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Prevention of ischaemic events by early treatment of cerivastatin after acute myocardial infarction - PRINCESS
Description:
The goal of the trial was to evaluate an early versus delayed use of the lipid-lowering therapy cerivastatin among patients with acute myocardial infarction (MI), regardless of baseline lipid values.
Hypothesis:
Early post-MI treatment with cerivastatin will be associated with a reduction in ischemic coronary events compared with a delayed initiation of treatment with cerivastatin.
Study Design
Study Design:
Patients Enrolled: 3,605
Mean Follow Up: 4.5 months
Mean Patient Age: Mean age 60 years
Female: 21
Patient Populations:
Acute MI with symptom onset within six hours, elevated biomarkers with ST elevation or depression, and randomization within 48 hours
Exclusions:
Prior statin therapy
Primary Endpoints:
Composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, and hospitalization for heart failure
Secondary Endpoints:
Death, reinfarction, recurrent coronary ischemia (defined as nonfatal MI, unstable angina, and ischemic coronary revascularization), and change in lipids
Drug/Procedures Used:
Patients with acute MI were randomized to an early-initiation strategy (n=1,795) or delayed-initiation strategy (n=1,810) with cerivastatin. Early initiation was cerivastatin 0.4 mg per day for three months followed by 0.4/0.8 mg per day for 21 months. Delayed initiation was placebo for three months followed by 0.4 to 0.8 mg per day for 21 months. The trial was designed to follow patients for two years, but the trial was discontinued early after cerivastatin was withdrawn from the market. Follow-up was then shortened to 4.5 months.
Principal Findings:
Follow-up at 4.5 months was complete in 44% of patients. Thrombolytic therapy was used in 48% of patients, and 29% had an intervention performed. Low-density lipoprotein levels at 15 days were significantly lower in the early cerivastatin group versus placebo (94 vs. 138 mg/dl, p<0.001), and remained lower through the 4.5-month follow-up (97 vs. 139 mg/dl, p<0.001), as was total cholesterol (175 vs. 221 mg/dl, p<0.001), and triglycerides (165 vs. 188 mg/dl, p<0.001).
The primary endpoint of cardiovascular death, MI, stroke, hospitalization for unstable angina, and hospitalization for heart failure at 4.5 months did not differ significantly between the treatment groups (p=0.37), but the data trended in favor of early cerivastatin therapy with event-free survival curves beginning to diverge early. The rate of recurrent ischemic events was lower in the early cerivastatin group (p=0.05). There was no difference in MI (p=0.38) or death.
The safety profile was similar in both groups, with serious adverse events reported in 30% in the cerivastatin group versus 28% in the placebo/cerivastatin group. Creatine phosphokinase >10 times the upper limit of normal was reported in 20 patients in the early cerivastatin group and nine patients in the placebo/cerivastatin group.
Interpretation:
Among patients with acute MI, early initiation of cerivastatin therapy was not associated with a significant reduction in the primary composite endpoint compared with a placebo/cerivastatin therapy, but was directionality in favor of early initiation despite being underpowered due to early trial discontinuation. Additionally, recurrent ischemic events were lower in the early cerivastatin group. These trends in efficacy and the safety profile, along with other large randomized trials such as PROVE-IT and MIRACL, support the early initiation of statin therapy in patients with a recent acute coronary syndrome.
References:
Wright RS. PRINCESS: Prevention of ischaemic events by early treatment of cerivastatin after acute myocardial infarction. Paper presented at the European Society of Cardiology Congress 2004, 29 August-1 September, Munich, Germany.
Keywords: Thrombolytic Therapy, Myocardial Infarction, Stroke, Acute Coronary Syndrome, Creatine Kinase, Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Disease-Free Survival, Pyridines, Lipoproteins, LDL, Cholesterol, Biomarkers, Heart Failure, Triglycerides
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