Download - INCIDENCE AND OUTCOME OF CORONARY DISSECTIONS LEFT UNTREATED AFTER DRUG-ELUTING STENT IMPLANTATION RECIPE (Real-world Eluting-stent Comparative Italian.

INCIDENCE AND OUTCOME OF INCIDENCE AND OUTCOME OF

CORONARYCORONARY

DISSECTIONS LEFT UNTREATED DISSECTIONS LEFT UNTREATED

AFTER AFTER

DRUG-ELUTING STENT IMPLANTATIONDRUG-ELUTING STENT IMPLANTATION

RECIPERECIPE ((RReal-world eal-world EEluting-stent luting-stent CComparative omparative IItalian retrostalian retrosPPective ective EEvaluation)valuation)

Giuseppe Biondi-Zoccai, MDGiuseppe Biondi-Zoccai, MDSan Raffaele HospitalSan Raffaele Hospital

EMO Centro Cuore Columbus EMO Centro Cuore Columbus

Milan, Italy Milan, Italy

on behalf of the RECIPE Investigatorson behalf of the RECIPE Investigators

European Society of Cardiology 2005European Society of Cardiology 2005 Congress, Stockholm, 3-7 September Congress, Stockholm, 3-7 September

ESC 05 – StockholmRECIPE

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Funding and conflict Funding and conflict

of interest disclosureof interest disclosure

• Supported by Cordis ItalySupported by Cordis Italy

• No other funding or conflict of interest to No other funding or conflict of interest to declaredeclare


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BackgroundBackground• There is large evidence on the detrimental There is large evidence on the detrimental

prognostic role of final dissections left untreated prognostic role of final dissections left untreated after PTCA, in both the balloon-only and bare-after PTCA, in both the balloon-only and bare-metal stent (BMS) erametal stent (BMS) era1-21-2

• While the impact of flow-limiting dissections is While the impact of flow-limiting dissections is obviously ominous,obviously ominous,33 the adverse role of minor the adverse role of minor and non-obstructive dissections has nonetheless and non-obstructive dissections has nonetheless been questionedbeen questioned44

• Drug-eluting stents (DES) are being increasingly Drug-eluting stents (DES) are being increasingly used, even if concerns of thrombogenicity have used, even if concerns of thrombogenicity have been raisedbeen raised55

• Yet, no data are available on the occurrence and Yet, no data are available on the occurrence and impact of dissections in DES-treated lesionsimpact of dissections in DES-treated lesions

1 - Holmes JACC 1988 2 - Sharma Am Heart J 19933 - Rogers J Invas Cardiol 2004 4 - Cappelletti JACC 1999

5 - McFadden Lancet 2004


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ObjectivesObjectives

• Assess the incidence, predictors and Assess the incidence, predictors and outcomes of coronary dissections left outcomes of coronary dissections left untreated after DES implantationuntreated after DES implantation

– Distinguishing dissection according to established Distinguishing dissection according to established morphologic criteriamorphologic criteria

– Appraising the rate of early (in-hospital and 1-month) Appraising the rate of early (in-hospital and 1-month) and mid-term (6-month) clinical eventsand mid-term (6-month) clinical events

– Assessing angiographic outcomes by means of off-Assessing angiographic outcomes by means of off-line quantitative coronary angiography (QCA) for line quantitative coronary angiography (QCA) for patients undergoing clinically-driven angiographic patients undergoing clinically-driven angiographic follow-upfollow-up


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MethodsMethods• Retrospective designRetrospective design

• Multicenter enrolment from 2002 to 2004Multicenter enrolment from 2002 to 2004

• Inclusion of all patients undergoing sirolimus- or Inclusion of all patients undergoing sirolimus- or paclitaxel-eluting stent implantation (respectively paclitaxel-eluting stent implantation (respectively SES [Cypher] and PES [Taxus]), without any SES [Cypher] and PES [Taxus]), without any exclusionexclusion

• Implantation of DES at operator’s discretion, with Implantation of DES at operator’s discretion, with the notable exception of patients the notable exception of patients >>75 years with 75 years with acute myocardial infarction (all treated with BMS)acute myocardial infarction (all treated with BMS)

• Independent clinical-event-committees for outcome Independent clinical-event-committees for outcome adjudicationadjudication

• Off-line qualitative and quantitative angiographyOff-line qualitative and quantitative angiography


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• Standard practice for stent implantation with direct Standard practice for stent implantation with direct stenting, kissing balloon dilation, DCA, RTB, CBA, and stenting, kissing balloon dilation, DCA, RTB, CBA, and glycoprotein IIb/IIIa inhibitors at operator’s discretionglycoprotein IIb/IIIa inhibitors at operator’s discretion

