Summary Table
| Study | Aim of Study | Study Size | Patient Population Inclusion and Exclusion Criteria | Endpoints | Statistical Analysis Reported | P Value (95% CI) | OR/HR/RR | Conclusion |
|---|---|---|---|---|---|---|---|---|
| CURRENT-OASIS 796; Mehta et al | To evaluate whether doubling the dose of loading and initial maintenance doses of clopidogrel is superior to the standard-dose clopidogrel regimen and to investigate if higher-dose ASA is superior to lower-dose ASA. Patients were assigned in a 2×2 factorial design to 600 mg of clopidogrel loading on Day 1, followed by 150 mg/d for 6 d, then 75 mg thereafter versus 300 mg clopidogrel loading on Day 1, followed by 75 mg/d thereafter and either ASA 300–325 mg/d versus lower-dose ASA 75–100 mg/d. | 25 086 | Inclusion criteria: Age ≥18 y with non–ST-segment ACS or STEMI. Requirements included ECG changes compatible with ischemia or elevated cardiac biomarkers and coronary angiographic assessment, with plan to perform PCI as early as possible but no later than 72 h after randomization. Exclusion criteria: Increased risk of or known bleeding and allergy to clopidogrel or ASA. | Primary outcome was CV death, MI, or stroke, whichever occurred first, at 30 d. Prespecified secondary endpoint was definite or probable stent thrombosis (by ARC definition) in patients who underwent PCI. Main safety outcome was major bleeding according to trial criteria. | Primary outcome for clopidogrel dose comparison: 4.2% in double-dose clopidogrel group versus 4.4% in standard-dose clopidogrel group. | 0.30 (0.83 to 1.06) | HR: 0.94 | This analysis of the overall trial in 25 086 patients failed to demonstrate a significant difference in the primary endpoint of CV death, MI, or stroke at 30 d between the double-dose clopidogrel for 7 d versus standard-dose clopidogrel and between the higher-dose versus lower-dose aspirin subgroups. The secondary endpoint of definite stent thrombosis in those undergoing PCI was reduced in the clopidogrel higher-dose group for both DES versus non-DES subtypes, but this benefit was offset by increased major bleeding in the higher-dose clopidogrel group. |
| Major bleeding for clopidogrel dose comparison: 2.5% in double-dose clopidogrel group versus 2.0% in standard-dose clopidogrel group. | 0.01 (1.05 to 1.46) | HR: 1.24 | ||||||
| Primary outcome for ASA dose comparison: 4.2% in higher-dose ASA group versus 4.4% in lower-dose ASA group. | 0.47 (0.86 to 1.09) | HR: 0.97 | ||||||
| Major bleeding for ASA comparison: 2.3% in higher-dose ASA group versus 2.3% in lower-dose ASA group. | 0.90 (0.84 to 1.17) | HR: 0.99 | ||||||
| Clopidogrel and ASA dose interaction— primary outcome for patients on higher-dose ASA: 3.8% in double-dose clopidogrel versus 4.6% in standard-dose clopidogrel. | 0.03 (0.69 to 0.98) | HR: 0.82 | ||||||
| Clopidogrel and ASA dose interaction— primary outcome for patients on lower-dose ASA: 4.5% in double-dose clopidogrel versus 4.2% in standard-dose clopidogrel. | 0.46 (0.90 to 1.26) | HR: 1.07 | ||||||
| Stent thrombosis in patients who underwent PCI: 1.6% with double-dose clopidogrel versus 2.3% with standard-dose clopidogrel. | 0.001 (0.55 to 0.85) | HR: 0.68 | ||||||
