GII/IIIB inhibitors in addition to LMWH unproven in unstable angina
Date First Published:
March 1, 2000
Last Updated:
May 23, 2001
Report by:
Katrina Richell-Herren, Research Fellow (Manchester Royal Infirmary)
Search checked by:
Kevin Mackway-Jones, Manchester Royal Infirmary
Three-Part Question:
In [a patient with acute myocardial ischaemia] is [a low molecular weight heparin better than a platelet glycoprotein IIb/IIIa complex inhibitor] at [reducing morbidity and mortality]?
Clinical Scenario:
A 45 year old man attends the Emergency department with 30 minutes of chest pain. An ECG shows ST segment depression in the inferior leads. You wonder whether he should be treated with low molecular weight heparin or a glycoprotein IIa/IIIb complex inhibitor.
Search Strategy:
Medline 1966-10/99 using the OVID interface.
Search Details:
[{exp angina, unstable OR unstable angina.mp OR exp myocardial ischemia OR myocardial ischemia$.mp OR myocardial ischaemia.mp} AND ({exp heparin OR exp heparin, low-molecular-weight OR heparin$.mp OR LMWH$.mp} AND {exp platelet aggregation inhibitors OR exp platelet glycoprotein gpiib-iiia complex OR tirofiban$.mp})] AND maximally sensitive RCT filter LIMIT to human AND english.
Outcome:
324 papers found of which 318 irrelevant or of insufficient quality for inclusion. The six remaining papers, which refer to five studies, are shown in the table.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. Gurfinkel EP, Manos EJ, Mejail RI et al. 1996 Argentina | 219 patients with unstable angina Aspirin alone vs aspirin and heparin vs aspirin and low-molecular-weight heparin |
Double-blind PRCT | Major end points (recurrent angina, myocardial infarction, urgent revascularisation, major bleeding, death) | Recurrent angina, myocardial infarction, and urgent revascularisation were significantly less frequent in the LMWH group. Major bleeding only occurred in the unfractionated heparin group | |
| Minor end points (silent myocardial ischemia, minor bleeding) | Silent myocardial ischemia was significantly less frequent in the LMWH group. Minor bleeding was significantly more frequent in the unfractionated heparin group. | ||||
| A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and safety of subcutaneous enoxaparin in non-Q-wave coronary events study group. Cohen M, Demers C, Gurfinkel EP et al. 1997 and 1998 USA | 3171 patients with angina at rest or non-Q-wave myocardial infarction enoxaparin vs unfractionated heparin |
Double-blind PRCT | Composite end point (recurrent angina, myocardial infarction, death) | No difference at 48h. Significantly better (16.6% vs 19.8%) in enoxaparin group at 14 days. Difference continues at 30 days. | |
| Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and Safety of subcutaneous Enoxaparin versus intravenous unfractionated heparin, in non-Q-wave coronary Cohen M, Demers C, Gurfinkel EP et al. 1998 | 3232 with unstable angina, myocardial ischemia, raised CK-MB or history of significant IHD. All on aspirin Unfractionated heparin or tirofiban |
Double-blind PRCT | Composite end point (refractory ischemia, myocardial infarction, death) | Significantly better (2.3% vs 3.6%) in tirofiban group at 48h. No difference at 14 and 30 days, although mortality was lower in tirofiban group at this time. No difference in mortality at 6 months | |
| A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. PRISM study investigators. 1998 | 1915 patients with unstable angina, myocardial ischemia or raised CK-MB. All on aspirin Unfractionated heparin or tirofiban or unfractionated heparin and tirofiban |
Double-blind PRCT | Composite end point (refractory ischemia, myocardial infarction, death) | Significantly worse mortality in tirofiban alone group at 7 days (4.6% vs 1.1% for heparin alone).<br><br>Significantly lower composite end point occurrence in tirofiban plus heparin group at 7 (12.9% vs 17.9%) and 30 days. | Tirofiban alone group stopped prematurely |
| Inhibition of platelet glycoprotein IIb/IIIa receptor with Tirofiban in unstable angina and non-Q-wave myocardial infarction. PRISM-PLUS study investigators. 1998 | 2282 patients with non-ST-elevation acute coronary syndromes. All on aspirin High or low dose tirofiban with or without unfractionated heparin vs heparin alone |
Double-blind PRCT | Composite end point (non-lethal myocardial infarction or death) | No differences at 30 days. Significantly lower composite end point occurrence at 6 months for low dose lamifiban and heparin. |
Author Commentary:
There is no trial that directly compares LMWHs with platelet glycoprotein IIb/IIIa complex inhibitors. Both treatments appear to be better than no treatment. The evidence that enoxaparin is better than unfractionated heparin is compelling (for unstable angina ORs 0.81 [0.68-0.96]), while that for tirofiban is less so. Even more work is required in this area.
Bottom Line:
All patients with unstable angina should receive LMWHs in preference to unfractionated heparin. The case for the use of platelet glycoprotein IIb/IIIa complex inhibitors in preference to LMWHs has not been established.
References:
- Gurfinkel EP, Manos EJ, Mejail RI et al.. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia.
- Cohen M, Demers C, Gurfinkel EP et al.. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and safety of subcutaneous enoxaparin in non-Q-wave coronary events study group.
- Cohen M, Demers C, Gurfinkel EP et al.. Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and Safety of subcutaneous Enoxaparin versus intravenous unfractionated heparin, in non-Q-wave coronary
- PRISM study investigators.. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina.
- PRISM-PLUS study investigators.. Inhibition of platelet glycoprotein IIb/IIIa receptor with Tirofiban in unstable angina and non-Q-wave myocardial infarction.
- The PARAGON investigators.. International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina.