ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines: A Focused Update of the ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use

Name: Work Video:
Duration: 3 min 30 s
Neena S. Abraham; Mark A. Hlatky; Elliott M. Antman; Deepak L. Bhatt; David J. Bjorkman; Craig B. Clark; Curt D. Furberg; David A. Johnson; Charles J. Kahi; Loren Laine; Kenneth W. Mahaffey; Eamonn M.M. Quigley; James M. Scheiman; Laurence S. Sperling; Gordon F. Tomaselli
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1343, 1359, 1589, 1694, 1732, 1741, 1779, 1805, 1814, 1816, 1862, 1895, 2139, 2219, 2244, 2246, 2291, 2350, 2631, 2637, 3494, 3583, 3995, 4151, 4170, 4184], 'medical': [362], 'technologies.': [363], 'cover': [367], 'topics': [368], 'for': [369, 624, 644, 692, 802, 848, 862, 896, 958, 993, 1097, 1115, 1181, 1448, 1542, 1680, 1845, 1874, 1905, 2155, 2172, 2197, 2474, 2541, 2785, 3029, 3192, 3302, 3344, 3515, 3561, 3720, 3800, 4232], 'which': [370, 511, 2699, 2732, 2913, 2987, 2996, 3170, 3415, 3575], 'evidence': [372, 433, 814, 1180], 'base,': [373], 'experience': [374], 'with': [375, 542, 546, 553, 558, 707, 728, 799, 807, 922, 928, 933, 942, 960, 979, 985, 1058, 1081, 1093, 1255, 1307, 1322, 1330, 1350, 1372, 1377, 1406, 1422, 1455, 1485, 1489, 1498, 1523, 1544, 1559, 1571, 1585, 1594, 1610, 1626, 1638, 1653, 1701, 1703, 1714, 1729, 1738, 1921, 1938, 1953, 1981, 1995, 2010, 2042, 2112, 2159, 2248, 2347, 2399, 2403, 2537, 2552, 2558, 2571, 2594, 2607, 2980, 3048, 3091, 3113, 3174, 3199, 3261, 3334, 3363, 3381, 3447, 3457, 3468, 3479, 3712, 3775, 3784, 3823, 3860, 4024, 4068, 4223, 4243], 'technology,': [376], 'is': [380, 399, 534, 631, 743, 883, 954, 1112, 1184, 1190, 1297, 1536, 1621, 1748, 1761, 1766, 1837, 1869, 2663, 2694, 2716, 2831, 2855, 2896, 2914, 2922, 2927, 3024, 3259, 3278, 3306, 3410, 3416, 3477, 3573, 3621], 'not': [381, 435, 562, 615, 955, 1113, 1191, 1260, 1564, 1762, 2095, 2216, 2380, 2884, 2915, 2959, 3042, 3099, 3627, 3827, 3879, 4159], 'considered': [382], 'sufficiently': [383], 'well': [384, 470, 638, 2278, 3836], 'be': [387, 437, 1231, 1801, 1902, 2188, 2261, 2286, 2415, 2701, 3185, 3379, 3394, 3602, 4088, 4095], 'evaluated': [388, 1273, 4132], 'formal': [391], 'ACCF/AHA': [392], 'Practice': [393], 'Guidelines': [394], 'process.': [395], 'Often,': [396], 'topic': [398], 'subject': [401], 'considerable': [403], 'ongoing': [404, 3904], 'investigation.': [405], 'Thus,': [406], 'reader': [408], 'should': [409], 'view': [410], 'as': [415, 450, 469, 471, 585, 637, 639, 768, 1034, 1160, 1238, 1274, 1538, 1908, 2096, 2099, 2277, 2279, 3056, 3270, 3531, 3558, 3728, 3835, 3837, 3854], 'best': [417, 3403], 'attempt': [418], 'in': [429, 518, 599, 715, 731, 797, 890, 940, 1091, 1195, 1234, 1252, 1267, 1279, 1299, 1602, 1682, 1707, 1780, 1848, 1929, 1943, 1951, 1978, 2013, 2025, 2085, 2101, 2134, 2254, 2336, 2401, 2420, 2444, 2490, 2513, 2667, 2718, 2728, 2731, 2802, 2861, 2871, 2892, 2918, 2945, 2950, 2955, 3004, 3014, 3119, 3138, 3316, 3461, 3475, 3504, 3520, 3523, 3543, 3580, 3596, 3632, 3662, 3701, 3779, 3786, 3796, 3888, 4062, 4074, 4081, 4111, 4134], 'where': [431], 'rigorous': [432], 'may': [434, 448, 757, 769, 1800, 2229, 2260, 2414, 2700, 2789, 2978, 3046, 3222, 3240, 3378, 4094], 'yet': [436, 871, 1261, 1678, 2916, 4108], 'available.To': [438], 'avoid': [439], 'actual,': [440], 'potential,': [441], 'perceived': [443], 'conflicts': [444], 'interest': [446], 'that': [447, 520, 1002, 1164, 1193, 2482, 2673, 2835, 2904, 3630, 3848], 'arise': [449], 'a': [451, 531, 538, 551, 792, 816, 839, 1042, 1067, 1082, 1107, 1170, 1206, 1317, 1423, 1439, 1490, 1622, 1627, 1670, 2105, 2175, 2189, 2332, 2341, 2426, 2441, 2516, 2545, 2564, 2567, 2602, 2626, 2664, 2719, 2748, 2833, 2858, 2888, 3160, 3262, 3288, 3458, 3469, 3482, 3497, 3603, 3702, 3746, 3816, 3829, 3838, 3841, 3868, 3936, 4012, 4141, 4164, 4224], 'result': [452], 'industry': [454, 547], 'relationships': [455, 484, 545], 'personal': [457], 'interests': [458], 'among': [459, 759, 1079, 1783, 2088, 2363, 2535, 3944, 4173, 4185, 4203, 4221], 'writing': [461, 467, 494, 532, 652, 676], 'committee,': [462, 468], 'all': [463, 481, 580, 977], 'members': [464, 541, 665], 'peer': [472, 590], 'reviewers': [473], 'document,': [476], 'asked': [478], 'disclose': [480], 'current': [482, 