Differences in lipid treatment patterns in women versus men in a large cohort of patients with atherosclerotic cardiovascular disease in Ontario, Canada

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fairbairn ◽  
R Goeree ◽  
S.G Goodman ◽  
R.M Rogoza ◽  
M Packalen ◽  
...  

Abstract Background/Introduction The prevalence of ischaemic heart disease is lower in women vs men in Canada. Studies have shown that women are more likely to be underdiagnosed and less likely to receive guideline-recommended treatments than men. Women receiving lipid-lowering therapies (LLTs) are also less likely to attain treatment goals vs men. Purpose We analysed use of LLTs and attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in a recent longitudinal cohort of patients with ASCVD with public drug coverage in Ontario to describe differences observed between female and male patients. Methods Patients ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1 year follow up period for LDL-C goal attainment (<2.0 mmol/L or 50% reduction from index LDL-C as per Canadian Cardiovascular Society Guidelines) and analysed by LLT category. Results 143,302 patients with ASCVD ≥65 years on LLTs were identified of which 41% were female. A higher proportion of female vs male patients were prescribed low (3% vs 2%) and medium intensity statins (51% vs 44%) compared with high intensity statins (43% vs 52%). A higher proportion of women failed to attain LDL-C goal compared to men (33% vs 24%) (Figure). When analysed by low, moderate or high intensity statin, 65%, 35%, and 27% of female patients and 49%, 25% and 19% of male patients failed to attain LDL-C goal at follow up. Conclusions In this retrospective study, women with a diagnosis of ASCVD were more frequently treated with low/moderate intensity statins whereas men were more frequently treated with high intensity statins. Approximately 2 of 3 women and 3 of 4 men receiving statin treatment attained LDL-C goal during the 1-year follow up period. Overall, there appear to be treatment differences between female and male patients with ASCVD, with males receiving higher intensity statin therapy and attaining LDL-C goal more frequently. Further research is needed to determine why these discrepancies exist. This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fairbairn ◽  
P Oh ◽  
R Goeree ◽  
R.M Rogoza ◽  
M Packalen ◽  
...  

Abstract Background/Introduction Limited real-world data are available on attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Canada. Purpose A retrospective observational study was conducted to describe types of ASCVD events/procedures, time between events and use of lipid lowering treatment (LLT) in patients who did not achieve LDL-C goal. Methods Patients in Ontario ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1-year follow up period for LDL-C goal attainment (<2.0 mmol/L or 50% reduction from index LDL-C) and analysed by LLT and by index event type. Results Overall, 28% of 143,302 patients ≥65 years on LLT failed to attain LDL-C goal at follow up (Figure). The proportion of patients failing to achieve LDL-C goal decreased from 35% to 22% over the 11-year study period. Mean time between index and follow up LDL-C (based on lowest score >2 weeks and up to 1 year after index LDL-C) was 203±97 days. When analysed by low-, moderate- or high-intensity statin, 57%, 30%, and 22% of patients failed to achieve LDL-C goal at follow up, respectively. Conclusions In this study, more than 1 in 4 patients with ASCVD in Ontario failed to achieve guideline recommended LDL-C goal despite treatment. In particular, ∼1 in 3 patients with cerebral and peripheral arterial disease were not at goal. An opportunity exists to better manage these high risk ASCVD patients with further statin intensification and additional LLTs This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
M Feudjo Tepie ◽  
A.L Catapano ◽  
P Giovas ◽  
S Bray ◽  
...  

