The clinical outcomes of triple antiplatelet therapy versus dual antiplatelet therapy for high-risk patients after coronary stent implantation: a meta-analysis of 11 clinical trials and 9,553 patients

Figures & data

Table 1 Baseline characteristics of the included trials

Study	Design	TAPT regimen	DAPT regimen
DECLARE-LONG trial^Citation14	RCT	Loading: aspirin 200 mg, clopidogrel 300 mg, cilostazol 200 mg; maintenance: aspirin 200 mg/d, clopidogrel 75 mg/d, cilostazol 100 mg twice daily; >6 m	Loading: aspirin 200 mg, clopidogrel 300 mg; maintenance: aspirin 200 mg/d, clopidogrel 75 mg/d; >6 m
DECLARE-LONG II trial^Citation16	RCT	Loading: aspirin 200 mg, clopidogrel 300 mg, cilostazol 200 mg; maintenance: aspirin 200 mg/d, clopidogrel 75 mg/d, ≥12 m; cilostazol 100 mg twice daily, for 8 m	Loading: aspirin 200 mg, clopidogrel 300 mg; maintenance: aspirin 200 mg/d, clopidogrel 75 mg/d; ≥12 m
Lee et al^Citation9	Obs	DAPT + cilostazol, ≥3 m	Aspirin + clopidogrel or ticlopidine
*COBIS II Registry^Citation17	Obs	Loading: aspirin 300 mg, clopidogrel 300–600 mg, cilostazol 200 mg; maintenance: aspirin indefinitely, clopidogrel 75 mg/d, ≥6 m; + cilostazol	Loading: aspirin 300 mg, clopidogrel 300–600 mg; maintenance: aspirin indefinitely, clopidogrel 75 mg/d; ≥6 m
Youn et al^Citation29	RCT	Loading: aspirin 300 mg, clopidogrel 300 mg, cilostazol 200 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d, for 12 m; cilostazol 100 mg twice daily, for 3 m	Loading: aspirin 300 mg, clopidogrel 300–600 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d, for 12 m
Kim et al^Citation25	RCT	Loading: aspirin 300 mg, clopidogrel 600 mg, cilostazol 400 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d; + cilostazol 200 mg, for 1 m	Loading: aspirin 300 mg, clopidogrel 600 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d, for 1 m
Chen et al^Citation10	Obs	Loading: aspirin 200 mg, clopidogrel 300–600 mg, cilostazol 200 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d, ≥6 m; cilostazol 100 mg twice daily, ≥1 m	Loading: aspirin 200 mg, clopidogrel 300–600 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d; ≥6 m
Han et al^Citation27	RCT	Aspirin 300 mg/d for 1 m, followed by 100 mg/d indefinitely; clopidogrel 300–600 mg, followed by 75 mg/d, for 3–12 m; + cilostazol 100 mg twice daily, for 6 m	Aspirin 300 mg/d for 1 m, followed by 100 mg/d indefinitely; clopidogrel 300–600 mg, followed by 75 mg/d, for 3–6 m
Ahn et al^Citation28	RCT	Loading: aspirin 200 mg, clopidogrel 300 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d, for 24 m, cilostazol 100 mg twice daily	Loading: aspirin 200 mg, clopidogrel 300 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d, for 24 m
Jeong et al^Citation26	RCT	Loading: aspirin 300 mg, clopidogrel 600 mg; maintenance: aspirin 200 mg/d, clopidogrel 75 mg/d, for 1 m; cilostazol 100 mg twice daily, for 1 m	Loading: aspirin 300 mg, clopidogrel 600 mg; maintenance: aspirin 200 mg/d, clopidogrel 75 mg/d, for 1 m
Lee et al^Citation9	Obs	Loading: aspirin 300 mg, clopidogrel 450–600 mg, cilostazol 200 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d, ≥6 m; cilostazol 100 mg twice daily, ≥1 m	Loading: aspirin 300 mg, clopidogrel 450–600 mg; maintenance: aspirin 100 mg/d, clopidogrel 75 mg/d, ≥6 m

Note:

* Subgroup following propensity score matching.

Abbreviations: COBIS, COronary BIfurcation Stent; d, day; DAPT, dual antiplatelet therapy; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; m, month; Obs, observational trials; RCT, randomized controlled trials; TAPT, triple antiplatelet therapy.

Table 2 Characteristics of the patients’ past medical histories among the included trials

Study	TAPT/DAPT							Follow-up
	Patients, n	Age, y	Males, n	Hypertension, n	Diabetes, n	Dyslipidemia, n	Smokers, n
DECLARE-LONG trial^Citation14	250/250	60.9/61.2	162/159	137/138	85/81	75/71	94/93	9 months
DECLARE-LONG II trial^Citation16	250/249	60.9/62.1	175/178	146/161	92/84	106/112	76/75	12 months
Lee et al^Citation9	124/121	63.8/64.9	90/70	75/71	44/31	88/84	32/25	12 months
*COBIS II Registry^Citation17	651/651	61.9/62.0	462/455	380/365	196/189	NA	162/149	36 months
Youn et al^Citation29	308/307	65.0/64.2	194/197	210/202	100/95	152/146	149/135	12 months
Kim et al^Citation25	30/30	62.3/63.9	21/21	17/14	9/8	6/4	18/18	1 month
Chen et al^Citation10	1,634/2,569	62.0/62.0	1,224/1,917	716/1,165	390/629	116/207	795/1,265	8 months
Han et al^Citation27	604/608	59.6/60.2	446/443	350/341	141/122	275/276	NA	12 months
Ahn et al^Citation28	64/66	62.1/65.2	39/42	28/24	14/15	16/13	28/30	24 months
Jeong et al^Citation26	30/30	61.3/64.0	21/22	17/11	9/4	9/13	16/21	1 month
Lee et al^Citation9	195/532	69/72	125/317	100/263	48/149	15/39	94/241	12 months

Note:

* Subgroup following propensity score matching.

