Journal club drug eluting balloon for cad

Journal club

08-02-2017

CLINICAL SCENARIO

• A 60 years old female diabetic with past history of AWMI, post P+S to LAD with XIENCE V 3.0X 22 mm , 4 years back, comes with AOE-111

• CART- type 2 ISR (diffuse) with maximum 95% stenosis.

• Angioplasty done – residual 20%• What to do after this?

Questions?

• POBA Sufficient• BMS• DES

– SAME DRUG– SPLIT DRUG

DES or SOMETHING ELSEDrug-coated balloon catheters are the most advanced proven alternative to DES for local intravascular drug therapy and already approved for use in ISR

Problems with DES• 75-85% Of stented vessel wall area is not covered

by the stent struts, - low tissue levels of antiproliferative agent in these areas.

• Low drug concentrations require much longer exposure times to achieve sufficient results.

• Polymers help in this- but increase inflammation- late ISR and stent thrombosis

• Delayed re-endothelialization of stented segment (by drug effect that limits ISR)- risk of ST increases – require long term DAPT.

Problems with DES cont.- why ISR important despite low prevalence rates

• Risk of ISR is very less with DES as compared to BMS, but risk increases in complex lesions esp bifurcations, small vessel (<2.5 mm) , long segment disease, diabetes and saphenous venous grafts.

• Around 18% in these circumstances• Important because >50% ISR present with ACS• Those with ISR have a poorer long term

prognosis

DRUG ELUTING BALLOON

APPROACH TO THE USE OF DEB

DES DEB/DCB

SLOW RELEASE IMMEDIATE RELEASE

PERSISTENT DRUG EXPOSURE SHORT LASTING EXPOSURE

100-200 ug DOSE 300-600 ug DOSE

POLYMER + NO POLYMER

STENT MANDATORY/ METALLIC BODY WILL PERSIST

ABSENT/ NO RESIDULA METAL BEHIND

INFLAMMATORY RESPONSE TO METAL BODY NOT SEEN

VASOMOTOR TONE LOST PRESERVED

LONG TERM DAPT MANDATORY NOT MANDATORY – 1-3 MONTHS USUALLY

LIMITED EFFICACY/UTILITY IN (ALTHOUGH STILL 1ST CHOICE)DiabetesCKDLong segmentSmall diameter vessels(<2.5 mm)Saphenous venous graftsBifurcation lesions

THEORETICALLY BENEFICIAL IN SUCH SETTINGS

APPROVED ONLY FOR ISR TREATMENT SO FAR

That’s how the story of DEB began

POSSIBLE BENEFITS

• BLEEDING EVENTS/ HIGH BLEEDING RISK• SURGERY PLANNED IN NEAR FUTURE• NEED FOR ORAL ANTICOAGULATION/TRIPPLE

THERAPY– ATRIAL FIBRILLATION– MECHANICAL PROSTHETIC HEART VALVES– LV THROMBUS

• NO RISK OF STENT THROMBOSIS IN DENOVO LESIONS

2014 ESC/EACTS Guidelines on myocardial revascularization

Problems with these meta-analysis:1. Limited RCTs comparing DEB with new

generation DES2. Studies mainly included those studies which

compared safety and efficacy of DEB to first generation DES

3. No use of bioresorbable polymer coated stents4. High Risk lesions and complex cases like diabetes

, bifurcation lesions , long segment disease , small vessels , CKD were excluded

5. Angiographic follow up Vs Clinical MACE

Kaplan-Meier curves are shown for overall major adverse cardiac events (MACE) (A), target lesion revascularization (TLR) in the overall cohort (B), TLR in focal ISR group (C), and TLR in the nonfocal ISR group (D...

.

Hiroyoshi Kawamoto, Neil Ruparelia, Azeem Latib, etal .Drug-Coated Balloons Versus Second-Generation Drug-Eluting Stents for the Management of Recurrent Multimetal-Layered In-Stent Restenosis. JACC: Cardiovascular Interventions, Volume 8, Issue 12, 2015, 1586–1594

AIM/OBJECTIVE

• To sought and evaluate the safety and efficacy of DEB and newer generation DES as treatment options

• for ISR from BMS or DES • from an unrestricted, real world population of

dedicated large scale Korean multicenter ISR registries.

INTERVENTIONAL PROCEDURES AND MEDICATIONS

• Coronary interventions were performed according to current standard techniques.

• DEB angioplasty for ISR was performed using a commercialized paclitaxel-eluting balloon that was coated with 3 μg of paclitaxel per square millimeter (SeQuent® Please, B. Braun, Melsungen, Germany).

