Medical Cost and Healthcare Resource Utilization Influenced by Anti-Platelet Agent Selection in Patients with Acute Coronary Syndrome

Acute coronary syndrome (ACS), after receiving percutaneous coronary intervention (PCI), requires appropriate long-term antiplatelet therapy with a P2Y12 combination with aspirin.[1,2] Clopidogrel, a 2nd generation P2Y12 antagonist, has stood as the gold-standard, but two alternative options, prasugrel and ticagrelor, are now available in the US healthcare market. Multiple studies retrospectively analyzed and compared outcomes of different anti-platelet strategies in real-world ACS populations using administrative databases. However, due to methodological limitations, the studies potentially overestimated overall cost or did not account for the adherence on the initial treatment.

Medical Cost and Healthcare Resource Utilization Influenced by Anti-Platelet Agent Selection in Patients with Acute Coronary Syndrome Kibum Kima,b, Todd A. Leec, Daniel R. Touchettec, Robert J. Didomenicod, Amer K. Ardatie, Surrey M. Waltonc a Pharmacothearpy Outcomes Research Center, University of Utah; b Department of Pathology, University of Utah; c Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy University of Illinois at Chicago; d Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago; e Division of Cardiology, College of Medicine, University of Illinois at Chicago Background Results • Acute coronary syndrome (ACS), after receiving percutaneous coronary intervention (PCI), requires appropriate long-term antiplatelet therapy with a P2Y12 combination with aspirin.[1,2] Clopidogrel, a 2nd generation P2Y12 antagonist, has stood as the gold-standard, but two alternative options, prasugrel and ticagrelor, are now available in the US healthcare market.[3,4] • Multiple studies retrospectively analyzed and compared outcomes of different anti-platelet strategies in real-world ACS populations using administrative databases. However, due to methodological limitations, the studies potentially overestimated overall cost or did not account for the adherence on the initial treatment.[5-7] Table 1. Baseline Characteristics Objectives • This study analyzed aggregated costs and resource utilization associated with the use of clopidogrel, prasugrel and ticagrelor for the treatment of ACS treated with PCI (ACS-PCI) using a nationally collected insurance claims database. • The analyses were performed for those who have initiated one of the three agents, and the subset of the first cohort including those who maintained the initial treatment over a 180-day period. This multi-cohort approach helped in trying to characterize the impact of switching or discontinuation of the initial treatment plan on economic outcomes. Methods • • • • • • Study Design and Analytic Cohort A retrospective cohort study using the Truven Health Marketscan Research Database was designed to compare 6-month overall and pharmacy costs as well as medical resource utilization including number of admission, length of hospital stay and office visit. The analyses were separately performed for all-cause and cardiovascular outcomes. Patients who received a PCI during hospitalization (index admission) with a primary diagnosis of ACS between September 2011 to December 2013 were identified using procedure and diagnosis codes.