| CURRENT-OASIS 728; Mehta et al | The goal of this prespecified subgroup analysis of CURRENT-OASIS 796 was to examine efficacy and safety outcomes in patients who underwent PCI. | 17 263 | Inclusion criteria: Patients with ACS (with or without ST-segment elevation) and either ECG evidence of ischemia or elevated biomarkers. Patients were required to have coronary angioplasty with intent to undergo PCI as early as possible but not later than 72 h after randomization. Exclusion criteria: Increased risk of bleeding or active bleeding. Additional information on study eligibility criteria in study Web appendix. | Primary outcome was composite of CV death, MI, or stroke from randomization to Day 30. Secondary outcomes included primary outcome plus recurrent ischemia, individual components of composite outcomes, and stent thrombosis per ARC criteria. | Primary outcome in clopidogrel dose comparison reduced with double-dose clopidogrel: 3.9% in double-dose clopidogrel group versus 4.5% in standard-dose clopidogrel group. | 0.039 (0.74 to 0.99) | Adjusted HR: 0.86 | This substudy of CURRENT-OASIS-7 analyzed the 69% of patients (n=17 263) who underwent PCI, a prespecified analysis in a postrandomization subset. In this PCI subgroup, the primary outcome of CV death, MI, or stroke at 30 d was reduced in those randomized to higher-dose clopidogrel, and this was largely driven by a reduction in myocardial (re)infarction. Definite stent thrombosis also was reduced in the higher clopidogrel dose group with consistent results across DES versus non-DES subtypes. Outcomes were not significantly different by ASA dose. Major bleeding was more common with higher-dose clopidogrel but not with higher-dose ASA. |
| Secondary outcome (CV death, MI, stroke, or recurrent ischemia) in clopidogrel dose comparison was reduced with double-dose clopidogrel: 4.2% in double-dose clopidogrel versus 5.0% in standard-dose clopidogrel. | 0.025 (0.74 to 0.98) | HR: 0.85 | ||||||
| Rates of definite stent thrombosis were lower with double-dose clopidogrel (0.7%) versus standard-dose clopidogrel (1.3%). | 0.0001 (0.39 to 0.74) | HR: 0.54 | ||||||
| CURRENT-defined major bleed was more common with double-dose (0.1%) than standard-dose clopidogrel (0.04%); however, no difference in TIMI-defined severe or major bleeding. | 0.16 (0.71 to 7.49) | HR: 2.31 | ||||||
| TIMACS38; Mehta et al | To study efficacy of an early invasive strategy (within 24 h of presentation) compared with delayed invasive strategy (any time >36 h after presentation). | 3031 | Inclusion criteria: Presentation to a hospital with UA or MI without ST-segment elevation within 24 h after onset of symptoms and if 2 of the following 3 criteria for increased risk are present: age ≥60 y, cardiac biomarkers above ULN, or results on ECG compatible with ischemia (ie, ST-segment depression ≥1 mm or transient ST-segment elevation or T-wave inversion >3 mm). Exclusion criteria: Patient who is not a suitable candidate for revascularization. | Composite of death, MI, or stroke at 6 mo. | At 6 mo, the primary outcome occurred in 9.6% of patients in early intervention group versus 11.3% of delayed-intervention group. | 0.15 (0.68 to 1.06) | HR: 0.85 | TIMACS initially targeted enrollment of 4000 patients but terminated enrollment at 3031 patients due to recruitment challenges, limiting its power. For the overall trial population, there was only a nonsignificant trend to a reduction in the primary ischemic endpoint in the early compared with delayed intervention groups. The prospectively defined secondary endpoint of death, MI, or refractory ischemia was reduced by early intervention, mainly because of a reduction in refractory ischemia. Heterogeneity was observed in the primary ischemic endpoint by a prespecified estimate of baseline risk according to the GRACE score, with patients in the highest tertile experiencing a sizeable risk reduction and suggesting a potential advantage of early revascularization in this high- risk subgroup. |
| 28% risk reduction in secondary outcome of death, MI, or refractory ischemia in early intervention group (9.5%) versus delayed-intervention group (12.9%). | 0.003 (0.58 to 0.89) | HR: 0.72 | ||||||
| Prespecified analyses indicated early intervention improved the primary outcome in the third of patients at highest risk. | 0.006 (0.48 to 0.89) | HR: 0.65 | ||||||
