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1 Supplementary Online Content Berwanger O, Santucci EV, de Barros e Silva PGM, et al; SECURE-PCI Investigators. Effect of loading dose of atorvastatin prior to planned percutaneous coronary intervention on major adverse cardiovascular events in acute coronary syndrome: the SECURE-PCI randomized clinical trial. JAMA. doi: /jama eappendix 1. Inclusion and Exclusion Criteria eappendix 2. Outcomes Definitions etable 1. Study-Drug Administration etable 2. Study-Drug Administration and Protocol Adherence According to Initial Diagnosis etable 3. Procedural Characteristics etable 4. Laboratory Results etable 5. Sensitivity Analyses on the Primary Outcome This supplementary material has been provided by the authors to give readers additional information about their work.

2 eappendix 1. Inclusion and Exclusion Criteria Inclusion Criteria Patients of both genders, older than 18 years that had accepted to participate in the study by signing the Informed Consent Form, and during the acute coronary syndrome with intention to be treated with angioplasty on the same hospitalization in up to 07 (seven) days from ACS diagnosis (including those with ST segment elevation with planned primary angioplasty) that present at least 2 of the following criteria: Angina-like chest pain or ischemic equivalent; Electrocardiographic abnormalities compatible (ST segment elevation higher than 2mm on precordial leads and 1mm on peripheral or new left bundle branch block, ST segment depression of at least 0.5mm or T wave inversion greater than 0.2mV) on at least two contiguous leads; Abnormalities above the upper normal limit for myocardial necrosis biomarkers (troponin and/or CKMB). * Unstable angina were considered the cases with the firs 2 criteria but normal myocardial necrosis markers. Myocardial infarction (MI) was considered the cases with the third criteria plus one or 2 additional criteria. The presence of ST segment elevation higher than 2mm on precordial leads and 1mm on peripheral or new left bundle branch block were used to classify a MI as a ST segment elevation MI (STEMI).. Exclusion Criteria Pregnant or breastfeeding women and women under 45 years old not using effective contraceptive methods (regular use of contraceptive pills, IUD, tubal ligation). Previous inclusion in this study. Refusal to provide the Informed Consent Form (ICF). Concurrent participation in other randomized clinical trials with any hypolipemiant agents. Drug hypersensitivity. History of advanced liver disease (primary biliary cirrhosis, sclerosing cholangitis, acute hepatitis, persistent elevations of liver transaminases >3 times above the upper normal limit). Use of any statin at maximum dose in the last 24 hours before PCI a. Fibrate intake in the last 24 hours prior to using the study loading dose. a Previous use of statins (for any time prior to inclusion in this study) was not considered an exclusion criterion for the SECURE-PCI Trial. In this way, both statin-naive patients and patients that were previously exposed to this drug class were included. However, the patient could not have received maximum statin dose in the last 24 hours prior to PCI to be eligible due to safety concerns. It was considered maximum dose as follows: Atorvastatin 80mg; Rosuvastatin 40mg; Sinvastatin 80mg; Pravastatin 40mg or Fluvastatin 80mg. Possible differences in the treatment effect among these patients were assessed using pre-specified subgroup analysis.