[8,9] Eligible patients filled one of the three oralantiplatelet agents within 14 days from the discharge date. Patients needed to be continuously enrolled in the data over 6 months prior to the index admission. The analyses were performed for those who enrolled in the data over 6 months (CFU), and for those who maintained the initial treatment over 6 months (CTX). Analysis Differences in baseline characteristics over the six month period were compared using Student t-test, χ2 test or Fisher's exact test. The median, minimum and maximum value of cost and resource use for each treatment group as well as the mean and standard deviation were descriptively analyzed. Statistical significance of the differences in the mean and median were tested using Student ttest and Mood's median test, respectively Incremental outcomes were estimated for patients treated with the newer agents vs. clopidogrel patients, and ticagrelor vs. prasugrel patients. The association between the selection of an anti-platelet agent and outcome was estimated using a generalized model. We applied a bootstrap approach to estimate a 95% confidence intervals of the treatment effect. Clopidogrel (N =17,047) Table 2. Descriptive statistics of Costs and Healthcare Utilization Prasugrel (N = 6,630) Ticagrelor (N =1,287) ‡ Baseline Cost (USD) Mean (SD) Median (Min - Max) 8,794 (23,186) 3,253 (0 - 1,016,574) Male Age (Mean ± SD) Age groups 65<= 55-64 <55 Index STEMI CABG CHF CVE IS ICH TIA Other DM DM w/ comp. Pulmonary Disorder Dementia Dyslipidemia ECH HIV Para or Hemiplegia Hypertension Liver Disorder Cancer MI Renal Disorder Rheumatoid Substance Abuse 12,166 (71.4) 61.9 (12.4) 6,136 (36.0) 6,278 (36.8) 4,633 (27.2) 8,141 (47.8) 96 (0.6) 2,742 (16.1) 1,293 (7.6) 299 (1.8) 47 (0.3) 213 (1.2) 1051 (6.2) 4,564 (26.8) 930 (5.5) 510 (3.0) 95 (0.6) 10,040 (58.9) 1,329 (7.8) 51 (0.3) 80 (0.5) 10,528(61.8) 466 (2.7) 1,017 (6.0) 1,734 (10.2) 1,707 (10.0) 397 (2.3) 3,633 (21.3) Clopidogrel (N=13,088) ‖ Prasugrel (N = 4,810) ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ † ‡ 5,321 (80.26) 56.0 (9.1) 1,020 (15.4) 2,933 (44.2) 2,677 (40.4) 3,795 (57.2) 28 (0.4) 720 (10.1) 204 (3.1) 32 (0.5) 2 (0.03) 33 (0.5) 155 (2.3) 1,666 (25.1) 272 (4.1) 123 (1.9) 7 (0.1) 3,981 (60.0) 362 (5.5) 28 (0.4) 8 (0.1) 3,810 (57.5) 174 (2.6) 255 (3.8) 546 (8.2) 379 (5.7) 123 (1.9) 1,598 (24.1) ¶ 961 (74.7) 58.7 (11.3) 310 (24.1) 527 (41.0) 450 (35.0) 708 (55.0) 7(0.5) 160 (12.4) 72 (5.6) 12 (0.9) 6 (0.5) 11 (0.9) 59 (4.6) 325 (25.3) 53 (4.1) 26 (2.0) 4 (0.3) 756 (58.7) 74 (5.7) 4 (0.3) 5 (0.4) 743 (57.7) 28 (2.2) 67 (5.2) 95 (7.4) 105 (8.2) 26 (2.0) 246 (19.1) ¶ ¶ ¶ ‖ ¶ ¶ * ‖ ¶ ¶ ¶ 9,368 (71.551) 61.5 (12.2) 6,342 (13,623) 2,531 (0 - 312,866) ‡ 3,882 (80.71) 56.0 (9.0) ‡ ‡ 4,526 (34.6) 4,918 (37.6) 3,644 (27.8) 6,397 (48.9) 63 (0.5) 2,003 (15.3) 889 (6.8) 196 (1.5) 32 (0.24) 147 (1.1) 720 (5.5) 3,324(25.4) 667 (5.1) 368 (2.8) 61 (0.5) 7,755 (59.3) 963 (7.4) 34 (0.3) 56 (0.4) 7,972 (60.9) 345 (2.64) 723 (5.5) 1,268 (9.7) 1,214 (9.3) 315 (2.4) 2,789 (21.3) Clopidogrel 6,814 (18,828) 2,638 (0-335,311) ¶ 665 (76.17) 58.7 (11.1) ¶ ¶ 722 (15.0) 2,148 (44.7) 1940 (40.3) 2,789 (58.0) 21 (0.4) 496 (10.31) 144 (3.0) 22 (0.46) 1 (0.02) 23 (0.5) 110 (2.3) 1,145 (23. 8) 184 (3.8) 90 (1.9) 4 (0.08) 2,896 (60.2) 253 (5.3) 20 (0.4) 6 (0.12) 2,734 (56.8) 118 (2.5) 182 (3.8) 380 (7.9) 256 (5.3) 99 (2.1) 1,162 (24.2) ‡ ‡ ‡ ‡ ‡ ‡ ‡ † ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡ * ‡ 207 (23.7) 268 (42.2) 298 (34.1) 482 (55.2) 3 (0.3) 115 (13.17) 44 (5.0) 5 (0.57) 1 (0.1) 8 (0.9) 41 (4.7) 220 (25.2) 39 (4.5) 16 (1.8) 2 0.23) 517 (59.2) 50 (5.7) 4 (0.5) 2 (0.23) 510 (58.4) 17 (1.9) 45 (5.2) 61 (7.0) 67 (7.0) 15 (1.7) 155 (17.8) ‖ ¶ ¶ ‖ ¶ ¶ 17,366 (34,351) Total All-cause 7,071 Medical (0 - 1,394,303) 2,377 Cost ($), CFU (3,281) Pharmacy 1,764 (0 - 139,457) 0.22 (0.59) Admission 0 (0 -11) All-cause Days in 5.70 (7.40) Resource 4 (1 - 143) Hospital* Utilization 0.40 (0.85) ER visit (count), 0 (0 - 23) CFU 6.13 (4.51) Office Visit 5 (0 -164) -3000 6-month Follow up 6-month Adherence -1500 0 -282 328 -1,753 -96 1500 980 -354 1,022 0 0.02 0.04 -0.029 0.001 -250 0 250 500 -0.004 1000 Δ Total