• Aspirin + thienopyridines for Aspirin + thienopyridines for >>6 months6 months

• Clinical follow-up at discharge, 1, and 6 monthsClinical follow-up at discharge, 1, and 6 months

• Clinically-driven angiographic follow-upClinically-driven angiographic follow-up

• Coronary dissections adjudicated off-line by angiographers Coronary dissections adjudicated off-line by angiographers unaware of baseline or procedural characteristics, and unaware of baseline or procedural characteristics, and distinguished as:distinguished as:– 1) final vs non-final,1) final vs non-final,

– 2) proximal vs distal vs on side branch2) proximal vs distal vs on side branch

– 3) according to the NHLBI classification3) according to the NHLBI classification

MethodsMethods


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• (A) minor radiolucent areas within the coronary lumen during (A) minor radiolucent areas within the coronary lumen during contrast injection with little or no persistence of contrast after the contrast injection with little or no persistence of contrast after the dye has cleared, dye has cleared,

• (B) parallel tracts or a double lumen separated by a radiolucent area (B) parallel tracts or a double lumen separated by a radiolucent area during contrast injection, with minimal or no persistence after dye during contrast injection, with minimal or no persistence after dye clearance, clearance,

• (C) contrast outside the coronary lumen with persistence of contrast (C) contrast outside the coronary lumen with persistence of contrast after dye has cleared from the lumen, after dye has cleared from the lumen,

• (D) spiral luminal filling defects, (D) spiral luminal filling defects,

• (E) appear as new, persistent filling defects within the coronary (E) appear as new, persistent filling defects within the coronary lumen,lumen,

• (F) dissections leading to total occlusion of the coronary lumen (F) dissections leading to total occlusion of the coronary lumen without distal antegrade flow without distal antegrade flow

National Heart Lung and Blood Institute (NHLBI) National Heart Lung and Blood Institute (NHLBI) classification of coronary dissectionsclassification of coronary dissections11

1 - Holmes et al JACC 1988


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• Primary end-point: 1-month hierarchical rate of major Primary end-point: 1-month hierarchical rate of major

adverse cardiovascular events (MACE, ie the composite adverse cardiovascular events (MACE, ie the composite

of death, AMI or target vessel revascularization [TVR]of death, AMI or target vessel revascularization [TVR]

• Secondary end-points: individual rates of 1-month Secondary end-points: individual rates of 1-month

adverse events, as well as the hierarchical rate of adverse events, as well as the hierarchical rate of

MACE and of its individual components at 6 monthsMACE and of its individual components at 6 months

• In addition, angiographic adjudication of stent In addition, angiographic adjudication of stent

thrombosis (ST), distinguished as intraprocedural thrombosis (ST), distinguished as intraprocedural

(occurring before leaving the cath lab), subacute ((occurring before leaving the cath lab), subacute (<<30 30

days but after leaving the cath lab), or late (>30 days)days but after leaving the cath lab), or late (>30 days)

End-pointsEnd-points


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Comparisons of interestComparisons of interest

• Patients with final dissectionsPatients with final dissections

versusversus

Patients without final dissectionsPatients without final dissections

• Lesions with final dissectionsLesions with final dissections

versusversus

Lesions without final dissectionsLesions without final dissections


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Continuous variables presented as mean±SD, categorical Continuous variables presented as mean±SD, categorical variables as n/N (%), odds ratios (OR) and pertinent 95% CIvariables as n/N (%), odds ratios (OR) and pertinent 95% CI

Student t, Mann-Whitney U, chi-square and Fisher exact tests Student t, Mann-Whitney U, chi-square and Fisher exact tests when appropriatewhen appropriate

Exploratory multivariable logistic regression analysis by means Exploratory multivariable logistic regression analysis by means of a backward stepwise algorithm to select independent of a backward stepwise algorithm to select independent predictors of dissections and to test the adjusted prognostic predictors of dissections and to test the adjusted prognostic role of dissections for 1-month MACE (including direct stenting, role of dissections for 1-month MACE (including direct stenting, final maximum device length, ACC/AHA lesion type, chronic final maximum device length, ACC/AHA lesion type, chronic total occlusion, calcific lesion, intra-procedural dissection, total occlusion, calcific lesion, intra-procedural dissection, bifurcation with balloon-only dilation of the side branch, use of bifurcation with balloon-only dilation of the side branch, use of glycoprotein IIb/IIIa inhibitors, and vessel site) glycoprotein IIb/IIIa inhibitors, and vessel site)