908], 'healthcare-related': [483], 'those': [486, 1306, 3351, 3826, 4222], 'existing': [487], '12': [488, 1451, 2361], 'months': [489], 'before': [490, 2948], 'initiation': [491], 'effort.': [495, 671], 'The': [496, 752, 878, 1028, 1178, 1291, 1913, 2688, 2742, 3164, 3252, 3273, 3323, 3440, 3472, 3568, 3613, 3669, 3903, 4032, 4056, 4217], 'Clinical': [501, 3986, 3991], '(CECD)': [505], 'reviews': [506], 'these': [507, 1196, 3633, 3884], 'disclosures': [508], 'determine': [510], 'companies': [512], 'make': [513], 'products': [514], '(on': [515], 'market': [516], 'development)': [519], 'pertain': [521], 'under': [525], 'development.': [526], 'Based': [527], 'information,': [530], 'committee': [533, 653, 664, 677, 684], 'formed': [535], 'include': [537, 1009, 3955], 'majority': [539], 'no': [543, 554, 1059, 1704, 3082, 3181, 4053, 4201], 'relevant': [544, 555, 559], '(RWI),': [548], 'led': [549, 1527, 2439], 'chair': [552], 'RWI.': [556, 575], 'Authors': [557], 'RWI': [560, 576, 592, 614], 'permitted': [563], 'draft': [565], 'vote': [567], 'text': [569], 'recommendations': [571], 'pertaining': [572], 'their': [574, 667, 747, 750, 763, 974, 2226, 3015, 3135], 'reviewed': [578], 'conference': [581], 'calls': [582, 673], 'updated': [584], 'changes': [586, 1194, 3631], 'occur.': [587], 'Author': [588], 'reviewer': [591], 'pertinent': [593, 616], 'disclosed': [598], 'Appendixes': [600], '2,': [603, 2825], 'respectively.': [604], 'Additionally,': [605], 'ensure': [607], 'complete': [608], 'transparency,': [609], "authors'": [610], 'comprehensive': [611], 'disclosure': [612, 642], 'information—including': [613], 'document—is': [619], 'available': [620, 633, 3003], 'online.': [621], 'Disclosure': [622], 'information': [623, 855], 'CECD': [630], 'also': [632, 1838, 1881, 1898, 2832, 2971], 'online': [634], 'at': [635, 647, 990, 1117, 1301, 1430, 1449, 2181, 2232, 3646, 3980], 'www.cardiosource.org/ACC/About-ACC/Leadership/Guidelines-and-Documents-Task-Forces.aspx,': [636], 'policy': [643], 'development': [646], 'www.cardiosource.org/Science-And-Quality/Practice-Guidelines-and-Quality-Standards/Relationships-With-Industry-Policy.aspx.The': [648], 'work': [649], 'supported': [655, 3307], 'exclusively': [656], 'without': [660, 1324], 'commercial': [661], 'support.': [662], 'volunteered': [666], 'time': [668], 'Conference': [672], 'were': [678, 1357, 2353, 2432, 2614, 3886, 4219], 'confidential': [679], 'attended': [681], 'only': [682, 3516], 'members.1.': [685], 'IntroductionThe': [686], 'potential': [687, 817, 832, 1128, 3110, 3191, 3301], 'benefits': [688], 'antiplatelet': [690, 720, 809, 869, 926, 997, 1102, 1174, 1285, 1328, 1404, 1557, 1736, 1786, 1826, 1841, 1852, 1993, 2044, 2142, 2161, 2227, 2307, 2407, 2493, 3233, 3304, 3441, 3463, 3566, 3695, 3870, 3951, 3970], 'therapy': [691, 927, 1254, 1270, 1329, 1405, 1447, 1558, 1737, 1787, 1853, 1994, 2162], 'atherosclerotic': [693, 1500], 'cardiovascular': [694], '(CV)': [695], 'disease': [696, 1546, 1808, 1868, 2405, 2609], 'have': [697, 835, 1125, 1212, 1315, 1854, 2163, 2331, 2395, 2736, 2887, 3080, 3108, 3176, 3360, 3878, 3900, 4007, 4016, 4038], 'been': [698, 836, 846, 1262, 1272, 1855, 1899, 1941, 2164, 2179, 2299, 3081, 3361, 3628, 3901, 4066, 4131], 'amply': [699], 'demonstrated': [700, 3862, 3880], 'over': [701, 1389, 2325, 2360], 'past': [703], '2': [704, 3453], 'decades,': [705], 'especially': [706], 'regard': [708], 'role': [711, 1243], 'thienopyridine': [713, 1624, 2258, 2568, 2584, 2981], 'drugs': [714, 1020, 3049, 3239], 'preventing': [716, 2421], 'stent': [717, 951, 1319, 1411, 1425, 1441, 3502], 'thrombosis.': [718], 'However,': [719, 2409, 2780, 3508], 'agents': [721], 'increase': [722, 1003, 2023], 'risk': [724, 800, 967, 981, 992, 1005, 1029, 1038, 1052, 1095, 1119, 1293, 1336, 1492, 1511, 1717, 1843, 1872, 1886, 1915, 1926, 1933, 1972, 1989, 2001, 2022, 2040, 2081, 2486, 2504, 2527, 2539, 2592, 3274, 3399, 3485, 3500, 4019, 4069], 'bleeding': [726, 805, 988, 995, 1008, 1032, 1056, 1065, 1078, 1099, 1365, 1399, 1531, 1580, 1658, 1665, 1709, 1724, 1782, 1799, 1847, 1861, 1919, 1936, 1957, 1975, 2004, 2039, 2084, 2119, 2133, 2157, 2185, 2231, 2253, 2304, 2447, 2489, 2503, 2530, 2575, 3979], 'associated': [727, 978, 1937, 2041, 2158, 2570, 3362, 3456, 3478, 4242], 