Radiation for restenosis:the dark side of arteries

Robert S Schwartz MDProfessor of MedicineMayo ClinicRochester, MN

Stimulation of neointima within an irradiated artery

Figure 1

Minimal neointimal neoplasia post stent placement

Figure 2

External beam radiation

• major US center• 11 patient pilot study• 8 Gy external beam radiation• 11/11 restenosis

the restenosis rate was 100%

Radiation injury to blood vessels

• capillary injury is greatest• obliteration of capillaries

one mechanism of anti-tumor action• thrombosis, rupture, fibrosis• occasionally lymphocytic vasculitis• venous lesions are uncommon

Induction of neointima post external beam radiation

Figure 3

Venezuelan study

the late loss is too high

Figure 4: late loss (millimeters)

0.44 0.400.33 0.32 0.28 0.27 0.26 0.25

Condado LRT MARCATOR BENESTENT HELVETICA CARPORT MERCATOR PARK

Condado J, Circulation 1997;96:727

3 questions on radiation

• Q: Is arterial radiation feasible?A: “Yes”

• Q: Is it safe?A: “We doubt it”

• Q: Is it efficacious?A:”We don’t think so”

Serruys et al, Circulation 1997;96:709-712

Neointimal hyperplasia at former sites of radiation

Figure 5

PREVENT trial

Figure 6Restenosis in the treated segment

Raizner et al, PREVENT trial 1998

9.1%

22.2%

0.0%

25.0%

P 32 Control

PREVENT trial

Figure 7Restenosis in the adjacent segment

Raizner et al, PREVENT trial 1998

22.7%

11.1%

0.0%

25.0%

P 32 Control

PREVENT trial

Figure 8Restenosis in the treated and adjacent segments

Raizner et al, PREVENT trial 1998

22.7% 22.2%

0.0%

25.0%

P 32 Control

BERT trial

• restenosis rate of 17%• 6 patients with an “edge problem”

• overall restenosis rate of 25%

Beta emitting stents and restenosis

Figure 9Restenosis in the treated and adjacent segments

56.0%(10/18)

39.0%(11/28)

45.0%(5/11)

50.0%(1/2)

0.75-3 uCi 3-6 uCi 6-12 uCi 12-20 uCi

Cellular neointimal hyperplasia of in-stent restenosis

Figure 10

Neointimal hyperplasia at former sites of radiation

Figure 11

• European registry, 150 patients• PTCA up to 2 vessels• Beta-Cath system, 90-Sr/Y• 12,14,16 Gy to 2 mm from source• target vessel restenosis 30%• late loss index 13%

Serruys, 1999

The BRIE trial

Human coronary artery thrombus in situ

Figure 12

Multi-layered thrombus in a pig coronary artery

Figure 13

Old thrombus

New thrombus

Absence of neointima

Intracoronary beta radiation

Figure 14Effects of intracoronary beta-radiation after 6 months in stented vessels

2.843.16

0

1

2

3

4

control treated

Neoin

tim

al

are

a (

mm

2)

P=NS

Figure 15Angiographic restenosis rate

54%

17%

control radiated

SCRIPPS trial

Figure 16The SCRIPPS radiated group, a long term analysis

0

1

2

3

post 6 months 3 years

Min

imu

m l

um

inal

dia

mete

r (m

m)

ControlRadiated

SCRIPPS trial

P=NS

Figure 17GAMMA-I 6 month follow-up

0

1

2

3

before pre post f/u

Min

imu

m l

um

inal

dia

mete

r (m

m)

ControlRadiated

GAMMA-I in-stent measures

EVG Actin

Heat injury

Figure 18