| Prespecified analyses did not show that early intervention improved primary outcome in the two thirds at low to intermediate risk. | 0.48 (0.81 to 1.56) | HR: 1.12 | ||||||
| CARE165; Solomon et al | To compare iopamidol and iodixanol in patients with CKD (eGFR 20–59 mL/min) who underwent cardiac angiography or PCI. | 482 | Inclusion criteria: Men and women (≥18 y) with moderate to severe CKD scheduled for diagnostic cardiac angiography or PCI. Exclusion criteria: Pregnancy, lactation, administration of any investigational drug within the previous 30 d, intra-arterial or IV administration of iodinated CM from 7d before to 72 h after administration of the study agents, medical conditions or circumstances that would have substantially decreased chance to obtain reliable data (NYHA class IV CHF, hypersensitivity to iodine-containing compounds, hyperthyroidism or thyroid malignancies, uncontrolled DM, unstable renal drug dependence, psychiatric disorders, dementia), administration of any medication to prevent CIN other than N-acetylcysteine, or intake of nephrotoxic medications from 24 h before to 24 h after administration of the study agent. | Primary endpoint was postdose SCr increase of 0.5 mg/dL (44.2 mol/L) over baseline. Secondary outcome was postdose SCr increase ≥25%, a postdose estimated GFR decrease ≥25%, and mean peak change in SCr. | In 414 patients, contrast volume, presence of DM, use of N-acetylcysteine, mean baseline SCr, and eGFR were comparable in the 2 groups. SCr increases of ≥0.5 mg/dL occurred in 4.4% (9 of 204 patients) after use of iopamidol and 6.7% (14 of 210 patients) after iodixanol. | 0.39 (−6.7 to 2.1) | In this randomized trial of moderate size, the rate of CIN in higher-risk patients with moderate CKD was not significantly different between the low-osmolar contrast medium iopamidol and the iso-osmolar contrast medium iodixanol. | |
| Rates of SCr increases ≥25% were 9.8% with iopamidol and 12.4% with iodixanol. | 0.44 (−8.6 to 3.5) | |||||||
| In patients with DM, SCr increases to ≥0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13% (12 of 92 patients) with iodixanol. | 0.11 | |||||||
| In patients with DM, SCr increases ≥25% were 10.3% with iopamidol and 15.2% with iodixanol. | 0.37 | |||||||
| Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 mg/dL with iopamidol versus 0.12 mg/dL with iodixanol). | 0.03 | |||||||
| In patients with DM, SCr change from baseline was 0.07 mg/dL with iopamidol versus 0.16 mg/dL with iodixanol. | 0.013 | |||||||
| Decreases in eGFR ≥25% were recorded in 5.9% (12 patients) with iopamidol and 10% (21 patients) with iodixanol. | 0.15 (−9.3 to 1.1) | |||||||
| Relative renal safety of iodixanol compared with LOCM167; Reed et al | Meta-analysis to compare nephrotoxicity of the iso-osmolar contrast medium iodixanol with LOCM. | 16 trials (2763 subjects) | Patients enrolled in RCTs that compared incidence of CI-AKI with either iodixanol or LOCM. | Primary endpoint was incidence of CI-AKI. Secondary endpoints were need for renal replacement therapy and mortality. | No significant difference in incidence of CI-AKI in iodixanol group than in LOCM group (overall summary). | 0.19 (0.56 to 1.12) | Summary RR: 0.79 | In this updated meta-analysis of 16 CIN trials, data supporting a reduction in CIN favoring the iso-osmolar medium iodixanol compared with LOCM were no longer significant. Subanalyses suggested potential variations in relative renal safety by specific LOCM with reductions in CIN for iodixanol compared with the ionic LOCM ioxaglate and with iohexol, a nonionic LOCM, but not with 4 other LOCM. |
| CI-AKI was reduced when iodixanol was compared with ioxaglate | 0.022 (0.37 to 0.92) | RR: 0.58 | ||||||