'mucosal': [729, 1820, 2275], 'breaks': [730, 1821], 'upper': [733, 803, 1054, 1063, 1085, 1121, 1876, 1888, 2117, 2422, 2445, 2555, 2573], 'lower': [735, 1118], 'gastrointestinal': [736], '(GI)': [737], 'tract.': [738], 'Rational': [739], 'use': [740, 790, 1013, 1104, 1137, 1166, 1221, 1681, 2241, 2259, 2313, 2438, 2459, 2523, 2562, 2585, 3219, 4046, 4155, 4240], 'thienopyridines': [742, 824, 1141, 1223, 1256, 1296, 1939], 'based': [744, 761, 3319], 'weighing': [746], 'risks': [748, 756, 1145], 'against': [749, 3396], 'benefits.': [751], 'magnitude': [753, 771, 4057], 'vary': [758, 3013], 'patients,': [760, 4100], 'history': [764, 1083, 1859], 'characteristics,': [767], 'benefits.An': [774], 'earlier': [775], 'Document,': [778], '"Reducing': [779], 'GI': [781, 804, 876, 983, 987, 1007, 1031, 1055, 1064, 1077, 1086, 1098, 1122, 1152, 1530, 1770, 1798, 1835, 1846, 1877, 1889, 1906, 1918, 1935, 1956, 1974, 2003, 2038, 2083, 2118, 2132, 2156, 2176, 2184, 2213, 2252, 2303, 2423, 2446, 2488, 2529, 2542, 2556, 2574, 2623, 3401, 3978], 'Use,"': [787], 'recommended': [788, 957, 1074, 1114, 1427, 1443, 1537, 1749], 'proton': [793], 'pump': [794], 'inhibitor': [795], '(PPI)': [796], 'patients': [798, 864, 941, 959, 1080, 1092, 1116, 1300, 1313, 1321, 1356, 1371, 1437, 1454, 1497, 1543, 1637, 1728, 1784, 1979, 2089, 2100, 2110, 2135, 2337, 2346, 2364, 2402, 2430, 2491, 2514, 2536, 2551, 2606, 2640, 3505, 3707, 3735, 3744, 3757, 3771, 3812, 3832, 3858, 3947, 4010, 4025, 4146, 4175, 4188], 'factors': [801, 1039, 1096, 1844, 1927, 2540, 4083], 'treated': [806, 1360, 1376, 1593, 1980, 2111, 3711, 3859], 'dual': [808, 1327, 1446, 1556, 2043, 2141, 2160, 3950], 'therapy.1': [810], 'Since': [811], 'its': [812, 2868, 2937, 3232, 3965], 'publication,': [813], 'adverse': [818, 833, 1925, 3487], 'drug': [819, 3193, 3276, 3281], 'interaction': [820, 834, 1183, 1229, 3194, 3254], 'between': [821, 1185, 4044, 4084], 'PPIs': [822, 1061, 1088, 1139, 1258, 2398, 2413, 2483, 3117, 3147, 3172, 3198, 3221, 3258, 3877, 3930, 3989, 4093, 4126, 4205], 'has': [825, 845, 1259, 1271, 1897, 1909, 1940, 2178, 2298, 3626, 4065, 4130], 'emerged.2': [826], 'Many': [827], 'investigations': [829], 'performed,': [837], 'using': [838, 1157, 3891], 'variety': [840], 'research': [842, 904], 'designs.': [843, 3894], 'It': [844, 1189, 3625], 'difficult': [847], 'practitioners': [849], 'assimilate': [851], 'flood': [853], 'develop': [858, 1789], 'optimal': [859], 'treatment': [860, 1283, 3392, 4060], 'strategies': [861], 'managing': [863, 1253], 'who': [865, 872, 1100, 1124, 1314, 1419, 1458, 2090, 2352, 2431, 2613, 3341, 3352, 3948], 'might': [866, 873, 3068], 'benefit': [867, 1130], 'from': [868, 875, 1131, 1295, 1345, 1366, 1392, 1400, 1648, 1659, 1666, 1696, 1790, 1833, 2174, 3390, 3678], 'therapy,': [870, 2045], 'suffer': [874], 'bleeding.': [877, 1087, 1831, 1890, 2424, 2543], 'purpose': [879], 'review': [885], 'critically': [886], 'developments': [889], 'area,': [892], 'provide': [893, 2034], 'provisional': [894], 'guidance': [895], 'management,': [898], 'highlight': [900], 'future': [903], 'necessary': [905], 'address': [907], 'knowledge': [909], 'gaps.1.1.': [910], 'Summary': [911], 'Findings': [913], 'RecommendationsClopidogrel': [916], 'reduces': [917, 936, 949, 1050, 1172, 1410], 'major': [918, 937, 1364, 1386, 1398, 1473, 1513, 1567, 1603, 1645, 1657, 1708, 1723], 'CV': [919, 938, 1150, 1217, 1268, 1289, 1303, 1387, 1501, 1514, 1545, 1568, 1604, 1646, 2198, 2404, 2608, 2968, 3373, 3388, 3491, 4021, 4048, 4105, 4167, 4248], 'events': [920, 939, 1388, 1475, 1569, 1605, 1647, 2624, 4022, 4115], 'compared': [921, 932, 1057, 1349, 1484, 1522, 1570, 1609, 1652, 1700, 2009, 2397, 3333, 3783, 4023], 'placebo': [923, 2371], 'aspirin.Dual': [925], 'clopidogrel': [929, 1168, 1331, 1382, 1409, 1466, 1503, 1560, 1595, 1654, 1758, 1996, 2137, 2383, 2618, 2644, 2788, 3073, 3200, 3227, 3246, 3256, 3383, 3444, 3462, 3665, 3698, 3753, 3777, 3824, 3864, 3958, 4015, 4027, 4150], 'aspirin,': [931, 1739, 1815, 2355, 2995], 'aspirin': [934, 971, 1282, 1333, 1351, 1384, 1407, 1468, 1486, 1524, 1562, 1572, 1597, 1611, 1747, 1760, 1968, 1982, 1998, 2011, 2243, 2434, 2612, 3713], 'alone,': [935, 970, 972, 1352], 'established': [943, 1192, 1499, 3629], 'ischemic': [944, 962, 1516, 1587, 1591, 1730, 