Effect of Time to Titration to Maximum Dose of Statins on Cardiovascular Outcomes

Abstract

Background

Recent trials have shown that high-dose HMG-CoA reductase inhibitor (statin) therapy reduces cardiovascular events in high-risk subjects within weeks of initiating therapy. We investigated the effect of time to titration to maximum dose of statin therapy on cardiovascular events.

Methods

From a list of all patients actively taking simvastatin 80 mg/day as of April 2003 at our hospital, two clinical pharmacists reviewed 213 electronic medical records including pharmacy records from November 1992 to April 2003. Data on cardiovascular risk factors, laboratory results, titration schedules, and outcomes were extracted from the electronic database. Titration period time frames were compared between patient groups using a Student t-test and multiple-variable logistic regression to account for other risk factors.

Results

Titration schedules and time frames to attain a regimen of simvastatin 80 mg/day were available for 154 (73%) subjects. Titrations ranged from 1 to 8 and averaged 2.3± 1.3 titrations per patient (median titrations = 2) over 1 month to 8.4 years. On follow-up, 47 patients experienced 80 cardiovascular-related outcomes. The average time to titration to maximum dose of statin therapy was longer for patients who experienced a cardiac event than for those who did not (3.5 ± 2.2 vs 2.1 ± 1.8 years; p = 0.0004). After accounting for other risk factors, the titration period was still significantly related to the presence of a cardiac event (p = 0.0060, odds ratio per month increase in the titration period 1.3, 95% CI 1.08, 1.58).

Conclusions

Despite potential limitations, the results of our study show that an excessive delay in titrating statin therapy to the optimal dose may lead to an increased risk of atherosclerosis-related events in high-risk patients.