| and when iodixanol was compared with iohexol, | (0.07 to 0.56) | RR: 0.19 | ||||||
| but no difference was noted when iodixanol was compared with iopamidol, | 0.55 (0.66 to 2.18) | RR: 1.20 | ||||||
| iodixanol was compared with iopromide, | 0.84 (0.47 to 1.85) | RR: 0.93 | ||||||
| or iodixanol was compared with ioversol. | 0.68 (0.60 to 1.39) | RR: 0.92 | ||||||
| No significant difference between iodixanol and LOCM noted in rates of postprocedure hemodialysis. | 0.20 (0.08 to 1.68) | RR: 0.37 | ||||||
| No significant difference between iodixanol and LOCM in rates of death. | 0.663 (0.33 to 5.79) | RR: 1.38 | ||||||
| Nephrotoxicity of iso-osmolar iodixanol compared with nonionic low-osmolar contrast168; Heinrich et al | Meta-analysis of RCTs to compare nephrotoxicity of iso-osmolar iodixanol with nonionic LOCM. | 25 trials (3270 subjects) | Inclusion criteria: RCTs analyzing SCr levels before and after intravascular application of iodixanol or LOCM. | Incidence of CIN and change in SCr levels. | Iodixanol did not significantly reduce risk of CIN (or risk of SCr increase) compared with LOCM overall. However, risk of intra-arterial iohexol was greater than that of iodixanol. | 0.10 (0.61 to 1.04) | RR: 0.80 | In this contemporary meta-analysis of 25 trials, the incidence of CIN was similar for a pooled comparison of all nonionic LOCM other than iohexol and for the iso-osmolar medium iodixanol, indicating equivalent safety for these 2 classes of CM. |
| No significant risk reduction after IV administration of CM. | 0.79 (0.62 to 1.89) | RR: 1.08 | ||||||
| In patients with intra-arterial administration and renal insufficiency, risk of CIN was greater for iohexol than for iodixanol. | <0.01 (0.21 to 0.68) | RR: 0.38 | ||||||
| No difference between iodixanol and the other (noniohexol) LOCM. | 0.86 (0.50 to 1.78) | RR: 0.95 | ||||||
| EARLY-ACS37; Giugliano et al | To evaluate upstream use of GP IIb/IIIa inhibitor eptifibatide versus provisional eptifibatide administration in the catheterization lab in high-risk patients with NSTE ACS. | 9492 | Inclusion criteria: Patients at least 18 y of age were randomized within 8–12 h after presentation and assigned to an invasive treatment strategy no sooner than the next calendar day. To qualify as having a high-risk UA/NSTEMI, patients were required to have at least 2 of the following: ST-segment depression or transient ST elevation, elevated biomarker levels (CK-MB or troponin), and age ≥60 y. The study protocol was later amended to permit enrollment of patients 50–59 y of age with elevated cardiac biomarker levels and documented vascular disease and clarified the timing of angiography as ≥12 h after randomization. Exclusion criteria: Increased risk of bleeding, allergy to heparin or eptifibatide, pregnancy, renal dialysis within previous 30 d, intention of investigator to use a nonheparin anticoagulant, recent use of a GP IIb/IIIa inhibitor, and any other condition that posed increased risk. | The primary efficacy composite endpoint was death of any cause, MI, recurrent ischemia requiring urgent revascularization, or thrombotic bailout at 96 h. The secondary efficacy endpoint was composite of death of any cause or MI within the first 30 d. Safety endpoints included rates of hemorrhage, transfusion, surgical reexploration, stroke, thrombocytopenia, and serious adverse events at 120 h after randomization. | The primary endpoint was less in the early-eptifibatide group (9.3%) versus the delayed-eptifibatide group (10%), but not significant. | 0.23 (0.80 to 1.06) | OR: 0.92 | In the setting of frequent early (precatheterization) use of clopidogrel, the administration of early, routine eptifibatide (double-bolus and infusion) did not achieve statistically significant reductions in ischemic events at 96 h (ie, 8%, primary endpoint) and 30 d ( ie, 11%, secondary endpoint) compared with provisional administration of eptifibatide, given after angiography but before PCI. Early, routine eptifibatide was associated with a greater risk of bleeding. No significant interactions were noted between efficacy endpoints and prespecified baseline characteristics. |