1734], 'heart': [945], 'disease,': [946, 1502], 'it': [948, 3057], 'coronary': [950, 1309, 1318, 1415, 3709, 3755], 'thrombosis': [952, 1412, 3503], 'but': [953, 1362, 1396, 1488, 1577, 1655, 1713, 1754, 2019, 2225, 3041, 3385, 3883, 4041, 4050], 'routinely': [956], 'prior': [961, 986], 'stroke': [963, 1344, 1480, 1588, 1695, 1731], 'because': [964, 4078], 'bleeding.Clopidogrel': [969], 'combination': [975, 1743, 1756], 'increased': [980, 1363, 1397, 1578, 1656, 1716, 1999, 3369, 3387, 3398, 3499, 4018, 4245], 'bleeding.Patients': [984], 'highest': [991], 'recurrent': [994, 1752, 3372], 'therapy.': [998, 1060, 2143, 2408, 2494, 3952], 'Other': [999], 'characteristics': [1001], 'advanced': [1010], 'age;': [1011], 'concurrent': [1012, 2595], 'anticoagulants,': [1015, 1893], 'steroids,': [1016, 1894], 'nonsteroidal': [1018], 'anti-inflammatory': [1019], '(NSAIDs)': [1021], 'including': [1022, 2845, 3490, 4207], 'aspirin;': [1023], 'Helicobacter': [1025], 'pylori': [1026, 1812, 1911], 'infection.': [1027], 'increases': [1033, 1883, 1920], 'number': [1036, 1923, 2058, 3449], 'increases.Use': [1040], 'PPI': [1043, 1108, 1171, 2437, 2522, 2565, 2596, 3115, 3548, 3817, 3839, 3968, 3983, 4013, 4045, 4157, 4239], 'histamine': [1045], 'H2': [1046, 2310], 'receptor': [1047, 1675], 'antagonist': [1048], '(H2RA)': [1049], 'reduce': [1062, 1076, 1288, 1566, 2470, 2484, 3242], 'greater': [1068, 1298, 1491, 2442, 3279, 3484], 'degree': [1069, 3168, 4003], 'than': [1070, 2369, 2418, 2457, 2583, 2639, 3666, 3734, 3770, 3825], 'do': [1071, 2215, 2958, 3098], 'H2RAs.PPIs': [1072], 'appropriate': [1090], 'multiple': [1094], 'require': [1101, 3949], 'therapy.Routine': [1103], 'either': [1106, 1245, 2288, 4149, 4172], 'an': [1110, 1182, 1275, 1539, 1599, 1715, 1930, 2047, 2670, 2704, 2897, 2923, 2932, 3368, 3397, 4017, 4119, 4244], 'H2RA': [1111, 2458, 2999, 3937], 'bleeding,': [1123, 1907, 2633], 'much': [1126, 3539], 'less': [1127, 1529, 2092, 2572, 3654, 3725, 3763, 3820], 'prophylactic': [1132], 'therapy.Clinical': [1133], 'decisions': [1134], 'regarding': [1135], 'concomitant': [1136, 1165, 1220, 2206, 2561], 'must': [1142, 3393], 'balance': [1143], 'overall': [1144], 'benefits,': [1147], 'considering': [1148], 'both': [1149, 2753, 2872, 2941], 'complications.Pharmacokinetic': [1153], 'pharmacodynamic': [1155], 'studies,': [1156, 4092], 'platelet': [1158, 1249, 1634, 2678, 2686, 2908, 3250, 3365, 3376, 3521, 3544, 3570, 3578, 3611, 3657, 3676, 3688, 3726, 3764, 3821, 3852, 3942], 'assays': [1159, 3853], 'surrogate': [1161, 1197, 3559, 3634, 3855], 'endpoints,': [1162, 3857], 'suggest': [1163, 2412, 2481], 'effects': [1175, 1215, 1827, 2228, 2774, 3696, 3926], 'clopidogrel.': [1177, 1188, 3715], 'strongest': [1179, 1871], 'omeprazole': [1186, 2620, 3692, 3719, 3760, 3781, 3861, 4208], 'endpoints': [1198, 1959, 3635], 'translate': [1199, 3636], 'into': [1200, 3637], 'clinically': [1201, 1227, 2889, 3638, 4113], 'meaningful': [1202, 2890, 3639], 'differences.Observational': [1203], 'studies': [1204, 1946, 2145, 2589, 3084, 3165, 3885, 3899, 3997, 4037, 4064], 'single': [1207, 3289], 'randomized': [1208, 1965, 2014, 2342, 2393, 2604, 2615, 2641, 3717, 3736, 3758, 3772, 3846, 4138, 4147], 'trial': [1210, 2343, 3920], '(RCT)': [1211], 'shown': [1213, 1900, 4039], 'inconsistent': [1214, 3178], 'outcomes': [1218, 3954], 'PPIs.': [1225], 'important': [1228, 2738, 4114, 4120], 'cannot': [1230, 4087], 'excluded,': [1232], 'particularly': [1233, 1305, 2737], 'certain': [1235], 'subgroups,': [1236], 'such': [1237, 3530], 'poor': [1239, 3682], 'metabolizers': [1240], 'clopidogrel.The': [1242], 'pharmacogenomic': [1246], 'testing': [1247, 1251], 'function': [1250, 2797, 3555, 3571], 'established.2.': [1263], 'Role': [1264], 'Thienopyridines': [1266], 'DiseaseThienopyridine': [1269], 'alternative': [1276, 1540], 'addition': [1280, 1380], '("dual': [1284], 'therapy")': [1286], 'events.': [1290], 'absolute': [1292, 1885, 1988, 2021, 2526], 'reduction': [1294, 1601, 2443, 2593, 3460], 'higher': [1302, 1977, 3382, 3747], 'risk,': [1304], 'acute': [1308, 3535], 'syndromes': [1310], '(ACS)': [1311], 'had': [1316, 1598, 2621, 3652, 3673, 3685, 3723, 3761, 3818, 3840], 'implanted.In': [1320], 'ACS': [1323, 1639], 'ST-segment': [1325, 1373], 'elevation,': [1326], 