Disease Prevalence and Number of Candidates for TAVI
The systematic literature search yielded 1,523 studies. After the title and abstract were screened, 1,408 studies were excluded because they did not focus on the epidemiology of disease. After assessing full-text articles, another 109 studies were excluded because they were not performed in the general elderly population, AS was not assessed, or because it was not an original publication. After the inclusion of an additional study through cross-referencing, our final analysis consisted of 7 studies, with a total of 9,723 elderly patients (Fig. 1). The characteristics of these studies are outlined in Table 1. The 7 studies reported the prevalence of AS in 9 study populations on 3 continents. The study periods ranged from 1989 to 2009. All studies had a cross-sectional character, and most were part of larger population-based cohort studies. In all 7 studies, echocardiography was used to diagnose AS, although definitions of AS and its severity were variable (Table 1).
(Enlarge Image)
Figure 1.
Flowchart of Study Selection
AS = aortic stenosis.
The combined prevalence of AS in the elderly was reported in 6 studies and ranged from 2.6% to 22.8% (Fig. 2A). The pooled prevalence was 12.4% (95% CI: 6.6% to 18.2%) using a random-effects model (I = 98.5%; Q = 337.70, p < 0.001). The prevalence of severe AS in the elderly was reported separately in 5 studies and ranged from 1.2% to 6.1% (Fig. 2B). The pooled prevalence of severe AS was 3.4% (95% CI: 1.1% to 5.7%) using a random-effects model (I = 85.7%; Q = 27.99, p < 0.001).
(Enlarge Image)
Figure 2.
Forest Plots on the Prevalence of AS
(A) Mild, moderate, and severe aortic stenosis (AS) in the elderly, using a random-effects model. I = 97.1%, Q = 140.25, p < 0.001. (B) Severe AS in the elderly, using a random-effects model. I = 85.7%, Q = 27.99, p < 0.001. CI = confidence interval.
These estimates of the prevalence of AS in patients ≥75 years old correspond to approximately 4.9 million elderly patients with AS in the European countries and 2.7 million in North America. If only symptomatic severe AS is considered, this translates to 1.0 million elderly patients in the European countries and 540,000 in North America. In 2011, 8.5% of the population in the 19 European countries was ≥75 years of age, and this number is expected to increase to 10.7% in 2025 and 16.6% in 2050. In North America, similar increases in the population demographics of the elderly are expected (2025, 8.3%, and 2050, 11.8%). These numbers correspond to approximately 1.3 million and 2.1 million patients with symptomatic severe AS in the 19 European countries in 2025 and 2050, respectively. In North America, there will be an estimated 0.8 million and 1.4 million patients with symptomatic severe AS in 2025 and 2050, respectively.
The number of elderly patients who could potentially benefit from TAVR was estimated using the model outlined in Figure 3, with inputs from the systematic search and meta-analyses (Fig. 4). Seven studies reported the percentage of patients with severe AS who were symptomatic, resulting in a pooled estimate of severe symptomatic AS of 75.6% (95% CI: 65.8% to 85.4%) (Fig. 4A, Online Table 1). Of these patients with symptomatic severe AS, 40.5% (95% CI: 35.8% to 45.1%) did not undergo SAVR and thus could be considered candidates for TAVR (Fig. 4B, Online Table 2). Nine studies reported the percentage of patients referred for TAVR who actually received a transcatheter valve (Online Table 3). Three of these studies were performed in Europe, and 6 in the United States. The pooled percentage including both European and U.S. studies was 28.7% (95% CI: 22.8% to 34.6%) (Fig. 4C and 4D, respectively). The European pooled percentage was 40.3% (95% CI: 33.8% to 46.7%), whereas the U.S. pooled percentage was 24.4% (95% CI: 18.9% to 29.8%). In total, 12.3% of patients with symptomatic severe AS at prohibitive surgical risk are TAVR candidates.
(Enlarge Image)
Figure 3.
