Chinese Medical Sciences Journal ›› 2017, Vol. 32 ›› Issue (1): 1-12.doi: 10.24920/J1001-9242.2007.001
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Efficacy of Short-term Dual Antiplatelet Therapy after Implantation of Second-generation Drug-eluting Stents: A Meta-analysis and Systematic Review
Huang Peisen1#, Yu Yuan1#, Han Xikun1, Yang Yuejin1, *(
)
- 1State Key Laboratory of Cardiovascular Disease
2National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
-
Published:2017-03-31Online:2017-04-10 -
Contact:Yang Yuejin E-mail:yangyjfw@126.com
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Huang Peisen, Yu Yuan, Han Xikun, Yang Yuejin. Efficacy of Short-term Dual Antiplatelet Therapy after Implantation of Second-generation Drug-eluting Stents: A Meta-analysis and Systematic Review[J].Chinese Medical Sciences Journal, 2017, 32(1): 1-12.
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Figure 1.
PRISMA flow chart for the trial selection process. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; RCT: randomized controlled trial; DES: drug-eluting stent."
Figure 1.
Table 1
Results of bias risk assessment of the 5 included studies"
| Methodological items | ITALIC12 | OPTIMIZE14 | RPRODIGY15 | RESET16 | SECURITY13 |
|---|---|---|---|---|---|
| Random sequence generation | Yes (Web-based) | Yes | Yes (Computer- generated) | Yes (Web-based) | Yes |
| Allocation concealment | Yes (Centralized randomization) | Unclear | Yes (Sealed envelopes) | Unclear | Unclear |
| Blinding of participants* | Yes | Yes | Yes | Yes | Yes |
| Blinding of outcome assessment | Yes | Yes | Yes | Yes | Yes |
| Incomplete outcome data | Yes | Yes | Yes | Yes | Yes |
| Selective outcome reporting | Yes | Yes | Yes | Yes | Yes |
| Sample size calculation | Yes | Yes (Non-inferiority design) | Yes | Yes (Non-inferiority design) | Yes (Non inferiority design) |
| Funding sources disclosure | Yes (Industry-funded) | Yes (Industry-funded) | Yes (Investigator- driven) | Yes (Public Health- and Industry-funded ) | Yes (Public Health-funded ) |
| Other bias | Yes (Prematurely terminative) | No | No | No | Yes (Prematurely terminative) |
Table 1
Table 2
Main characteristics of the 5 included trials"
| Items | ITALIC12 | SECURITY13 | OPTIMIZE14 | PRODIGY15* | RESET16 |
|---|---|---|---|---|---|
| Patients (n) | 1850 | 1399 | 3119 | 988 | 2117 |
| Age (yrs) | 61.6 | 65.2 | 61.6 | 67.7 | 62.4 |
| Male (%) | 80 | 77.2 | 63.3 | 78.7 | 63.6 |
| BMI (kg/m2) | 27 | NA | NA | 27.5 | 25 |
| Current smoker (%) | 51.8 | 22.2 | 17.9 | 23.9 | 24 |
| Previous PCI (%) | 23.3 | 17.7 | 20.0 | NA | 3.3 |
| Comorbidities | |||||
| Diabetes (%) | 37.0 | 30.7 | 35.4 | 23.3 | 29.3 |
| Dyslipidaemia (%) | 67.1 | 63 | 61.1 | 60.0 | 58.8 |
| Hypertension (%) | 65.0 | 72.8 | 87.2 | 69.6 | 61.9 |
| Severity of illness | |||||
| Ejection fraction (%) | NA | 56.5 | NA | 50.8 | 64.1 |
| Silent ischemia (%) | 20.2 | - | 8.9 | - | - |
| Stable CAD (%) | 41.3 | 50.7 | 59.2 | 25.2 | 45.4 |
| ACS (%) | 23.5 | 31.6 | 31.9 | 74.8 | 54.6 |
| Procedural characteristics | |||||
| Multivessel disease (%) | NA | 42.3 | 25.9 | 71.4 | 22.7 |
| LAD treated (%) | 72.8 | 43.5 | 47.2 | 58.9 | 53.2 |
| Lesion length (mm) | NA | 19 | 18.4 | 13.45 | 19.8 |
| Stent/lesion | NA | NA | 1.2 | 1.2 | 1.0 |
| Type of DES used | EES | ZES, EES | ZES | ZES, EES | EES, SES, ZES |
| Thienopyridine category | Clopidogrel (98.2%), prasugrel and ticagrelor (1.8%) | Clopidogrel (99.9%), prasugrel and ticagrelor (0.1%) | Clopidogrel (100%) | clopidogrel (100%) | Clopidogrel (100%) |
| Main inclusion criteria | ≥18 years; PCI suitability; Xience V DES implantation; all clinical situations excluding primary PCI for acute MI and treatment of the left main artery | Stable angina or unstable angina or patients with documented silent ischemia; second-generation DES implantation <24 hours; ≥1 coronary artery lesion; ≥70% DS; ≥18 years, no other DES implantation; no BMS implantation ≤3 months | Stable angina, silent ischemia, unstable angina, recent (but not acute) MI (<30 days); ≥1 lesion; ≥50% DS; RVD ≥2.5 mm; PCI suitablity | ≥18 years; ≥1 coronary artery lesion; ≥50% DS; PCI suitability; RVD ≥2.25 mm; chronic stable coronary artery disease or ACS (NSTEMI/ STEMI) | ≥20 years; ≥50% DS; RVD 2.5 to 4.0 mm; elective PCI; stable angina, unstable angina, or acute MI |
| Items | ITALIC12 | SECURITY13 | OPTIMIZE14 | PRODIGY15* | RESET16 |