'plus': [1332, 1561, 1596, 2619, 4014], 'reduced': [1334, 1385, 1469, 1505, 1644, 1686, 2262, 2510, 2524, 2796, 3364], 'cardiac': [1338], 'death,': [1339, 1692, 2193, 3492, 4168], 'myocardial': [1340], 'infarction': [1341], '(MI),': [1342], '11.4%': [1346], '9.3%,': [1348], 'irrespective': [1353], 'whether': [1355, 4009], 'revascularized': [1358], 'medically3': [1361], '2.7%': [1367], '3.7%.': [1369], 'In': [1370, 1453, 1636, 1963, 2104, 2144, 2340, 2374, 2425, 2495, 2518, 2544, 2598, 3739, 3791, 3807, 4090, 4140, 4196, 4228], 'elevation': [1374], 'MI': [1375], 'fibrinolytics,': [1378], '30': [1390], 'days': [1391, 3722], '10.9%': [1393], '9.1%': [1395], '1.7%': [1401], '1.9%.4,5Dual': [1403], 'following': [1413], 'percutaneous': [1414], 'intervention': [1416], '(PCI).6': [1417], 'Patients': [1418, 1584, 3716], 'implanted': [1421], 'bare-metal': [1424], 'receive': [1429, 1445, 2617, 2643], 'least': [1431, 1450, 3647, 3687], 'month': [1433], 'clopidogrel,': [1435, 1702, 1740, 1970, 2113, 2436, 2745, 3679], 'receiving': [1438, 1785, 3506], 'drug-eluting': [1440], 'months.': [1452], 'atrial': [1456], 'fibrillation': [1457], 'unable': [1460, 1547], 'take': [1462, 1549], 'vitamin-K': [1463], 'antagonists,': [1464], 'adding': [1465], 'rate': [1471, 2115, 3370, 4246], 'vascular': [1474, 1520, 1691], '(7.6%': [1476], '6.8%)': [1478], '(3.3%': [1481], '2.4%)': [1483], 'alone': [1487, 1504, 1573, 1612, 2012, 2138, 2645, 4028], 'bleeding—2.0%': [1494], 'per': [1495, 2122, 2507, 2533], 'year.7In': [1496], '(5.8%': [1506], '5.3%)': [1508], 'combined': [1510], 'events,': [1515, 4049], 'stroke,': [1517, 1753, 3495, 3976, 4171], 'MI,': [1518, 1693, 3493, 3974, 4169], 'death': [1521, 2173], 'alone8': [1525], '(2.7%': [1532], '2.0%).': [1534], 'Clopidogrel': [1535, 1777, 2715, 2762, 2810, 3212, 3296, 3799, 3917, 3994], 'agent': [1541], 'aspirin.': [1550, 2339], '9–12In': [1551], 'primary': [1553, 1688], 'prevention': [1554], 'setting,': [1555], 'did': [1563, 2379, 3667, 4158], 'significantly': [1565, 1882, 2381, 3653, 3724, 3762, 3819], '(6.8%': [1574], 'versus': [1575, 1711], '7.3%)': [1576], 'severe': [1579], '(1.3%': [1581, 1618], '1.7%).13': [1583], 'transient': [1590, 1733], 'attack': [1592], 'insignificant': [1600], '(16.7%': [1606], '15.7%)': [1608], 'experienced': [1614], 'more': [1615, 2416, 3540, 3587, 3604], 'life-threatening': [1616], 'hemorrhages': [1617], '2.6%).14Prasugrel': [1620], 'new': [1623], 'derivative': [1625, 2860], 'rapid': [1628], 'onset': [1629], 'consistent': [1631, 1903, 3260], 'inhibition': [1632, 3076, 3248, 3366, 3377, 3609, 3655, 3677, 3765, 3822], 'aggregation.': [1635, 2687, 3612], 'planned': [1641], 'PCI,': [1642, 4154], 'prasugrel': [1643, 1765, 3834, 4152], '12.1%': [1649], '9.9%': [1651], '1.8%': [1660], '2.4%': [1662], 'fatal': [1664], '0.1%': [1667], '0.4%.15Ticagrelor,': [1669], 'novel,': [1671], 'reversible,': [1672], 'direct-acting': [1673], 'P2Y12': [1674, 2682, 2907, 3619], 'blocker': [1676], '(not': [1677], 'approved': [1679, 2917], 'United': [1684, 2920, 3006, 3121], 'States)': [1685], 'endpoint': [1689], '11.7%': [1697], '9.8%': [1699], 'significant': [1705, 2190, 4042, 4054], 'difference': [1706, 1990, 4202], '(11.6%': [1710], '11.2%)': [1712], 'noncoronary': [1719], 'artery': [1720], 'bypass': [1721], 'graft': [1722], '(3.8%': [1725], '4.5%).16For': [1727], 'attack,': [1735], 'dipyridamole': [1745], 'prevent': [1751, 2302], 'recommended,17': [1763], 'contraindicated.153.': [1767], 'Risk': [1768], 'Bleeding': [1771, 1832], 'Related': [1773, 3297], 'Mortality': [1774], 'Associated': [1775], 'With': [1776], 'Alone': [1778], 'CombinationGI': [1781], 'can': [1788, 2285, 2316, 3184], 'many': [1791], 'different': [1792, 3171, 3889, 3892, 3999], 'lesions': [1793, 2237], 'anatomic': [1795], 'sites.': [1796], 'Upper': [1797, 2212, 2251], 'due': [1802], 'esophagitis18': [1804], 'peptic': [1806, 1866, 2272, 2348], 'ulcer': [1807, 1867, 2636], 'related': [1809, 2305], 'H.': [1811, 1910, 2249], 'infection,': [1813], 'NSAIDs.19': [1818], 'These': [1819], 'aggravated': [1823], 'thienopyridines,': [1829], 'promoting': [1830, 2269], 'sites': [1836], 'exacerbated': [1839], 'therapy.20–27Several': [1842], 'setting': [1850, 2256], 'reported': [1856, 3253], 'consistently.': [1857], 'complications': [1864], 'factor': [1873], 