| At 30 days, the rate of death or MI was 11.2% in the early-eptifibatide group versus 12.3% in the delayed-eptifibatide group. | 0.08 (0.79 to 1.01) | OR: 0.89 | ||||||
| Patients in the early-eptifibatide group experienced higher TIMI major hemorrhage compared with the delayed-eptifibatide group (2.6% versus 1.8%, respectively), higher rates of moderate GUSTO bleeding (6.8% in the early-eptifibatide group versus 4.3% in the delayed-eptifibatide group; P<0.001), similar severe GUSTO bleeding (0.8% early-eptifibatide group versus 0.9% in delayed-eptifibatide group; P=0.97), and need for red-cell transfusion was increased in the early-eptifibatide group compared with the delayed-eptifibatide group (8.6% versus 6.7%, respectively; P=0.001). | 0.02 (1.07 to 1.89) | OR: 1.42 | ||||||
| ABOARD120; Montalescot et al | To determine if immediate intervention on admission can result in reduction of MI versus delayed intervention. | 252 | Inclusion criteria: Presence of at least 2 of the following: ischemic symptoms, ECG abnormalities in at least 2 contiguous leads, or positive troponin, TIMI risk score ≥3. Exclusion criteria: Hemodynamic or arrhythmic instability requiring urgent catheterization, chronic oral anticoagulation, or thrombolytic therapy in the preceding 24 h. | Primary endpoint was peak troponin value during hospitalization. Secondary endpoints were composite of death, MI, or urgent revascularization at 1-mo follow-up. | No difference was found in peak troponin-I between groups (median 2.1 ng/mL [0.3 to 7.1 ng/mL) versus 1.7 ng/mL [0.3 to 7.2 ng/mL] in immediate- and delayed-intervention groups, respectively). | 0.70 (N/A) | (N/A) | Immediate (at a median of 70 min) versus delayed (at a median of 21 h) angiography and revascularization in UA/NSTEMI patients conferred no advantage with regard to the primary endpoint (myocardial necrosis by TnI), nor did it result in even a trend toward improved outcome in the clinical secondary endpoint of death, MI, or urgent revascularization by 1 mo. |
| Secondary endpoint was seen in 13.7% (95% CI: 8.6% to 18.8%) of immediate-intervention group versus 10.2% (95% CI: 5.7% to 14.6%) of delayed-intervention group. The other endpoints did not differ between the 2 strategies. | 0.31 | (N/A) | ||||||
| TRITON-TIMI 3822; Wiviott et al | To evaluate treatment with prasugrel compared with clopidogrel among patients undergoing planned PCI for ACS. | 13 608 | Inclusion criteria: Scheduled PCI for ACS. For UA/NSTEMI patients, ischemic symptoms ≥10 min within 72 h of randomization, TIMI risk score ≥3, and either ST-segment deviation ≥1 mm or elevated cardiac biomarker of necrosis. For STEMI patients, symptom onset within 12 h of randomization if primary PCI was scheduled or within 14 d if medically treated for STEMI. Exclusion criteria: Included increased bleeding risk, anemia, thrombocytopenia, intracranial pathology, or use of any thienopyridine within 5 d. | Primary endpoints were death of CV causes, nonfatal MI, or nonfatal stroke. Key safety endpoint was major bleeding. | Primary endpoint was significantly lower in prasugrel group compared with clopidogrel group (9.9% versus 12.1%, respectively). | <0.001 (0.73 to 0.90) | HR: 0.81 | TRITON-TIMI-38 compared the new thienopyridine prasugrel to clopidogrel in 13 608 moderate- to high-risk STEMI and NSTEMI patients scheduled to undergo PCI. Prasugrel was associated with a reduction in the composite ischemic event rate over 15 mo of follow-up, including stent thrombosis, but it was associated with a significantly increased rate of bleeding. In subgroup analyses, those with prior stroke/TIA fared worse on prasugrel, and no advantage was seen in those ≥75 y of age or <60 kg in weight. |