3 eappendix 2. Outcomes Definitions Death Deaths will be classified in Cardiovascular, Non-cardiovascular and Unknown. The cause of the death is determined by the main condition that caused the death, not the immediate modality of the death. All death causes will be considered of cardiovascular nature, unless there is one noncardiovascular cause clearly defined, except for the death without any additional information that will be classified as Unknown cause. Cardiovascular death includes, but is not limited to, atherosclerotic coronary heart disease (acute myocardial infarction, sudden cardiac death, nonsudden death associated with cardiac symptoms with gradual worsening, unwitnessed death without defined alternative cause, death related to the cardiac surgical procedure or to coronary angiography), vascular atherosclerotic disease (cerebrovascular disease including ischemic and hemorrhagic cerebrovascular stroke, aortic, mesenteric, renal vascular, or peripheral arterial disease, death related to the non-coronary vascular procedure), and other cardiovascular (pulmonary embolism, endocarditis, congestive heart failure, cardiac valvular disease, arrhythmias). Example of non-cardiovascular death includes the primary cause of death as being infectious, related to malignancy, pulmonary, gastrointestinal, accidental trauma, suicide, renal. Cardiovascular death will be then classified as sudden, non-sudden and unwitnessed. Cardiovascular Sudden Death Sudden cardiovascular death is defined as unexpected that is: a) witnessed: occurring within 60 minutes of the symptoms onset, in the absence of another clearly non-cardiovascular cause. b) unwitnessed: within 24 hours of being seen alive, in the absence of pre-existing conditions of circulatory failure or other non-cardiovascular cause of death. All sudden deaths will be classified according to the fulfillment of criteria (a) or (b). Unwitnessed cardiovascular death Death of unexpected occurrence, without the patient having been seen in the last 24 hours and having no other major causes of death identified. Myocardial Infarction All AMI events were classified by the adjudication committee using the following definitions as guidelines: Periprocedural Myocardial Infarction Periprocedural Myocardial Infarction is defined as any one of the following criteria. Cardiac ischemic symptoms are not necessary. If normal cardiac biomarkers at admission: CKMB elevation 3 times the upper normal limit (UNL) or Troponin 5 times the upper reference limit (URL) (if CKMB is not available) within 48 hours after PCI If elevated cardiac biomarkers at admission and tending to decrease before the AMI suspicion: CKMB elevation 3 times the UNL or Troponin 5 times the URL (if CKMB is not available) AND Biomarkers elevation greater than or equal to 20% when compared to pre-procedural value (baseline or 2 hours sample) If elevated cardiac biomarkers at admission and tending to increase or are unknown before the

4 AMI suspicion: New ischemic symptoms for at least 20 minutes AND Additional elevation of CK-MB or Troponin levels at post-procedural, with levels of at least CK- MB 3 times the UNL or Troponin 5 times URL (if CK-MB is not available) AND at least one of the following: Report of complication during the percutaneous coronary intervention, registered at cineangiocoronarygraphy New ischemic changes in the 12-lead ECG during or after the procedure Evidence of AMI on the autopsy (if not index AMI) Summary of definitions of periprocedural AMI Cardiac biomarkers at Angiographic evidence; CKMB admission ECG; ischemic symptoms Normal baseline Not necessary CKMB >3 times the UNL or Troponin >5 times the URL (if CKMB is not available) Elevated tending to decrease Not necessary New elevation