Abbreviations: COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet therapy; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; NA, not available; TAPT, triple antiplatelet therapy; y, years.

Table 3 Angiographic and procedural characteristics

Study	LM, n	LAD, n	LCX, n	RCA, n	Type of implanted stents	Stent length, mm	Stent number, n	Stent diameter, mm	Study quality
DECLARE-LONG trial^Citation14	0/0	155/152	23/29	72/69	DES	41.4/40.3	1.49/1.47	NA	2
DECLARE-LONG II trial^Citation16	0/0	149/155	40/29	61/65	DES	37.3/39.1	1.5/1.6	NA	5
Lee et al^Citation9	124/121	NA	NA	50/51	DES	42.6/33.9	2.0/1.6	3.51/3.47	9#
*COBIS II Registry^Citation17	212/267	300/287	55/76	24/21	DES	NA	2.0/2.0	NA	8#
Youn et al^Citation29	NA	NA	NA	50/51	DES	51.1/49.7	2.3/2.2	3.08/3.05	3
Kim et al^Citation25	0/0	12/16	3/6	15/8	DES	NA	NA	NA	2
Chen et al^Citation10	23/21	866/1,387	169/242	576/919	DES	25.7/25.3	1.53/1.35	3.18/3.17	8#
Han et al^Citation27	16/14	489/485	165/166	333/353	DES/BMS	37.9/38.8	1.58/1.56	3.12/3.16	3
Ahn et al^Citation28	0/0	44/40	10/14	10/12	DES	24.5/25.0	2.38/2.36	2.9/2.8	2
Jeong et al^Citation26	0/0	12/10	12/9	6/11	DES	33/31	1.4/1.3	3.2/3.0	3
Lee et al^Citation9	2/14	100/248	26/77	66/188	NA	26.0/26.1	1.6/1.4	3.1/3.1	8#

Notes:

# The qualities of observational trials were assessed by the Newcastle–Ottawa Scale, and the maximum score =9. The qualities of included randomized trials were assessed by the Jadad score.

* Subgroup following propensity score matching.

Abbreviations: BMS, bare mental stents; COBIS, COronary BIfurcation Stent; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; DES, drug-eluting stent; LAD, left anterior descending artery; LCX, left circumflex artery; LM, left main coronary artery; RCA, right coronary artery; NA, not available.

Figure 1 Flow chart depicting the selection of the studies included in this meta-analysis.

Figure 2 The ORs of MACE associated with TAPT compared with DAPT.

Notes: Forest plots of the efficacy and safety end points of the included trials. Weights are from random-effects analysis. *Subgroup following propensity score matching.
Abbreviations: ACS, acute coronary syndrome; AMI, acute myocardial infarction; CI, confidence interval; COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet treatment; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; MACE, major adverse cardiac events; OR, odds ratio; TAPT, triple antiplatelet treatment.

Figure 3 The ORs of all-cause mortality associated with TAPT compared with DAPT.

Notes: Forest plots of the efficacy and safety end points of the included trials. *Subgroup following propensity score matching.
Abbreviations: ACS, acute coronary syndrome; AMI, acute myocardial infarction; CI, confidence interval; COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet treatment; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; OR, odds ratio; TAPT, triple antiplatelet treatment.

Figure 4 The ORs of myocardial infarction associated with TAPT compared with DAPT.

Notes: Forest plots of the efficacy and safety end points of the included trials. *Subgroup following propensity score matching.
Abbreviations: ACS, acute coronary syndrome; AMI, acute myocardial infarction; CI, confidence interval; COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet treatment; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; OR, odds ratio; TAPT, triple antiplatelet treatment.

Figure 5 The ORs of TVR associated with TAPT compared with DAPT.

Notes: Forest plots of the efficacy and safety end points of the included trials. Weights are from random-effects analysis. *Subgroup following propensity score matching.
Abbreviations: ACS, acute coronary syndrome; AMI, acute myocardial infarction; CI, confidence interval; COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet treatment; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; OR, odds ratio; TAPT, triple antiplatelet treatment; TVR, target vessel revascularization.

Figure 6 The ORs of stroke associated with TAPT compared with DAPT.

Notes: Forest plots of the efficacy and safety end points of the included trials. *Subgroup following propensity score matching.
Abbreviations: ACS, acute coronary syndrome; AMI, acute myocardial infarction; CI, confidence interval; COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet treatment; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; OR, odds ratio; TAPT, triple antiplatelet treatment.

Figure 7 The ORs of stent thrombosis associated with TAPT compared with DAPT.

Notes: Forest plots of the efficacy and safety end points of the included trials. *Subgroup following propensity score matching.
Abbreviations: ACS, acute coronary syndrome; AMI, acute myocardial infarction; CI, confidence interval; COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet treatment; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; OR, odds ratio; TAPT, triple antiplatelet treatment.

Figure 8 The ORs of major bleeding associated with TAPT compared with DAPT.

Note: Forest plots of the efficacy and safety end points of the included trials.
Abbreviations: CI, confidence interval; COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet treatment; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; OR, odds ratio; TAPT, triple antiplatelet treatment.

Figure 9 The ORs of minor bleeding associated with TAPT compared with DAPT.

Note: Forest plots of the efficacy and safety end points of the included trials.
Abbreviations: CI, confidence interval; COBIS, COronary BIfurcation Stent; DAPT, dual antiplatelet treatment; DECLARE-LONG II, drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions; OR, odds ratio; TAPT, triple antiplatelet treatment.

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