2.1

Study population and randomization

The study population and methods has been previously described . In brief, patients older than age 18 with ischemic symptoms or evidence of myocardial ischemia (inducible or spontaneous) in the presence of a restenosis ≥ 50% located in the native vessel segment treated with sirolimus-eluting stent were considered eligible. The study was conducted in accordance with the provisions of the Declaration of Helsinki and with the International Conference on Harmonization Good Clinical Practices. The trial protocol was approved by the institutional ethics committee responsible for the participating centres, Deutsches Herzzentrum and 1. Medizinische Klinik, Klinikum rechts der Isar, both in Munich, Germany.

Full details of treatment allocation, study devices and adjunctive antithrombotic therapy have been previously reported . In the ISAR-DESIRE 2 Trial patients were randomly assigned to receive either the sirolimus-eluting Cypher stent (Cordis, Miami Lakes, FL, USA) or paclitaxel-eluting Taxus stent (Boston Scientific, Natick, MA, USA). Patient allocation to each of the two treatment groups was in equal proportions. Both treatment groups were studied concurrently. Time zero was defined as the time of randomization and patients were considered enrolled in the study at this time point. The same randomly assigned stent had to be implanted in all lesions in those patients who required stenting in multiple lesions and the use of more than one stent per lesion was also allowed.

2.2

Procedures and follow-up

An oral loading dose of 600 mg clopidogrel was administered to all patients prior to the intervention, regardless of whether the patient was taking clopidogrel prior to admission. During the procedure, patients were given intravenous aspirin, heparin or bivalirudin; glycoprotein IIb/IIIa inhibitor usage was at the discretion of the operators. Procedural success was defined as residual stenosis < 30% and TIMI 3 flow achieved in the treated vessel using the assigned stent. After the intervention all patients, irrespective of treatment allocation, were prescribed 200 mg/day aspirin indefinitely, clopidogrel 150 mg for the first 3 days (or until discharge) followed by 75 mg/day for at least 6 months and other cardiac medications according to the judgment of patient’s physician (e.g. ß-blockers, ACE-inhibitors, statins etc.). After enrolment patients remained in hospital for at least 48 hours. Blood samples were drawn every 8 hours for the first 24 hours after randomization and daily afterwards for the determination of cardiac markers (CK, CK-MB, Troponin T). Daily recording of ECG was also performed until discharge. All patients were evaluated at 1 and 12 months by phone or office visit. Repeat coronary angiography was scheduled for all patients at 6–8 months.

2.3

Data management, end points, and definitions

Relevant data were collected and entered into a computer database by specialised personnel of the Clinical Data Management Centre. All events were adjudicated and classified by an event adjudication committee blinded to the treatment groups. Baseline, post procedural, and follow-up coronary angiograms were digitally recorded and assessed off-line in the quantitative angiographic (QCA) core laboratory (ISARESEARCH Center, Munich. Germany) with an automated edge-detection system (CMS version 7.1, Medis Medical Imaging Systems) by two independent experienced operators unaware of the treatment allocation. Measurements were performed on cineangiograms recorded after the intracoronary administration of nitro-glycerine. Baseline QCA measurements were performed using the single worst view projection for the index lesion; the same view projection was used for the measurements after stent implantation. In the follow-up angiogram, the QCA measurements were performed using the single worst-view projection at that time point. The contrast-filled non-tapered catheter tip was used for calibration. Quantitative analysis was performed on both the “in-stent” and “in-segment” area (including the stented segment, as well as both 5-mm margins proximal and distal to the stent. Restenosis morphology was adjudicated according to criteria modified from Mehran et al . Restenosis was defined as diameter stenosis ≥ 50% in the in-segment area (including stent area as well as 5 mm margins proximal and distal to the stent). At baseline angiogram of the index lesion, the stent was defined as the previously implanted SES. At follow-up angiogram of the recurrent restenotic lesion, the stent was defined as the new implanted stent in the setting of the present study (SES or PES).

The primary endpoint of this analysis was in-stent late lumen loss at follow-up angiography (defined as the difference between the minimal luminal diameter at the end of the procedure and the minimal luminal diameter at follow-up angiography). Secondary endpoints were in-segment binary angiographic restenosis (defined as diameter stenosis ≥ 50% in the in-segment area at follow-up angiography); the need for target lesion revascularization (TLR; defined as any revascularization procedure involving the target lesion due to luminal re-narrowing in the presence of symptoms or objective signs of ischemia at one year follow-up); the combined incidence of death or myocardial infarction. Additional definite stent thrombosis was also evaluated. Detailed definition of myocardial infarction has been previously described . Stent thrombosis was classified according to Academic Research Consortium criteria .

2.4

Statistical analysis

The aim of the present analysis is to compare sirolimus-eluting stents with paclitaxel-eluting stents in the pre-specified subgroups of patients with and without diabetes mellitus regarding primary and secondary endpoints of the ISAR-DESIRE 2 trial. Continuous data are presented as mean (SD) or median [25th-75th percentiles]. Categorical data are presented as counts or proportions (%). Differences between groups were checked for significance using Student’s t-test for continuous data and chi-squared test (or Fisher’s exact test where the expected cell value was < 5) for categorical variables. Survival was assessed using the methods of Kaplan-Meier. Relative risk was calculated using time-to-event analyses and compared using the log-rank test. All analyses are by intention to treat using all patients randomized in the study, regardless of the treatment actually received.