of CKMB >3 times the UNL and/or Troponin >5 times the URL (if CKMB is not available) and a 20% increase in relation to the smallest pre-procedural value Abnormal baseline and tending to increase or unknown New ischemic symptoms for at least 20 minutes and report of angiographic complications during PCI or new ischemic changes in the 12-lead ECG Continuous elevation of CKMB >3 times the UNL and/or Troponin >5 times the URL (if CKMB is not available) Spontaneous Myocardial Infarction (usually after 48 hours from PCI) Spontaneous acute myocardial infarction is defined by elevation and/or decrease of cardiac biomarkers (CKMB or troponin) with at least one value above the reference and at least one of the following criteria: Clinical presentation consistent with ischemia Electrocardiographic evidence of acute myocardial ischemia Development of new pathological Q wave Evidence on imaging test of new change in segmental contractility of myocardial wall or loss of viable myocardium The autopsy exam with AMI evidence may be used as isolated criterion for the infarction. If the biomarkers are elevated due to a previous infarction, the spontaneous AMI diagnosis will need the following: Evidence that cardiac biomarkers values are decreasing before the AMI suspicion AND CKMB 3 times the UNL or Troponin 5 times the URL and this value corresponds to a 20% increase of the biomarkers in relation to the lowest value after angioplasty and at least one of the following: Clinical presentation consistent with ischemia Electrocardiographic evidence of acute myocardial ischemia Development of new pathological Q wave Evidence on imaging test of new change in segmental contractility of myocardial wall or

5 loss of viable myocardium Autopsy exam with evidence of new AMI may be used as isolated criterion for the spontaneous infarction. Perioperative myocardial infarction (myocardial revascularization surgery) Perioperative infarction related to myocardial revascularization surgery (CABG) is defined according to the following criteria. Myocardial ischemia symptoms are not necessary. Biomarkers elevation within 72 hours from CABG with CK-MB >5 times the UNL or Troponin >10 times the URL (if CK-MB is not available) AND No evidences that biomarkers are elevated before procedure Evidence that cardiac biomarkers are decreasing before procedure AND 50% increase on cardiac biomarkers - AND o One of the following: o New persistent pathological Q wave for 30 days o New persistent left bundle branch block not related to frequency o New graft or native coronary occlusion documented on angiography o Other complication during the operative event resulting in myocardial loss o Evidence on imaging test of new loss of viable myocardium Evidence of AMI on autopsy Stroke Stroke is defined as an acute focal neurological deficit of sudden onset: a) that is not reversible in 24 hours or that results in death (in less than 24 hours) and is not due to an identifiable cause (e.g. tumor or trauma) b) that resolves in <24 hours and is accompanied by a clear evidence of stroke in brain imaging test. Stroke will be subclassified in subtypes: Non-hemorrhagic cerebral infarction: it is the stroke without intracerebral blood focal collections in brain imaging test. This category will be subclassified between suspects of embolism versus other. Non-hemorrhagic cerebral infarction with hemorrhagic transformation: it is the blood cerebral infarction that seems to represent hemorrhagic transformation and not primary hemorrhage. Hemorrhagic conversion usually occurs at the cortical surface. Deeper hemorrhagic transformation requires evidence of non-hemorrhagic infarction at the same vascular territory. Evident micro-hemorrhages on magnetic resonance imaging (MRI) in