'subsequent': [1875], 'bleeding.28': [1878], 'Advanced': [1879], 'age': [1880], 'NSAIDs': [1896], 'predictors': [1904], 'infection.29–35': [1912], 'relative': [1914], '(RR)': [1916], 'present': [1928], 'individual': [1931], 'patient.36The': [1932], 'assessed': [1942, 1955, 3700], 'several': [1944, 4036], 'case-control': [1945, 2547], '(Online': [1947, 1960, 1983, 2016, 4029], 'Table': [1948, 1961, 1984, 2017, 4030], '1)': [1949], 'RCTs': [1952], 'prospectively': [1954], 'safety': [1958], '2).': [1962], 'head-to-head': [1964, 3897], 'trials': [1966, 2015, 2394, 3847], '2),': [1985, 2018], 'although': [1986], 'small.Dual': [1992], '2-': [2006], '3-fold': [2008, 3498], 'range': [2027], '0.6%': [2029], '2.0%.': [2031], 'Two': [2032], 'RCTs3,7': [2033], 'specific': [2035, 3605], 'data': [2036, 2078, 2126, 2411, 2480, 3309], 'demonstrating': [2046], 'RR': [2048, 2171], '1.78': [2050], '(95%': [2051, 2067], 'confidence': [2052], 'interval': [2053], '[CI]:': [2054], '1.25': [2055], '2.54;': [2057], 'needed': [2059], 'harm': [2061], '[NNH]': [2062], '130)': [2064], '1.96': [2066], 'CI:': [2068, 2388, 2453, 2463, 2579, 2651, 4180, 4192], '1.46': [2069], '2.63;': [2071], 'NNH': [2072], '167).': [2074], 'There': [2075], 'fewer': [2077, 2356, 2622], 'routine': [2086], 'selected': [2093], 'closely': [2097], 'monitored': [2098], 'trials.': [2103, 4139], 'cohort': [2106, 2427, 2497, 2588], 'Tennessee': [2108], 'Medicaid': [2109], '1.2%': [2121, 2506], 'year.36There': [2123], 'few': [2125], 'mortality': [2129], 'attributable': [2130], 'varying': [2147], 'duration': [2148], 'design,': [2150], 'case': [2152], 'fatality': [2153], 'rates': [2154], 'low': [2165, 3109], '(0%': [2166], '0.3%).3,29–31': [2168], 'Nevertheless,': [2169], 'bleed': [2177], 'estimated': [2180, 4104], '2.5,37': [2182], 'appears': [2186, 3512, 3600], 'predictor': [2191], 'even': [2194, 3866, 4249], 'after': [2195, 3708, 3754, 4153], 'adjustment': [2196], 'morbidity,': [2199], 'age,': [2200], 'sex,': [2201], 'diabetes,': [2202, 3532], 'PCI': [2203, 3814], 'status,': [2204], 'therapy.37,384.': [2207], 'Strategies': [2208], 'Prevent': [2210], 'Thienopyridine-Related': [2211], 'BleedingThienopyridines': [2214], 'cause': [2217], 'ulcers': [2218, 2273, 2349, 2358], 'erosions': [2220], 'digestive': [2223], 'tract,39': [2224], 'promote': [2230], 'site': [2234], 'preexisting': [2236], 'caused': [2238], 'NSAIDs,': [2245], 'infection': [2247], 'pylori.40': [2250], 'suppressing': [2264], 'gastric': [2265, 2318, 2471, 3019, 3144], 'acid': [2266, 2319, 2472, 3020], 'production,': [2267], 'thereby': [2268, 2684, 3230], 'healing': [2270], 'erosions,': [2276], 'stabilizing': [2281], 'thrombi.41': [2282], 'Acid': [2283], 'production': [2284, 2320, 3332], 'suppressed': [2287], 'H2RAs': [2290, 2315, 2378, 2400, 2419, 3001], 'PPIs;': [2293], 'efficacy': [2295, 3244, 3389, 3464, 4129], 'each': [2297], 'examined': [2300, 4008], 'use.4.1.': [2308], 'Histamine': [2309], 'Receptor': [2311], 'AntagonistsThe': [2312], 'suppress': [2317], '37%': [2322], '68%': [2324], '24': [2326], 'hours,42,43': [2327], 'standard': [2329, 3569, 3660], 'doses': [2330], 'modest': [2333], 'protective': [2334], 'effect': [2335, 2792, 2891, 3312, 3442, 3966, 4061, 4124], 'taking': [2338, 2354, 2610, 3815, 3833], '404': [2345], 'esophagitis': [2351], 'gastroduodenal': [2357, 2502, 2635], 'weeks': [2362], 'assigned': [2365], 'famotidine': [2367, 3037, 3095], '(3.8%)': [2368], '(23.5%;': [2372], 'P=0.0002).18': [2373], 'another': [2375, 3740], 'study,': [2376, 2498, 2521, 4198], 'however,': [2377, 4117], 'protect': [2382], 'users': [2384], '(RR:': [2385, 2576], '0.83;': [2386], '95%': [2387, 2452, 2462, 2578, 2650, 4179, 4191], '0.20': [2389], '3.51).44': [2391], 'No': [2392], 'directly': [2396, 3446, 3923], 'observational': [2410, 4091], 'effective': [2417], '987': [2429], 'prescribed': [2433, 2515, 3929, 4011, 4026, 4097], '(odds': [2448], 'ratio': [2449, 2647], '[OR]:': [2450], '0.04;': [2451], '0.002': [2454], '0.21)': [2456], '(OR:': [2460], '0.43;': [2461], '0.18': [2464, 2652], '0.91).304.2.': [2466], 'InhibitorsPPIs': [2469], 'secretion': [2473], 'up': [2475, 3480], '36': [2477], 'hours.45': [2478], 'Observational': [2479], 'baseline': [2500], 'clopidogrel-related': [2501], 'year': [2508, 2534], '50%': [2512, 3483], 