| Primary endpoint was consistent in UA/NSTEMI cohort (9.9% with prasugrel versus 12.1% with clopidogrel; 18% RR). | 0.002 (0.73 to 0.93) | HR: 0.82 | ||||||
| Primary endpoint in STEMI cohort (10% in prasugrel versus 12.4% in clopidogrel; 21% RR). | 0.02 (0.65 to 0.97) | HR: 0.79 | ||||||
| Efficacy benefit evident by 3 d (4.7% in prasugrel group versus 5.6% in clopidogrel group). | 0.01 (0.71 to 0.96) | HR: 0.82 | ||||||
| Efficacy benefit evident from Day 3 to end of follow-up (5.6% in patients receiving prasugrel versus 6.9% of patients receiving clopidogrel). | 0.003 (0.70 to 0.93) | HR: 0.80 | ||||||
| Definite or probable stent thrombosis occurred less frequently in prasugrel group than in clopidogrel group (1.1% versus 2.4%, respectively). | <0.001 (0.36 to 0.64) | HR: 0.48 | ||||||
| Safety endpoint of TIMI major non-CABG bleeding was higher with prasugrel compared with clopidogrel (2.4% versus 1.8%, respectively). | 0.03 (1.03 to 1.68) | HR: 1.32 | ||||||
| Increase in bleeding consistent for different categories of TIMI major bleeding, including life-threatening bleeding (1.4% in prasugrel versus 0.9% in clopidogrel; HR: 1.52; 95% CI: 1.08 to 2.13; P=0.01), fatal bleeding (0.4% in prasugrel versus 0.1% in clopidogrel; HR: 4.19; 95% CI: 1.58 to 11.11; P=0.002), and nonfatal bleeding (1.1% in prasugrel versus 0.9% in clopidogrel; HR: 1.25; 95% CI: 0.87 to 1.81; P=0.23). | 0.01 (1.08 to 2.13) | HR: 1.52 | ||||||
| CABG-related TIMI major bleeding increased with prasugrel compared with clopidogrel (13.4% versus 3.2%, respectively). | <0.001 (1.90 to 11.82) | HR: 4.73 | ||||||
| No difference in mortality (death of any cause) between groups (3.0% in prasugrel group versus 3.2% in clopidogrel group). | 0.64 (0.78 to 1.16) | HR: 0.95 | ||||||
| Net clinical benefit endpoint (composite of death, MI, stroke or TIMI major bleeding) favored prasugrel over clopidogrel (12.2% versus 13.9%, respectively). | 0.004 (0.79 to 0.95) | HR: 0.87 | ||||||
| SWEDEHEART161; Szummer et al | To describe distribution of CKD and use of early revascularization, as well as to determine if an invasive approach is associated with lower mortality at every level of renal function. | 23 262 | Inclusion criteria: NSTEMI patients ≤80 y of age from nationwide CCU register (2003 and 2006). | Description of 1-y survival according to renal function stage. | Patients treated with early revascularization had overall improved survival rate at 1 y. | <0.001 (0.56 to 0.73) | HR: 0.64 | A contemporary nationwide Swedish registry, evaluated the use of early revascularization after NSTEMI across all stages of CKD, and stratified outcomes by stage of CKD. Early revascularization was associated with improved adjusted 1-y survival in UA/NSTEMI patients with mild-to-moderate CKD, but no association was observed in those with severe and end-stage disease. SWEDEHEART is limited by its observational nature, but by capturing unselected patients, it may be quite reflective of real-world experience. |
| 1-y mortality for patients with eGFR ≥90: 1.9% for invasive treatment versus 10% for medical treatment. | 0.001 (0.42 to 0.80) | HR: 0.58 | ||||||
| 1-y mortality for patients with eGFR 60 to 89: 2.4% for invasive treatment versus 10% for medical treatment. | <0.001 (0.52 to 0.80) | HR: 0.64 | ||||||
