D. D. TSIKADERIS MD, FESC SAINT LUKES THESSALONIKI

Transcription

1 D. D. TSIKADERIS MD, FESC SAINT LUKES THESSALONIKI

2 EPIDEMIOLOGY DIAGNOSIS RESPONSE TO THERAPY PROGNOSIS UNDERREPRESENTED IN TRIALS

3 THE SUCCESS RATE OF THERAPY FOR CHD IS SIMILAR IN WOMEN AND MAN THE COMPLICATION RATE DIFFERS

4 SIMILAR BENEFIT WITH MEN IN BIOMARKER POSITIVE WOMEN O DONOGUE ET AL:EARLY INVASIVE VS CONSERVATIVE TREATMENT STRATEGIES IN WOMEN AND MEN WITH USTABLE ANGINA AND NON-ST-SEGMENT ELEVATIONMYOCARDIAL INFARCION:A META ANALYSIS.JAMA 2008:300:71

5 Worse Outcomes in Women Compared to Men After Primary PCI in STEMI Are Not Explained by Infarct Size: A Collaborative Patient-Level Pooled Analysis of 10 Randomized Trials Bjorn Redfors MD, PhD, Ioanna Kosmidou, MD, PhD, Rushad Dordi, Harry P. Selker, MD, Holger Thiele, MD, Manesh R. Patel, MD, James E. Udelson, MD, E. Magnus Ohman, MD, Ingo Eitel, MD, Christopher B. Granger, MD, Akiko Maehara, MD, Ajay Kirtane, MD, SM, Philippe Genereux, MD, Paul L. Jenkins, PHD Ori Ben-Yehuda, MD and Gregg W. Stone, MD

6 1. Jneid Circulation. 2008;118: Redfors JAHA. 2015; 14:4(7); 3. Stone. JACC. 2016;67: ; Study Rationale Women and STEMI Higher risk of adverse outcomes after STEMI compared to men 1 Attributable to older age and comorbidities 2 Less likely to receive guideline-directed therapy compared to men 2 Including timely reperfusion Infarct size after STEMI 3 Strong independent predictor of worse clinical outcomes 3 Objective: To assess whether women develop larger infarcts and therefore have higher risk of adverse event after STEMI

7 Methods Random effect models : Infarct size in women vs. men Multiple linear regression Also studied LVEF and cardiac volume indices 1-year risk of death or heart failure hospitalization in women vs. men Cox proportional hazards regression Includes interaction term between gender and infarct size

8 Results Characteristic Women N=587 Men N=2045 p-value Age ± 0.51 (N=587) ± 0.26 (N=2045) <0.001 Diabetes mellitus 25.47% (149/585) 15.07% (307/2037) <0.001 Smoking (current) 37.88% (214/565) 43.97% (879/1999) Hypertension 63.82% (374/586) 48.58% (992/2042) <0.001 Prior MI 3.58% (21/587) 7.10% (145/2041) Prior CABG 1.70% (10/587) 1.17% (24/2044) 0.35 Symptom-onset to balloon (min) 216 (148, 302; N=563) 182 (130, 265; N=1963) LAD as culprit vessels 63.18% (369/584) 61.83% (1262/2041) 0.15 Baseline TIMI flow 2 Baseline TIMI flow 3 Final TIMI flow 2 Final TIMI flow % (201/547) 22.49% (123/547) 95.65% (550/575) 87.30% (502/575) 35.91% (698/1944) 20.63% (401/1944) 96.99% (1932/1992) 90.71% (1807/1992) Creatinine (mg/ml) 0.80 (0.69, 0.95; N=533) 1.00 (0.86, 1.13; N=1859) 0.007

9 Ejection Fraction (%) LVEF and volume indices

10 Conclusions Worse clinical outcomes in women after STEMI are not explained by larger infarct size or worse systolic cardiac function in women.