both the cortex and the deeper cerebral structures are not considered to be consistent with the hemorrhagic transformation outcome. Primary hemorrhage o Intracerebral hemorrhage: stroke with focal collections of intracerebral blood seen in brain imaging tests (computed tomography (CT) or MRI) or in postmortem exam, not representing hemorrhagic conversion. Primary hemorrhages cause hematomas that are usually easily distinguished by their subcortical location and round or elliptical shape. Micro hemorrhages incidentally found in brain imaging tests in the absence of symptomatology will not be considered a primary

6 intracranial hemorrhagic outcome. o Subarachnoid hemorrhage: collection of high density fluid in the subarachnoid space in brain imaging tests or presence of blood in the subarachnoid space at autopsy. o Uncertain: any stroke without brain imaging test (CT or MRI) or documentation by autopsy or if tests are inconclusive. Subdural hematoma will not be classified as stroke, but will be classified as bleeding outcome (intracranial bleeding). Micro intracerebral hemorrhages will be classified into separate categories for analysis. Micro hemorrhage is defined as rounded focus of less than 10mm that appears hypointense and that are different of other causes of signal loss or echo in the MRI sequences gradient (e.g. vascular flow emptying, leptomeningeous hemosiderosis and non-hemorrhagic subcortical mineralization). Transient ischemic attack is defined as: a. a focal neurological deficit lasting <24 hours and no identifiable non-vascular cause (e.g. cerebral tumor, trauma), AND b. absence of new infarction in brain imaging test (if available). Coronary revascularization Unplanned coronary revascularization is defined as coronary revascularization that was not planned at the first cineangiocoronarygraphy performed due to ACS index event (inclusion criterion). The indication of an unplanned revascularization should be related to new findings (e.g. ischemic symptoms) and include both surgical and percutaneous revascularization cases, both during hospitalization and after hospital discharge from index event. It also includes revascularization attempt even without success. Potential ischemic events that fit the AMI criterion will not be validated with urgency coronary revascularization (only as AMI). Target vessel revascularization Target vessel revascularization is defined as a new percutaneous or surgical procedure resulting from restenosis of the target lesion segment. All target lesion revascularization will be guided by symptoms or by objective evidence of ischemia in noninvasive tests. Stent thrombosis Stent thrombosis is defined according to the Academic Research Consortium (ARC) criteria and is divided into three categories: definitive stent thrombosis, probable stent thrombosis and possible stent thrombosis, the definitions are below. a) Definitive stent thrombosis: the stent thrombosis will be defined by the angiographic or pathologic confirmation. The presence of thrombus originating from stent or at 5mm proximal or distal from the stent and the presence of at least one of the criteria within a 48-hour window (the angiographic documentation of stent occlusion in the absence of clinical signs or symptoms will not be considered as stent thrombosis {silent occlusion}): o Onset of ischemic symptoms at rest o New ECG changes suggesting acute ischemia o Typical curve of cardiac biomarkers that represent AMI o Non-occlusive thrombus: non-calcified intracoronary thrombus ((spherical, ovoid or irregular) defined as filling failure or contrast retention (on 3 sides or within a coronary stenosis) seen in multiple projections, or persistence of contrast material inside lumen, or visible embolization of intraluminal materials distal to obstruction.

