Drug-Coated Balloons for Small Coronary Artery Disease ... · BASKET-SMALL 2 Raban V. Jeger,Ahmed...
Transcript of Drug-Coated Balloons for Small Coronary Artery Disease ... · BASKET-SMALL 2 Raban V. Jeger,Ahmed...
Drug-Coated Balloons for
Small Coronary Artery Disease:
BASKET-SMALL 2Raban V. Jeger, Ahmed Farah, Marc-Alexander Ohlow, Norman Mangner, Sven Möbius-Winkler, Gregor Leibundgut, Daniel Weilenmann, Jochen Wöhrle, Stefan Richter, Matthias Schreiber, Felix Mahfoud, Axel Linke, Frank-Peter Stephan, Christian Mueller, Peter Rickenbacher, Michael Coslovsky, Nicole Gilgen, Stefan Osswald, Christoph Kaiser, and Bruno Scheller, for the BASKET-SMALL 2 Investigators
BASKET-SMALL 2
Funding
• Swiss National Science Foundation
• Basel Cardiovascular Research Foundation
• B. Braun Medical AG, Switzerland
No influence of the funding sources on design, conduct, or analysis of the trial
BASKET-SMALL 2
Background: Coronary Angioplasty
Meier B, N Engl J Med 2001;344:144-5
1977 2000
Acute Vessel Closure
(Elastic Recoil, Flow-limiting Dissections)
No Dual Antiplatelet Therapy
Stents to Prevent Acute Vessel Closure
BASKET-SMALL 2
Background: Drug-Coated Balloons
Byrne RA et al, Nat Rev Cardiol 2014;11:13-23
Highly
Lipophilic
Drug &
Coating
Matrix
Fast and
Homogenous
Drug Delivery
into the
Vessel Wall
BASKET-SMALL 2
Rationale
• 2nd-generation drug-eluting stents (DES) are the preferred treatment for de-novo
coronary lesions
• Efficacy of DES is limited in small vessels due to high rates of instent-restenosis
• Drug-coated balloons (DCB) are an established treatment strategy for in-stent
restenoses of bare metal stents and DES
• The efficacy and safety of DCB in de-novo stenoses is unknown
BASKET-SMALL 2
Design
• Multicenter, randomized controlled non-inferiority trial (14 centers in Germany,
Switzerland, and Austria)
• Patients undergoing PCI in native coronary arteries <3 mm
• Initial comparison Sequent Please® DCB (B.Braun Melsungen) vs. Taxus Element® DES
(Boston Scientific), then changed to Xience® DES (Abbott Vascular) after appr. 25% of
patients
• Primary endpoint: Non-inferiority for major adverse cardiac events (MACE; cardiac
death, non-fatal myocardial infarction, and target vessel revascularization) @ 12 months
• Expected MACE rates of 7% for DCB and 10% for DES with non-inferiority margin <4%
(upper limit of the two-sided 95% confidence interval of the absolute risk difference)
• Sample size calculation (based on Xience®): 758 patients
BASKET-SMALL 2
Clinical Baseline Characteristics
DCB (n=382) DES (n=376)Age (mean, SD) 67.2 (10.3) 68.4 (10.3)Sex Male (%) 295 (77.2) 262 (69.7)Current/former smoker (%) 226 (60.4) 195 (53.1)Hypercholesterolemia (%) 262 (68.8) 259 (70.0)Arterial hypertension (%) 324 (84.8) 332 (88.8)Family history of CAD (%) 150 (42.6) 128 (38.0)Diabetes mellitus (%) 122 (32.0) 130 (34.9)Previous MI (%) 160 (41.9) 133 (35.4)Cerebrovascular insult (%) 29 (7.6) 37 (9.8)PAOD (%) 27 (7.1) 26 (6.9)COPD (%) 28 (7.3) 36 (9.6)Renal failure (%) 54 (14.1) 59 (15.7)
p=0.0232
BASKET-SMALL 2
Angiographic Baseline Characteristics
DCB (n=382) DES (n=376)
Target vessel
Left anterior descending artery (%) 128 (33.5) 116 (30.9)
Left circumflex artery (%) 179 (46.9) 183 (48.7)
Right coronary artery (%) 75 (19.6) 77 (20.5)
Bifurcation lesion (%) 22 (5.8) 29 (8.0)
Procedural success (%, mean, SD) 96 (19) 98 (13)
Number of DCB or DES (mean, SD) 1.68 (0.82) 1.26 (0.55)
Length of DCB or DES (mm; mean, SD) 23.93 (11.74) 23.18 (12.85)
Effective size of DCB or DES (mm; mean, SD) 2.75 (2.14) 2.57 (0.25)
Inflation pressure (atm; mean, SD) 11.06 (3.54) 13.58 (3.90)
Duration of inflation (sec; mean, SD) 48.45 (28.24) 23.36 (18.92)
BASKET-SMALL 2
Primary Endpoint (Non-Inferiority)
Set
PPS
FAS
Level
DES
DCB
DES
DCB
Events
27 / 359 (7.52%)
28 / 370 (7.57%)
28 / 376 (7.45%)
28 / 382 (7.33%)
Difference
0.0005
−0.0012
CI
[−0.038, 0.039]
[−0.040, 0.037]
p
0.0217
0.0152
−0.06 −0.04 −0.02 0 0.02 0.04 0.06DCB (%) − DES (%)Favors DCB Favors DES
PPS, per protocol set; FAS, full analysis set.
