Several randomized studies and meta-analyses have suggested that pretreatment with statins may decrease periprocedural myocardial infarction (MI) in patients undergoing percutaneous coronary intervention (PCI). The purpose of this randomized study was to investigate the effect of a 2-day atorvastatin therapy before PCI on long-term clinical outcome. Two hundred statin-naive patients with stable angina pectoris referred for PCI were enrolled and randomized (ratio 1:1) to 2-day pretreatment with atorvastatin 80 mg/day and subsequent PCI (atorvastatin group), or immediate PCI (control group). The registry group comprised 182 consecutive patients on long-term statin therapy referred for immediate PCI during the same period as randomized patients. We compared the first occurrence of MI or death during long-term follow-up. There were no significant differences in most clinical characteristics and early results among the 3 groups. Median follow-up was 45 months (1 to 59). Incidences of death/MI were 11.4%, 12.9%, and 13.8% in the atorvastatin, control, and registry groups, respectively. In the same groups, age-adjusted estimated 4-year freedom from death/MI was 0.78 versus 0.75 versus 0.80, respectively (p = 0.882, log-rank test). In multivariate analysis, only age of patients (odds ratio 1.04, 95% confidence interval 1.02 to 1.07, p <0.001) was identified as a significant predictor of death or MI during follow-up. In conclusion, these results suggest that 2-day therapy with high-dose atorvastatin before PCI did not influence occurrence of periprocedural MI or long-term clinical outcomes.
The role of pretreatment with statins in patients undergoing percutaneous coronary intervention (PCI) for stable angina pectoris has not yet been clarified and short-term results are mostly positive but still controversial. Most studies have suggested that the incidence of periprocedural myocardial infarction (PMI) can be decreased when statins have been administered upstream of PCI. The Atorvastatin Influences the Risk of Percutaneous Coronary Intervention (TIP 1) study ( http://ClinicalTrials.gov , identifier NCT00469326 ) demonstrated that 2-day therapy with atorvastatin (80 mg) before PCI did not decrease the occurrence of PMI in patients with stable angina pectoris undergoing elective PCI. The main limitation of the TIP 1 study was the unknown long-term outcomes of the study population. Therefore, we decided to determine the long-term clinical outcome (median follow-up 45 months) of statin-naive patients treated (or not) before PCI with a high-dose of atorvastatin and to compare it to the long-term outcome of a registry group of patients who had taken statins for >2 weeks before PCI.
Methods
Patients with stable angina pectoris, not taking statins, with a de novo lesion with 50% to 99% luminal diameter referred for PCI were enrolled in this study and randomized in 1:1 fashion to receive 2-day pretreatment with atorvastatin 80 mg/day (atorvastatin group, 100 patients) or immediate PCI without atorvastatin pretreatment (control group, 100 patients). In addition, we analyzed a group of consecutive patients with stable angina who had taken statins for >2 weeks, had a de novo lesion with 50% to 99% luminal diameter referred for PCI (registry group, 182 patients), were prospectively enrolled in the registry group, and were treated within the same period and by the same medical team as the randomized patients. Out of these, 19 patients (10%) were on atorvastatin 10 mg/day, 48 (26%) were on atorvastatin 20 mg/day, 14 (8%) were on atorvastatin 40 mg/day, 18 (10%) were on fluvastatin 20 mg/day, 62 (34%) were on simvastatin 20 mg/day, 20 (11%) were on simvastatin 40 mg/day, and 1 (1%) was on lovastatin 20 mg/day.
Patients with acute coronary syndromes within the previous 2 weeks and patients with chronic renal insufficiency (creatinine ≥150 μmol/L) were excluded from the study. Written informed consent was obtained from each patient and the local ethics committee approved all study protocols.
Full details regarding PCI are described elsewhere. In brief, all patients received aspirin (100 mg) and clopidogrel (300 mg) before the procedure. All patients received unfractionated heparin 50 to 80 IU/kg as an intra-arterial bolus at the start of PCI. Number of treated lesions and inflation pressures were determined individually by the operators. Stent delivery was followed by high-pressure dilation. After PCI, aspirin, atorvastatin, and other optimal medical treatments were prescribed to all patients. Clopidogrel (75 mg/day) was prescribed for 1 month after implantation of bare metal stents and for 6 to 12 months after implantation of drug-eluting stents. In addition, all patients received medical therapy consistent with current standard of care including therapy for atherosclerosis, diabetes, heart failure, and hypertension. All patients were treated with statins; randomized patients were treated with atorvastatin (20 to 80 mg/day according to lipid profile), and patients in the registry group were treated with the same statins as before PCI.
To assess clinical outcomes after hospital discharge, all patients were contacted by telephone or mail using a standardized questionnaire every 12 months after the procedure. All drugs used during follow-up were recorded. All adverse events were confirmed by reviewing medical records. Incidence of PMI in the atorvastatin and control groups was published previously.
