Are statins being underdosed in clinical practice? Data from TACTICS-TIMI 18.

BACKGROUND

Although clinical trials in the 1990s have found significant reductions in cardiovascular events with fixed doses of statins, specifically 40 mg of simvastatin or pravastatin, in clinical practice, treatment is usually initiated at lower doses. It is not clear, however, if the doses are then titrated upward after the initial dosing.

METHODS

We examined the dosing for patients receiving statins at the time of entry and at 6 months follow-up in the Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction (TACTICS-TIMI) 18 trial, and their relationship to the measured low-density lipoprotein cholesterol (LDL-C) on admission.

RESULTS

In the TACTICS-TIMI 18 trial, 727 of 2220 (33%) patients with unstable angina and non-ST elevation MI were on statins at study entry, of whom 371 had both LDL-C measurements and statin dose recorded on admission: 132 (36%) received atorvastatin, 126 (34%) simvastatin, 58 (16%) pravastatin, and the remainder lovastatin, fluvastatin, or cerivastatin. Only 18% and 38% of patients were treated with the 40-mg dose of simvastatin or pravastatin, respectively. Only 3 patients on atorvastatin were treated with 80 mg. At entry, 46% of these patients had LDL-C < or =100 mg/dL (and even among all patients with either prior MI, CABG, PTCA, or diabetes, only 33% had LDL-C < or =100 mg/dL, increasing modestly to 48% for those also on a statin). At 6 months after the UA/NSTEMI event, although more patients (1113, 50%) were on statins, the doses used were not higher then those used at baseline.

CONCLUSION

We observed that the doses of statins in clinical practice were usually lower than those used in the clinical efficacy trials. Furthermore, LDL-C of < or =100 mg/dL was achieved in fewer then 50% of acute coronary syndrome patients receiving statins at time of presentation. These data suggest that, in addition to previously documented underutilization of statins in clinical practice, there is also underdosing of this important class of drugs.