Internal validation of predictors generated by multivariable Internal validation of predictors generated by multivariable logistic regression analsys was performed by means of logistic regression analsys was performed by means of bootstrapbootstrap

Statistical analysisStatistical analysis


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2418 patients4707 lesions

4630 lesions

2351 patients

NO DISSECTIONS

DISSECTIONS

77 lesions

67 patients


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77 lesions

67 patients

•Location: proximal to the DES in 24 (32%) and distal in 47 (61%)

•NHLBI classification: A in 23 (30%), B in 32 (42%), C in 11 (14%), D in 5 (7%), E in 1 (1%), and F in 5 (7%)

•Reason for leaving dissection untreated: 1) limited dye staining in the target lesion with normal distal flow (42 [55%[), 2) side branch dissection after balloon-only angioplasty to optimize bifurcation treatment with provisional T-stenting technique (6 [8%]), and 3) undeliverability of further stents for distal location or major vessel tortuosity (29 [38%])


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Age (years)Male (n,%)LVEF (%)DM (n,%)Hypertension (n,%)Hypercholesterolemia (n,%)Current smokers (n,%)Stable angina (n,%)History of MI (n,%)Prior PCI (n,%)Prior CABG (n,%)Multivessel disease (n,%)Target vessel (n,%) LAD LCX RCAGlycoprotein IIb/IIIa inhibitors (n,%) elective bail-outASA+TNP at discharge (n,%)

62±111949 (83%)

52±10647 (28%)

1470 (63%)1421 (60%)469 (20%)852 (36%)

1023 (44%)506 (22%)400 (17%) 1702 (72%)

1162 (49%)489 (21%)462 (20%)570 (24%)543 (23%)27 (1%)

2341 (99%)

Final dissectionN=67

62±1061 (91%)50±12

17 (25%) 42 (63%)41 (61%)11 (16%)26 (39%)32 (48%)11 (16%)7 (10%)

48 (72%)

47 (70%) 9 (13%) 10 (15%)26 (39%)17 (25%)9 (13%)

66 (99%)

P

0.810.0790.170.410.980.900.480.670.490.320.160.89

0.011

0.0070.6630.0010.27

No final dissectionN=2351


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In-stent restenosis (n,%)CTO (n,%)Calcification (n,%)Thrombus (n,%)Bifurcation (n,%)ACC/AHA type B2-C (n,%)Maximum dilation pressure (ATM)Maximum balloon diameter (mm)Maximum balloon length (mm)Directional atherectomy (n,%)Cutting balloon (n,%)Direct stenting (n, %)Post-dilation (n, %)Sirolimus-eluting stent (n,%)Paclitaxel-eluting stent (n,%)Side branch lesion with balloon- only dilation (n,%)IVUS (n,%)Dissection before stenting (n,%)Final TIMI flow <3 (n,%)

451 (10%)242 (5%)

632 (14%)303 (7%)

1074 (23%)1309 (28%)15.0±3.4

2.94±0.4123.6±10.0

50 (1%)25 (1%)

700 (15%)792 (17%)

2368 (51%)2063 (45%)

199 (4%)427 (9%)97 (2%)65 (1%)

Final dissectionN=77

9 (12%)11 (14%)20 (30%)6 (8%)

19 (25%)34 (44%)14.5±3.1

2.86±0.4128.6±13.7

01 (1%)4 (5%)

9 (12%)42 (55%)29 (38%)

6 (8%)7 (9%)

50 (65%)16 (21%)

P

0.570.0010.0020.660.76

0.0020.250.09

0.0011.00.35

0.0150.210.710.15

0.0190.97

0.0010.001



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Baseline (N=4627) RVD (mm) MLD (mm) Lesion length (mm) Diameter stenosis (%)Post-procedural (N=4513) RVD (mm) MLD (mm) Diameter stenosis (%)Follow-up (N=1881) RVD (mm) MLD (mm) Lesion length (mm) Diameter stenosis (%) Late loss (mm) Binary restenosis (n,%) Healed [improved diss.] (n,%)

2.69±0.550.87±0.5016.1±11.1

71±17

3.03±0.522.71±0.52

11±8

2.80±0.591.81±0.77

9.2±7.4 27±26

0.43±1.03 177 (19%)

-

2.60±0.540.61±0.5319.0±14.4

79±17

2.94±0.462.59±0.46

13±10

3.02±0.432.01±1.18

9.6±9.7 34±36

0.53±1.077 (22%)

24 (63%) [7 (18%)]