Model for the Estimation of TAVR Candidates Among the Elderly
AS = aortic stenosis; SAVR = surgical aortic valve replacement; STS-PROM = The Society of Thoracic Surgery Predicted Risk of Mortality; TAVR = transcatheter aortic valve replacement.
(Enlarge Image)
Figure 4.
Forest Plots of the Different Steps in Estimation Model
(A) Severe aortic stenosis (AS) and symptomatic; (B) not treated with surgical aortic valve replacement (SAVR), potentially treatable with transcatheter aortic valve replacement (TAVR); (C) treated with TAVR, European studies; and (D) treated with TAVR, all studies. CI = confidence interval.
To assess the proportion of elderly SAVR patients who was deemed to be at high surgical risk, we used a study that reported on all elderly SAVR patients in the United States between 1999 and 2007. Among elderly patients undergoing isolated SAVR, 5.2% (95% CI: 4.9% to 5.4%) were at high risk (STS-PROM ≥10%), 15.8% (95% CI: 15.4% to 16.2%) at intermediate risk (STS-PROM 5% to 10%), and 79.1% (95% CI: 78.6% to 79.5%) at low risk (STS-PROM <5%). A recent study showed that in a group of operable patients with a EuroSCORE (European System for Cardiac Operative Risk Evaluation) ≥15, approximately 80% were treated with TAVR).
In 2011, there were 39,316,978 people ≥75 years of age in the European countries and 21,182,683 in North America. Combining these figures with the Monte Carlo simulations in the model (Fig. 3), we estimated that a total of 292,000 high- or prohibitive-risk elderly patients with symptomatic severe AS are candidates for TAVR. Specifically, there are 189,836 (95% CI: 80,281 to 347,372) TAVR candidates in the European countries and 102,558 (95% CI: 43,612 to 187,002) in North America. Annually there are 17,712 (95% CI: 7,590 to 32,691) new TAVR candidates in the European countries and 9,189 (95% CI: 3,898 to 16,682) in North America. The total and annual number of TAVR candidates in the individual countries is presented in Figure 5 and 6, respectively.
(Enlarge Image)
Figure 5.
Total of TAVR Candidates in Different Countries Under Current Treatment Indications
*Due to the simulation process, the totals are not exactly the same as the sum of the individual countries. CI = confidence interval; TAVR = transcatheter aortic valve replacement.
(Enlarge Image)
Figure 6.
Annual Number of TAVR Candidates in Different Countries Under Current Treatment Indications
*Due to the simulation process, the totals are not exactly the same as the sum of the individual countries. CI = confidence interval; TAVR = transcatheter aortic valve replacement.
The intermediate surgical risk group comprises approximately 145,000 elderly patients with symptomatic severe AS. Specifically, there are 94,730 (95% CI: 40,574 to 171,896) patients at intermediate risk in the European countries and 50,733 (95% CI: 22,148 to 90,451) in North America. The low surgical risk group includes approximately 730,000 patients with symptomatic severe AS. Specifically, there are 477,314 (95% CI: 206,798 to 862,958) patients at low-risk in the European countries and 255,727 (95% CI: 108,549 to 460,026) in North America.
In the pre-specified sensitivity analysis that varied the proportion of patients receiving TAVR after referral for TAVR assessment according to study location (28.7%, 95% CI: 22.8% to 34.6% in Europe and the United States combined), we estimated that approximately 220,000 patients are TAVR candidates. Of these, 142,658 (95% CI: 61,065 to 263,795) candidates lived in the European countries and 76,962 (95% CI: 32,805 to 140,673) in North America.
In the sensitivity analysis varying the percentage of high-risk operable patients who would undergo TAVR, the total number of TAVR candidates was 277,570 (95% CI: 119,406 to 512,707) assuming that 50% would undergo TAVR whereas there were 302,865 (95% CI: 129,433 to 550,562) candidates if all the high-risk patients would undergo TAVR. Finally, we estimated that the total number of patients with symptomatic severe AS in the intermediate-risk category was 145,936 (95% CI: 62,802 to 263,340), and 733,861 (95% CI: 310,623 to 1,302,586) in the low-risk category.