| Main exclusion criteria | Aspirin resistance; prior DES implantation <1 year; bleeding diathesis or active bleeding; DAPT contraindications; major surgery <6 weeks; severe liver failure; elective surgery planned <1 year; life expectancy <2 years | Patients treated for saphenous vein graft and in-stent restenosis; <48 hours STEMI; <6 months NSTEMI; LVEF <30%; DAPT contraindications; creatinine >177 μmol/L; bleeding diathesis or active bleeding; life expectancy <2 years | STEMI presenting for primary or rescue PCI; BMS implantation <6 months; previous treatment with any DES; elective surgery planned <12 months; DAPT contraindications; saphenous vein graft lesion | Elective surgery planned <24 months after index PCI (unless DAPT could be maintained thro- ughout the peri-surgical period); bleeding diathesis; major surgery <15 days; active bleeding or previous stroke <6 months; concomitant or foreseeable need for anticoagulants | Cerebral/peripheral atherosclerotic arterial disease, thromboembolic disease or ST history; LVEF <40%; restenotic lesion; CTO; LM disease requi- ring intervention; cardiogenic shock; STEMI<48 hours |
| Primary endpoint | Composite of all-cause death, MI, repeat emergency TVR, stroke, or major bleeding | Composite of cardiac death, MI, stroke, ST, or BARC type 3 or 5 bleeding | NACCE (composite of all-cause death, MI, stroke, or major bleeding) | Composite of all-cause death, MI or CVAs | Composite of cardiac death, MI, ST, ID-TVR and TIMI major or minor bleeding |
| Secondary endpoint | All-cause death, MI, repeat emergency TVR, stroke; minor and minimal bleeding | Cardiac death, MI, stroke, ST, or BARC type 2, 3, or 5 bleeding; CI of the individual components of the primary endpoint; ID-TVR; all-cause mortality | ST; ID-TVR; MACE (composite of all-cause death, MI and any revascularization); bleeding | All-cause death; MI; CVAs; cardiac death; ST | Composite of all-cause death; MI; ST |
| Time to randomization | 6 months after index PCI | At index PCI | At index PCI | 1 month after index PCI | At index PCI |
| DAPT duration(mon) | |||||
| Short-term DAPT group | 6 | 6 | 3 | 6 | 3 |
| Standard DAPT group | 12 | 12 | 12 | 24 | 12 |
| Year of publication | 2015 | 2014 | 2013 | 2013 | 2012 |
| Registration number | NCT01476020 | NCT00944333 | NCT01113372 | NCT00611286 | NCT01145079 |
Table 2
Figure 2.
Comparison of total efficacy of short-term dual antiplatelet therapy (DAPT) vs. standard DAPT. The squares and the horizontal lines indicate the risk ratio and the (95% CI) for each trial included; the size of each square is proportional to the statistical weight of a trial in the meta-analysis; diamond indicates the effect estimate derived from meta-analysis, with the center indicating the point estimate and the left and the right ends of the (95% CI)."
Figure 2.
Figure 3.
Comparison of individual safety indicator of short-term DAPT vs. standard DAPT. A. Odds ratio with (95% CI) for all-cause death; B. myocardial infarction; C. definite or probable stent thrombosis; D. cerebrovascular accidents."
Figure 3.
Figure 4.
Comparison of major bleeding risk of patients receiving short-term DAPT vs. standard DAPT. The squares and the horizontal lines indicate the risk ratio and the (95% CI) for each trial included; the size of each square is proportional to the statistical weight of a trial in the meta-analysis; diamond indicates the effect estimate derived from meta-analysis, with the center indicating the point estimate and the left and the right ends of the (95% CI)."
Figure 4.
Figure 5.
Funnel plots were done to access the probable publication bias. A. Funnel plot for efficacy effect; B. all-cause death; C. myocardial infarction; D. definite or probable stent thrombosis; E. cerebrovascular accidents; F. safety effect. RR: relative risk."
Figure 5.
Figure 6.
Sensitivity analysis of all studies assessing association of difference in DAPT duration between study arms on meta- analysis results for overall efficacy endpoint and individual endpoints.A. Meta-regression for efficacy effect; B. all-cause death; C. myocardial infarction; D. definite or probable stent thrombosis; E. cerebrovascular accidents. RR: relative risk."
Figure 6.
Figure 7.
Sensitivity analysis of all studies assessing association of proportion of patients with acute coronary syndrome (ACS%) between study arms on meta-analysis results for overall efficacy endpoint and individual endpoints.A. Meta-regression for efficacy effect; B. all-cause death; C. myocardial infarction; D. definite or probable stent thrombosis; E. cerebrovascular accidents."
Figure 7.
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