Investigating the prevalence, predictors and prognosis of suboptimal statin therapy early after a non-ST elevation acute coronary syndrome

Background: This study aimed to determine the prevalence of suboptimal statin therapy in the community early after discharge on a high dose statin following hospital admission for a non-ST elevation acute coronary syndrome (NSTE-ACS), determine predictors of suboptimal statin therapy, and its association with clinical outcomes.

Methods: 1,017 patients, from a UK-based prospective cardiovascular study discharged on a high dose statin (atorvastatin 80mg, rosuvastatin 20mg or 40mg daily) following NSTE-ACS, were included. At one month post discharge, patients were divided into constant high dose statin users, and those with suboptimal statin utilisation defined by high dose statin discontinuation, dose reduction, switching statin to a lower equivalent dose and/or non-adherence. Follow up after month one was a median of 23 months. The endpoints were a composite of cardiovascular death and non-fatal myocardial infarction or ischaemic stroke (MACE) and all-cause mortality (ACM). Multiple imputation and logistic and cox regression statistical analyses were undertaken.

Results: There were 151 suboptimal (~15%) and 866 constant statin users. Independent predictors of suboptimal statin therapy were female sex (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.11-2.51, p=0.014) and muscular symptoms (OR 2.54, 95% CI 1.05-6.11, p=0.039), alongside a trend for increased concomitant use of CYP3A4-inhibiting drugs (OR 1.72, 95% CI 0.96-3.06, p=0.066). Suboptimal statin therapy was associated with increased adjusted risks of MACE (hazard ratio (HR) 2.18, 95% CI 1.39-3.43, p=0.001) and ACM (HR 2.62, 95% CI 1.54-4.44, p<0.001) (Figure 1). Subgroup analysis confirmed increased MACE/ACM risks for statin discontinuation/non-adherence (n=92, MACE HR 2.77, 95% CI 1.56-4.91, p=0.001; ACM HR 3.73, 95% CI 1.80-7.73, p=0.001); lower magnitude non-significant trends for elevated MACE/ACM risk were detected for statin dose reduction/switching (n=59, MACE HR 1.65, 95% CI 0.81-3.34, p=0.17; ACM HR 1.82, 95% CI 0.82-4.07, p=0.14).

Figure 1. Adjusted cumulative survival curves for suboptimal statin (green) and constant statin users (blue) comparing group survival free from;

A) major adverse cardiovascular events and;

B) all-cause mortality

Conclusion: Suboptimal statin therapy is common early after NSTE-ACS, and appears related to muscular symptoms. Statin discontinuation/non-adherence carries an adverse prognosis, and statin dose reduction/switching potentially increases adverse clinical events. Although these results are limited by the potential for uncontrolled confounders and a limited case size, they suggest notable potential for interventions that enhance statin utilisation to improve post NSTE-ACS outcomes.