Prof Samir R Kapadia MD
Director, Sones Cardiac Catheterization Laboratories
Cleveland Clinic Cleveland, OH
For patients with severe symptomatic aortic stenosis (AS) who are not candidates for surgical valve replacement, transcatheter aortic valve replacement (TAVR) offers superior benefit to standard therapy, as measured by all-cause mortality, cardiovascular mortality, repeat hospital admission and functional status. PARTNER 1B 5 year data were published simultaneously with PARTNER 1A 5 year data in 2 separate manuscripts in the Lancet (March 15 2105).
In this landmark trial, TAVR produced a 22 percent survival benefit and a 28 percent reduced risk of cardiovascular mortality, compared with standard treatment.
According to Cleveland Clinic interventional cardiologist Samir Kapadia, MD, lead author of PARTNER 1B, these findings have changed the treatment paradigm for severe Aortic Stenosis patients who can’t undergo surgical Aortic Valve Replacement.
“This trial is the first—and will probably be the only—randomized AS trial that includes a standard treatment group, since these results will make it unethical to treat severe AS patients with medical therapy alone without aortic valve replacement. ” he says.
Superior survival benefit with TAVR
PARTNER 1B is the only rigorous randomized trial of extreme-risk aortic stenosis patients that has prospectively reported the outcomes of TAVR versus standard treatment in patients for whom the estimated probability of death or serious irreversible morbidity after surgical aortic valve replacement was 50 percent or greater.
The trial enrolled 358 patients between May 11, 2007 and March 16, 2009; 179 patients were assigned to TAVR with the first-generation Sapien valve and 179 to standard therapy which includes medical therapy and balloon aortic valvuloplasty. TAVR was performed under general anesthesia with common femoral artery access. Guidance was provided by transesophagel echocardiography and fluoroscopy. The mean age of participants was 83.
The primary endpoint was all-cause survival. Secondary endpoints included cardiovascular mortality, stroke, vascular complications, major bleeding and functional status.
At the end of the 5-year follow-up, the overall mortality rate was 71.8 percent in the TAVR group and 93.6 percent in the standard treatment group. Only six patients who had undergone standard therapy were still alive; of these, five had undergone AV replacement and leaving only one surviving patient without aortic valve replacement. This patient had a balloon valvuloplasty. Mean survival in the TAVR group was 31 months, versus 11.7 months in the standard treatment group.
“This reinforces that aortic valve replacement must be considered very seriously for these patients,” says Dr. Kapadia.
Despite the low number of survivors in the standard-treatment group, landmark analysis showed that the differences in survival remained significant between 3 and 5 years. For patients who were alive at 3 years, the risk of all-cause mortality at 5 years was 38.9% for TAVR patients and 66.7% in the standard treatment cohort.
Superior results in secondary endpoints
At 5-year follow-up, TAVR bested standard treatment in multiple measures:
- Cardiovascular mortality. The risk of cardiovascular mortality was 57.5 percent in the TAVR group and 85.9 percent in the standard treatment group.
- Repeat hospitalization. Only 47.6 percent of TAVR patients required rehospitalization, compared with 87.3 percent of the standard treatment group.
- Valve durability. No increase in transvalvular gradient, attrition of valve area or worsening of aortic regurgitation was seen. No patient had structural valve deterioration requiring intervention.
- Functional status. Of the 49 TAVR patients surviving at 5 years, 86 percent were NYHA class I or II.
“This benefit is remarkable for inoperable elderly patients and a first- generation device,” says Dr. Kapadia.
Equivalent stroke risk
The stroke risk at 5 years was 16 percent with TAVR and 18.2 percent with standard treatment—essentially equivalent. Since so few patients in the standard treatment group survived, the researchers conducted a competing risk analysis for mortality and stroke. “It confirmed there was no continuous hazard of stroke associated with TAVR after the initial procedure risk,” says Dr. Kapadia.
Fine-tuning patient selection
TAVR conferred cardiovascular mortality and all-cause mortality benefits in patients with multiple comorbidities, as indicated by higher STS scores. Early survival was not different in these patients, underscoring the probable effect of the comorbidities on early survival, despite successful TAVR.
“This shows the importance of making every attempt to differentiate patients who will derive survival benefit from those who are unlikely to survive, despite successful TAVR,” says Dr. Kapadia. “Although clinical outcomes with TAVR are encouraging, better patient selection and reduction in procedural complications will help make TAVR even more beneficial.”
5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial
Samir R Kapadia, Martin B Leon, Raj R Makkar, E Murat Tuzcu, Lars G Svensson, Susheel Kodali, John G Webb, Michael J Mack, Pamela S Douglas, Vinod H Thourani, Vasilis C Babaliaros, Howard C Herrmann, Wilson Y Szeto, Augusto D Pichard, Mathew R Williams, Gregory P Fontana, D Craig Miller, William N Anderson, Craig R Smith, for the PARTNER trial investigators, Jodi J Akin, Michael J Davidson
5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial
Michael J Mack, Martin B Leon, Craig R Smith, D Craig Miller, Jeffrey W Moses, E Murat Tuzcu, John G Webb, Pamela S Douglas, William N Anderson, Eugene H Blackstone, Susheel K Kodali, Raj R Makkar, Gregory P Fontana, Samir Kapadia, Joseph Bavaria, Rebecca T Hahn, Vinod H Thourani, Vasilis Babaliaros, Augusto Pichard, Howard C Herrmann, David L Brown, Mathew Williams, M
Both from The Lancet March 1 2015
Director, Sones Cardiac Catheterization Laboratories (2015). TAVR Bests Standard Therapy For Sick, Elderly Patients With Severe Aortic Stenosis