4. Clinical endpoints in trials of early statin therapy versus control in acute coronary syndromes.
| Trial (reference) | Total death, MI, stroke, n (%) * | Total death, n (%) | Cardiovascular death, n (%) | Total MI, n (%) | Total stroke, n (%) | Revascularization (CABG/PCI), n (%) | Unstable angina, n (%) | Adverse events, n (%) | Acute heart failure | QOL | ||||||||||||||
| Rhabdomyolysis | CK > 10x ULN | ALT > 3x ULN | ||||||||||||||||||||||
| Statin | Control | Statin | Control | Statin | Control | Statin | Control | Statin | Control | Statin | Control | Statin | Control | Statin | Control | Statin | Control | Statin | Control | Statin | Control | Statin | Control | |
| LAMIL 1997 | NA | NA | 1 (2.8) | 0 (0) | 1 (2.8) | 0 (0) | 1 (2.8) | 0 (0.0) | NA | NA | NA | NA | NA | NA | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA |
| 3 (8.3) | 3 (9.1) | 1 (2.8) | 0 (0) | 1 (2.8) | 0 (0) | 3 (8.3) | 3 (9.1) | 0 (0) | 0 (0) | 1 (2.8) | 1 (3.0) | NA | NA | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| RECIFE 1999 | 0 (0) | 1 (3.3) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0.0) | 1 (3.3) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (3.3) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (3.3) | NA | NA |
| L‐CAD 2000 | 1 (1.4) | 0 (0) | 1 (1.4) | 0 (0) | 0 (0) | 0 (0) | 0 (0.0) | 0 (0.0) | 0 (0) | 0 (0) | 0 (0) | 2 (3.6) | NA | NA | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA |
| 1 (1.4) | 1 (1.9) | 1 (1.4) | 1 (1.9) | 0 (0) | 0 (0) | 0 (0.0) | 0 (0.0) | 0 (0) | 0 (0) | 2 (2.9) | 9 (16.1) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| 1 (1.4) | 1 (1.9) | 1 (1.4) | 1 (1.9) | 0 (0) | 0 (0) | 0 (0.0) | 0 (0.0) | 0 (0) | 0 (0) | 6 (8.6) | 12 (21.4) | 6 (8.6) | 10 (17.9) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| PAIS 2001 | 2 (4.0) | 3 (6.1) | 1 (2.0) | 2 (4.1) | 1 (2.0) | 2 (4.1) | 2 (4.0) | 2 (4.1) | 0 (0) | 1 (2.0) | 4 (8.0) | 2 (4.1) | 16 (32.0) † | 11 (22.4) † | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA |
| 4 (8.0) | 4 (8.2) | 2 (4.0) | 2 (4.1) | 2 (4.0) | 2 (4.1) | 4 (8.0) | 2 (4.1) | 0 (0) | 2 (4.1) | 11 (22.0) | 9 (18.4) | 24 (48.0) † | 21 (42.9) † | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| PTT 2002 | 4 (5.1) | 14 (16.5) | 3 (3.8) | 9 (10.6) | 3 (3.8) | 7 (8.2) | 3 (3.8) | 5 (5.9) | 2 (2.5) | 7 (8.2) | 12 (15.2) | 15 (17.6) | 11 (13.9) † | 25 (29.4) † | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA |
| 2 (5.0) | 7 (18.9) | 1 (2.5) | 3 (8.1) | 0 (0) | 3 (8.1) | 1 (2.5) | 6 (16.2) | 0 (0) | 1 (2.7) | 11 (27.5) | 16 (43.2) | 12 (30.0) † | 22 (59.4) † | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| PACT 2004 | 86 (5.0) | 96 (5.7) | 27 (1.6) | 39 (2.3) | 26 (1.5) | 34 (2.0) | 67 (3.9) | 70 (4.1) | 8 (0.5) | 10 (0.6) | NA | NA | 123 (7.2) | 126 (7.4) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 7 (0.4) | 5 (0.3) | 28 (1.6) | 31 (1.8) | NA | NA |
