Effect of Previous Statin Therapy in Patients With Acute Coronary Syndrome and Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: Statin therapy after percutaneous coronary intervention (PCI) has been associated with reduced major adverse cardiovascular events (MACE). However, it has been less clear as to whether statin therapy before acute coronary syndrome (ACS) is beneficial. We studied the effect of previous statin therapy, initiated > or =1 month before PCI, on the outcome of patients with ACS who had undergone early invasive strategies. SUBJECTS AND METHODS: We stratified 479 consecutive patients with ACS who had undergone PCI, according to preprocedural statin administration as follows: previous statin-treated patients (statin group, n=237) and statin-naive patients (control group, n=242). The incidence of periprocedural myocardial infarction (MI) and in-hospital MACE was assessed. RESULTS: The incidence of Braunwald class III angina and MI presentation were significantly lower in the statin group than in the control group. Angiographic and procedural characteristics were similar between the two groups; however, slow/no reflow phenomenon occurred more frequently in the control group. After PCI, the incidence of periprocedural MI was higher in the control group than in the statin group (6.6% vs. 2.1%, p=0.016). Multivariate analysis revealed that no prior use of statin {odds ratio (OR)=2.8; 95% confidence interval (CI)=1.1-7.2; p=0.038), procedural complication (OR=4.0; 95% CI=1.5-10.5; p=0.004), stent overlap (OR=4.7; 95% CI=1.3-16.4; p=0.015), and old age (OR=3.2; 95% CI=1.2-8.0; p=0.016) were independent predictors for in-hospital MACE. CONCLUSION: Previous statin therapy before ACS was associated with milder clinical presentation and lower incidence of in-hospital MACE after early invasive strategies. The beneficial outcome is attributable to a significant reduction in periprocedural MI after PCI.

Human hydroxymethylglutaryl-coenzyme A reductase (HMGCR) and statin sensitivity.

While statins, hydroxymethylglutaryl-coenzyme A reductase (HMGCR) inhibitors, are clinically proven to reduce plasma cholesterol levels, a wide variation in inter-individual response to statin therapy has been observed. Pharmacogenetic studies have identified multiple loci that potentially contribute towards the statin response, including the HMGCR gene. To examine, if a statin-resistant, catalytically-active isoform of the human HMGCR could be generated, we have rationally altered the protein to include additional residues in the flap domain, which has a role in statin binding. Comparative enzyme assays with purified wild-type and mutant isoforms reveal the alteration imposes a slight (38%) decrease in the for the substrate, a near 2-fold increase in turnover number, and a 480% increase in the Ki for lovastatin. Thus, alterations in HMGCR could contribute towards the synergistic effects of multiple loci in the statin response.

The Short-term Effect of Atorvastatin on Flow-Mediated Vasodilation, Pulse Wave Velocity and Carotid Intima-Media Thickness in Patients With Moderate Cholesterolemia

BACKGROUND AND OBJECTIVES: The mechanism for the improved endothelial function after treatment with statins has been shown to be the increased bioavailability of nitric oxide, which is independent of the cholesterol-lowering effects of statin therapy. The aim of this study was to evaluate the short-term effect on flow-mediated vasodilation (FMD), the pulse wave velocity (PWV) and the carotid intima-media thickness (IMT) of statin treatment, as based on the dose and duration of therapy. SUBJECTS AND METHODS: We enrolled 51 patients with moderate cholesterolemia (total cholesterol: 200-250 mg/dL). The patients were randomly divided into two groups according to the dose of atorvastatin (10 mg: 27 patients, 40 mg: 24 patients). We measured the FMD of the brachial artery, the carotid-radial PWV, the IMT of both common carotid arteries, the lipid profile and the serum C-reactive protein (CRP) at baseline, one week and eight weeks after statin treatment. RESULTS: The total cholesterol and low density lipoprotein (LDL) cholesterol levels in both groups were significantly decreased one week and eight weeks later. However, a difference between the groups was only noted at eight weeks. The FMD for both groups was significantly increased at one and eight weeks; however, the difference was not significantly different between the two groups. The carotid-radial PWV of the 40 mg group was decreased at one and eight weeks, and the change of the PWV at eight weeks was significantly different between the two groups. However, the change in the PWV was not correlated with a change in the LDL-cholesterol. CONCLUSION: Early improvement of the FMD and PWV following statin treatment might be related to the dose and duration of statin therapy and these effects of statin treatment may be independent of lipid lowering.