Does Optical Coherence Tomography Optimize Results of Stenting? Rationale & study design of the DOCTORS study.

Nicolas Meneveau CHU Jean Minjoz, Besançon
RATIONALE

• OCT may have potential advantages as compared to angiography or IVUS for the analysis of lesion characteristics (1,2).

• OCT has emerged as the ideal imaging tool for the assessment of superficial components of coronary plaques and vascular response to PCI (3).

• OCT is used to evaluate vulnerable atherosclerotic plaques and assess immediate and long term results of stenting with a view to further optimizing outcomes (1).

1. Tearney GJ et al. JACC 2012;59:1058-72. 2. Habara M et al. Circ Cardiovasc Interv 2012;5:193-201. 3. Raber L et al. Eurointervention 2012;8:765-71.

Real clinical impact of OCT findings ? Can OCT-guided PCI improve clinical outcomes?

Angiography alone versus angiography plus optical coherence tomography to guide decision-making during percutaneous coronary intervention: the Centro per la Lotta contro l’Infarto-Optimisation of Percutaneous Coronary Intervention (CLI-OPCI) study.
Francesco Prati, MD; Luca Di Vito, MD, PhD; Giuseppe Biondi-Zoccai, MD; Michele Occhipinti, MD et 7 autres.
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The study above found that :
Patients undergoing PCI with angiographic plus OCT guidance (OCT group) compared with matched patients undergoing PCI with angiographic only guidance (Angio group).
Primary endpoint : one-year rate of cardiac death or myocardial infarction (MI).
670 patients included

CLI-OPCI Study : OCT guidance for PCI decision making;

OCT performed after optimal angiographic result

Additional balloon inflation (malapposition, underexpansion, residual thrombus) : 22.3%
Additional stenting (edge dissection, residual narrowing) : 12.4%.

Prati F et al. EuroIntervention 2012;8:823-29.

Can OCT-guided PCI improve clinical outcomes?

Angiographic + OCT guidance was associated with a significantly lower one-year risk of MACE.

RATIONALE (2)

Potential additional advantages of the use of OCT in the setting of ACS :

– visualization of features that characterize unstable lesions

– optimisation of PCI strategy of complex lesions

It remains to be investigated whether the use of additional interventions will translate into a benefit in clinical terms.

To date, no randomized study has investigated the value of OCT in optimizing the results of angioplasty, specifically in the context of NSTE-ACS.

Kume T et al. Am J Cardiol 2006;97:1713-7.

Aim of the Study

To evaluate whether OCT-guided angioplasty :

• will provide useful clinical information, beyond that obtained by angiography, that will subsequently modify physician strategy,

• will impact on the functional result of angioplasty as assessed by fractional flow reserve (FFR) measured after stent implantation on a lesion responsible for NSTE-ACS.

Study design and primary endpoint

Study design :

• randomized, prospective, multicenter, open-label clinical trial involving 9 participating centers

• registered on ClinicalTrials.gov under the identifier NCT01743274

• funded by the French government’s national hospital research program (PHRC)

Primary end point :

• Functional result of the angioplasty procedure as assessed by FFR measured at the end of the procedure (the average of 3 consecutive measures will be recorded and compared between groups).

Secondary Endpoints

Safety endpoints

• Procedural complications

• PCI-related MI (peak troponin at 24 hours postprocedure)

• Change in creatinine clearance at 24 hours vs baseline

• Duration of the procedure

• Fluoroscopy time

• Quantity of contrast medium used

Suboptimal result of angioplasty as assessed by OCT

Percentage with change in procedural strategy based on information obtained from OCT images

Quantitative OCT variables that best predict final FFR measurement MACE at 6-month clinical follow-up.

Inclusion Criteria

Pts aged 18-80 y inclusive, admitted for ACS with the following symptoms :

• Chest pain at rest lasting for at least 10 min in the previous 72 h ;

• AND at least 1 of the following 2 criteria :

– New ST-segment depression ≥1 mm or transitory ST-segment elevation (<30 min) (≥1 mm) on at least 2 contiguous leads of the EKG ; OR

– Elevation (>ULN) of cardiac enzymes (CK-MB, troponin I or T)

• AND presenting an indication for coronary angioplasty with stent implantation of the target lesion (single lesion on the culprit artery without diffuse disease on the same vessel) considered to be responsible for the ACS.

