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CYCLE: IV cyclosporine fails to reduce injury in reperfused MI
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Use of a single IV bolus of cyclosporine A before primary PCI did not decrease reperfusion-related injury among patients with acute MI in the CYCLE trial.
The multicenter, randomized, open-label, controlled trial included 410 adults (mean age, 63 ± 12 years) with STEMI who were enrolled from 31 Italian centers between 2012 and April 2014. Eligible participants had a large area at risk, defined as ST-segment elevation in three or more leads in anterior MI, and ST-segment elevation in at least four leads in non-anterior MI. Other criteria for enrollment included presentation within 6 hours of symptom onset, TIMI flow grade 0 to 1 at admission and before PCI, and the decision to treat with PCI.
The patient population was 80% male, and 40% were smokers. Fourteen percent had diabetes, and more than half had hypertension.
Participants were randomly allocated in a 1:1 fashion to IV bolus 2.5 mg/kg cyclosporine A (n = 207) or conventional treatment without cyclosporine (n = 203).
The primary efficacy endpoint was the incidence of at least 70% resolution of ST-segment elevation 1 hour after PCI. The key secondary endpoint was the level of high-sensitivity cardiac troponin T (hs-cTnT) measured 4 days after PCI. Additional secondary endpoints included regional and global left ventricular function assessed at 4 days and 6 months, CV-related rehospitalization, all-cause and CV mortality, HF and cardiogenic shock at 6 months.
According to the results, the average time from onset of symptoms to first antegrade flow was 180 minutes. ST-segment deviation was observed on a median of five electrocardiography leads. About half of the MIs were anterior. Overall, 52% of patients assigned cyclosporine and 49% of controls had ST-segment resolution ≥ 70% (P = .55).
The researchers observed no difference in the time course of centrally tested high-sensitivity cardiac troponin T between the two groups on day 4, even after patients were stratified by MI site. The median high-sensitivity cardiac troponin T level on day 4 was 2,160 ng/L in the cyclosporine group vs. 2,068 in the control group (P = .85). The median areas under the high-sensitivity cardiac troponin T level vs. time (enrollment to day 4) were 268 ng·mL-1·h in the cyclosporine group vs. 250 ng·mL-1·h in the control group (P = .66).
In addition, no differences were observed between the two groups in LV ejection fraction at day 4 or 6-month follow-up. No acute allergic reactions were observed in either group.
Eighteen patients died, 12 of whom (5.7%) were in the cyclosporine group and six (3.2%) were in the control group (P = .17). Thirteen of the deaths were determined to have a CV cause; of these deaths, nine (4.4%) were in the cyclosporine group and four (2.2%) were in the control group (P = .18). Cardiogenic shock occurred in six (2.4%) patients in the cyclosporine group and three (1.5%) in the control group (P = .33). The two groups had similar rates of CV rehospitalization.
“[IV] administration of cyclosporine A immediately before primary coronary angioplasty within 6 hours from the onset of symptoms in patients with STEMI did not improve markers of myocardial injury, ventricular remodeling or clinical outcomes, indicating that this strategy did not prevent or reduce reperfusion-related injury,” the researchers wrote. “Additional research is needed to identify more effective adjunctive strategies to attenuate ischemia/reperfusion injury in patients with STEMI undergoing [primary] PCI.” – by Jennifer Byrne
Disclosure: One researcher reports receiving consultant fees from Abbott, AstraZeneca, Eli Lilly, Biotronik, Boston Scientific and Merck.
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