Statin administration before percutaneous coronary intervention Carlo Briguori

Following percutaneous coronary intervention (PCI), 5% to 30% of patients may experience an increase in cardiac enzymes.1-3 This complication negatively affects event-free survival after PCI.4-7 Optimal antiplatelet therapy is necessary to prevent periprocedural myocardial infarction (MI).8,9 Apart from their cholesterol-reducing effects, HMG-CoA reductase inhibitors (statins) have also been shown to exert antithrombotic properties.10,11 We evaluated whether administering statins before elective coronary stent implantation would prevent an increase in cardiac enzymes following the procedure.

Methods

Patients scheduled for elective stent implantation were randomly assigned to one of two groups: a control group, in which patients received no statin treatment, or a statin group, in which patients received statins 3 or more days before the procedure. Decisions regarding the dosage and type of drug to be used were left up to the physician. At least 3 days before the procedure, all patients were given 75 mg of clopidogrel (Plavix) daily, 250 mg of ticlopidine (Ticlid) twice a day, and 325 mg aspirin daily. According to the choice of the operator, glycoprotein IIb/IIIa inhibitors were given. Before the procedure, 6 hours after the procedure, and 12 hours after the procedure, cardiac troponin I (upper limit of normal [ULN] ≤ 0.10 ng/mL) and creatine kinase (CK)-MB (ULN ≤ 3.5 ng/mL) levels were assessed. The day before the procedure, plasma C-reactive protein (CRP) levels were evaluated. The rate of a large non—Q-wave MI, as shown by an increase in CK-MB level over five times ULN, by itself or with ST-segment or T-wave abnormalities or chest pain5-12 was the end point of the study.

The Student’s t test and Mann-Whitney U test were used to analyze normally and nonnormally distributed variables, respectively, between the two groups. The chi-square test was used to evaluate categorical variables. To determine independent predictors for CK-MB increase over five times ULN after the procedure, a multivariable logistic regression model was constructed.

Results

Two hundred twenty-five patients were enrolled in the control group, and 226 were enrolled in the statin group, for a total of 451 patients. Therapy with statins was started from 3 to 31 (mean, 17 ± 8) days before PCI. Fluvastatin (Lescol XL; 80 mg/day) was given to 3% of patients, simvastatin (Zocor; mean dose, 24 ± 9 mg/day) was given to 39% of patients, pravastatin (Pravachol; mean dose, 32 ± 10 mg/day) was given to 29% of patients, and atorvastatin (Lipitor; mean dose, 22 ± 9 mg/day) was given to 29% of patients. As shown in Table 1, the two groups were similar with regard to clinical characteristics. Compared with the statin group, patients in the control group more frequently had high CRP levels at the time of the procedure (27% versus 13.8%, P = .007). Angiographic and procedural characteristics are summarized in Table 2. Fifty-four percent of control patients and 46% of statin patients received glycoprotein IIb/IIIa inhibitors.

In the statin group, the median peak CK-MB level was 1.70 (interquartile range, 1.10—3.70) ng/mL, and it was 2.20 (interquartile range, 1.30–5.60) ng/mL in the control group (P = .015). As shown in the Figure, panel A, 35 patients (15.6%) in the control group and 18 patients (8%) in the statin group had an increased CK-MB level over five times ULN (P = .012; odds ratio [OR] = 0.47; 95% confidence interval [CI] = 0.26–0.86). As shown in panel B of the Figure, 72 patients (32%) in the control group and 53 patients (23.5%) in the statin group had a cardiac troponin I level over five times ULN (OR = 0.65; 95% CI = 0.42–0.98; P = .043). Age over 65 years (OR = 2.58; 95% CI = 1.09–6.11; P = .031), statin pretreatment (OR = 0.33; 95% CI = 0.13–

0.86; P = .023), and angiographic complications (OR = 9.36; 95% CI = 3.06—28.64; P < .001) were shown to be independent predictors of CK-MB elevation over five times ULN.

Discussion

The cardioprotective effects of statin therapy before PCI, as have been shown in other studies,13-15 were also shown in this study. Patients who received statin therapy prior to the procedure had a markedly reduced incidence of periprocedural non—Q-wave MI (as evidenced by CK-MB elevation five times ULN). The extent as opposed to the overall incidence of periprocedural MI was significantly reduced in patients receiving statin treatment before the procedure, as shown in experimental studies. In addition to their lipid-lowering effects, the cardiovascular benefits of statins include the nonlipid-related mechanisms (or pleiotropic effects), such as anti-inflammatory effects, plaque stabilization, and antithrombotic effects.10,11

The fact that the beneficial effect of statin treatment on cardiac enzyme elevation after PCI was independent of preprocedural CRP level suggests that the anti-inflammatory effect of statins may have a minor role in preventing myonecrosis during stent implantation.11,15 A reduction in the relative content of cholesterol esters that are significant factors affecting plaque stability is induced by statin therapy.11 Platelet aggregation and thromboxane production are decreased by statins, which also interfere with tissue factor activity, conversion of prothrombin to thrombin, and thrombin activity.11 Furthermore, statins trigger fibrinolysis.11

Conclusion

As shown by the results of this study, treatment with statins before PCI reduces the rate of periprocedural myocardial injury following the procedure.