'PPI.36': [2517], 'same': [2520], '2.8%': [2532], '≥3': [2538], 'large': [2546], 'study': [2548, 3741, 3893, 4075, 4085, 4142], 'comparing': [2549, 3187], '2779': [2550], 'endoscopically': [2553], 'confirmed': [2554], 'hemorrhage': [2557], '5532': [2559], 'controls,': [2560], '0.19;': [2577], '0.07': [2580], '0.49)': [2582], 'alone.44': [2586], 'Smaller': [2587], 'confirm': [2590], 'similar': [2591, 3622, 4220], 'prescription.31': [2597], 'results': [2600, 4033, 4076, 4218], 'trial.46': [2605], 'enteric-coated': [2611], '(ie,': [2625, 3931], 'composite': [2627, 4165], 'outcome': [2628, 4162], 'overt': [2630], 'occult': [2632], 'symptomatic': [2634], 'erosion)': [2638], '(hazard': [2646], '[HR]:': [2648], '0.34;': [2649], '0.63).5.': [2654], 'Drug': [2655], 'Metabolism:': [2656], 'Thienopyridine,': [2657], 'H2RA,': [2658], 'PPI5.1.': [2660], 'Thienopyridine': [2661, 2807], 'MetabolismClopidogrel': [2662], 'pro-drug': [2665, 2834], 'converted': [2666, 3133], 'vivo': [2668, 3851, 3941], 'active': [2671, 2692, 2839, 2869, 2899, 2924, 2933, 2938, 3136, 3143, 3330], 'metabolite': [2672, 2693, 2870, 2939, 3331], 'irreversibly': [2674], 'binds': [2675], 'adenosine': [2679, 2817, 2901], 'diphosphate': [2680], '(ADP)': [2681], 'receptor,': [2683], 'inhibiting': [2685], 'bioavailability': [2689], 'determined': [2695], 'intestinal': [2697], 'absorption,': [2698], 'influenced': [2702], 'ABCB1': [2705], 'polymorphism,': [2706], 'metabolism': [2709, 2963, 3023], 'through': [2710], 'cytochrome': [2712, 2820, 2842, 3053, 3092, 3103, 3153], 'P-450': [2713, 2843, 3054, 3104, 3154], 'pathway.47': [2714], 'activated': [2717], '2-step': [2720], 'process': [2721], '(Figure': [2722, 2740, 2783, 2852, 2878, 2910], '1A)': [2723, 2784], 'mediated': [2724], 'oxidative': [2726], 'biotransformation': [2727, 2837, 3071], 'liver,': [2730], 'CYP2C19': [2733, 2776, 2851, 2881, 3175, 3317, 3338, 3358, 3476, 3650, 4226], 'CYP3A': [2735, 2846], 'roles': [2739], '1A).48,49': [2741], 'parent': [2743], 'compound': [2744, 2925], 'lesser': [2749, 3161], 'extent': [2750], '2-oxo-clopidogrel,': [2751], 'substrates': [2754], 'inhibitors': [2756, 2777, 2794], 'CYP1A2,': [2758, 3059], 'CYP2B6,': [2759, 2848], 'CYP2C19.50': [2761], '2-oxo-clopidogrel': [2764], 'extensively': [2766], 'hydrolyzed': [2767, 2856], 'inactive': [2769], 'metabolites,': [2770], 'potentially': [2771, 4101], 'magnifying': [2772], 'polymorphisms.51': [2779], 'redundant': [2781], 'pathways': [2782], 'activation': [2786, 3225], 'mitigate': [2790], 'polymorphisms': [2798, 3359], 'CYP450': [2800, 2975, 2992], 'isoenzymes': [2801, 2957], 'vitro.49,52Download': [2803], 'figureDownload': [2804], 'PowerPointFigure': [2805], '1.': [2806], 'Metabolism.': [2808], '(A)': [2809], 'prasugrel;': [2812], '(B)': [2813], 'ticagrelor.': [2814], 'ATP': [2815], 'indicates': [2816], 'triphosphate;': [2818], 'CYP,': [2819], 'P-450;': [2821], 'hCE1': [2823], 'human': [2826], 'carboxylesterases': [2827], '2.Prasugrel': [2830], 'requires': [2836], 'metabolites': [2840], 'enzymes,': [2844], 'isoforms,': [2847], 'CYP2C9,': [2849], '1A).': [2853], 'Prasugrel': [2854], 'thiolactone': [2859], 'intestine': [2863, 2874], 'then': [2865], 'oxidized': [2866], 'liver': [2877, 2947], '1A).51,53': [2879], 'Reduced-function': [2880], 'alleles': [2882, 3328, 3346], 'believed': [2885], 'prasugrel-treated': [2893], 'patients.54Ticagrelor': [2894], '(AZD6140)': [2895], 'orally': [2898, 3030], 'cyclopentyltriazolopyrimidine': [2900], 'triphosphate': [2902], 'analog': [2903], 'reversibly': [2905], 'inhibits': [2906, 3058], 'receptors': [2909], '1B).': [2911], 'Ticagrelor,': [2912], 'States,': [2921], 'metabolized': [2928, 2942, 2972, 2989, 3050, 3149], 'CYP3A4': [2930], 'metabolite.55,56': [2934], 'Ticagrelor': [2935], 'glucuronidated': [2944], 'elimination': [2949, 3027], 'urine.': [2952], 'Genetic': [2953, 3299], 'variations': [2954, 3315], 'CYP': [2956], 'appear': [2960], 'affect': [2962, 4160], 'ticagrelor.Other': [2965], 'frequently': [2966], 'used': [2967, 3118, 3849], 'medications': [2969], 'system51,52': [2976], 'interact': [2979, 3047, 3112, 3173], 'metabolism.': [2982], 'Of': [2983], 'note': [2984], 'statins,': [2986], 'system,51,52': [2993], 'induces': [2997], 'CYP2C19.575.2.': [2998], 'MetabolismThe': [3000], 'currently': [3002], 