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
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.