7 o Occlusive thrombus: TIMI 0 or 1 intrastent or proximal to the stent to the most proximal adjacent branch or main branch (originates from the lateral branch) Evidence of recent thrombus inside the stent determined by autopsy or by biopsy of tissue removed by thrombectomy. b) Probable stent thrombosis: considered when thrombosis occurs after angioplasty and in the following cases: Death without a known cause within 30 days Any infarct related to acute ischemia in the implanted stent territory, without angiographic confirmation of stent thrombosis and in the absence of any other obvious reason, independent of time. c) Possible stent thrombosis: Considered when any death of unknown cause occurs after 30 days from angioplasty until the end of follow up. The TIMI group also defines stent thrombosis with the following criteria to determine whether the event was angiographically/pathologically confirmed or clinically confirmed: Stent thrombosis angiographically or pathologically confirmed Ischemic chest discomfort or ischemic syndrome determining coronary angiography and angiographic confirmation of thrombosis or presumed thrombotic occlusion of the stent segment. Phatological confirmation of acute stent thrombosis at autopsy. Stent thrombosis clinically confirmed Unexplained cardiovascular death defined as sudden or unwitnessed death without a clear cause of cardiovascular origin. Acute ischemic death (defined as death after presentation of ischemic cardiac event at the stent territory with death occurring before confirmation of coronary angiographic diagnosis). Myocardial infarction related to target vessel is defined as one of the MI signs/symptoms below: Pain of cardiac origin and ST elevation >20 minutes; New Q wave on the electrocardiogram; Ischemic discomfort lasting >10 minutes and biomarkers elevation (1 time UNL not associated to the procedure, 3 times UNL within 48 hours from PCI, 5 times UNL within 48 hours from MRI). AND Evidence of either electrocardiographyc, echocardiographic or nuclear medicine occurrence at the territory of the previously implanted stent without angiographic evidence of stent thrombosis. AND No pathological or angiographic evidence of another guilty injury. Bleeding Hemorrhagic complications were classified according to the bleeding criteria of TIMI Group (Thrombolysis In Myocardial Infarction) 1, GUSTO group (Global Utilization of Streptokinase and t-pa for Occluded Coronary Arteries) 1 and ISTH (International Society on Thrombosis and Haemostasis) Mehran R, Rao SV, Bhatt D, et al. Standardized Bleeding Definitions for Cardiovascular

8 Clinical Trials: A Consensus Report From the Bleeding Academic Research Consortium. Circulation 2014; 123: Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005;3:

9 etable 1. Study-Drug Administration Study-drug Administration Atorvastatin (n=2087) (n=2104) Total First loading dose, No./total No. (%) 2039/2085 (97.8) 2054/2102 (97.7) 4093/4187 (97.8) Second loading dose, No./total No. (%) 1594/2085 (76.5) 1622/2102 (77.2) 3216/4187 (76.8) Atorvastatin 40mg at 30-days a, mean (SD) (34.1) 87 (32.1) 86 (33.1) In patients that underwent PCI First loading dose, No./total No. (%) 1337/1351 (99) 1337/1359 (98.4) 2674/2710 (98.7) Second loading dose, No./total No. (%) 1292/1351 (95.6) 1297/1359 (95.4) 2589/2710 (95.5) Atorvastatin 40mg at 30-days a, mean (SD) (20.2) 94.8 (19.7) 94.6 (20) Time of study-drug administration - n/total no. (%) In patients underwent PCI More than 12h before PCI, No./total No. (%) 50/1349 (3.7) 76/1357 (5.6) 126/2706 (4.7) 2h to 12h before PCI, No./total No. (%) 699/1349 (51.7) 685/1357 (50.5) 1384/2706 (51.1) Until 2h before PCI, No./total No. (%) 577/1349 (42.8) 