11 The PLATINUM DIVERSITY Study Outcomes in Women and Minorities Compared with White Men One Year After Everolimus-eluting Stent Implantation Wayne Batchelor, M.D. and Roxana Mehran, M on behalf of the PLATINUM DIVERSITY investiga

12 Disparities in Clinical Practice and Research Whites account for 64% of population but 85-90% of PCI vo and clinical trial enrollment US Population 2010* 5% 3% 16% 12% 3% 1% 8% 2% 64% US PCI Procedures 2012* 87% White Black BSC ION, Libertē and PE Plus Studies**: Pooled Patient Demographics Other Pacific AI/AN Asian Latino Black White Overall 0 Men Women 50 Composi Registry US N= *MedPar 2012, 2013 Master Hospital file & US 2010 Census **Data supplied by Dr. P. Underwood, BSC

13 PURPOSE 1. Construct a novel study design that woul specifically address the diversity gap 2. Determine if there are significant differe 1 year clinical outcomes between women minorities compared with white men in th of second generation DES 3. To characterize and evaluate the impact social/behavioral/economic determinant health in women and minorities

14 STUDY DESIGN: STATISTICS 1 Endpoint: Death/MI/TVR at 12 months Primary Analyses Women vs White men Expected rates: White men = 7.3% (n=1628 PE Plus PAS) Women = 10.1% (pooled PE Plus PAS (n=806) & PLATINUM Diversity) 2-sided α = 5% Power = ~0.80 Expected attrition = 5% n=1000 (Women in PLATINUM Diversity) Minorities vs White men Expected rates: White men = 7.3% (n=1628 PE Plus PAS Minority = 10.6 % (pooled PE Plus PAS (N=284) & PLATINUM Diversity) 2-sided α = 5% Power = ~0.80 Expected attrition = 5% n=700 (Minority in PLATINUM Divers

15 SECONDARY ENDPOINTS Death MI (STEMI and NonSTEMI) TVR Death/MI Definite/Probable ST (ARC) Definitions for above are as reported in the following: One-Year Outcomes in "Real-World" Patients Treated With a Thin-Strut, Platinum-Chromium, Everolimus-Eluting Stent (from the PROMUS Element Plus US Post-Approval Study [PE-Plus PAS]). Kandzari et al. Am J Cardiol. 2016

16 STUDY DESIGN Total Patients N=4,188 Platinum DIVERSITY N=1,501 PE Plus PAS N=2,687 Women N=1,863 White Men N=1,635 Minority N=1, month Followup 94% (N=1,755) 12-month Followup 95% (N=1,556) 12-month Followup 93% (N=982)

17 Events at 12 Months, % PRIMARY ENDPOINT: DEATH/MI/TVR White men Women Minority 1 Endpoint Components of 1Endpoint P =0.33 P =0.04 P =0.06 P =0.27 P =0.08 P =0.03 P = P = Death/MI/TVR Death MI TVR Binary Rates; Per protocol, MI definition based on CK > 2x ULN; P -value from χ 2

18 Death/MI, % SECONDARY ENDPOINT: DEATH/MI White men Women Minority 10 P -values White men vs Women P= White men vs Minority P = Time (Days) At-risk Patients White Men Women Minority Kaplan Meier Rates; P -value from log-rank test

19 CONCLUSIONS Women showed an increased risk of death/mi Minorities showed an increased risk of MI and de Similar rates of TVR and ST among all 3 groups s that device failure is unlikely to account for the differences These results highlight the heterogeneity confe sex and race and suggest further study into the b social, behavioral, and economic factors that im risk after DES

20 EXCEL Outcomes in Men and Women Patrick W. Serruys, MD, PhD Imperial College London, London, UK Rafael Cavalcante, MD, PhD Erasmus MC, Rotterdam, The Netherlands InCor, University of Sao Paulo, Sao Paulo, Brazil Monday, Oct 31, Room 207, Level 2, 3:47 pm 3:55 pm

21 SYNTAX trial (n=1800) All-cause death at 5 years PCI CABG Women Men Log-rank p= % Log-rank p= % 8.5% 11.4% Days since randomization Days since randomization Sotomi Y, et al. Submitted for publication

22 BEST and PRECOMBAT trials (n=1480) All-cause death at 5 years PCI CABG Women Men Log-rank p=0.52 Log-rank p= % 5.8% 6.4% 5.6% Days since randomization Days since randomization Sotomi Y, et al. Submitted for publication