Results
The systematic literature search yielded 1,523 studies. After the title and abstract were screened, 1,408 studies were excluded because they did not focus on the epidemiology of disease. After assessing full-text articles, another 109 studies were excluded because they were not performed in the general elderly population, AS was not assessed, or because it was not an original publication. After the inclusion of an additional study through cross-referencing, our final analysis consisted of 7 studies, with a total of 9,723 elderly patients (Fig. 1). The characteristics of these studies are outlined in Table 1. The 7 studies reported the prevalence of AS in 9 study populations on 3 continents. The study periods ranged from 1989 to 2009. All studies had a cross-sectional character, and most were part of larger population-based cohort studies. In all 7 studies, echocardiography was used to diagnose AS, although definitions of AS and its severity were variable (Table 1).
(Enlarge Image)
Figure 1.
Flowchart of Study Selection
AS = aortic stenosis.
The combined prevalence of AS in the elderly was reported in 6 studies and ranged from 2.6% to 22.8% (Fig. 2A). The pooled prevalence was 12.4% (95% CI: 6.6% to 18.2%) using a random-effects model (I = 98.5%; Q = 337.70, p < 0.001). The prevalence of severe AS in the elderly was reported separately in 5 studies and ranged from 1.2% to 6.1% (Fig. 2B). The pooled prevalence of severe AS was 3.4% (95% CI: 1.1% to 5.7%) using a random-effects model (I = 85.7%; Q = 27.99, p < 0.001).
(Enlarge Image)
Figure 2.
Forest Plots on the Prevalence of AS
(A) Mild, moderate, and severe aortic stenosis (AS) in the elderly, using a random-effects model. I = 97.1%, Q = 140.25, p < 0.001. (B) Severe AS in the elderly, using a random-effects model. I = 85.7%, Q = 27.99, p < 0.001. CI = confidence interval.
These estimates of the prevalence of AS in patients ≥75 years old correspond to approximately 4.9 million elderly patients with AS in the European countries and 2.7 million in North America. If only symptomatic severe AS is considered, this translates to 1.0 million elderly patients in the European countries and 540,000 in North America. In 2011, 8.5% of the population in the 19 European countries was ≥75 years of age, and this number is expected to increase to 10.7% in 2025 and 16.6% in 2050. In North America, similar increases in the population demographics of the elderly are expected (2025, 8.3%, and 2050, 11.8%). These numbers correspond to approximately 1.3 million and 2.1 million patients with symptomatic severe AS in the 19 European countries in 2025 and 2050, respectively. In North America, there will be an estimated 0.8 million and 1.4 million patients with symptomatic severe AS in 2025 and 2050, respectively.
Estimates of TAVR Candidates
The number of elderly patients who could potentially benefit from TAVR was estimated using the model outlined in Figure 3, with inputs from the systematic search and meta-analyses (Fig. 4). Seven studies reported the percentage of patients with severe AS who were symptomatic, resulting in a pooled estimate of severe symptomatic AS of 75.6% (95% CI: 65.8% to 85.4%) (Fig. 4A, Online Table 1). Of these patients with symptomatic severe AS, 40.5% (95% CI: 35.8% to 45.1%) did not undergo SAVR and thus could be considered candidates for TAVR (Fig. 4B, Online Table 2). Nine studies reported the percentage of patients referred for TAVR who actually received a transcatheter valve (Online Table 3). Three of these studies were performed in Europe, and 6 in the United States. The pooled percentage including both European and U.S. studies was 28.7% (95% CI: 22.8% to 34.6%) (Fig. 4C and 4D, respectively). The European pooled percentage was 40.3% (95% CI: 33.8% to 46.7%), whereas the U.S. pooled percentage was 24.4% (95% CI: 18.9% to 29.8%). In total, 12.3% of patients with symptomatic severe AS at prohibitive surgical risk are TAVR candidates.
(Enlarge Image)
Figure 3.
Model for the Estimation of TAVR Candidates Among the Elderly
AS = aortic stenosis; SAVR = surgical aortic valve replacement; STS-PROM = The Society of Thoracic Surgery Predicted Risk of Mortality; TAVR = transcatheter aortic valve replacement.