0.230.0010.0410.001

0.260.080.19

0.530.260.830.310.730.72

Final dissectionN=77 P



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11,9

3

6

3

0,6

5,2

0,6

4,4

0,1 0,6

0

3

6

9

12

15

MACE Death MI CABG TVR

Inci

denc

e %

In-hospital follow-up

Dissections (N=67) No dissections (N=2351)

P=0.017

P=0.002


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13,4

3

6

34,5

6

1,1

4,6

0,10,9

0

4

8

12

16

20


Inci

denc

e %

One-month follow-up (N=2386 - 99% of eligible patients)


P=0.013

P=0.004

P=0.029


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18,5

6,2

9

3

6,2

11,2

2

4,9

0,5

5,5

0

5

10

15

20

25


Inci

denc

e %

Six-month follow-up (N=2342 - 97% of eligible patients)


P=0.043


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3,1 3

0

6,3

0,3 0,6 0,3

1,3

0

2

4

6

8

10

Acute <30 d >30 d Total

Inci

denc

e %

Stent thrombosis (N=2342 - 97% of eligible patients)


P=0.030

P=0.011


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Exploratory multivariable analysisExploratory multivariable analysis• Multivariable analysis identified the presence of calcification Multivariable analysis identified the presence of calcification

(OR=1.93, CI=1.06-3.5, p=0.032) and maximum balloon (OR=1.93, CI=1.06-3.5, p=0.032) and maximum balloon length (OR=1.03, CI=1.01-1.05, p<0.001), as independent length (OR=1.03, CI=1.01-1.05, p<0.001), as independent predictors of the occurrence of final dissectionspredictors of the occurrence of final dissections

• Multivariate logistic regression (including vessel, technique, Multivariate logistic regression (including vessel, technique, maximum balloon length, occurrence of dissection before maximum balloon length, occurrence of dissection before stenting, ACC/AHA lesion type, Gp IIb/IIIa inhibitors, and stenting, ACC/AHA lesion type, Gp IIb/IIIa inhibitors, and whether the lesion was calcific or a CTO) showed that the whether the lesion was calcific or a CTO) showed that the presence of a residual dissection remained an independent presence of a residual dissection remained an independent predictor of 1-month MACE (OR=2.9, CI=1.36-6.1, p=0.005)predictor of 1-month MACE (OR=2.9, CI=1.36-6.1, p=0.005)

• Boostrap confirmed the predictive role of final dissections Boostrap confirmed the predictive role of final dissections (OR=2.9, 95% bias-corrected CI=1.09-5.6)(OR=2.9, 95% bias-corrected CI=1.09-5.6)

• Both logistic regression models appeared in adequate fit Both logistic regression models appeared in adequate fit with the data (Hosmer-Lemeshow p>0.05) with the data (Hosmer-Lemeshow p>0.05)


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Additional analysesAdditional analyses• No significant difference was found when No significant difference was found when

comparing the prognostic role of proximal comparing the prognostic role of proximal vs distal dissections vs distal dissections

• No significant difference was found when No significant difference was found when comparing the prognostic role of dissections comparing the prognostic role of dissections according to the specific procedural reason for according to the specific procedural reason for leaving it untreatedleaving it untreated

• On the other hand, even non-obstructive On the other hand, even non-obstructive dissections with TIMI 3 flow conferred a dissections with TIMI 3 flow conferred a significantly worse 1-month prognosissignificantly worse 1-month prognosis (p=0.043) (p=0.043)

HOWEVER ALL OF THESE SUB-ANALYSES ARE HOWEVER ALL OF THESE SUB-ANALYSES ARE LIMITED BY THE RISK OF ALPHA/BETA ERRORSLIMITED BY THE RISK OF ALPHA/BETA ERRORS


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ConclusionsConclusions


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ConclusionsConclusions• Dissections left untreated after DES implantation Dissections left untreated after DES implantation

may have a major adverse impact at both early may have a major adverse impact at both early and mid-term follow-upand mid-term follow-up

• More and more complex lesions, with their More and more complex lesions, with their inherent risk of thrombosis, are being treated with inherent risk of thrombosis, are being treated with DES, and yet angiography is largely unable at DES, and yet angiography is largely unable at evaluating if a residual dissection is benign or notevaluating if a residual dissection is benign or not

• Thus, while waiting for further studies, these Thus, while waiting for further studies, these findings prompt us to pursue a strategy of findings prompt us to pursue a strategy of managing residual dissections in DES-treated managing residual dissections in DES-treated lesions by completely covering intimal flaps with lesions by completely covering intimal flaps with additional stentsadditional stents


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