BASKET-SMALL 2
MACE (12 Months)
+++++ + + + + ++++++ + ++++++++++++++++++++++++++++++++++++++
++ + ++ ++++++ + +
++ +++++++++++++++++++++++++++++++++
0.00
0.05
0.10
0.15
0.20
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Cum
ulat
ive
MA
CE
eve
nt r
ate +
+DES
DCB
MACE
376 366 360 355 355 350 346 337 333 332 331 317 284382 376 373 371 368 367 362 351 347 346 343 326 295DCB
DES
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Number at risk
HR 0.97, 95% CI 0.58 to 1.64; p=0.9180
BASKET-SMALL 2
Single Components of MACE (12 Months)
+++ ++ + + + + ++++++ + +++++++++++++++++++++++++++++++++++++++ + + +++++++++ ++ ++ ++++++++++++++++++++++++++++++++++
0.00
0.05
0.10
0.15
0.20
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Cum
ulat
ive
CD
eve
nts
++
stent
balloon
CD
376 370 368 365 365 364 361 356 354 354 353 340 305382 378 376 375 373 372 369 360 357 357 355 340 308balloon
stent
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Number at risk
+++ ++++ + ++ + + ++++++ ++ ++++++++++++++++++++++++++++++++++++++
+ + + + ++ + ++ +++++++ +++ + ++ +++++++++++++++++++++++++++++++++++0.00
0.05
0.10
0.15
0.20
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Cum
ulat
ive
Non
−fa
tal M
I eve
nts
++
stent
balloon
Non−fatal MI
376 366 361 357 357 353 350 345 342 342 341 327 293382 376 375 374 372 371 368 358 354 354 352 336 305balloon
stent
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Number at risk
+++ ++++ + ++ + + ++++++ ++ ++++++++++++++++++++++++++++++++++++++
+ + + + ++ + ++ +++++++ +++ + ++ ++++++++++++++++++++++++++++++++++
0.00
0.05
0.10
0.15
0.20
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Cum
ulat
ive
TV
R e
vent
s
++
stent
balloon
TVR
376 367 362 358 358 355 351 342 339 338 337 323 289382 377 375 373 370 369 364 353 350 349 346 330 298balloon
stent
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Number at risk
3.1 vs. 1.3%; HR 2.33, 95% CI 0.82 to 6.61; p=0.1131 1.6 vs. 3.5%; HR 0.46, 95% CI 0.17 to 1.20; p=0.1123 3.4 vs. 4.5%; HR 0.75, 95% CI 0.36 to 1.55; p=0.4375
Cardiac
Death
Non-fatal
Myocardial Infarction
Target-vessel
Revascularization
BASKET-SMALL 2
Major Bleeding (BARC ≥3, 12 Months)
++ ++++ ++ + + ++++++ ++ ++++++++++++++++++++++++++++++++++++++
+ + + + ++ + ++++++++++ +++ + ++ +++++++++++++++++++++++++++++++++++0.00
0.05
0.10
0.15
0.20
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Cum
ulat
ive
Maj
or b
leed
ing
even
ts
++
stent
balloon
376 369 366 361 360 359 356 351 348 348 346 333 300382 377 376 374 372 371 367 358 355 355 353 338 306balloon
stent
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Number at risk
1.1 vs. 2.4%; HR 0.45, 95% CI 0.14 to 1.46; p=0.1834
+++ ++
++ +++++++++++++++++++++++++++++++
+
++ +
+ ++
+++
++
++++++++++++++++++++++++++++++++++
0.00
0.05
0.10
0.15
0.20
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Cum
ulat
ive
MA
CE
eve
nt r
ate
356 352 349 348 346 345 340 335 332 331 328 311 28419 19 19 18 18 18 18 17 17 17 17 17 1393 90 88 87 87 86 85 82 81 81 81 80 80
243 239 236 233 233 229 229 228 227 226 225 212 185XienceTaxus
DCB+DESDCB
0 30 60 90 120 150 180 210 240 270 300 330 360Follow up days
Number at risk
BASKET-SMALL 2
MACE (12 Months) for Device Subgroups
+ DCB
+ DCB+DES
+ Taxus
+ Xience
15.8 vs. 7.0%; HR 2.11, 95% CI
0.62 to 7.19; p=0.2306
12.8 vs. 5.7%, HR 2.04, 95% CI
0.88 to 4.76; p=0.0987
BASKET-SMALL 2
Conclusions
• First large randomized controlled trial testing the efficacy of a paclitaxel-iopromide-coated
DCB vs. second-generation DES in a large all-comer population regarding clinical endpoints
• DCB are non-inferior to DES in lesions of small native coronary arteries regarding MACE up
to 12 months, with similar event rates for both treatment groups
Small native coronary artery disease may safely be treated with DCB after
successful predilatation