Abstract Background 2016 and 2019 EAS/ESC dyslipidemia guidelines recommend lipid lowering therapy (LLT) to reduce LDL-C in patients with peripheral arterial disease (PAD) with or without established cardiovascular (CV) disease, and recommend target LDL-C goals based on individual CV risk. Data regarding the implementation of these guidelines in clinical practice across Europe is currently lacking. Purpose Describe LLT and achievement of the target LDL-C goals recommended in EAS/ESC dyslipidemia guidelines in patients with PAD. Methods The cross-sectional Da Vinci study enrolled consenting adults who had received LLT in the 12 months prior to the study visit and had at least one LDL-C measurement in the 14 months prior to the study visit, seen in a primary or secondary care setting across 18 European countries. Patients with coronary, peripheral and cerebral disease were enrolled at a ratio of 1:2:2. FH patients with prior CV events were excluded. Data were collected from medical records at a single visit between Jun '17–Nov '18, including LLT and most recent LDL-C. Primary outcome was LDL-C goal attainment ≥28 days after starting most recent LLT (treatment-stabilised LLT). Results Of 5888 patients enrolled, 2794 met our definition of atherosclerotic cardiovascular disease (ASCVD). Of these ASCVD patients, 1036 (37%) had PAD. 31% (323/1036) of PAD patients were female and mean (SD) age was 69 (9.4) years. Concomitant CV risk factors included diabetes mellitus (473/1036 patients [46%]), hypertension (809/1036 [78%]) and smoking (794/1036 [77%]). 26% (271/1036) of patients with PAD also had coronary vascular disease and 12% (122/1036) also had cerebrovascular disease. At the visit date, approximately half (497/1036 [48%]) of all PAD patients were receiving moderate intensity statins and 41% (421/1036) were receiving high intensity statins. 818 (73%) of the PAD patients had a treatment-stabilised LDL-C measurement (median, 2.20 mmol/L), of whom 40% (326/818) achieved the 2016 EAS/ESC LDL-C goal of 1.8 mmol/L and only 19% (159/818) achieved the 2019 goal of 1.4mmol/L. Conclusions European patients with PAD are not treated as per EAS/ESC recommendations, with a large proportion receiving suboptimal LLT and fewer than half achieving target LDL-C levels. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K K Ray ◽  
E Bruckert ◽  
P Filardi ◽  
C Ebenbichler ◽  
A Vogt ◽  
...  

Abstract Background 2019 ESC/EAS guidelines recommend a 50% lowering in untreated LDL-C and use of PCSK9 inhibitors (PCSK9i) for patients (pts) at very high cardiovascular (CV) risk when LDL-C goals of <1.4mmol/L are not met despite maximally tolerated statins and ezetimibe. However, the LDL-C threshold at which PCSK9i are reimbursed are higher than the goals recommended in clinical guidelines. Purpose This prospective observational cohort study describes clinical characteristics and LDL-C control among pts initiating evolocumab across 12 EU countries. Methods Pts are followed from evolocumab initiation (baseline). Demographic/clinical characteristics, lipid lowering therapy (LLT) and lipid values are being collected from medical records (6 months before evolocumab up to 30 months post initiation). We report interim data from pts initiating evolocumab from August 2015 followed-up until July 2020. Results Of the 1,952 pts in whom evolocumab was initiated as per local reimbursement criteria, most (1844 [94%]) had 12 months follow-up, 785 (40%) had 24 months follow-up; mean follow-up: 20 months. Mean (SD) age was 60 (10.8) years; 85% of pts had a history of CV disease, 45% had familial hypercholesterolemia, 19% had type 2 diabetes, 65% were hypertensive, 7% had chronic kidney disease and 51% were prior/current smokers. At evolocumab initiation, 60% reported statin intolerance and 41% were on no background LLT. Fewer than half (846 [43%]) were receiving a statin (± ezetimibe); of these, most received a high/moderate intensity (68%/22%), with 13% receiving statin monotherapy. Median (Q1, Q3) baseline LDL-C was 3.98 (3.17, 5.07) mmol/L. Within 3 months of initiation median LDL-C fell by 58% to 1.63mmol/L. This reduction was maintained over time (Figure 1). Overall, 58% of pts achieved at least one LDL-C <1.4mmol/L during follow-up. Among pts receiving background statins ± ezetimibe at evolocumab initiation, 67% (710/1053) achieved at least one LDL-C <1.4mmol/L, versus 44% (317/714) of pts not receiving background statins/ezetimibe. During follow-up background oral LLT did not materially change; 40–45% pts received no LLT, 41–44% received statin ± ezetimibe, 12–14% received statin monotherapy. Conclusion In Europe, pts initiated on evolocumab had baseline LDL-C levels almost 3x higher than the present threshold for PCSK9i use recommended in guidelines reflecting disparities between local reimbursement criteria and guidelines. Although evolocumab led to a >50% reduction in LDL-C, only ∼50% pts achieved an LDL-C <1.4mmol/L, as approximately 41% received only evolocumab as monotherapy. LDL-C goal attainment was however higher among pts receiving evolocumab with background LLT. Therefore, lowering the LDL-C threshold for PCSK9i reimbursement, would result in more patients receiving combination therapy with oral LLT plus PCSK9i, thus increasing the likelihood of more pts achieving very-high risk LDL-C goals. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen Europe GmbH


