In the Journals

Intensive statin therapy linked with prevention of first occurrence of death, MI, unstable angina after ACS

Patients receiving intensive lipid-lowering therapy with atorvastatin following acute coronary syndromes had reduced primary and subsequent adverse events, results of an analysis of the PROVE IT-TIMI 22 trial suggested.

The researchers analyzed primary study endpoints including first occurrence of death, MI or unstable angina, as well as on the occurrence of subsequent events. They randomly assigned 4,162 patients to receive either moderate lipid-lowering therapy with 40 mg pravastatin (Pravachol, Bristol-Meyers Squibb) or intensive lipid-lowering therapy with 80 mg atorvastatin (Lipitor, Pfizer).

A total of 877 adverse events occurred in the pravastatin group and 739 occurred in the atorvastatin group (P=.001). According to the results, patients in the atorvastatin group had 16% reduction in the occurrence of primary events (464 vs. 537; HR=0.84; 95% CI, 0.74-0.95) and a 19% reduction in subsequent events (275 vs. 340, P=.009) vs. the pravastatin group. There was more unstable angina requiring hospitalization (123 vs. 84, P=.009) in the pravastatin group vs. the atorvastatin group, as well as a trend toward more occurrences of death (67 vs. 47, P=.053). No differences between the study groups for occurrences of stroke (P=.529), MI (P=.218) and revascularization after 30 days (P=.081) were reported. A Cox proportional hazards model suggested a benefit in the atorvastatin group vs. the pravastatin group (P=.008).

“This analysis from the PROVE IT-TIMI 22 trial demonstrates that intensive lipid-lowering therapy with high-dose atorvastatin therapy after an ACS prevented not only the first occurrence of the primary endpoint of death, MI, stroke, unstable angina requiring hospitalization or revascularization, but also reduced subsequent, and thus the total number of, primary endpoint events among patients with an ACS,” the researchers wrote in their discussion. “These findings suggest that continued therapy with a regimen that maintains low LDL is central to preventing additional atherosclerotic development and CV events, including recurrent events.”

In an accompanying editorial, Steven E. Nissen, MD, a professor of medicine at the Cleveland Clinic Lerner College of Medicine, noted that despite finding the results useful, he did not feel they provided enough evidence for the use of subsequent events in addition to primary events for prospectively designed clinical trials.

“The risks of overstating benefits of any studied therapy are considerable, and the reliability of efficacy analyses may be compromised,” he wrote. “Some adjustment in the use of the hardest endpoints (stroke, MI and CV death) must be considered because of the explosion of sample size in contemporary trials and the recognition that some soft endpoints contribute to the overall morbidity of this disease.”

Murphy S. J Am Coll Cardol. 2009;54:2358-2362.

Patients receiving intensive lipid-lowering therapy with atorvastatin following acute coronary syndromes had reduced primary and subsequent adverse events, results of an analysis of the PROVE IT-TIMI 22 trial suggested.

The researchers analyzed primary study endpoints including first occurrence of death, MI or unstable angina, as well as on the occurrence of subsequent events. They randomly assigned 4,162 patients to receive either moderate lipid-lowering therapy with 40 mg pravastatin (Pravachol, Bristol-Meyers Squibb) or intensive lipid-lowering therapy with 80 mg atorvastatin (Lipitor, Pfizer).

A total of 877 adverse events occurred in the pravastatin group and 739 occurred in the atorvastatin group (P=.001). According to the results, patients in the atorvastatin group had 16% reduction in the occurrence of primary events (464 vs. 537; HR=0.84; 95% CI, 0.74-0.95) and a 19% reduction in subsequent events (275 vs. 340, P=.009) vs. the pravastatin group. There was more unstable angina requiring hospitalization (123 vs. 84, P=.009) in the pravastatin group vs. the atorvastatin group, as well as a trend toward more occurrences of death (67 vs. 47, P=.053). No differences between the study groups for occurrences of stroke (P=.529), MI (P=.218) and revascularization after 30 days (P=.081) were reported. A Cox proportional hazards model suggested a benefit in the atorvastatin group vs. the pravastatin group (P=.008).

“This analysis from the PROVE IT-TIMI 22 trial demonstrates that intensive lipid-lowering therapy with high-dose atorvastatin therapy after an ACS prevented not only the first occurrence of the primary endpoint of death, MI, stroke, unstable angina requiring hospitalization or revascularization, but also reduced subsequent, and thus the total number of, primary endpoint events among patients with an ACS,” the researchers wrote in their discussion. “These findings suggest that continued therapy with a regimen that maintains low LDL is central to preventing additional atherosclerotic development and CV events, including recurrent events.”

In an accompanying editorial, Steven E. Nissen, MD, a professor of medicine at the Cleveland Clinic Lerner College of Medicine, noted that despite finding the results useful, he did not feel they provided enough evidence for the use of subsequent events in addition to primary events for prospectively designed clinical trials.

“The risks of overstating benefits of any studied therapy are considerable, and the reliability of efficacy analyses may be compromised,” he wrote. “Some adjustment in the use of the hardest endpoints (stroke, MI and CV death) must be considered because of the explosion of sample size in contemporary trials and the recognition that some soft endpoints contribute to the overall morbidity of this disease.”

Murphy S. J Am Coll Cardol. 2009;54:2358-2362.