Cyclosporine before PCI in Patients with Acute Myocardial Infarction

Susan Kellum, Mercer University College of Pharmacy

Current guidelines for the management of acute myocardial infarction suggest early and successful myocardial reperfusion with the use of fibrinolysis or percutaneous coronary intervention (PCI) as the most effective strategy for improving clinical outcomes.1 According to an article in the New England Journal of Medicine, this restoration of blood flow to the ischemic myocardium can induce injury known as myocardial reperfusion injury, and currently there are no specific treatments that target this.2 A recently published study suggests reperfusion injury contributes to the final infarct size, and cyclosporine could reduce the myocardial infarct size in patients with ST- segment elevation myocardial infarction (STEMI).3

Table 1

Title: Cyclosporine before PCI in Patients with Acute Myocardial Infarction 3
Design Multicenter, double-blind, randomized study; N = 970
Objective To test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling
Study Groups Cyclosporine injection group (n = 395) or placebo group (n = 396)
Methods Patients with an acute anterior ST- segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset received a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before PCI.
Duration April 2011 to February 2014
Primary Outcome Measure Composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalizaiton for heart failure, or adverse left ventricular remodeling at one year

Baseline Characteristics

Table 1. Characteristics of the Patients at Baseline*
Characteristics Cyclosporine
(n = 474)
Control
(n = 495)
Age – yr 60.4 + 13.1 59.5 + 12.7
Male sex – no. (%) 399 (84.2) 396 (80)
Body- mass index 26.9 + 4.3 26.8 + 4.1
Current smoking – no. (%) 185 (39) 226 (45.7)
Hypertension – no. (%) 178 (37.6) 183 (37)
Diabetes – no. (%) 65 (13.7) 58 (11.7)
Previous MI – no. (%) 28 (5.9) 26 (5.3)
Previous ischemic heart disease – no. (%) 31 (6.5) 32 (6.5)
*See article for complete list of baseline characteristics
Results The rate of the primary outcome was 59% in the cyclosporine group and 58.1% in control group (odds ratio, 1.04; 95% CI, 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events. No significant difference in the safety profile was observed between the two treatment groups.
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at one year.

 In this study, adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. Patients were followed for twelve months following PCI. A primary outcome event occurred in 233 of 395 patients (59%) in the cyclosporine group and in 230 of 396 (58.1%) in the control group. Adverse left ventricular remodeling occurred in 42.8% of the patients in the cyclosporine group and 40.7% of those in the control group (P = 0.53; CI 0.82 to 1.46). A total of seven patients were lost to follow-up at one year. This study shows administration of cyclosporine did not result in a lower risk of any of the individual components of the combined outcome. 3


References
:

1] Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation. 2004;110(5):588-636.

2] Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med 2007;357:1121-1135

3] Cung TT, Morel O, Cayla G, et al. Cyclosporine before PCI in Patients with Acute Myocardial Infarction. N Engl J Med. 2015

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