analysis odds ratio 0.52, 95% credible interval 0.30 to 0.93.
Commentary (continued from page JC2)
References
risk prediction tool to assist in that decision because the variables that predict ischemic risk also predict bleeding risk. In patients with acute coronary syndromes, ≥ 12 months of DAPT is still recommended, regardless of whether a DES was implanted. Eric R. Bates, MD University of Michigan Ann Arbor, Michigan, USA
1. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44-122. 2. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007;115:813-8. 3. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007;356:998-1008. 4. Baber U, Mehran R, Sharma SK, et al. Impact of the everolimus-eluting stent on stent thrombosis: a meta-analysis of 13 randomized trials. J Am Coll Cardiol. 2011;58:1569-77.
21 Jul 2015
Annals of Internal Medicine
ACP Journal Club
JC3
姝 2015 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/934240/ by a Uppsala Universitetsbibliotek User on 07/11/2017