| LIPS 2002 | 3 (0.7) | 1 (0.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 3 (0.7) | 1 (0.2) | 0 (0) || | 0 (0) || | 77 (18.5) | 87 (21.4) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 8 (1.9) | 3 (0.7) | 1 (0.2) | 0 (0) | 1 (0.2) | 0 (0) | 7 (1.7) | 3 (0.7) | 0 (0) || | 0 (0) || | 78 (18.7) | 88 (21.6) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| 11 (2.6) | 10 (2.5) | 3 (0.7) | 4 (1.0) | 2 (0.5) | 3 (0.7) | 8 (1.9) | 6 (1.5) | 0 (0) || | 0 (0) || | 79 (18.9) | 88 (21.6) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| FLORIDA 2002 | 5 (1.9) | 5 (1.8) | 1 (0.4) | 3 (1.1) | 1 (0.4) | 3 (1.1) | 4 (1.5) | 2 (0.7) | 0 (0) | 1 (0.4) | 16 (6.0) | 12 (4.4) | 6 (2.3) ¶ | 5 (1.8) ¶ | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10 (3.8) | 10 (3.6) | 2 (0.8) | 6 (2.2) | 2 (0.8) | 6 (2.2) | 8 (3.0) | 6 (2.2) | 0 (0) | 1 (0.4) | 30 (11.3) | 32 (11.6) | 11 (4.2) ¶ | 9 (3.3) ¶ | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| 14 (5.3) | 14 (5.1) | 3 (1.1) | 6 (2.2) | 3 (1.1) | 6 (2.2) | 11 (4.2) | 10 (3.6) | 0 (0) | 1 (0.4) | 36 (13.6) | 41 (14.9) | 14 (5.3) ¶ | 14 (5.1) ¶ | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| 28 (10.6) | 28 (10.2) | 7 (2.6) | 11 (4.0) | 6 (2.3) | 11 (4.0) | 21 (7.9) | 16 (5.8) | 2 (0.8) | 5 (1.8) | 46 (17.4) | 51 (18.5) | 16 (6.0)¶ | 18 (6.5)¶ | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| MIRACL 2001 | 101 (6.6) | 96 (6.2) | 32 (2.1) | 30 (1.9) | 27 (1.8) | 21 (1.4) | 80 (5.2) | 67 (4.3) | 7 (0.5) | 10 (0.6) | 162 (10.5) | 147 (9.5) | 72 (4.7) # | 87 (5.6) # | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | NA | NA |
| 162 (10.5) | 183 (11.8) | 64 (4.2) | 68 (4.4) | 51 (3.3) | 60 (3.9) | 118 (7.7) | 131 (8.5) | 12 (0.8) | 24 (1.6) | 254 (16.5) | 250 (16.1) | 95 (6.2) # | 130 (8.4) # | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 38 (2.5) | 9 (0.6) | 43 (2.8) | 40 (2.6) | NA | NA | |
| Colivicchi 2002 | 0 (0) | 3 (7.3) | 0 (0) | 1 (2.4) | 0 (0) | 1 (2.4) | 0 (0.0) | 3 (7.3) | 0 (0) | 0 (0) | 0 (0) ** | 0 (0) ** | 1 (2.5) # | 1 (2.4) # | 0 (0) | 0 (0) | 1 (2.5)## | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA |
| 5 (12.5) | 9 (22.0) | 2 (5.0) | 3 (7.3) | 1 (2.5) | 2 (4.9) | 3 (7.5) | 7 (17.1) | 1 (2.5) | 1 (2.4) | 0 (0) ** | 0 (0) ** | 2 (5.0) # | 3 (7.3) # | 0 (0) | 0 (0) | 1 (2.5)## | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| 7 (17.5) | 13 (31.7) | 3 (7.5) | 4 (9.8) | 2 (5.0) | 3 (9.8) | 5 (12.5) | 10 (24.4) | 1 (2.5) | 2 (4.9) | 0 (0) ** | 0 (0) ** | 2 (5.0) # | 6 (14.6) # | 0 (0) | 0 (0) | 1 (2.5)## | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| ESTABLISH 2004 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0.0) | 0 (0.0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA |
| 0 (0) | 1 (2.9) | 0 (0) | 1 (2.9) | 0 (0) | 0 (0) | 0 (0.0) | 0 (0.0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| 0 (0) | 1 (2.9) | 0 (0) | 1 (2.9) | 0 (0) | 0 (0) | 0 (0.0) | 0 (0.0) | 0 (0) | 0 (0) | 8 (22.9) | 8 (22.9) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| A‐to‐Z 2004 | 99 (4.4) | 105 (4.7) | 20 (0.9) | 29 (1.3) | 20 (0.9) | 29 (1.3) | 86 (3.8) | 98 (4.4) | 10 (0.4) | 6 (0.3) | 19 (0.8) †† | 22 (1.0) †† | 27 (1.2) ‡‡ | 30 (1.3) ‡‡ | 3 (0.1) | 0 (0) | 0 (0) | 1 (0.04) | 1 (0.04) | 27 (1.2)§§ | 31 (1.4)§§ | NA | NA | NA |
| 161 (7.1) | 160 (7.2) | 44 (1.9) | 48 (2.2) | 42 (1.9) | 48 (2.2) | 130 (5.7) | 140 (6.3) | 16 (0.7) | 12 (0.5) | 60 (2.6) †† | 60 (2.7) †† | 56 (2.5) ‡‡ | 61 (2.7) ‡‡ | 3 (0.1) | 0 (0) | 7 (0.3) | 1 (0.04) | 13 (5.7) | 45 (2.0)§§ | 55 (2.5)§§ | 98 (5.0) | NA | NA | |
