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Myocardial Infarction Incidence in Clinical Trials of 4 Protease Inhibitors P. COPLAN1, K. CORMIER2, A. JAPOUR3, H. MARADIT-KREMERS4, A. NIKAS1, R. LEWIS2, and Y. XU3.
1Merck Res. Labs.; 2Agouron Pharm.; 3Abbott Labs.; and 4Hoffman-La Roche
Background: The incidence of myocardial infarction (MI) was assessed
in clinical trials of 4 protease inhibitors (PIs) with randomization to
PIs + reverse transcriptase inhibitors (RTIs) or RTI-only therapy.
Methods: MIs were ascertained from investigator reports in trials.
Person-years (PY) on therapy for each patient were calculated from treatment
start to MI onset or to stop dates for RTI therapy and to study end for
PI. PY were pooled for each PI. Analyses were conducted for randomized
and randomized plus extension phases with switching from RTI-only to PI;
since results were similar, the latter with longer follow-up are shown.
All MI rates and 95% confidence intervals (CIs) shown are rates per 1,000
PY.
MI rates were similar among patients on PIs or on RTI-only therapy. Mean
follow-up was around 12 months. Exact 95% CIs for MI rates were: Indinavir
(0.6-5.3), Nelfinavir (0.02-4.9), Invirase (0.7-3.7), and Ritonavir (0.6-5.7).
MI rates on PI therapy were consistent with a MI rate of 2.73 in a 2-year
trial of RTIs without PIs (ACTG 193a, n=1,313, CD4<50) and with
MI rates in the general male population (per 1000 PY): 1.03 (30-34 yrs),
3.17 (34-44 yrs), and 5.46 (45-54 yrs) in Framingham (Kannel 1984); 3.10
(40-75 yrs) in Health Professionals (Ascherio 1996); 2.80 (45-50 yrs)
in ENIM (Jungers 1997); and 6.32 (45-64 yrs) in MONICA (Stender 1993).
Conclusions: The data suggest that the risk of MI is not increased
by PI therapy in ~12 months of follow-up.
Key Words: clinical trials, myocardial infarction, protease inhibitor
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