Six RCTs and 1 open-labelled dose ranging study were included in the review with 14,386 participants.
The narrative results of the seven included studies are listed individually below:
1. There was a significant reduction in the number of patients reaching the primary end point of recurrent angina, nonfatal MI, urgent revascularisation, or death in the nadroparin group compared with the UFH and placebo groups. Patients receiving nadroparin had significantly less recurrent angina than the patients in the UFH or placebo groups. There was no significant difference in major bleeding complications, however, more patients in the UFH group experienced minor bleeding. There was a trend toward favourable results using nadroparin to prevent MI and the need for revascularisation, but the sample size was insufficient to conclusively evaluate this end point.
2. Results after 6 days indicated a 63% reduction in the primary end point of death or MI in the dalteparin group compared with the placebo group. The absolute risk reduction of 3% correlates to 1 death or MI prevented at 6 days for every 34 dalteparin-treated patients. The difference between the 2 groups was not significant when evaluated at 40 and 150 days. The dalteparin-treated groups experienced more minor bleeding complications.
3. At 6 days there was no significant difference between the 2 groups in reaching the same composite triple end point. There was no difference in major and minor bleeding complications between the 2 groups. The authors concluded that dalteparin seemed to be equivalent to UFH in the acute phase of unstable angina or non-Q-wave MI, and that prolonged administration of a reduced dose of dalteparin offered no advantage over long-term therapy with aspirin alone. The trial was not powered to detect a difference in death, MI, or recurrent angina during the acute phase.
4. The primary end point was major hemorrhage occurring within 2 weeks of enrolment, which occurred more frequently in patients receiving 1.25 mg/kg of enoxaparin than in the 1.0 mg/kg group. No difference was found in any of the secondary end points of death, MI or recurrent ischemia requiring revascularisation. Since this trial was an unblinded dose-ranging study, no definitive conclusions could be made about the efficacy of enoxaparin in unstable angina.
5. At the conclusion of the trial, significantly fewer enoxaparin- treated patients reached the primary end point of death, nonfatal MI, or recurrent angina at 14 days. This significant difference was maintained at 30 days. There was no difference between groups at 48 hours, nor was there a difference in the combination end point of death or MI at 14 and 30 days. Results after 1 year of follow-up have been presented, and the early benefit of enoxaparin in the primary end point was maintained (32% for enoxaparin versus 35.7% for UFH; P = 0.02). There was no difference between the groups in major bleeding complications; however more patients in the enoxaparin groups experienced minor bleeding.
6. Results indicate that fewer enoxaparin-treated patients reached the primary end points of death, nonfatal MI, and severe recurrent ischemia requiring revascularisation during the acute phase. This initial benefit was maintained at 43 days, however no relative reduction on events occurred during the chronic phase. Superiority of enoxaparin in the acute phase was not associated with any increase in major bleeding, however there was an increase in major hemorrhage during the chronic phase.
Combined analysis of trials 5) and 6) showed a consistent reduction in the odds of the triple end point of death, MI, or urgent revascularisation at 8, 14, and 43 days after randomisation. Overall, there was a relative 20% reduction at 43 days (OR = 0.80, 95% CI: 0.71, 0.91). This reduction was also evident when the double end point of death or MI was evaluated at 43 days (OR = 0.82, 95% CI: 0.69, 0.98).
7. Results indicated no significant difference in the primary end point between the 3 treatment groups for cardiovascular death, MI, or refractory or recurrent angina at 14 days, with event rates of 17.8%, 20.0%, and 18.1% respectively. Major bleeding was similar between the groups when evaluated at 6 days, however a higher major bleeding rate occurred in the 14-day nadroparin arm compared with the 6-day nadroparin and UFH groups (3.5%, 1.5%, and 1.6% respectively) when evaluated at 14 days.