American college of cardiology 2013 meeting PPT

1. ACC 2013
What did we learn

2. • Vinod H. Thourani, MD, of Emory University (Atlanta, GA),
presented 3-year data from cohort A of the PARTNER
(Placement of AoRTic traNscatheterER valves) trial, following
up on the 1- and 2-year findings presented in 2011 and 2012,
respectively, at the annual ACC meeting, which showed similar
mortality rates between TAVR and surgery but prompted
concern over stroke rates with the transcatheter procedure.

3. • Cohort A enrolled 699 high-risk, operable patients at 26
centers with a median age of 84.1 years. The patients, all of
whom had symptomatic, severe aortic stenosis, were
randomized to undergo either surgery (n = 351) or TAVR (n =
348) with the Edwards Sapien aortic valve system (Edwards
Lifesciences, Irvine, CA).

5. Study Devices
Transfemoral Transapical
Edwards SAPIEN THV RetroFlex Ascendra
23 and 26 mm valves 22 and 24 F sheaths 24 and 26 F sheaths

7. • “TAVR should be considered an alternative to surgery with
similar mortality and similar other major clinical outcomes,”
Dr. Thourani said. “Periprocedural stroke concerns after TAVR
have diminished with longer term follow-up, and TAVR valve
hemodynamics have remained stable, although
periprocedural regurgitation, even mild, has emerged as a
predictor of late mortality.”

8. 60.8%
53.7%
44.6%
38.2%
32.5%
26.0% 35.3%
25.6%
12.3%
No. at Risk
None-Tr 131 121 114 102 93 80 63
Mild 171 146 125 117 110 94 62
Mod-Sev 34 24 21 18 15 12 9

9. 51.0%
45.8%
50.4%
33.3%
37.7%
33.9%
28.9%
24.3%
14.4%
No. at Risk
None-Tr 168 150 142 130 120 106 81
Mild 139 119 98 91 83 67 42
Mod-Sev 24 18 16 14 13 11 9

10. PARTNER II Cohort B Demonstrates Safety,
Efficacy of Lower Profile TAVR Device
• PARTNER II compared inoperable patients randomized to
Sapien or Sapien XT
• Improved procedural outcomes, similar low 30-day mortality,
reduced vascular complications seen with XT
• Operator experience, lessons learned from PARTNER I are
improving outcomes

11. For Placement of AoRTic
traNscathetER valve II
(PARTNERB.II) MD, of Columbia University Medical
• Cohort B, Martin Leon,
Center, (New York, NY), and colleagues enrolled 560 patients
with severe aortic stenosis who were judged unsuitable
candidates for surgery at 28 US centers.

12. • Patients were enrolled from April 2011 through February 2012
and were randomly assigned to undergo TAVR using either the
standard Edwards Sapien aortic valve system (n = 276;
Edwards Lifesciences, Irvine, CA) or the newer Sapien XT (n =
284).

13. • Patients in both groups had multiple comorbid characteristics
including COPD, dementia, liver disease, porcelain aorta, and
hostile chest.

15. • Compared with the original device, Sapien XT was associated
with improved vascular and bleeding events at 30 days,
reducing major vascular complications from 15.5% to 9.6%
(P = 0.04) and disabling bleeding from 12.6% to 7.8% (P =
0.06). Looking more closely at vascular complication
categories, there were significant reductions in perforations
(P = 0.003) as well as dissections (P = 0.03) with the XT.

16. Aspirin Alone Just as Good as Dual
Antiplatelet Therapy Beyond 12 Months
• Aspirin monotherapy results in similar rates of ischemic
outcomes while decreasing bleeding compared with dual
antiplatelet therapy beyond 12 months in stable patients who
receive drug-eluting stents (DES).
• Results from the DES LATE trial were presented March 10,
2013, at the American College of Cardiology/i2 Scientific
Session.

18. • Over a full 4 years of follow-up, the only endpoint that
differed was TIMI major bleeding, which was reduced with
aspirin monotherapy (2.5% vs. 3.9%; HR 0.67; 95% CI 0.47-
0.95; P = 0.026).

19. Rosuvastatin Helps Stave Off Contrast Nephropathy in NSTE-ACS
Patients
• CIN is defined as a rise in creatinine of at least 0.5 mg/dl or at
least 25% from baseline within 72 hours—the primary
endpoint.

20. • presented data from the PRATO-ACS trial in which 504 NSTE-
ACS patients were randomly assigned to standard preventive
therapy with (n = 271) or without rosuvastatin (n = 272; 40 mg
on admission plus 20 mg daily until discharge).

21. • Patients were enrolled between July 2010 and August 2012,
were statin naïve, and received iodixanol as the contrast agent
prior to imaging.

22. • was significantly lower in patients randomized to rosuvastatin
compared with controls (6.7% vs. 15.1%; P = 0.001). After
adjustment for sex, age, diabetes and other confounders,
statin treatment remained an independent predictor of
reduced risk of CIN (OR 0.38; 95% CI 0.20-0.71). The number-
needed-to-treat to prevent 1 case of CIN was 12.