569/1357 (41.9) 1146/2706 (42.4) Until 2h after PCI, No./total No. (%) 8/1349 (0.6) 4/1357 (0.3) 12/2706 (0.4) 2h to 4h after PCI, No./total No. (%) 1/1349 (0.1) 1/1357 (0.1) 2/2706 (0.1) In patients who did not underwent PCI More than 12h before angiography, No./total No. (%) 32/714 (4.5) 38/725 (5.2) 70/1439 (4.9) 2 to 12h before angiography, No./total No. (%) 323/714 (45.2) 325/725 (44.8) 648/1439 (45) Until 2h before angiography, No./total No. (%) 306/714 (42.9) 317/725 (43.7) 623/1439 (43.3) Until 24h after angiography, No./total No. (%) 11/714 (1.5) 14/725 (1.9) 25/1439 (1.7) More than 24h after angiography, No./total No. (%) 10/714 (1.4) 5/725 (0.7) 15/1439 (1) Abbreviations: PCI denotes percutaneous coronary intervention a Mean of individual percentages ± SD,

10 etable 2. Study-Drug Administration and Protocol Adherence According to Initial Diagnosis Protocol Adherence Time from randomization to study drug (hours) STEMI NSTEMI Unstable Angina Ativo (n=495) Ativo (n=1241) Ativo (n=295) (n=517) (n=1236) (n=296) Mean (SD) 2.6 (16.5) 2.8 (11.8) 7.6 (37.2) 6.3 (29.6) 5.3 (18.3) 4.4 (11.3) Median (Interquartile range) 0.1 [0-0.3] 0.1 [0-0.3] 0.2 [0-0.6] 0.2 [0-0.6] 0.2 [0-0.8] 0.2 [ ] Time from hospital admission to PCI (hours) Mean (SD) 27.1 (62.5) 23.7 (46.4) 55.7 (64.1) 52.7 (65.2) 73.4 (78.2) 79.0 (82.0) Median (Interquartile range) 2 [1-20] 2 [1-23] 31 [8-86] 26 [ ] 54.5 [ ] 50 [20-123] Time from randomization to PCI (hours) Mean (SD) 5.9 (27.1) 5.8 (18.3) 14 (41.9) 13.7 (33.1) 12.7 (27.6) 15.4 (27.1) Median (Interquartile range) 1 [0-2] 1 [0-3] 3 [2-8] 3 [2-8] 4 [2-8] 5 [2-19.5] First loading dose, No./total No. (%) 484/495 (97.8) 503/517 (97.3) 1220/1241 (98.3) 1215/1236 (98.3) 285/295 (96.6) 285/296 (96.3) Second loading dose, No./total No. (%) 428/495 (86.5) 453/517 (87.6) 968/1241 (78) 958/1236 (77.5) 168/295 (56.9) 173/296 (58.4) Atorvastatin 40mg at 30-days a, mean (SD) (27.3) 92.2 (24.9) 85.6 (33.3) 88 (31.0) 74.2 (42.9) 75.6 (41.5) In patients that underwent PCI First loading dose, No./total No. (%) 413/417 (99.0) 439/448 (98.0) 800/809 (98.9) 779/788 (98.9) 106/106 (100) 100/103 (97.1) Second loading dose, No./total No. (%) 392/417 (94.0) 423/448 (94.4) 778/809 (96.2) 757/788 (96.1) 103/106 (97.2) 98/103 (95.1) Atorvastatin 40mg at 30-days a, mean (SD) 93.4 (22.8) 93.4 (22.6) 94.9 (18.4) 95.9 (17.3) 93.3 (23.0) 92.3 (24.1) Time of study-drug administration - N/total no. (%) In patients underwent PCI More than 12h before PCI 7/417 (1.7) 11/448 (2.5) 31/808 (3.8) 56/787 (7.1) 10/105 (9.5) 8/103 (7.8) 2h to 12h before PCI 89/417 (21.3) 103/448 (23.0) 542/808 (67.1) 502/787 (63.8) 66/105 (62.9) 68/103 (66) Until 2h before PCI 311/417 (74.6) 322/448 (71.9) 223/808 (27.6) 219/787 (27.8) 29/105 (27.6) 24/103 (23.3) Until 2h after PCI 6/417 (1.4) 3/448 (0.7) 2/808 (0.2) 0/787 (0.0) 0/105 (0.0) 0/103 (0.0) 2h to 4h after PCI 0/417 (0.0) 0/448 (0.0) 1/808 (0.1) 1/787 (0.1) 0/105 (0.0) 0/103 (0.0) In patients who did not underwent PCI

11 Protocol Adherence STEMI NSTEMI Unstable Angina Ativo (n=495) Ativo (n=1241) Ativo (n=295) (n=517) (n=1236) (n=296) More than 12h before angiography 4/75 (5.3) 4/67 (6.0) 19/428 (4.4) 18/442 (4.1) 8/178 (4.5) 13/184 (7.1) 2 to 12h before angiography 35/75 (46.7) 40/67 (59.7) 180/428 (42.1) 183/442 (41.4) 97/178 (54.5) 84/184 (45.7) Until 2h before angiography 26/75 (34.7) 18/67 (26.9) 203/428 (47.4) 216/442 (48.9) 60/178 (33.7) 74/184 (40.2) Until 24h after angiography 3/75 (4.0) 0/67 (0.0) 5/428 (1.2) 10/442 (2.3) 3/178 (1.7) 3/184 (1.6) More than 24h after angiography 0/75 (0.0) 0/67 (0.0) 9/428 (2.1) 3/442 (0.7) 0/178 (0.0) 2/184 (1.1) Abbreviations: STEMI denotes ST elevation myocardial infarction. NSTEMI denotes Non- ST elevation myocardial infarction.