Author(s):  
Peter P Toth ◽  
Xuehua Ke ◽  
Zhenxiang Zhao ◽  
Nicole Bonine ◽  
Mark J Cziraky ◽  
...  

Background: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the treatment of hypercholesterolemia marked a departure from previously established guidelines in regards to pharmacologic therapy. This study identified patients with atherosclerotic cardiovascular disease (ASCVD) using the new guidelines, and examined their patterns of lipid lowering medication (LLM) use in a real-world environment. Methods: This retrospective cohort study utilized claims data from the HealthCore Integrated Research Database (HIRD SM ). Newly diagnosed ASCVD patients aged ≥18 years were identified between 1/1/2007 and 11/30/2012 (index date=first ASCVD diagnosis date). Patients had both ≥ 12 months pre- and post- index health plan enrollment and no LLM use at baseline. Index LLM was identified based on earliest fill of LLM within 6 months after the index date. Index LLM dose titration, discontinuation, switch, and augmentation were examined among monotherapy initiators only. Descriptive statistics were used to examine patterns of LLM use at 12 and 36 months follow-up among all patients and those with ≥36 months post-index health plan enrollment respectively. Results: The study identified 128,017 ASCVD patients with a mean age of 59 years, 43.1% (55,136 of 128,017) female, and 48.8% (62,493 of 128,017) with ≥36 months follow-up. Within 6 months after the index date, 7.8% (9,929 of 128,017) initiated high-intensity statin monotherapy; 27.8% (35,634 of 128,017) moderate/low-intensity statin monotherapy; 1.6% (2,024 of 128,017) non-statin monotherapy; 1.4% (1,770 of 128,017) combination therapy; and 61.4% (78,660 of 128,017) had no fills for any LLM. Among monotherapy initiators over 12 and 36 months follow-up, 8.8% (4,180 of 47,587) and 12.4% (2,635 of 21,198) had up-titration of index LLM, 54.5% (25,938 of 47,587) and 77.8% (16,488 of 21,198) discontinued index LLM, 9.6% (4,579 of 47,587) and 13.9% (2,935 of 21,198) switched their index LLM, and 3.0% (1,403 of 47,587) and 2.8% (586 of 21,198) augmented index LLM. Among all patients over 12 and 36 months follow-up, 41.4% (53,049 of 128,017) and 49.7% (31,057 of 62,493) had statins, 10.6% (13,522 of 128,017) and 13.0% (8,134 of 62,493) had high-intensity statins, 5.8% (7,361of 128,017) and 12.8% (7,989 of 62,493) had ≥2 types of statins, 4.9% (6,253 of 128,017) and 9.3% (5,798 of 62,493) had both statins and non-statin LLMs, and 56.9% (72,897 of 128,017) and 47.9% (29,923 of 62,493) had no LLM. Conclusions: Few patients initiated a high-intensity statin within 6 months of ASCVD diagnosis and at 12 months and 36 months follow-up. Our findings suggest that treatment for ASCVD patients was not optimal in relation to the recent ACC/AHA guideline recommendations and significant modifications in prescribing patterns should be made towards use of high-intensity statins to improve treatment outcomes.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Bruckert ◽  
G Desamericq ◽  
A Khachatryan ◽  
P Ngo ◽  
G Gusto ◽  
...  