23. • Current US and European guidelines recommend statins for all
acute coronary syndrome patients, regardless of cholesterol
levels, within 1 to 4 days after admission.
• But panel discussion centered on whether statins given before
PCI to lower creatinine results in a reduction in ‘hard’ clinical
events.

24. Without Preprocedural Aspirin, PCI Carries
Higher Risk of In-Hospital Death, Stroke
• Registry study looks at preprocedural aspirin use in more than
65,000 patients undergoing PCI
• Aspirin not given to 7%, with only a small minority having a
documented contraindication
• In-hospital death, stroke risk both higher without aspirin

26. Cangrelor Consistently Comes Out Ahead
of Clopidogrel in All PCI Patients
• CHAMPION PHOENIX trial looks at cangrelor vs. clopidogrel
use in entire spectrum of PCI patients
• Lower rates of primary, secondary efficacy endpoint with
newer antiplatelet at 48 hours, maintained at 30 days
• No differences in GUSTO severe bleeding between treatment
options

28. • randomly assigned 10,942 patients who were undergoing
either urgent or elective PCI and were receiving guideline-
recommended therapy to receive either a bolus and infusion
of cangrelor (The Medicines Company, Parsippany, NJ, n =
5,472) or to receive a loading dose of 600 mg or 300 mg of
clopidogrel (n = 5,470). Patients were treated at 153
institutions from September 30, 2010 to October 3, 2012.

30. Coronary CTA Predictive, Resource-Saving When
Used in Emergency Department
• ACRIN PA 4005 looks at 1-year outcomes in patients
presenting to the emergency department with chest pain
screened with coronary CTA
• Negative coronary CTA predicts low risk of 1-year
death/AMI/revascularization
• Screening method also helps to more accurately distribute
resources

33. Advance Access Online Publication March 11, 2013

34. Objective
• To examine the effect of digoxin
on 30-day all-cause hospital
admission in older, potentially
Medicare-eligible, adults with
heart failure and reduced ejection
fraction in the main DIG trial

35. Digitalis Investigation Group
(DIG)
• Ambulatory chronic heart failure (N=6800)
• Ejection fraction ≤45%
• Normal sinus rhythm
• From United States and Canada
• Randomized to receive either digoxin or placebo
• During 1991-1993
• Followed for an average of 3 years
• >90% on ACE inhibitors and >80% on diuretics
• 3405 (50% of 6800) were ≥65 years of age

36. Baseline Characteristics (1)
Variables Placebo Digoxin
P value
n (%) or mean (±SD) (n=1712) (n=1693)
Age (years) 72 (5) 72 (5) 0.974
Female 426 (25%) 415 (25%) 0.802
Non-whites 194 (11%) 180 (11%) 0.514
Body mass index (kg/m2) 26.2 (4.7) 25.9 (4.5) 0.040
Heart rate (per minute) 78 (12) 78 (12) 0.445
Systolic BP (mm Hg) 128 (20) 128 (20) 0.643
Serum creatinine (mg/dL) 1.4 (0.4) 1.4 (0.4) 0.938
LVEF (%) 29 (9) 29 (9) 0.855
Cardiothoracic ratio 0.54 (0.08) 0.54 (0.07) 0.855
NYHA Class III-IV 602 (35%) 603 (36%) 0.599

37. 30-Day Hospital Admission
Due to All Causes
Absolute Hazard
Placebo Digoxin P
Risk ratio
(n=1712) (n=1693) value
Difference (95% CI)
0.66
8.1% 5.4% –2.7% 0.002
(0.51–0.86)
In the 30 days after randomization, in patients assigned to
digoxin, the absolute risk and relative risk for all-cause hospital
admission was reduced by an 2.7% and 34%, respectively

38. 60-Day and 90-Day
All-Cause Hospital Admission
Hazard ratio (95% CI) P value
At 60 days 0.76 (0.63–0.91) 0.003
At 90 days 0.75 (0.63–0.88) <0.001
The effect of digoxin on 30-day all-cause hospital admission
persisted during 60 and 90 days after randomization, suggesting
the early benefit of digoxin was not at the cost of later harm

39. 30-Day Hospital Admission
Due to Cardiovascular Causes
Absolute Hazard
Placebo Digoxin P
Risk ratio
(n=1712) (n=1693) value
Difference (95% CI)
0.53
6.5% 3.5% –3.0% <0.001
(0.38–0.72)
In the 30 days after randomization, digoxin reduced the risk of
hospital admission due to cardiovascular causes by 47%

40. 30-Day Mortality
Hazard ratio (95% CI) P value
All-cause 0.55 (0.27-1.11) 0.096
Cardiovascular 0.64 (0.31-1.31) 0.222
Progressive
0.22 (0.05-1.04) 0.056
heart failure
Although few deaths (n=34) occurred, they were numerically
fewer in the digoxin group (0.7% vs. 1.3% for placebo)…