'States': [3007, 3122], '(cimetidine,': [3008], 'ranitidine,': [3009], 'famotidine,': [3010], 'nizatidine)': [3012], 'ability': [3016], 'inhibit': [3018, 3224], 'secretion.': [3021], 'Hepatic': [3022], 'dominant': [3026], 'pathway': [3028], 'administered': [3031], 'cimetidine': [3032, 3067], '(60%),': [3033], 'ranitidine': [3034], '(73%),': [3035], '(50%': [3038], '80%)': [3040], 'nizatidine': [3043, 3097], '(22%).58': [3044], 'Cimetidine': [3045], 'via': [3051], 'pathway,': [3055], '2C9,': [3060], '2C19,': [3061], '2D6,': [3062], '2E1,': [3063], '3A4.59–61': [3065], 'Although': [3066], 'decrease': [3069, 3329], 'competitive': [3075], 'CYP2C19,': [3078, 3157, 3229], 'there': [3079, 4199], 'controlled': [3083], 'hypothesis.': [3087], 'Ranitidine': [3088], 'interacts': [3089], 'weakly': [3090], 'P-450,58,62,63': [3093], 'bind': [3100], 'system': [3105], 'and,': [3106, 3158], 'therefore,': [3107], 'clopidogrel.58,625.3.': [3114], 'MetabolismAll': [3116], '(omeprazole,': [3123], 'esomeprazole,': [3124], 'pantoprazole,': [3125, 3774, 3933], 'rabeprazole,': [3126], 'lansoprazole,': [3127], 'dexlansoprazole)': [3129], 'weak': [3131], 'bases': [3132], 'forms': [3137], 'acidic': [3140], 'environment': [3141], 'parietal': [3145], 'cells.64': [3146], 'hepatic': [3152], 'system,': [3155], 'predominantly': [3156], 'extent,': [3162], 'CYP3A4.65': [3163], 'assessing': [3166], 'yielded': [3177], 'results,': [3179], 'so': [3180], 'definitive': [3182], 'conclusions': [3183], 'drawn': [3186], 'pharmacokinetics': [3189], 'various': [3197], 'prasugrel.6.': [3202], 'Hypotheses': [3203], 'Regarding': [3204], 'PPI-Antiplatelet': [3206], 'Interaction6.1.': [3207], 'Reduced': [3208, 3292, 3375], 'Biological': [3209, 3293], 'Action': [3210, 3294], 'Through': [3213], 'Competitive': [3214], 'Metabolic': [3215], 'Effects': [3216], 'CYP2C19Concomitant': [3218], 'competitively': [3223], 'attenuating': [3231], 'effect.': [3234], 'Coadministration': [3235], 'CYP2C19-inhibiting': [3238], 'further': [3241], 'aggregation.66': [3251], 'set': [3263], 'pharmacokinetic': [3266], 'findings': [3267], 'referred': [3268], 'high-risk': [3271], 'pharmacokinetics.66': [3272], 'inefficacy': [3277], 'when': [3280, 3867], 'concentrations': [3282], 'depend': [3283], 'variable': [3285], 'activity': [3286, 3305], 'metabolic': [3290], 'pathway.6.2.': [3291], 'PolymorphismsThe': [3300], 'impaired': [3303, 3863], 'natural': [3314], 'activity,': [3318, 3971], 'genetic': [3321, 3473], 'polymorphisms.': [3322], 'CYP2C19*2,': [3324], 'CYP2C19*3,': [3325], 'CYP2C19*4': [3327], 'common': [3337, 3407], 'genotype.': [3339], 'Individuals': [3340], 'heterozygous': [3343], 'loss-of-function': [3345, 3408, 3451], '"intermediate': [3348], 'metabolizers,"': [3349], 'homozygous': [3354], '"poor': [3356], 'metabolizers."': [3357], 'events.53,67,68': [3374], 'overcome': [3380], 'doses,69': [3384], 'any': [3386], 'higher-dose': [3391], 'weighed': [3395], 'bleeding.70The': [3402], 'characterized': [3404], 'polymorphism': [3409, 3963], 'CYP2C19*2': [3412, 3510, 3962], 'allele': [3413, 3651], '(53),': [3414], 'carried': [3417], '51%': [3419], '55%': [3421], 'Asians,': [3423], '33%': [3424], '40%': [3426], 'African': [3428], 'Americans,': [3429], '24%': [3430], '30%': [3432], 'Caucasians,': [3434], '18%': [3436], 'Mexican': [3438], 'Americans.53,71–75': [3439], 'varies': [3445], 'alleles;': [3452], 'copies': [3454], '65%': [3459], 'copy': [3467], '47%': [3470], 'reduction.71–75': [3471], 'variation': [3474, 3519], 'outcomes,': [3489], 'clopidogrel.53,72': [3507], 'variant': [3511], 'account': [3514], '12%': [3517], 'aggregability': [3522], 'response': [3524, 3663], 'ADP;': [3526], 'factors,': [3529], 'obesity,': [3533], 'ischemia,76': [3536], 'likely': [3537], 'contribute': [3538], 'variability': [3542], 'response.72,73,777.': [3545], 'Evidence-Based': [3546], 'Review:': [3547], 'Clopidogrel/Thienopyridine': [3550], 'Pharmacokinetic': [3551], 'Pharmacodynamic': [3553], 'EffectPlatelet': [3554], 'tests': [3556], 'serve': [3557], 'markers': [3560], 'effectiveness': [3564], 'drugs.': [3567], 'test': [3572, 3589], 'aggregometry,': [3574], 'measures': [3576], 'ADP-stimulated': [3577], 'aggregation': [3579, 3658, 3943], 'whole': [3581, 3597], 'blood': [3582, 3598], 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