Abstract Background introduction Many patients, especially those at very high cardiovascular (CV) risk, do not reach low-density lipoprotein cholesterol (LDL-C) targets for at least 2 reasons: they may not receive a sufficiently intensive regimen, and/or they may not adhere to their medication. Purpose Describe demographic, clinical characteristics and treatment intensity and adherence in patients on lipid lowering therapies (LLT) following an Acute Coronary Syndrome (ACS) in France. Methods Retrospective cohort study on the PGRx (the Pharmacoepidemiologic General Research eXtension program)-ACS dataset in France, with data collected retrospective and prospectively via physicians, prescription records and patient interviews. Patients were accrued prospectively and/or retrospectively by centres from the PGRx Cardiology and General Practitioners networks. We included adult patients (≥18 years) suffering an ACS between 2013 and 2016 who received LLT at or within 92 days of their ACS hospital discharge. Follow-up was censored at time of new CV event, death, lost to follow-up or interview date (mean duration 12.4 months). Outcomes of interest included LLT intensity (high, moderate and low intensity statins with or without ezetimibe) and adherence measured as proportion of days covered (PDC). Results 2695 eligible patients were included (77% men); mean age (SD) 63.1 (12.8), 18% had diabetes mellitus, mean (SD) LDL-C 112.1 (46.4) mg/dl. Treatment with LLT at discharge is summarised in table below. Age and baseline LDL-C were drivers of treatment intensity with higher proportion of patients on high intensity statins in younger patients and in those with higher baseline LDL-C. Overall 70% of patients were adherent (PDC≥80%). Patients on moderate intensity were more adherent (76%) than those on low (63%) or high intensity statins (67%). Treatment patterns with LLT after an ACS LLT following ACS N (%) PDC at 1 year, Mean (SD) Adherent, N (%) Not Adherent, N (%) Ezetimibe 34 (1.3%) 82.8% (31.3%) 26 (76.5%) 8 (23.5%) Low intensity statins 64 (2.4%) 74.8% (33.8%) 40 (62.5%) 24 (37.5%) Moderate intensity statins 993 (37.1%) 82.0% (30.9%) 751 (75.6%) 242 (24.4%) High intensity statins 1515 (56.6%) 74.6% (36.2%) 1007 (66.5%) 508 (33.5%) Statin + ezetimibe 59 (2.2%) 75.9% (34.7%) 40 (67.8%) 19 (32.2%) Overall 2695 (100%) 77.6% (34.3%) 1871 (69.9%) 807 (30.1%) Conclusion(s) Our data show a substantial proportion of patients in France are not treated with high intensity statins after an ACS despite guidelines recommendation. Adherence to LLT is acceptable in patients after an ACS although it appears to worsen when high intense statins are used Acknowledgement/Funding Study has been funded by Amgen GmbH


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
E Bruckert ◽  
B Van Hout ◽  
M Feudjo Tepie ◽  
I Bridges ◽  
...  

