A investigational IMPROVE-IT study has met its primary and all secondary composite efficacy endpoints. Treatment with Simvastatin in combination with Ezetimibe ( Vytorin ) has significantly reduced cardiovascular events more than Simvastatin ( Zocor ) alone in patients presenting with acute coronary syndromes ( ACS ), even though the enrolled patients’ LDL-cholesterol levels were already around current recommended targets.
The results from this 18,144-patient study of high-risk patients presenting with acute coronary syndromes, which began in 2005, have been presented at the American Heart Association 2014 Scientific Sessions.
Acute coronary syndromes is an umbrella term for a heart attack or episode of unstable angina. In the UK, almost a third of patients who have had a heart attack will go on to have a subsequent cardiovascular event in the first year.
Patients taking the LDL-cholesterol lowering medicine Simvastatin plus Ezetimibe have significantly experienced fewer major cardiovascular events than patients treated with Simvastatin alone ( as measured by a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, re-hospitalisation for unstable angina or coronary revascularisation occurring at least 30 days after randomisation ).
At seven years, 32.7% of patients taking Simvastatin plus Ezetimibe experienced a primary endpoint event compared to 34.7% of patients taking Simvastatin alone ( hazard ratio of 0.936, p=0.016 ).
Based on the LDL-cholesterol range compared in the study’s treatment arms ( at one year, a mean LDL-C of 53 mg/dL [ 1.37mmol/L ] versus 70 mg/dL [ 1.81 mmol/L ], respectively for Simvastatin plus Ezetimibe and Simvastatin alone ) the 6.4% relative risk reduction observed in the Simvastatin plus Ezetimibe arm in this clinical trial was consistent with the treatment effect that had been projected based on prior studies of statins.
Current guidelines such as the European Society Guidelines and Joint British Society Guidelines recommend an LDL-C target of 1.8mmol/L ( or equivalent ), based on available evidence from statin trials to date.
IMPROVE-IT aimed to reduce patients’ cholesterol levels to a normal range that is between approximately1.3mmol/L to 1.8mmol/L.
There were no significant differences between treatment groups in adverse events of special interest, which included myopathy and rhabdomyolysis, gallbladder adverse events, liver enzyme elevations greater than or equal to three times the upper limit of normal ( ULN ) and cancer.
Among 9,067 patients in the Simvastatin plus Ezetimibe group versus 9,077 patients in the Simvastatin group, myopathy was reported in 0.2% vs 0.1% of patients, respectively; rhabdomyolysis was reported in 0.1% vs 0.2%; gallbladder-related adverse events were reported in 3.1% vs 3.5%; cholecystectomy was reported in 1.5% vs 1.5%; and alanine aminotransferase ( ALT ) and/or aspartate transaminase ( AST ) elevations ( greater than or equal to three times ULN, consecutive ) were reported in 2.5% vs 2.3% of patients.
Over seven years, cancer was reported in 10.2% of patients in both treatment groups. ( Xagena )
Source: MSD UK, 2014