ACC 2013What did we learn

• 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.

• 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).

Study DevicesStudy Devices

Edwards SAPIEN THV23 and 26 mm valves

RetroFlex 22 and 24 F sheaths

Ascendra 24 and 26 F sheaths

Transfemoral Transapical

• “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.”

131 121 114 102 93 80 63

171 146 125 117 110 94 62

34 24 21 18 15 12 9

None-Tr

Mild

Mod-Sev

No. at Risk

53.7%

25.6%

32.5%38.2%

12.3%

26.0%

60.8%

35.3%

44.6%

168 150 142 130 120 106 81

139 119 98 91 83 67 42

24 18 16 14 13 11 9

None-Tr

Mild

Mod-Sev

No. at Risk

28.9%

14.4%

45.8%

24.3%

37.7%33.3%

51.0%

33.9%

50.4%

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

For Placement of AoRTic traNscathetER valve II (PARTNER II)• Cohort B, Martin B. Leon, MD, of Columbia University Medical

Center, (New York, NY), and colleagues enrolled 560 patients with severe aortic stenosis who were judged unsuitable candidates for surgery at 28 US centers.

• 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).

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

• 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.

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.

• 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).

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.

• 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).

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

• 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.

• 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.

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

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

• 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.

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

Advance Access Online Publication March 11, 2013

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

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

Baseline Characteristics (1) Variables n (%) or mean (±SD)

Placebo(n=1712)

Digoxin(n=1693) P value

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

30-Day Hospital Admission Due to All Causes

Placebo(n=1712)

Digoxin(n=1693)

Absolute RiskDifference

Hazard ratio (95% CI)

P value

8.1% 5.4% –2.7%0.66 (0.51–0.86)

0.002

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

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

Placebo(n=1712)

Digoxin(n=1693)

Absolute RiskDifference

Hazard ratio (95% CI)

P value

6.5% 3.5% –3.0%0.53 (0.38–0.72)

<0.001

In the 30 days after randomization, digoxin reduced the risk of hospital admission due to cardiovascular causes by 47%

30-Day Hospital Admission Due to Cardiovascular Causes

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

Progressiveheart failure 0.22 (0.05-1.04) 0.056

Although few deaths (n=34) occurred, they were numerically fewer in the digoxin group (0.7% vs. 1.3% for placebo)…