Abstract Background 2019 ESC/EAS dyslipidaemia guidelines recommend a 50% lowering in untreated LDL-C and use of PCSK9 inhibitors (PCSK9i) for patients at very-high cardiovascular (CV) risk when LDL-C target goals of <1.4 mmol/L or <1.0 mmol/L (for those with 2 CV events within two-years) are not met despite maximally tolerated statins and ezetimibe. Purpose This observational study describes a cohort of patients initiating evolocumab across 10 EU countries. Methods Patients are followed from evolocumab initiation (baseline). Demographic/clinical characteristics, lipid modifying therapy (LLT) and lipid values were collected from medical records (6 months prior to evolocumab initiation through 30 months post initiation). We report interim data from patients initiating evolocumab from August 2015 with follow-up through October 2019. Results 1896 patients initiated on evolocumab as per local reimbursement criteria were included in this interim analysis (planned sample size: N=2,000). Most (1663 [88%]) had 12 months follow-up, 665 (35%) had 18 months follow-up; mean follow-up, 16.3 months. Mean (SD) age was 60.0 (10.8) years; 85% of patients had a history of CV disease (CVD), 44% had a diagnosis of familial hypercholesterolemia (FH), 19% had type 2 diabetes, 66% were hypertensive, 7% had renal impairment and half (51%) were prior or current smokers. The majority (60%) reported statin intolerance and 42% were not receiving any LLT at evolocumab initiation. Fewer than half (805 [43%]) were receiving a statin (±ezetimibe) at evolocumab initiation; of these, most were on a high/moderate intensity (68%/22%). 12% of patients were receiving statin monotherapy. Median (Q1, Q3) baseline LDL-C was 3.98 (3.16, 5.06) mmol/L. Within 3 months of evolocumab initiation median LDL-C fell by 58% to 1.62 mmol/L. This reduction was maintained over time (Figure). Overall, 58% of patients achieved at least one LDL-C <1.4 mmol/L during follow-up. Among patients receiving background statins and/or ezetimibe at evolocumab initiation, 67% (667/990) achieved at least one LDL-C <1.4 mmol/L, compared with 43% (295/679) of patients not receiving background statins/ezetimibe. During follow-up, 39–46% patients received no background LLT, 40–44% received statin ±ezetimibe, 11–14% received statin monotherapy. Conclusion In Europe, patients initiated on evolocumab had baseline LDL-C levels almost 3 times higher than the present threshold for PCSK9i use, reflecting local reimbursement criteria. Evolocumab resulted in a more than 50% reduction in LDL-C; however, only approximately half of all patients achieved an LDL-C <1.4 mmol/L. LDL-C goal attainment was higher among patients receiving evolocumab with background LLT, suggesting that achievement of EAS/ESC LDL-C goals requires multiple LLTs and a lower threshold for PCSK9i initiation. LDL-C levels after evolocumab initiation Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Escobar Cervantes ◽  
I Campos Tapias ◽  
F Sorio Vilela ◽  
J Lozano ◽  
D.A Kahangire ◽  
...  

Abstract Background/Introduction Reduction in low-density lipoprotein cholesterol (LDL-C) significantly reduces cardiovascular (CV) risk, especially in patients with atherosclerotic CV disease. There is, however, a lack of evidence on the association between achieved LDL-C and resource utilization and costs. Purpose Assess the association of achieved LDL-C levels and resource use and costs in patients treated with lipid-lowering therapies (LLT) following a myocardial infarction (MI). Methods Retrospective observational study using the BIG-PAC® database, with anonymized electronic medical records from 1.9 million inhabitants from 7 regions in Spain. Eligible patients were adults (≥18 years), hospitalized for an MI (index date) between January 2015 and December 2017, treated with LLTs (statins and/or ezetimibe) during follow-up (up to 18 months), and with recorded LDL-C values at baseline and follow-up. Direct (related to health care interventions) and indirect (related to loss of productivity) costs were estimated in 2018€. Costs incurred during follow-up were computed by achieved LDL-C. Achieved LDL-C was obtained in the year following the MI and at least 2 months after the index date. LDL-C categories were defined as per the 2016 and 2019 ESC/EAS guidelines for dyslipidaemias management: <55 mg/dL, 55–69 mg/dL, 70–99 mg/dL, 100–129 mg/dL and ≥130 mg/dL. Results were adjusted for age, gender, CV disease history and comorbidities. Results 6025 patients were included. Mean age (SD) was 69.7 (12.2) and 77% were male. Resource use (not reported in this abstract) and costs monotonically increased with achieved LDL-C. Mean total costs ranged from 5044€ for patients with LDL-C <55 mg/dL to 7567€ for patients with LDL-C ≥130 mg/dL (Table 1). Only 11% (641/6025) of patients reached recommended LDL-C levels for very-high-risk patients as per 2016 ESC/EAS guidelines (<70 mg/dL), and 1% (68/6025) the LDL-C levels (<55 mg/dL) proposed in the 2019 guidelines. Conclusions Achieving lower LDL-C levels following an MI may be associated to lower resource use and costs. Many patients do not achieve recommended LDL-C levels despite treatment with LLT. These data suggest that use of more intense LLT, with a greater reduction in LDL-C, would be beneficial from a clinical and economic perspective. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen (Europe) GmbH


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M De Carlo ◽  
R Liga ◽  
G.M Migaleddu ◽  
M Scatturin ◽  
C Spaccarotella ◽  
...  