Cost ($) Cohort 0.028 -22 117 Newer agents vs. Clopidogrel 0 Conclusion • The use of a 3rd generation anti-platelet agent is associated with a reduction of healthcare resource utilization including hospital admissions over a 6-month post discharge period. • Substantial increases in drug costs associated with the use of the new agents were offset by this decreased resource utilization. Limitation • The research is subject to general limitations found in retrospective studies, such as the potential for miscoding, and the potential for unmeasured confounders, and selection bias. -0.05‖ +120 +0.01 0‖ -0.59§ 0 +1.02§ -1‡ -0.06‖ +1 +0.05§ 0‖ -0.59‖ 0§ +0.05‖ 0‖ -717‡ 0‡ +71 +956‖ +836‖ +862 +240§ +755‖ -0.06‖ 0‖ -0.63‖ 0§ -0.07‖ 0‖ -0.59‖ 0‖ +114‖ +0.003 0 +0.54 +1 +0.04 0‡ +0.50‖ 0 1 R² = 0.9375 -1000 0.8 0 1000 0.7 0.7 Ticagrelor vs. Prasugrel 1.2 0 1 -2000 -1000 0 -1000 1000 0.8 0.9 1 1.4 R² = 0.8994 1000 -2000 Note. Blue, Third generation agent vs. Clopidogrel,;Red, Ticagrelor vs. Prasugrel, analysis. +659‖ 0.9 2000 271 +192§ Number of Admission (Rate Ratio) -1000 803 877 957 +634‖ +869 Figure2. Correlation between all-cause and cardiovascular outcomes -72 62 208 -0.052 -0.038 -0.025 -0.036 750 +712‖ Note: Student t-test for means and Mood's test for median Symbols: *Days in hospital per patient who had at least one hospital admission; ‡p-value < 0.1; §p-value <0.05; ‖p-value <0.01 668 731 809 0.035 16,998 (27,100) 8,533 (361 - 314,748) 3,172 (3,259) 2,522 (0 - 62,463) 0.18 (0.52) 0 (0-5) 5.96 (6.90) 4 (1 - 52) 0.38 (0.77) 0 (0 - 8) 5.93 (4.02) 5 (0 - 31) 1000 Δ Drug Cost (US $ in 2015) -0.043 -0.029 -0.015 1,348 -577 93 739 -1,767 Δ Number of Admission -0.06 -0.04 -0.02 16,409 (29,345) 7,663 (0 - 697,239) 2,980 (2,693) 2,402 (0 - 48,575) 0.17 (0.49) 0 (0-7) 4.93 (5.77) 3 (1 - 75) 0.33 (0.72) 0 (0 - 9) 5.46 (3.53) 5 (0 - 34) R² = 0.8662 Figure 1. Incremental Cost, Healthcare Resource Utilization and 95% CI estimates Δ Total Cost (US$ in 2015) Ticagrelor 15,6550 14,927 14,998 (30,345) (25,056) (19,930) Total All-cause 6,911 7,715 8,577 Medical (31 - 1,394,303) (80 - 697,2397) (361 - 240,500) 2,404 3,204 3,444 Cost ($), CTX (3,802) (2,667) (3,414) Pharmacy 1,847 2,575 2,690 (0 - 139,457) (0 - 41,194) (0 - 62,463) 0.19 (0.53) 0.13 (0.41) 0.13 (0.42) Admission 0 (0 - 11) 0 (0 - 6) 0 (0 - 4) All-cause Days in 4.78 (5.01) 4.06 (4.34) 4.60 (3 34) Resource 3 (1 - 66) 3 (1 - 40) 4 (1 - 16) Hospital* Utilization 0.36 (0.79) 0.29 (0.65) 0.33 (0.66) ER visit (count), 0 (0 - 23) 0 (0 - 6) 0 (0 - 6) CTX 6.04 (6.04) 5.38 (3.43) 5.88 (3.87) Office Visit 5 (0 - 164) 5 (0 - 34) 5 (0 - 28) Note. Results from the CFU cohort are presented on the left side of the table. The CTS results are on the right side. Fisher's exact test was performed when an expected number of event in each group was less than 5. Baseline cost comparisons were performed using a Student t-tests for log-transformed values. Symbols: hird generation agent vs. clopidogrel, *p-value < 0.1, †p-value <0.05, ‡p-value <0.01; Ticagrelor vs. Prasugrel, §p-value <0.1, ‖p-value <0.05, ¶p-value <0.01 Cohort Prasugrel ‖ Researcher Names 7,315 (17,503) 7,856 (13,624) 8,182 (20,279) 3,097 3,943 Research Center, 1Pharmacotherapy 3,176 Outcomes (0 - 880,264) (0 - 335,311) (0 - 1,016,574) ‡ Mean (S.D.) Median (Range) Ticagrelor (N = 873) TP T vs. C vs. P Mean Mean Median Median -861‖ +589 2000 R² = 0.9701 0.8 0.6 0.6 0.8 1 1.2 1.4 Note. Results from the CFU cohort. Y-axis: Measure of the treatment effect on all-cause costs and resource utilization. X-axis: Measure of the treatment effect on healthcare costs and resource utilization for cardiovascular condition. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 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