• The DEB was carefully prepared and delivered rapidly to the site of the lesion within 1 min.

• The DEB inflation time was uniformly at least 60 s, in line with current guidelines, although total inflation time and pressure were decided by the operator in response to the patient's tolerability and reaction of treated lesions.

• DEB angioplasty was considered successful if the final residual stenosis was <30% with Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow.

• Unless there was an undisputed reason for discontinuing dual antiplatelet therapy, all patients treated with DEB or DES were advised to take aspirin (at least 100 mg/day) indefinitely and clopidogrel (75mg/day) for at least 6 months after the index procedure.

FOLLOW UP

• After the index procedure, clinical follow-ups were performed at 1, 3, 6 or 9, and 13 months.

• Angiographic follow-up was optional at the 6- or 9-month visit after the index procedure, but it was not mandated in all the included registries.

• The clinical events that occurred within 1-year follow-up were analyzed, and the median follow-up duration was 372.0 days.

PRIMARY OUTCOME

• The primary outcome was • Target lesion failure (TLF),

– A composite of cardiac death, target-lesion related myocardial infarction (any MI not clearly attributed to a non-target vessel), or a clinically indicated target lesion revascularization (TLR).

SECONDARY OUTCOME

• The key secondary outcome, the patient oriented composite outcome (POCO), – included all-cause mortality, any MI (including

non-target vessel territory), and any revascularization.

• Other secondary outcomes included individual components of TLF and POCO, stent thrombosis and CVA.

Inverse probabilit yweighted comparison of clinical outcomes.

Comparison of cumulative incidences of TLF by exploratory subgroups. Although most of the subgroups showed similar results, significant interaction was observed between the subgroup of BMS and DES-ISR.

LIMITATIONS

• NOT A RCT- comparison bias• ONLY 1 YEAR FOLLOW UP- LATE CATCH UP

POSSIBLE• NO ANGIO CORRELATION ESPECIALLY THE

EXTENT OF ISR• ONLY 1 TYPE OF DEB USED

TAKE HOME MESSAGES

• This study demonstrated the real world scenario of using a DEB

• This study demonstrated that clinical efficacy(REPEAT REVASC) for treatment of ISR was better with contemporary DES than DEB, while clinical safety(MI, CARDIAC DEATH,ST) was not different between DES and DEB in a real world population with BMS or DES-ISR.

• DES will remain the first choice for ISR except in certain conditions like : patient planned for early surgery , require tripple OAC , high bleeding risk with DAPT

THANKS!

2 DIFFERENT CAUSES OF RE-STENOSIS

GERMAN CONSENSUS GROUP RECOMMENDATIONS

DCB they have been proven to be very effective in

patients with both BMS-ISR and DES-ISR

The RIBS V (Restenosis Intra-stent: Drug-eluting Balloon vs. Everolimus-eluting Stent) trial reported the first data from a

randomized comparison of DCB with second-generation everolimus-DES in 189 patients with BMS-ISR.

In this study, the minimal lumen diameter at follow-up was better after everolimus-DES (2.01 mm vs. 2.36 mm; p < 0.001), although binary restenosis

(4.7% vs. 9.5%; p <0.22) and clinical events at 1 year were low and similar in both groups.

the RIBS V Clinical Trial. J Am Coll Cardiol 2014;63:1378–86.

The study suggested that second-generation DES exhibit some evidence of superiority in terms of angiographic endpoints but

without a clear signal of clinical benefit.

Therefore, additional studies with a larger number of patients and a longer follow-up are required to address this important

question.

The value of DCB in patients with DES-ISR has also been well tested

Recently, the larger ISAR-DESIRE 3 (Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis)

multicenter randomized trial investigated the efficacy of DCB versus paclitaxel-DES versus conventional BA in patients with

limus DES-ISR.

This study demonstrated that DCB were noninferior to paclitaxel- DES and that both DCB and paclitaxel-DES were superior to BA

alone

Lancet 2013;381:461–7.

PEPCAD- DES

It was suggested that by obviating the need of an additional stent layer, DCB might emerge as the treatment strategy of choice for patients with

DES-ISR.

In summary, data from the available randomized clinical trials suggest that DCB are superior to BA and similar to first-

generation DES in patients with BMS-ISR or DES-ISR

Although largely speculative, currently DCB may be preferred over DES in patients with ISR and multiple metal layers, in those

with large side branches, and in those at high bleeding risk undergoing prolonged dual antiplatelet therapy.

Alternatively, DES may be preferred over DCB in patients with stent fracture or restenosis extending outside the stent edge and also in patients with suboptimal results after lesion predilation.

COMPARISON OF RESTENOSIS IN DES VS BMS