(Enlarge Image)
Figure 4.
Forest Plots of the Different Steps in Estimation Model
(A) Severe aortic stenosis (AS) and symptomatic; (B) not treated with surgical aortic valve replacement (SAVR), potentially treatable with transcatheter aortic valve replacement (TAVR); (C) treated with TAVR, European studies; and (D) treated with TAVR, all studies. CI = confidence interval.
To assess the proportion of elderly SAVR patients who was deemed to be at high surgical risk, we used a study that reported on all elderly SAVR patients in the United States between 1999 and 2007. Among elderly patients undergoing isolated SAVR, 5.2% (95% CI: 4.9% to 5.4%) were at high risk (STS-PROM ≥10%), 15.8% (95% CI: 15.4% to 16.2%) at intermediate risk (STS-PROM 5% to 10%), and 79.1% (95% CI: 78.6% to 79.5%) at low risk (STS-PROM <5%). A recent study showed that in a group of operable patients with a EuroSCORE (European System for Cardiac Operative Risk Evaluation) ≥15, approximately 80% were treated with TAVR).
In 2011, there were 39,316,978 people ≥75 years of age in the European countries and 21,182,683 in North America. Combining these figures with the Monte Carlo simulations in the model (Fig. 3), we estimated that a total of 292,000 high- or prohibitive-risk elderly patients with symptomatic severe AS are candidates for TAVR. Specifically, there are 189,836 (95% CI: 80,281 to 347,372) TAVR candidates in the European countries and 102,558 (95% CI: 43,612 to 187,002) in North America. Annually there are 17,712 (95% CI: 7,590 to 32,691) new TAVR candidates in the European countries and 9,189 (95% CI: 3,898 to 16,682) in North America. The total and annual number of TAVR candidates in the individual countries is presented in Figure 5 and 6, respectively.
(Enlarge Image)
Figure 5.
Total of TAVR Candidates in Different Countries Under Current Treatment Indications
*Due to the simulation process, the totals are not exactly the same as the sum of the individual countries. CI = confidence interval; TAVR = transcatheter aortic valve replacement.
(Enlarge Image)
Figure 6.
Annual Number of TAVR Candidates in Different Countries Under Current Treatment Indications
*Due to the simulation process, the totals are not exactly the same as the sum of the individual countries. CI = confidence interval; TAVR = transcatheter aortic valve replacement.
The intermediate surgical risk group comprises approximately 145,000 elderly patients with symptomatic severe AS. Specifically, there are 94,730 (95% CI: 40,574 to 171,896) patients at intermediate risk in the European countries and 50,733 (95% CI: 22,148 to 90,451) in North America. The low surgical risk group includes approximately 730,000 patients with symptomatic severe AS. Specifically, there are 477,314 (95% CI: 206,798 to 862,958) patients at low-risk in the European countries and 255,727 (95% CI: 108,549 to 460,026) in North America.
Sensitivity Analyses
In the pre-specified sensitivity analysis that varied the proportion of patients receiving TAVR after referral for TAVR assessment according to study location (28.7%, 95% CI: 22.8% to 34.6% in Europe and the United States combined), we estimated that approximately 220,000 patients are TAVR candidates. Of these, 142,658 (95% CI: 61,065 to 263,795) candidates lived in the European countries and 76,962 (95% CI: 32,805 to 140,673) in North America.
In the sensitivity analysis varying the percentage of high-risk operable patients who would undergo TAVR, the total number of TAVR candidates was 277,570 (95% CI: 119,406 to 512,707) assuming that 50% would undergo TAVR whereas there were 302,865 (95% CI: 129,433 to 550,562) candidates if all the high-risk patients would undergo TAVR. Finally, we estimated that the total number of patients with symptomatic severe AS in the intermediate-risk category was 145,936 (95% CI: 62,802 to 263,340), and 733,861 (95% CI: 310,623 to 1,302,586) in the low-risk category.