Periprocedural statin therapy has been shown to decrease the rate of myocardial infarctions (MIs) after percutaneous coronary intervention (PCI). However, the impact of long-term statin therapy on postprocedure MI remains unknown. We examined the impact of long-term statin therapy on cardiac enzyme (cardiac troponin I [cTnI] and creatine kinase-MB [CK-MB]) increases after PCI in patients undergoing nonemergency PCI. Using the 2004/2005 Cornell Angioplasty Registry, we evaluated 1,482 patients undergoing elective or urgent PCI with normal preprocedure cardiac enzymes levels (cTnI and CK-MB). The population was divided into 2 groups: (1) patients on long-term (≥7 days) statin therapy before PCI (n = 1,073) and (2) patients not on long-term statin regimen (n = 409). Cardiac enzyme levels after PCI were assessed at 8, 12, and 18 hours after PCI. An increase in cTnI ≥1 time upper-limit of normal (ULN) was observed in 830 patients (56.1%) and an increase in cTnI ≥3 times ULN was observed in 518 patients (35.0%). There was no difference in incidence of cTnI increases ≥3 times ULN in patients on long-term statin therapy versus those not on long-term statin therapy in the overall group (35.1% vs 34.5%, p = 0.855). There was a trend toward a lower incidence of small cTnI increases ≥1 time ULN in patients on long-term statin therapy versus those not receiving long-term statins (54.6% vs 59.7%, p = 0.090). Incidence of CK-MB increases ≥1 time or ≥3 times ULN and peak cTnI and CK-MB levels were similar between the 2 groups. In a subgroup of patients with unstable angina, long-term statin therapy decreased small cTnI increases (≥1 time ULN) after PCI (54.6% vs 64.3%, p = 0.023). The greatest benefit in decrease of MIs after PCI was seen in patients with unstable angina receiving long-term high-dose statin therapy. In conclusion, long-term statin therapy did not decrease the incidence of periprocedural MI in patients with stable coronary artery disease undergoing nonemergency PCI. In patients with unstable coronary syndromes, long-term statin therapy may be beneficial, particularly at a high dose.
Increases of cardiac enzymes after nonemergency percutaneous coronary intervention (PCI) are not uncommon and have been associated with an increased risk of cardiovascular events during follow-up. Benefits of statin therapy have been well established in primary and secondary preventions of cardiovascular disease. These benefits may result from long-term low-density lipoprotein cholesterol lowering and short-term pleiotropic effects of statins. Recent randomized controlled studies have demonstrated that a short course of preprocedural high-dose statin therapy may decrease the incidence of postprocedure myocardial infarction (MI) and subsequently decrease the incidence of major adverse cardiovascular events after PCI. However, there are limited data examining the protective effects of long-term statin therapy on the incidence of cardiac enzyme increases after PCI and PCI-related MI. The aim of this study was to examine the effect of long-term statin therapy on incidence of MI after PCI in a large cohort of patients undergoing nonemergency PCI in the current era of drug-eluting stenting.
Methods
Methods for data collection in this study have been previously described in detail. All patients undergoing PCI at New York Presbyterian Hospital, Weill Cornell Medical College (New York, New York) were enrolled in the Cornell Angioplasty Registry. A standard case-report form delineating comprehensive patient demographics, preintervention clinical status, procedural findings, and in-hospital complications was completed for each PCI performed. Patient follow-up was obtained by publicly available mortality data through the Social Security Death Index and through regularly scheduled telephone contacts. The present study included all consecutive patients from January 1, 2004 through December 31, 2005. Only patients with normal preprocedural cardiac troponin I (cTnI) levels (<0.15 ng/ml) and normal preprocedural creatine kinase-MB (CK-MB) levels (<4.5 ng/ml) were included in the study.
Patients presenting with MI ≤7 days, hemodynamic instability/shock, receiving thrombolytic therapy ≤7 days, or with severe renal insufficiency (serum creatinine ≥4 mg/dl) were excluded. The study was approved by the institutional review board of Weill Cornell Medical College. Blood samples for cardiac markers (CK, CK-MB, and cTnI) were obtained routinely before PCI and at 8, 12, and 18 hours after PCI. cTnI analysis was performed using a Bayer ACS:ADVIA Centaur assay (Bayer, Pittsburgh, Pennsylvania).
Patients were defined to have been on long-term statin therapy if they reported the use of a hydroxymethylglutaryl coenzyme A reductase inhibitor (including a statin as part of a combination pill) for ≥7 days before PCI and statins were continued after PCI. Patients were considered in the “no-statin” group if they did not report statin use before PCI and did not receive statin therapy immediately before PCI. Patients were excluded from the study if the timing of periprocedural statin therapy was missing. Patients on long-term statin therapy whose statin therapy was interrupted before PCI were excluded. Patients who were not on long-term statin therapy and received ≥1 dose of statins before PCI were excluded from analysis. High-dose statin therapy was defined as receiving simvastatin ≥40 mg/day, atorvastatin ≥20 mg/day, or any dose of rosuvastatin. All other statin doses were classified as low-dose statin therapy.