Abstract Background Most patients undergoing transcatheter aortic valve implantation (TAVI) develop silent cerebral ischemic lesions (SCIL) detectable at magnetic resonance imaging (MRI). The natural history and clinical relevance of SCIL are not well established. We aimed to assess the characteristics, predictors, evolution, and neurocognitive effects of SCIL. Methods Cerebral MRI was performed within 7 days before TAVI to assess baseline status and age-related white matter changes (ARWMC) score. MRI was repeated postoperatively to assess the occurrence, location, number and dimensions of SCIL. Patients developing SCIL underwent a third MRI at 3–5 months follow-up. A neurocognitive evaluation was performed before TAVI, at discharge and at 3-month follow-up. Results Of the 117 patients enrolled, 96 underwent a postprocedural MRI; SCIL were observed in 76% of patients, distributed in all vascular territories, with a median number of 2 lesions, median diameter 4.5 mm, and median total volume 140 mm3. Independent predictors of SCIL occurrence were a higher baseline ARWMC score and the use of self-expanding or mechanically-expanded bioprostheses. Among 47 patients who underwent follow-up MRI, only 26.7% of postprocedural SCIL evolved into a gliotic scar. SCIL occurrence was associated with a more pronounced transient neurocognitive decline early after TAVI and with a lower recovery at follow-up. Conclusions SCIL occur in the vast majority of patients undergoing TAVR and are predicted by a more diffuse white matter damage at baseline and by the use of non-balloon-expandable prostheses. Although most SCIL disappear within months, their occurrence has a limited but significant impact on neurocognitive function. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): unrestricted grants from Edwards Lifesciences SA, Nyon, Switzerland, and from Medtronic Italia SpA, Milan, Italy


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Medina-Inojosa ◽  
A Ladejobi ◽  
Z Attia ◽  
M Shelly-Cohen ◽  
B Gersh ◽  
...  

Abstract Background We have demonstrated that artificial intelligence interpretation of ECGs (AI-ECG) can estimate an individual's physiologic age and that the gap between AI-ECG and chronologic age (Age-Gap) is associated with increased mortality. We hypothesized that Age-Gap would predict long-term atherosclerotic cardiovascular disease (ASCVD) and that Age-Gap would refine the ACC/AHA Pooled Cohort Equations' (PCE) predictive abilities. Methods Using the Rochester Epidemiology Project (REP) we evaluated a community-based cohort of consecutive patients seeking primary care between 1998–2000 and followed through March 2016. Inclusion criteria were age 40–79 and complete data to calculate PCE. We excluded those with known ASCVD, AF, HF or an event within 30 days of baseline.A neural network, trained, validated, and tested in an independent cohort of ∼ 500,000 independent patients, using 10-second digital samples of raw, 12 lead ECGs. PCE was categorized as low<5%, intermediate 5–9.9%, high 10–19.9%, and very high≥20%. The primary endpoint was ASCVD and included fatal and non-fatal myocardial infarction and ischemic stroke; the secondary endpoint also included coronary revascularization [Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft (CABG)], TIA and Cardiovascular mortality. Events were validated in duplicate. Follow-up was truncated at 10 years for PCE analysis. The association between Age-Gap with ASCVD and expanded ASCVD was assessed with cox proportional hazard models that adjusted for chronological age, sex and risk factors. Models were stratified by PCE risk categories to evaluate the effect of PCE predicted risk. Results We included 24,793 patients (54% women, 95% Caucasian) with mean follow up of 12.6±5.1 years. 2,366 (9.5%) developed ASCVD events and 3,401 (13.7%) the expanded ASCVD. Mean chronologic age was 53.6±11.6 years and the AI-ECG age was 54.5±10.9 years, R2=0.7865, p<0.0001. The mean Age-Gap was 0.87±7.38 years. After adjusting for age and sex, those considered older by ECG, compared to their chronologic age had a higher risk for ASCVD when compared to those with <−2 SD age gap (considered younger by ECG). (Figure 1A), with similar results when using the expanded definition of ASCVD (data not shown). Furthermore, Age-Gap enhanced predicted capabilities of the PCE among those with low 10-year predicted risk (<5%): Age and sex adjusted HR 4.73, 95% CI 1.42–15.74, p-value=0.01 and among those with high predicted risk (>20%) age and sex adjusted HR 6.90, 95% CI 1.98–24.08, p-value=0.0006, when comparing those older to younger by ECG respectively (Figure 1B). Conclusion The difference between physiologic AI-ECG age and chronologic age is associated with long-term ASCVD, and enhances current risk calculators (PCE) ability to identify high and low risk individuals. This may help identify individuals who should or should not be treated with newer, expensive risk-reducing therapies. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Rapezzi ◽  
A.V Kristen ◽  
B Gundapaneni ◽  
M.B Sultan ◽  
M Hanna