| 1-y mortality for patients with eGFR 30 to 59: 7% for invasive treatment versus 22% for medical treatment. | 0.001 (0.54 to 0.81) | HR: 0.68 | ||||||
| 1-y mortality for patients with eGFR 15 to 29: 22% for invasive treatment versus 41% for medical treatment. | 0.740 (0.51 to 1.61) | HR: 0.91 | ||||||
| 1-y mortality for patients with eGFR <15/dialysis: 44% for invasive treatment versus 53% for medical treatment. | 0.150 (0.84 to 3.09) | HR: 1.61 | ||||||
| COGENT108; Bhatt et al | To investigate efficacy and safety of concomitant clopidogrel and PPI administration in patients with CAD receiving clopidogrel and ASA. | 3761 | Inclusion criteria: Age ≥21 y, clopidogrel therapy with concomitant ASA anticipated for at least next 12 mo, including patients with ACS or coronary stent placement. Exclusion criteria: Hospitalized patients for whom discharge not anticipated within 48 h of randomization; need for current/long-term use of PPI, H2-receptor antagonist, sucralfate, or misoprostol; erosive esophagitis or esophageal or gastric variceal disease or previous nonendoscopic gastric surgery; clopidogrel or other thienopyridine >21 d before randomization; receipt of oral anticoagulant unable to be discontinued safely; recent fibrinolytic therapy. | Primary GI safety endpoint: composite of GI overt or occult bleeding, symptomatic gastroduodenal ulcers or erosions, obstructions, or perforation. Primary CV safety endpoint: composite of death of CV causes, nonfatal MI, coronary revascularization, or ischemic stroke. | Total GI event rate: 1.1% with omeprazole versus 2.9% with placebo. | <0.001 (0.18 to 0.63) | HR: 0.34 | In this randomized, placebo controlled comparison in 3873 patients with an indication for dual-antiplatelet therapy, no difference was found in the primary composite CV endpoint between clopidogrel plus omeprazole and clopidogrel plus placebo at 180 d. The rate of GI bleeding and associated complications were reduced with omeprazole. Study limitations include premature termination of planned enrollment, limited power to discern small to moderate differences between therapies, and the use of a single-pill formulation, which might differ in release kinetics for its 2 components. |
| Overt upper GI bleeding rate: 0.1% with omeprazole versus 0.6% with placebo. | 0.001 (0.03 to 0.56) | HR: 0.13 | ||||||
| Total CV event rate: 4.9% with omeprazole versus 5.7% with placebo. | 0.96 (0.68 to 1.44) | HR: 0.99 |
ACS indicates acute coronary syndrome; ARC, academic research consortium; ASA, aspirin; CABG, coronary artery bypass graft; CAD, coronary artery disease; CCU, coronary care unit; CHF, congestive heart failure; CI-AKI, contrast-induced acute kidney injury; CI, confidence interval; CIN, contrast-induced nephropathy; CKD, chronic kidney disease; CK-MB, creatine kinase-MB; CM, contrast media; CURRENT, Clopidogrel optimal loading dose Usage to Reduce Recurrent EveNTs; CV, cardiovascular; DES, drug-eluting stent; DM, diabetes mellitus; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; GI, gastrointestinal; GP, glycoprotein; GRACE, Global Registry of Acute Coronary Events; GUSTO, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial; HR, hazard ratio; IV, intravenous; LD, loading dose; LOCM, low-osmolar contrast media; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction; NSTE, non-ST-elevation; NSTEMI, non–ST-elevation myocardial infarction; NYHA, New York Heart Association; OR, odds ratio; PCI, percutaneous coronary intervention; PPI, proton pump inhibitor; RCT, randomized controlled trial; RR, relative risk; SCr, serum creatinine; STEMI, ST-elevation myocardial infarction; TIA, transient ischemic attack; TIMI, Thrombolysis in Myocardial Infarction; TnI, troponin I; UA, unstable angina; and ULN, upper limit of normal.