Baseline characteristics and angiographic and procedural data in patients with versus without long-term statin therapy were compared. Primary end points analyzed were cTnI and CK-MB increases ≥1 time and ≥3 times upper limit of normal (ULN) after PCI. Secondary end point was long-term all-cause mortality. Long-term mortality data were obtained for 98.6% of patients using the Social Security Death Index with a mean follow-up period of 69.9 ± 12.3 months. Multivessel disease was defined as the presence of >70% lesion in ≥2 major coronary arteries/branches or a left main coronary artery lesion. Multivessel PCI was defined as a coronary intervention in ≥2 major coronary arteries/branches or a left main coronary artery. Congestive heart failure referred to New York Heart Association class III or IV heart failure during admission. Vascular injury referred to an access site complication requiring mechanical intervention. Major bleeding was defined as a decrease in hemoglobin ≥4 g/dl. Minor bleeding was defined as decreases in hemoglobin ≥2 and <4 g/dl. Angiographic success was defined as final stenosis ≤20% of the target vessel reference diameter.
Data management and analysis were performed with Excel 12.2.7 (Microsoft Corporation, Redmond, Washington) and SPSS Statistics 18.0 (IBM Corporation, Somert, New York). Data are presented as mean ± SD for continuous variables or proportions for dichotomous variables. Differences in prevalence between groups were compared with chi-square test or Fisher’s exact test for dichotomous variables, and mean values for continuous variables were compared with Student’s t test. A p value <0.05 was considered statistically significant. The relation of long-term statin therapy to the risk of cTnI increase after PCI was assessed with multivariate regression models. Univariate associations with cardiac enzyme increases were estimated for all clinical and procedural variables ( Tables 1 and 2 ). To test the independence of long-term statin therapy as a predictor of cardiac enzymes increases, long-term statin therapy was entered into the stepwise multivariate logistic regression model that also included univariate predictors of cardiac enzyme increases (significant at level of 0.15). Mortality rates were calculated and plotted according to Kaplan–Meier methods, and comparisons between groups were performed using log-rank statistic.
| Variable | Statin Therapy | p Value | |
|---|---|---|---|
| Yes (n = 1,073) | No (n = 409) | ||
| Age (years), mean ± SD | 67.0 ± 11.3 | 67.1 ± 11.7 | 0.910 |
| Men | 72.1% | 67.7% | 0.097 |
| White | 78.8% | 78.0% | 0.777 |
| Diabetes mellitus | 35.1% | 21.5% | <0.001 |
| Body mass index (kg/m 2 ), mean ± SD | 28.6 ± 5.1 | 28.4 ± 5.4 | 0.536 |
| Current congestive heart failure | 5.4% | 6.8% | 0.320 |
| Left ventricular ejection fraction (%), mean ± SD | 51.6 ± 9.5 | 51.4 ± 9.6 | 0.721 |
| Clinical presentation | |||
| Stable angina pectoris | 51.7% | 51.3% | 0.908 |
| Unstable angina pectoris | 48.3% | 48.7% | 0.908 |
| Canadian Cardiovascular Society angina class III or IV | 49.3% | 50.4% | 0.728 |
| Chronic obstructive pulmonary disease | 4.8% | 5.1% | 0.787 |
| Peripheral vascular disease | 7.2% | 7.3% | 0.911 |
| Previous stroke | 9.2% | 4.4% | 0.002 |
| Previous heart failure | 2.5% | 2.4% | 1.000 |
| Previous myocardial infarction | 36.3% | 21.8% | <0.001 |
| Previous percutaneous coronary intervention | 39.1% | 18.1% | <0.001 |
| Previous coronary artery bypass graft | 19.0% | 10.8% | <0.001 |
| Hemoglobin level (g/dl), mean ± SD | 13.0 ± 1.6 | 13.3 ± 1.7 | 0.005 |
| Creatinine clearance (ml/min), mean ± SD | 76.2 ± 31.6 | 78.3 ± 32.2 | 0.251 |
| Creatinine clearance <60 ml/min | 34.1% | 31.5% | 0.356 |
| Long-term aspirin therapy | 79.0% | 60.4% | <0.001 |
| Long-term clopidogrel therapy | 16.0% | 6.1% | <0.001 |
| Variable | Statin Therapy | p Value | |
|---|---|---|---|
| Yes (n = 1,073) | No (n = 409) | ||
| Nature of procedure | |||
| Elective | 63.4% | 65.0% | 0.586 |
| Urgent | 36.6% | 35.0% | 0.586 |
| Number of narrowed coronary arteries | |||
| 1 | 39.0% | 44.7% | 0.051 |
| 2 | 36.3% | 33.3% | 0.302 |
| 3 | 24.7% | 22.0% | 0.323 |
| Multivessel or left main coronary artery disease | 54.3% | 48.7% | 0.055 |