Statistical software S-PLUS, version 4.5 (S-PLUS, Insightful Corp, Seattle, WA) was used for analysis. Sample size calculation was performed using nQuery Advisor (Statistical Solutions, Cork, Ireland).

2.1

Study population and randomization

The study population and methods has been previously described . In brief, patients older than age 18 with ischemic symptoms or evidence of myocardial ischemia (inducible or spontaneous) in the presence of a restenosis ≥ 50% located in the native vessel segment treated with sirolimus-eluting stent were considered eligible. The study was conducted in accordance with the provisions of the Declaration of Helsinki and with the International Conference on Harmonization Good Clinical Practices. The trial protocol was approved by the institutional ethics committee responsible for the participating centres, Deutsches Herzzentrum and 1. Medizinische Klinik, Klinikum rechts der Isar, both in Munich, Germany.

Full details of treatment allocation, study devices and adjunctive antithrombotic therapy have been previously reported . In the ISAR-DESIRE 2 Trial patients were randomly assigned to receive either the sirolimus-eluting Cypher stent (Cordis, Miami Lakes, FL, USA) or paclitaxel-eluting Taxus stent (Boston Scientific, Natick, MA, USA). Patient allocation to each of the two treatment groups was in equal proportions. Both treatment groups were studied concurrently. Time zero was defined as the time of randomization and patients were considered enrolled in the study at this time point. The same randomly assigned stent had to be implanted in all lesions in those patients who required stenting in multiple lesions and the use of more than one stent per lesion was also allowed.

2.2

Procedures and follow-up

An oral loading dose of 600 mg clopidogrel was administered to all patients prior to the intervention, regardless of whether the patient was taking clopidogrel prior to admission. During the procedure, patients were given intravenous aspirin, heparin or bivalirudin; glycoprotein IIb/IIIa inhibitor usage was at the discretion of the operators. Procedural success was defined as residual stenosis < 30% and TIMI 3 flow achieved in the treated vessel using the assigned stent. After the intervention all patients, irrespective of treatment allocation, were prescribed 200 mg/day aspirin indefinitely, clopidogrel 150 mg for the first 3 days (or until discharge) followed by 75 mg/day for at least 6 months and other cardiac medications according to the judgment of patient’s physician (e.g. ß-blockers, ACE-inhibitors, statins etc.). After enrolment patients remained in hospital for at least 48 hours. Blood samples were drawn every 8 hours for the first 24 hours after randomization and daily afterwards for the determination of cardiac markers (CK, CK-MB, Troponin T). Daily recording of ECG was also performed until discharge. All patients were evaluated at 1 and 12 months by phone or office visit. Repeat coronary angiography was scheduled for all patients at 6–8 months.

2.3

Data management, end points, and definitions

Relevant data were collected and entered into a computer database by specialised personnel of the Clinical Data Management Centre. All events were adjudicated and classified by an event adjudication committee blinded to the treatment groups. Baseline, post procedural, and follow-up coronary angiograms were digitally recorded and assessed off-line in the quantitative angiographic (QCA) core laboratory (ISARESEARCH Center, Munich. Germany) with an automated edge-detection system (CMS version 7.1, Medis Medical Imaging Systems) by two independent experienced operators unaware of the treatment allocation. Measurements were performed on cineangiograms recorded after the intracoronary administration of nitro-glycerine. Baseline QCA measurements were performed using the single worst view projection for the index lesion; the same view projection was used for the measurements after stent implantation. In the follow-up angiogram, the QCA measurements were performed using the single worst-view projection at that time point. The contrast-filled non-tapered catheter tip was used for calibration. Quantitative analysis was performed on both the “in-stent” and “in-segment” area (including the stented segment, as well as both 5-mm margins proximal and distal to the stent. Restenosis morphology was adjudicated according to criteria modified from Mehran et al . Restenosis was defined as diameter stenosis ≥ 50% in the in-segment area (including stent area as well as 5 mm margins proximal and distal to the stent). At baseline angiogram of the index lesion, the stent was defined as the previously implanted SES. At follow-up angiogram of the recurrent restenotic lesion, the stent was defined as the new implanted stent in the setting of the present study (SES or PES).

The primary endpoint of this analysis was in-stent late lumen loss at follow-up angiography (defined as the difference between the minimal luminal diameter at the end of the procedure and the minimal luminal diameter at follow-up angiography). Secondary endpoints were in-segment binary angiographic restenosis (defined as diameter stenosis ≥ 50% in the in-segment area at follow-up angiography); the need for target lesion revascularization (TLR; defined as any revascularization procedure involving the target lesion due to luminal re-narrowing in the presence of symptoms or objective signs of ischemia at one year follow-up); the combined incidence of death or myocardial infarction. Additional definite stent thrombosis was also evaluated. Detailed definition of myocardial infarction has been previously described . Stent thrombosis was classified according to Academic Research Consortium criteria .