| Sakamoto 2005 | 4 (1.7) | 1 (0.4) | 4 (1.7) | 1 (0.4) | 4 (1.7) | 1 (0.4) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 12 (5.0) | 4 (1.6) | 6 (2.5) | 2 (0.8) | 6 (2.5) | 2 (0.8) | NA | NA | 3 (1.2) | 2 (0.8) | 18 (7.5) | 24 (9.8) | 6 (2.5) | 17 (6.9) | NA | NA | NA | NA | NA | NA | 1 (0.4) | 9 (3.7) | NA | NA | |
| Macin 2005 | 3 (6.8) | 5 (10.9) | 1 (2.3) | 3 (6.5) | 1 (2.3) | 3 (6.5) | 1 (2.3) | 3 (6.5) | 0 (0) | 0 (0) | 8 (18.2)¶ | 8 (17.4)¶ | 7 (1.6) | 8 (1.7) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 4 (9.3) | 10 (21.7) | NA | NA |
| Sato 2008 | 0 (0) | 1 (0.6) | 0 | 1 (0.6) | 0 (0) | 1 (0.6) | 0 (0.0) | 0 (0.0) | 0 (0) | 1 (0.6) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA |
| 4 (2.3) | 7 (4.0) | 3 (1.7) | 2 (1.1) | 1 (0.6) | 2 (1.1) | NA | NA | 0 (0) | 2 (1.1) | 22 (12.7) | 36 (20.6) | 5 (2.9) | 5 (2.9) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 5 (2.8) | NA | NA | |
| Shal'nev 2007 | NA | NA | 2 (3.6) | 3 (5.5) | NA | NA | NA | NA | NA | NA | NA | NA | 4 (7.3) | 7 (12.7) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| FACS 2005 | 2 (2.6) | 2 (2.6) | 1 (1.3) | 0 (0) | 0 (0) | 0 (0) | 1 (1.3) | 2 (2.6) | 0 (0) | 0 (0) | 3 (3.8) | 4 (5.1) | 2 (2.6) | 6 (7.7) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA |
| 2 (2.6) | 4 (5.1) | 1 (1.3) | 0 (0) | 0 (0) | 0 (0) | 1 (1.3) | 3 (3.8) | 0 (0) | 1 (1.3) | 3 (3.8) | 8 (10.3) | 3 (3.8) | 12 (15.4) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| 4 (5.1) | 10 (12.8) | 1 (1.3) | 4 (5.1) | 0 (0) | 2 (2.6) | 2 (2.6) | 5 (6.4) | 1 (1.3) | 3 (3.8) | 6 (7.7) | 15 (19.2) | 6 (7.7) | 16 (20.5) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA | NA | NA | |
| Ren 2009 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0.0) | 0 (0.0) | NA | NA | 0 (0) | 1 (2.3) | NA | NA | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | NA | NA |
* Combined primary endpoint; unique patients.
† Patients with “recurrent angina pectoris”.
‡ All 164 individuals were followed‐up for 1 month, a subgroup of 77 individuals with additional coronary angioplasty were followed‐up for 6 months.
§ These 824 individuals represent just the subgroup with unstable angina; the LIPS [Lescol Intervention Prevention Study]‐trial originally included another 853 individuals with stable angina.
|| Fatal strokes only; non‐fatal strokes were not recorded.
¶ Patients with “recurrent ischemia necessitating hospitalization”.
# Patients with “recurrent symptomatic myocardial ischemia with objective evidence and emergency hospitalization”.
** Individuals enrolled into the trial were not amenable for direct revascularization by coronary artery bypass grafting or percutaneous coronary intervention.
†† Revascularization procedures had to be urgent, occur more than 14 days after randomization, and were not allowed to be planned prior to enrollment.
‡‡ Patients with “readmission for acute coronary syndrome”.
§§ Patients with “new onset congestive heart failure requiring admission or initiation of heart failure medications”.
ALT: aminotransferase CABG: coronary artery bypass grafting
CK: creatin kinase MI: myocardial infarction NA: not applicable PCI: percutaneous coronary intervention QOL: quality of life
ULN: upper limit of normal values