| Target percutaneous coronary intervention coronary artery | |||
| Left anterior descending | 45.7% | 57.5% | <0.001 |
| Right | 32.1% | 30.3% | 0.532 |
| Left circumflex | 30.5% | 21.3% | <0.001 |
| Left main | 2.1% | 0.7% | 0.076 |
| Saphenous vein graft | 4.8% | 4.2% | 0.679 |
| Multivessel or left main percutaneous coronary intervention | 14.4% | 13.0% | 0.504 |
| Multilesion percutaneous coronary intervention | 47.4% | 44.7% | 0.382 |
| Device used | |||
| Stent | 95.0% | 92.4% | 0.062 |
| Drug-eluting stent | 89.1% | 86.1% | 0.105 |
| Sirolimus-eluting stent | 69.4% | 69.2% | 0.950 |
| Paclitaxel-eluting stent | 21.2% | 18.3% | 0.249 |
| Intravascular ultrasound | 18.9% | 19.1% | 0.941 |
| Glycoprotein IIb/IIIa used | 48.0% | 51.3% | 0.269 |
| Abciximab | 7.0% | 6.1% | 0.643 |
| Other glycoprotein IIb/IIIa agents | 41.0% | 45.2% | 0.142 |
| Clopidogrel loading dose ≤300 mg | 62.8% | 37.2% | <0.001 |
| Clopidogrel loading dose 600 mg | 53.1% | 46.9% | 0.002 |
| Stenosis severity before percutaneous coronary intervention (%), mean ± SD | 82.5 ± 11.6 | 84.0 ± 11.0 | 0.032 |
| Stenosis severity after percutaneous coronary intervention (%), mean ± SD | 2.9 ± 10.1 | 2.9 ± 10.4 | 0.994 |
Results
During the study period, there were 3,611 elective or urgent PCIs performed in 2,504 consecutive patients. Of these, 1,482 patients met the inclusion criteria and were included in the final analysis. There were 1,073 patients (72.4%) taking statins for ≥7 days before PCI and periprocedurally and 409 patients (27.6%) who were not on long-term statin therapy and did not receive such therapy before PCI. In our study population, atorvastatin (59%) and simvastatin (26%) were the most frequently used statins, whereas pravastatin, rosuvastatin, lovastatin, and fluvastatin were used less commonly. There were 830 patients (56.1%) with increased cTnI levels ≥1 time ULN (median 0.20 ng/ml, mean 0.27 ± 0.08) after PCI. There were 518 patients (35.0%) with increased cTnI levels ≥3 times ULN (median 1.50 ng/ml, mean 4.67 ± 11.12) after PCI.
Baseline characteristics of study patients are listed in Table 1 . Patients receiving long-term statin therapy were more likely to have a history of diabetes mellitus, stroke, MI, PCI or coronary artery bypass graft surgery and were more likely to be on long-term aspirin or clopidogrel therapy. A similar proportion of patients presented with unstable angina in the 2 groups. Angiographic and procedural characteristics are presented in Table 2 . There was a trend toward a higher frequency of single-vessel coronary artery disease (CAD) in the no-statin therapy group, whereas multivessel or left main coronary artery disease was more common in the long-term statin therapy group. The 2 groups had a high rate of stent (>92%) and drug-eluting stent (>86%) placement during PCI. There was a high rate of angiographic success (>99%) in all patients and a low rate of in-hospital events as listed in Table 3 . Most patients in the 2 groups had a short (1 day to 2 days) length of stay in total and after PCI.
| Variable | Statin Therapy | p Value | |
|---|---|---|---|
| Yes (n = 1,073) | No (n = 409) | ||
| Angiographic success | 99.7% | 99.5% | 0.620 |
| Death | 0.0% | 0.0% | 1.000 |
| Emergency revascularization | 0.2% | 0.0% | 1.000 |
| Stroke | 0.0% | 0.2% | 0.276 |
| Renal failure | 0.1% | 0.0% | 1.000 |
| Access site injury | 0.7% | 0.5% | 1.000 |
| Stent thrombosis | 0.0% | 0.0% | 1.000 |
| Bleeding | |||
| Major | 0.6% | 0.5% | 1.000 |
| Minor | 9.6% | 9.5% | 1.000 |
| Length of stay (total) (days) | |||
| 1–2 | 78.2% | 83.9% | 0.017 |
| 3–4 | 11.6% | 8.3% | 0.074 |
| ≥5 | 10.3% | 7.8% | 0.168 |
| Length of stay (after percutaneous coronary intervention) (days) | |||
| 1–2 | 88.0% | 89.0% | 0.652 |
| 3–4 | 7.2% | 6.8% | 0.910 |
| ≥5 | 4.8% | 4.2% | 0.679 |
| Troponin I ≥1 time upper limit of normal | 54.6% | 59.7% | 0.090 |
| Troponin I ≥3 times upper limit of normal | 35.1% | 34.5% | 0.855 |
| Creatine kinase-MB ≥1 time upper limit of normal | 10.6% | 10.8% | 0.925 |
| Creatine kinase-MB ≥3 times upper limit of normal | 5.8% | 5.6% | 1.000 |
| Median creatine kinase-MB peak (ng/ml) ⁎ | 11.9 | 11.8 | 0.961 |
| Median troponin I peak (ng/ml) † | 0.7 | 0.6 | 0.080 |
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