Trial Summary PARTNER
Title: Placement of Aortic Transcatheter Valves
Trial Sponsor: Edwards Lifesciences
Year Presented: 2010
Year Published: 2010
Topic(s): General Cardiology, Interventional Cardiology
Summary Posted: 09/22/2010
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Description:
As many as one-third of patients with severe aortic stenosis (AS) are high-risk surgical candidates and are conservatively managed. However, nonsurgical management of symptomatic AS is associated with a median survival of about 2 years. The PARTNER trial sought to compare outcomes between standard therapy and transcatheter aortic valve implantation (TAVI) in patients with inoperable AS. TAVI is a new procedure in which a bioprosthetic aortic valve is inserted through a catheter and implanted within the diseased native aortic valve.
Hypothesis:
TAVI would be superior to standard therapy in patients who are at high risk for mortality with aortic valve surgery.
Drugs/Procedures Used:
TAVI was performed under general anesthesia, and under transesophageal echocardiographic guidance. A standard balloon aortic valvuloplasty (BAV) was initially performed, followed by transfemoral insertion of either a 22- or 24-French sheath (for a 23 or 26 mm valve, respectively). The valve itself was part of the Edwards SAPIEN heart-valve system, which consists of a trileaflet bovine pericardial valve mounted on a balloon-expandable, stainless steel support frame. This system was advanced across the native aortic valve. The valve and support frame were then balloon expanded across the native valve during rapid ventricular pacing. Standard therapy consisted of medical management and BAV alone if deemed necessary.
Concomitant Medications:
All patients undergoing TAVI received heparin during the procedure, and dual antiplatelet therapy consisting of aspirin and clopidogrel for 6 months after the procedure.
Principal Findings:
Of the more than 3,000 patients with severe AS who were screened, a total of 358 patients (12%) were randomized across 21 sites, 179 to TAVI, and 179 to standard therapy. Baseline characteristics were fairly similar between the two arms. The mean Society of Thoracic Surgeons (STS) score was 11.6%, with a corresponding mean logistic EuroSCORE of 28.4. Other conditions contributing to a high-risk designation included heavily calcified (“porcelain”) aorta in 15.1%, chest wall deformity or irradiation (13.1%), oxygen-dependent respiratory insufficiency (23.5%), and frailty based on prespecified criteria (23.1%).
About 93% of the patients had New York Heart Association (NYHA) class III or IV symptoms, with a mean aortic valve area of 0.6 cm2, and a mean aortic valve gradient of 44 mm Hg. The mean left ventricular ejection fraction (LVEF) was 52%, with moderate to severe mitral regurgitation present in about 23% of the patients. Pulmonary hypertension was present in about 43% of the patients. Coexisting coronary artery disease was noted in about 71% of the patients, with 41% having undergone prior coronary artery bypass grafting, and 27% prior percutaneous coronary intervention. About 20% of patients had undergone BAV at some point prior to randomization.
There was no difference in 30-day mortality between the TAVI and standard therapy arms (5.0% vs. 2.8%, p = 0.41). However, at 1 year, the primary endpoint of all-cause mortality was significantly lower in the TAVI arm (30.7% vs. 50.7%, hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.40-0.74, p < 0.001).
Other outcomes such as cardiovascular death at 1 year (20.5% vs. 44.6%, HR 0.39, 95% CI 0.27-0.56, p < 0.001) and death or rehospitalization at 1 year (42.5% vs. 71.6%, HR 0.46, 95% CI 0.35-0.59, p < 0.001) were also lower in the TAVI arm. Major strokes at 30 days (5.0% vs. 1.1%, p = 0.06) and at 1 year (7.8% vs. 3.9%, p = 0.18) were numerically higher in the TAVI arm. Major vascular complications were significantly higher in the TAVI arm, both at 30 days (16.2% vs. 1.1, p < 0.001) and at 1 year (16.8% vs. 2.2%, p < 0.001). Similarly, major bleeding was higher in the TAVI arm at 30 days (16.8% vs. 3.9%, p < 0.001) and at 1 year (22.3% vs. 11.2%, p = 0.007).
Other complications such as acute kidney injury, endocarditis, and new pacemaker requirement were similar between the two arms. BAV was necessary in 36.9% of the patients in the standard therapy arm over 1 year of follow-up, whereas repeat TAVI was necessary in three (1.7%) patients in that time frame.