• AND written informed consent.

Hamm CW et al. Eur Heart J 2011

Exclusion Criteria

• Left main stem disease;

• In-stent restenosis;

• Presence of coronary artery bypass grafts, cardiogenic shock, or severe hemodynamic instability;

• Severely calcified or tortuous arteries;

• Persistent ST-segment elevation;

• One or more other lesions considered angiographically significant, or nonsignificant diffuse disease, located on the target vessel;

• Severe renal insufficiency (creatinine clearance ≤30 mL/min);

• Bacteremia or septicemia;

• Severe coagulation disorders;

• Pregnancy;

• Patients who refuse to sign the informed consent form.

Angioplasty Procedure

• Intracoronary bolus of 200 mg ISDN to prevent coronary spasm.

• PCI performed according to current guidelines*.

• Implantation of ≥ 1 DES or BMS

• Pts pretreated with aspirin and clopidogrel (loading dose of 600 mg) or other P2Y12 receptor inhibitor.

• The choice of anticoagulant (UFH, LMWH, bivalirudin) and option to use GP IIb/IIIa inhibitors at operator’s discretion.

• Aspirin + clopidogrel (or other P2Y12 inhibitor) maintained for 1 year after the procedure.

ESC Revascularisation guidelines. Windecker. Eur Heart J 2014

OCT image acquisition & analysis

• OCT images will be acquired using the FD-OCT C7XR system (Lightlab Imaging Incorporated, Westford, MA) and 6F guide catheter compatible Dragonfly Duo catheter (St Jude Medical).

• All OCT images will be centrally analyzed in the coordinating center by 2 independent operators blinded to the angiographic findings, procedural strategy, and final FFR value.

• OCT criteria for the definition of the end points were defined according to recent recommendations and established definitions (International Working Group for IVOCT & Expert’s OCT Review Document).

Tearney GJ et al. JACC 2012;59:1058-72. Prati F et al. Eur Heart J 2012

Definition of OCT criteria (1)

Definition of OCT criteria (2)

Stent underexpansion :

In-stent MLA < 80% of the average reference lumen area

Sample Size

• FFR value after stent implantation : 0.92 ± 0.07*

Hypothesis : the use of OCT would improve FFR by 0.03

• α risk of 5% and β risk of 10%

• 115 Pts required in each arm

• Additional 10% of pts added : pts lost to follow-up, technical failures, or images unsuitable for analysis

• 250 pts to be included in the study

DISCUSSION

FFR as a surrogate end point for clinical criteria :

– FFR has become an indispensable tool to guide
revascularization (1)

– Useful for the evaluation of the final results of PCI with stent implantation (2)

– Correlated with MACE, TLR, & death/MI at 6 months FUP3

– Applicable in the setting of NSTE-ACS (2,3,4)

Lesion severity before angioplasty will not be evaluated using FFR in order not to influence physician strategy (potential bias precluding identification of the contribution of OCT to the change in procedural strategy)

1. De Bruyne. NEJM 2012;367:991.
2. Fearon WF. Circulation 2001;104:1917
3. Pijls NH et al. Circulation 2002;105:2950
4. Layland. Eur Heart J. 2015;36:100

STUDY LIMITATIONS

• Foremost limitation : open-label design

– Protocol designed to guide physician strategy based on objective criteria recommended in consensus documents

• Cannot exclude that any additional interventions may be detrimental to final procedure outcome :

– Increased use of stents : greater troponin release ?

– Greater volume of contrast medium : deterioration of renal function ?

• Not primarily designed to address the impact of OCT on clinical outcomes or to identify prognostic impact of each OCT finding

CONCLUSION

• RCT assessing the impact of OCT on procedural or cardiovascular outcomes have never been performed.

• DOCTORS study : randomized, prospective, multicenter, open- label clinical trial

• To evaluate whether OCT guidance during angioplasty with stent implantation will provide useful information beyond that obtained by angiography alone and whether this information will impact on the functional results of angioplasty as assessed by FFR measurement in NSTE-ACS pts.

FURTHER READING
Does optical coherence tomography optimize results of stenting? Rationale and study design.
Nicolas Meneveau, MD, PhD, Fiona Ecarnot, MSc,Geraud Souteyrand, MD, Pascal Motreff, MD, PhD, Christophe Caussin, MD, et 5 autres
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