Abstract Background In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis was shown to be an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Further assessment of the efficacy of tafamidis in patients with more advanced ATTR-CM would aid treatment decisions. Purpose To characterize the benefits of tafamidis in patients with advanced ATTR-CM. Methods In ATTR-ACT, ATTR-CM patients were randomized to tafamidis (n=264) or placebo (n=177) for 30 months. Efficacy outcomes included all-cause mortality and frequency of cardiovascular (CV)-related hospitalisations. Key secondary endpoints were change from baseline to Month 30 in 6MWT distance and KCCQ-OS score. Efficacy assessments in NYHA Class III patients at baseline (n=141) were a pre-specified analysis. In a post-hoc analysis, mortality and CV-related hospitalizations were assessed in all patients grouped into quartiles of increasing disease severity based on 6MWT distance at baseline. Longer-term all-cause mortality (as of 1 Aug 2019) was assessed in NYHA Class III patients utilizing data from ATTR-ACT patients who enrolled in a long-term, extension study (LTE) and continued treatment with higher dose tafamidis (n=55; median treatment duration 51.6 months); or, if previously treated with placebo, started tafamidis treatment (placebo/tafamidis; n=63 [50.1 months]). Results In advanced ATTR-CM patients (NYHA Class III), tafamidis reduced the risk of death (HR [95% CI] 0.837, [0.541, 1.295], P=0.4253), and the decline in 6MWT distance (LS mean [SE], 31.6 (22.1) m; P=0.1526) and KCCQ-OS score (LS mean [SE], 13.1 (5.0); P=0.0090), vs placebo. Paradoxically, there was a higher frequency of CV-related hospitalizations with tafamidis (RR [95% CI] vs placebo, 1.411 [1.048, 1.900]). In all patients by 6MWT quartile, CV-related hospitalizations/year with tafamidis and placebo increased with disease severity, with the exception that placebo-treated patients in the highest severity quartile had fewer CV-related hospitalisations (0.73) than those in the third quartile (0.92). Mortality with tafamidis and placebo increased, and was greater with placebo, in every quartile (Figure). Survival (NYHA Class III patients in ATTR-ACT and LTE) was improved with high dose tafamidis with longer term follow-up (HR vs placebo/tafamidis [95% CI], 0.6569 [0.4175, 1.0336]; P=0.0692). Conclusions These analyses, including longer-term follow-up, demonstrate that patients with advanced ATTR-CM benefit from tafamidis. The decrease in CV-related hospitalisations in more severe patients treated with placebo suggests that the comparatively greater hospitalisation frequency in NYHA Class III patients treated with tafamidis is a consequence of their lower mortality rate. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer


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