2.4

Statistical analysis

The aim of the present analysis is to compare sirolimus-eluting stents with paclitaxel-eluting stents in the pre-specified subgroups of patients with and without diabetes mellitus regarding primary and secondary endpoints of the ISAR-DESIRE 2 trial. Continuous data are presented as mean (SD) or median [25th-75th percentiles]. Categorical data are presented as counts or proportions (%). Differences between groups were checked for significance using Student’s t-test for continuous data and chi-squared test (or Fisher’s exact test where the expected cell value was < 5) for categorical variables. Survival was assessed using the methods of Kaplan-Meier. Relative risk was calculated using time-to-event analyses and compared using the log-rank test. All analyses are by intention to treat using all patients randomized in the study, regardless of the treatment actually received.

Statistical software S-PLUS, version 4.5 (S-PLUS, Insightful Corp, Seattle, WA) was used for analysis. Sample size calculation was performed using nQuery Advisor (Statistical Solutions, Cork, Ireland).

3.1

Patient and lesion characteristics

Of a total of 450 patients enrolled in the ISAR-DESIRE 2 trial, 162 (36.0%) had a diagnosis of diabetes. In patients with diabetes 86 patients were randomly assigned to SES versus 76 to PES. In patients without diabetes 139 were assigned to SES versus 149 to PES. Baseline characteristics of the study patients are shown in Table 1 and were well matched between the two treatment groups in both subgroups of patients with and without diabetes mellitus.

Angiographic and procedural characteristics are displayed in Table 2 and were also well matched between the two treatment groups in both subgroups of patients with and without diabetes mellitus. A total of 483 lesions were treated, 175 lesions in the diabetic cohort (95 lesions in the SES arm versus 81 lesions in the PES arm, p = 0.56) and 298 in the non-diabetic cohort (149 lesions in the SES arm versus 159 lesions in the PES arm, p = 0.56).

Table 2

Angiographic and procedural characteristics in the randomized Groups according to diabetic status.

	SES DM n = 94	PES DM n = 81	p-value	SES no DM n = 149	PES no DM n = 159	p-value
Target vessel			0.19			0.64
Left anterior descending	34 (36)	38 (47)		53 (36)	55 (35)
Left circumflex	29 (31)	16 (20)		39 (26)	49 (31)
Right coronary artery	31 (33)	27 (33)		57 (38)	55 (35)
Bifurcation	9 (10)	10 (12)	0.56	27 (18)	29 (18)	0.98
Ostial	14 (15)	7 (9)	0.20	25 (17)	43 (21)	0.30
Lesion length, (mm)	12.5 ± 6.6	13.6 ± 8.9	0.39	13.1 ± 9.1	11.9 ± 6.9	0.43
Vessel size, (mm)	2.71 ± 0.47	2.68 ± 0.44	0.86	2.82 ± 0.46	2.78 ± 0.50	0.26
Stenosis, pre (%)	64.6 ± 17.4	64.3 ± 15.9	0.71	62.6 ± 18.8	66.3 ± 16.0	0.04
MLD, pre (mm)	0.97 ± 0.5	0.96 ± 0.5	0.64	1.06 ± 0.6	0.94 ± 0.5	0.03
Balloon diameter, (mm)	3.02 ± 0.49	3.04 ± 0.43	0.74	3.1 ± 0.48	3.1 ± 0.53	0.93
Balloon pressure, max, (atm)	15.2 ± 3.2	15.3 ± 2.8	0.69	15.6 ± 3.6	15.5 ± 3.1	0.80
MLD, post, in-stent (mm)	2.48 ± 0.46	2.5 ± 0.40	0.60	2.57 ± 0.43	2.54 ± 0.46	0.50
MLD, post, in-segment (mm)	2.17 ± 0.53	2.16 ± 0.51	0.99	2.22 ± 0.54	2.18 ± 0.54	0.52
Stenosis, post, in-stent (%)	12.4 ± 6.9	10.5 ± 6.2	0.07	11.4 ± 7.6	11.8 ± 7.5	0.44
Stenosis, post, in-seg (%)	23.7 ± 11.0	23.16 ± 11.9	0.45	24.2 ± 11.6	24.5 ± 11.8	0.86
Procedural success	94(100)	81(100)	n.s.	149 (99.3)	159 (100)	0.30

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Management of distal/bifurcation left main restenosis after drug eluting stents implantation: Single center experience
2. Calcification analysis by intravascular ultrasound to define a predictor of left circumflex narrowing after cross-over stenting for unprotected left main bifurcation lesions
3. A giant right coronary artery related to a small fistula to the coronary sinus
4. Erratum to “The role of oxidized phospholipids, lipoprotein (a) and biomarkers of oxidized lipoproteins in chronically occluded coronary arteries in sudden cardiac death and following successful percutaneous revascularization. Cardiovasc Revasc Med 2012;13:11-9”

Stay updated, free articles. Join our Telegram channel

Join