23 Baseline Characteristics in EXCEL Male (n=1464) Female (n=441) p value Age (years) 65.6 ± ± Hyperlipidemia 69.2% 74.4% Hypertension 72.6% 79.4% Medically treated Diabetes 25.2% 30.8% Congestive heart failure 5.5% 10.5% <0.001 Prior history of anemia 8.4% 13.9% <0.001 Mitral regurgitation (mild/moderate) 27.7% 35.2% Creatinine Clearance (ml/min) 91.6 ± ± 34.0 <0.001 Family history of premature CAD 69.3% 54.6% <0.001 Ever smoked 22.9% 20.9% 0.38 Prior TIA or CVA 6.4% 5.9% 0.72 Peripheral Vascular Disease 9.7% 9.1% 0.72 COPD 7.1% 9.5% 0.10 Stable angina at presentation 53.2% 53.0% 0.94

24 Anatomic and Procedural Characteristics SYNTAX score (Corelab) Lesion location Ostial lesion Mid shaft Distal lesion Bifurcation lesion IVUS use Minimal lumen area (mm 2 ) Minimum lumen area 6.0 mm 2 FFR use FFR Male (n=1464) Female (n=441) p value 27.2 ± % 40.9% 26.5% 33.6% % 35.8% 75.1% 4.7 ± % 9.3% 0.72 ± 0.07 < = > < = > < 24.2 ± % 37.1% 16.8% % 30.8% 83.9% 4.6 ± % 8.1% 0.71 ± 0.08 < <0.001 <

25 Procedural Characteristics Male(n=1464) Female(n=441) pvalue LesionstreatedbyPCI 1.9± ± Stentsimplanted 2.5± ± Vesselsbypassed 2.3± ± BITAuse 31.1% 20.7% Numberoftotalconduits 2.6± ± Numberofarterialconduits 1.4± ±0.5 <0.001 Numberofvenousconduits 1.2± ± No other significant differences regarding procedural characteristics and technique

26 Graft occlusion and Stent thrombosis in Men vs. Women Male Female p value Graft stenosis or occlusion Stent thrombosis (ARC definite/probable) 2.6% 0.7% 3.0% 0.5%

27 All-cause death, MI or stroke at 30 days p< % 8.4% 6.2% 3.6% Slide 11

28 All-cause death, MI, stroke or ischemia-driven revascularization at 30 days p< % 8.9% 6.6% 3.6%

29 All-cause death, MI or stroke at 3 years p= % 14.9% 14.1% 14.0% Slide 13

30 All-cause death, MI, stroke or ischemia-driven revascularization at 3 years 27.8% p= % 20.1% 18.8%

31 Individual 3-year Outcomes Female PCI Female CABG Male PCI Male CABG 16% p= % 12% p=0.16 p= % 11.3% p= % p= % 10% p= % 9.8% 8% 6% 4% 7.0% 7.2% 7.0% 6.3% 5.6% p= % 4.5% p= % 6.9% 2% 2.2% 0% Death MI Stroke Revascularization

32 Conclusions (1) As compared to men, women were older and showed worse baseline risk profile with: higher prevalences of Hypertension, diabetes, hyperlipidemia, heart failure, mitral regurgitation and anemia Worse renal function Women had less anatomic complexity and fewer coronary lesions treated IVUS use during PCI was more frequent in women No other significant differences in procedural technique were observed

33 Conclusions (2) The rate of the primary endpoint of death, MI or stroke at 3 years was numerically higher in women treated with PCI (19.7%) as compared to women treated with CABG (14.1%) and men treated with either strategy (14.9% CABG, 14.0% PCI) (p=0.10) At 30 days, death, MI or stroke occurred more frequently in women treated with PCI and men treated with CABG as compared to men treated with PCI An interaction effect between sex and CABG vs. PCI was observed for the primary endpoint, with borderline statistical significance This data is consistent with the finding of worse prognosis of women treated with PCI observed in the SYNTAX trial

34 ACC/AHA ESC WOMEN SHOULD BE TREATED IN A SIMILAR MANNER TO MEN