Echocardiographic parameters such aortic valve area (0.6-1.5 cm2) and mean aortic valve gradient (44.5-11.1 mm Hg) showed significant improvement in the TAVI arm at 30 days (p < 0.001 for both). Moderate or severe paravalvular and valvular aortic regurgitation were noted in 11.8% and 1.3% of the patients at 30 days, respectively, in the TAVI arm. NYHA class demonstrated significant improvements in the TAVI arm at 30 days and at 1 year, as compared with the standard therapy arm (p < 0.001).
Interpretation:
PARTNER is a landmark trial in the field of structural heart disease and in the management of patients with severe AS. Patients in this trial were very high risk to begin with, as evidenced by >50% mortality at 1 year in the standard therapy arm. The results of the inoperable group of patients (cohort B) are reported here. TAVI resulted in 45% reduction in all-cause mortality and 61% reduction in cardiovascular mortality at 1 year in these high-risk AS patients compared with standard therapy. Echocardiographic criteria such as aortic valve area and mean aortic valve gradients, and symptom criteria such as NYHA class, also demonstrated a significant improvement.
The procedure is complex and fraught with numerous complications, however, as evidenced by a significantly higher risk of major vascular complications and major bleeding, and a trend towards a higher risk of major stroke in the TAVI arm. Thus, while the overall results are very encouraging, the high complication rate should temper any tendencies toward the overaggressive use of TAVI (if FDA approved for the treatment of AS) in lower-risk patients, and surgical AVR should still be considered the gold standard for treatment of AS in these patients. The availability and performance of smaller profile TAVI delivery systems, a comparison of transfemoral to transapical TAVI (cohort A patients), and long-term follow-up are eagerly awaited.
On another note, the design and execution of the PARTNER trial highlight the importance of close collaboration between interventional cardiologists and cardiac surgeons in the management of this complex group of patients.
Conditions:
Valvular heart disease
Study Design:
Parallel. Randomized.
Primary Endpoints:
All-cause mortality at 1 year
Hierarchical composite of all-cause mortality or time to the first occurrence of repeat hospitalization after the index procedure due to valve-related or procedure-related clinical deterioration
Secondary Endpoints:
Cardiovascular mortality at 1 year
Repeat hospitalization after the index procedure due to valve-related or procedure-related clinical deterioration
NYHA class at 1 year
Six-minute walk distance at 1 year
Valve performance based on echocardiographic parameters at 1 year
Complications at 1 year
Patient Population:
Severe senile degenerative native valve AS (aortic valve area <0.8 cm2, mean aortic valve gradient ≥40 mm Hg, or peak aortic jet velocity ≥4 m/sec on Doppler echocardiography)
NYHA class II, III, or IV symptoms
High-risk surgical candidates (either an STS score of ≥10%, presence of coexisting conditions that would be associated with a predicted risk of death 30 days after surgery of ≥15%, presence of coexisting conditions that would be associated with a predicted risk of death or serious comorbidity of ≥50% within 30 days of surgery)
Agreement between at least two cardiac surgeons that patient was not a suitable candidate for surgery
Number of screened applicants: 3,105
Number of enrollees: 358
Duration of follow-up: 1 year
Mean patient age: 83.2 years
Percentage female: 54%
Ejection fraction: 52%
NYHA class: II (7%), III or IV (93%)
Exclusions:
Unicuspid, bicuspid, or noncalcified aortic valve
Aortic or mitral valve regurgitation >3+
Substantial coronary artery disease requiring revascularization
LVEF <20%
Aortic annulus diameter <18 mm or >25 mm
Transient ischemic attack/stroke within the preceding 6 months
Acute myocardial infarction within the preceding 6 months
Severe renal insufficiency (serum creatinine >3.0 mg/dl, or needing chronic dialysis)
Any invasive therapeutic coronary procedure within 30 days (or 6 months if drug-eluting stent implantation)
Pre-existing prosthetic heart valve in any position, prosthetic ring, or severe mitral annular calcification
White blood cell count <3000/mm3, hemoglobin <9 mg%, or platelet count <50,000/mm3
Bleeding diathesis or coagulopathy
Hemodynamic instability needing inotropic therapy or mechanical support devices
Need for emergent surgery for any reason
Hypertrophic obstructive cardiomyopathy
Active peptic ulcer disease or gastrointestinal bleeding within 3 months
Life-expectancy <12 months due to noncardiac causes
Significant abdominal or thoracic aortic disease
Iliofemoral vessel characteristics that would preclude safe placement of 22- or 24-French sheaths, such as severe calcification, severe tortuosity, or vessel diameter <7 mm (for 23 mm valve/22-French system) ,and <8 mm (for 26 mm valve/24-French system)
Bulky calcified aortic valve leaflets in close proximity to coronary ostia
Active bacterial endocarditis or other infections