12 etable 3. Procedural Characteristics Percutaneous cardiovascular intervention characteristics Atorvastatin (n=1351) (n=1359) Heparin used to support PCI, No. /total No. (%) 1196/1349 (88.7) 1199/1356 (88.4) Stent, No. /total No. (%) 1311/1350 (97.1) 1332/1356 (98.2) Bare-metal stent only 1013/1350 (75) 1020/1356 (75.2) 1 Drug-eluting stent 298/1350 (22.1) 312/1356 (23) Restenotic lesions, No. /total No. (%) 32/1350 (2.4) 42/1357 (3.1) Multivessel PCI, No. /total No. (%) 219/1350 (16.2) 214/1356 (15.8) Intravascular Ultrasound Use, No. /total No. (%) 28/1349 (2.1) 22/1357 (1.6) Ballon post-dilatation, No. /total No. (%) 651/1314 (49.5) 645/1314 (49.1) Stent deployment pressure, mean (SD), atm 17.9 (3.4) 17.9 (3.5) No. of stents per patient, No. /total No. (%) 0, No. /total No. (%) 88/1349 (6.5) 70/1356 (5.2) 1, No. /total No. (%) 994/1349 (73.7) 1023/1356 (75.4) 2, No. /total No. (%) 236/1349 (17.5) 233/1356 (17.2) 3 or more, No. /total No. (%) 31/1349 (2.3) 30/1356 (2.2) Procedural complications, No. /total No. (%) a 106/1350 (7.9) 99/1357 (7.3) Coronary Dissection 21/1349 (1.6) 15/1357 (1.1) Acute Coronary Artery Occlusion during PCI 4/1349 (0.3) 2/1357 (0.1) Coronary Slow-Flow Phenomenon 44/1349 (3.3) 36/1357 (2.7) Severe Side-Branch Stenosis 4/1349 (0.3) 5/1357 (0.4) Side-Branch Closure 11/1349 (0.8) 13/1357 (1) Acute Coronary Perforation during PCI 0/1349 (0) 4/1357 (0.3) Coronary Occlusion after PCI 2/1349 (0.1) 0/1357 (0) Temporary Coronary Occlusion during PCI 4/1349 (0.3) 4/1357 (0.3) No-reflow 16/1349 (1.2) 19/1357 (1.4) Distal Embolization 18/1349 (1.3) 11/1357 (0.8) Acute Stent Thrombosis 2/1349 (0.1) 0/1357 (0) a Procedural complications were defined as complications occurred during or after the percutaneous coronary intervention and were related to the procedure.

13 etable 4. Laboratory Results Laboratory Assays Prior to catheterism/pci Total Cholesterol LDL Cholesterol HDL Cholesterol Triglycerides Serum Creatinine Levels Alanine Transaminase (ALT) Aspartate Transaminase (AST) Creatine Phosphokinase (CPK) Atorvastatin Difference (n=2087) (n=2104) (95% CI)ª mean (SD) (48.1) (48.2) 1.1 (-2.3 to 4.4) median [IQR] [ ] [ ] 1.0 (-2.0 to 6.0) mean (SD) (42.5) (41) 1.2 (-1.7 to 4.3) median [IQR] [ ] [ ] 1.0 (-3.0 to 5.0) mean (SD) 37.8 (12.3) 37.7 (11.1) 0.1 (-0.7 to 0.9) median [IQR] 36.0 [ ] 36.0 [ ] 0.0 (-1.0 to 1.0) mean (SD) (124.9) (115.8) 1.2 (-7.3 to 9.7) median [IQR] [ ] [ ] -4.5 (-10.0 to 2.5) mean (SD) 1.04 (0.81) 1.03 (0.58) 0.01 (-0.04 to 0.05) median [IQR] 0.94 [ ] 0.94 [ ] 0.00 (-0.03 to 0.04) mean (SD) 69.6 (97.3) 70.2 (103.6) -0.6 (-7.7 to 6.5) median [IQR] 37.0 [ ] 38.0 [ ] -1.0 (-4.0 to 2.0) mean (SD) 44.9 (56.1) 44.1 (54.8) 0.8 (-3.1 to 4.8) median [IQR] 33.0 [ ] 34.0 [ ] -1.0 (-3.0 to 1.0) mean (SD) (864) (903.5) -1.2 (-62.5 to 60.2) median [IQR] [ ] [ ] -1.5 (-19.0 to 14.0) 30-days Total Cholesterol LDL Cholesterol HDL Cholesterol Triglycerides Serum Creatinine Levels Alanine Transaminase (ALT) Aspartate Transaminase (AST) Creatine Phosphokinase (CPK) mean (SD) (43.4) (35.3) 1.2 (-1.9 to 4.3) median [IQR] [ ] [ ] 1.0 (-3.0 to 3.0) mean (SD) 79.6 (56.4) 75.8 (34.7) 3.8 (0.1 to 7.6) median [IQR] 72.0 [ ] 71.0 [ ] 1.0 (-1.0 to 3.0) mean (SD) 37.9 (11.7) 37.8 (10.2) 0.1 (-0.7 to 1.0) median [IQR] 36.0 [ ] 36.0 [ ] 0.0 (-1.0 to 1.0) mean (SD) (91.6) (72.0) 3.7 (-2.7 to 10.2) median [IQR] [ ] [ ] -6.0 (-11.0 to 1.0) mean (SD) 1.11 (0.71) 1.13 (1.41) (-0.13 to 0.10) median [IQR] 1.00 [ ] 1.00 [ ] 0.00 (-0.03 to 0.04) mean (SD) 23.2 (10.4) 25.7 (55.1) -2.5 (-5.7 to 0.6) median [IQR] 21.0 [ ] 21.0 [ ] 0.0 (-0.4 to 1.0) mean (SD) 29.4 (20.3) 33.0 (80.2) -3.6 (-8.2 to 1.0) median [IQR] 25.0 [ ] 25.0 [ ] 0.0 (-2.0 to 1.0) mean (SD) (113.7) (102.2) 3.2 (-5.5 to 11.9) median [IQR] 81.0 [ ] 79.0 [ ] 2.0 (-3.0 to 6.0) Abbreviations : IQR denotes interquartile range, PCI denotes percutaneous coronary intervention, SD denotes standard deviation ª Mean difference according to student's t-test and median difference with 95% confidence interval estimated by 3,000 bootstrap replications.

14 etable 5. Sensitivity Analyses on the Primary Outcome Sensitivity Analyses Atorvastatin Excluding patients not 119/2039 receiving loading dose (5.8) Excluding patients with event a 118/2038 before loading (5.8%) dose Excluding patients not 81/1337 receiving loading dose (6.1) (PCI group) Excluding patients with event a 80/1336 before loading (6%) dose (PCI group) Excluding patients with 80/1350 eventª before PCI - first method b (5.9) Excluding patients with 55/1325 eventª before PCI - second method c (4.2) Post-hoc cox proportional hazard 130/2087 model with random (6.2) effect for site; frailty model. Post-hoc cox proportional hazard model with random effect for site (PCI group); frailty model 81/1351 (6.0) Absolute difference (%) Hazard ratio (95% CI) (95% CI) P Value 145/2054 (7.1) 1.22 (-0.33 to 2.78) 0.82 (0.64 to 1.05) /2053 (7%) 1.22 [-0.32 to 2.77] 0.82 [0.64 to 1.05] /1337 (8.4) 2.32 (0.28 to 4.35) 0.71 (0.54 to 0.95) /1337 (8.4%) 2.39 [0.36 to 4.42] 0.71 [0.53 to 0.94] /1359 (8.2) 2.32 (0.31 to 4.32) 0.71 (0.53 to 0.95) /1332 (6.4) 2.23 (0.46 to 4.00) 0.64 (0.46 to 0.90) /2104 (7.1) 0.85 (-0.70 to 2.41) 0.88 (0.69 to 1.11) /1359 (8.2) 2.25 (0.24 to 4.25) 0.72 (0.54 to 0.96) 0.02 Data presented as No/Total No (%). Abbreviations: PCI denotes percutaneous coronary intervention a Event: occurrence of primary outcome b Excluding patients who underwent PCI at least one day after an event. c Excluding patients who underwent PCI at the same day of the event or later.