Diagnosis of PMI was based on abnormal troponin I (TnI) values that were increased ≥3 times above the upper limit of normal (≥0.300 ng/ml) by a local laboratory (Architect, Abbott, Illinois). Blood samples for TnI measurements were drawn immediately before PCI and 16 to 24 hours thereafter. Additional samples of biomarkers were obtained if a patient developed signs of PMI. Q-wave MI was defined as the appearance of new pathologic Q waves on standard electrocardiogram in ≥2 leads.
The primary end point in this follow-up study was occurrence of PMI based on postinterventional release of TnI or subsequent Q-wave MI or all-cause death during long-term follow-up. All adverse events were confirmed by reviewing medical records and the national database of deaths.
Continuous variables were expressed as mean ± SD, and categorical variables as count and percentage. Because TnI data were skewed, these values were expressed as median with interquartile range. Data were tested for normal distribution using the Kolmogorov–Smirnov test. Differences between groups were tested using chi-square test or Fisher’s exact test for categorical variables and analysis of variance for continuous variables. Nonparametric Kruskal–Wallis test was used when data were not normally distributed. For significant differences between groups, tests were followed by a Bonferroni multiple-comparison procedure. Cox regression model was used to identify predictors of primary end points. All included explanatory variables were collected at the first patient presentation and consisted of age, diabetes, statin pretreatment, atorvastatin pretreatment, level of total cholesterol, length of stent, 3-vessel disease, and complete revascularization. Survival functions were constructed using Kaplan–Meier estimates adjusted for mean age and compared using log-rank test. A p value <0.05 was considered statistically significant. STATA 9.2 (Stata Corporation LP, College Station, Texas) and PRISM 4 (GraphPad Software, Inc., San Diego, California) were used for analysis.
Results
Three hundred eighty-two patients with stable angina pectoris were enrolled and underwent PCI. Most clinical and procedural variables were comparable among the 3 groups of patients ( Table 1 ).
| Variable | Atorvastatin Group | Registry | Control Group |
|---|---|---|---|
| (n = 100) | (n = 182) | (n = 100) | |
| Age (years) | 67.8 ± 11.0 (44–91) ⁎ ‡ | 64.7 ± 9.3 (42–84) ⁎ | 64.0 ± 10.0 (46–86) ‡ |
| Men | 54% ‡ | 66% | 79% ‡ |
| Angina pectoris class (Canadian Cardiology Society) | 2 ± 0.9 | 1.7 ± 1.2 | 1.9 ± 0.8 |
| Dyspnea class (New York Heart Association) | 1.4 ± 1.2 | 1.5 ± 1.1 | 1.2 ± 1.2 |
| Previous myocardial infarction | 23% ⁎ | 45% ⁎ † | 27% † |
| Current smoker | 16% | 18% | 23% |
| Hypertension | 77% | 78% | 65% |
| Total plasma cholesterol | |||
| mmol/L | 4.8 ± 1.0 | 4.1 ± 1.0 | 4.6 ± 1.3 |
| mg/dl | 185 ± 38 ⁎ | 158 ± 38 ⁎ † | 177 ± 50 † |
| Low-density lipoprotein cholesterol | |||
| mmol/L | 3.0 ± 0.8 | 2.5 ± 0.8 | 3.0 ± 1.0 |
| mg/dl | 115 ± 31 ⁎ | 97 ± 31 ⁎ † | 115.0 ± 38 † |
| High-density lipoprotein cholesterol | |||
| mmol/L | 1.1 ± 0.3 | 1.0 ± 0.3 | 1.0 ± 0.3 |
| mg/dl | 42 ± 12 | 38 ± 12 | 38 ± 12 |
| Plasma triglyceride | |||
| mmol/L | 1.7 ± 0.9 | 1.5 ± 1.1 | 1.5 ± 0.7 |
| mg/dl | 149 ± 79 ⁎ | 133 ± 97 ⁎ † | 131 ± 61 † |
| Diabetes mellitus | 26% | 31% | 25% |
| β Blockers | 63% ⁎ | 78% ⁎ † | 63% † |
| Calcium channel blockers | 25% | 22% | 15% |
| Angiotensin-converting enzyme inhibitors | 43% | 57% | 41% |
⁎ Difference between atorvastatin and registry groups.
† Difference between registry and control groups.
Angiographic and procedural characteristics and early results were similar in all 3 groups of patients ( Table 2 ). There were no deaths, Q-wave MI, urgent bypass surgery, or recurrent ischemia requiring urgent target lesion repeat PCI in this study.
| Variable | Atorvastatin Group | Registry | Control Group |
|---|---|---|---|
| (n = 100) | (n = 182) | (n = 100) | |
| Coronary narrowing location | |||
| Left anterior descending coronary artery | 54% | 41% | 53% |
| Right coronary artery | 27% | 28% | 18% |
| Left circumflex coronary artery | 21% | 27% | 29% |
| Saphenous vein graft | 1% | 1% | 0% |
| Left main coronary artery | 1% | 3% | 0% |
| Number of coronary arteries narrowed | |||
| 1 | 55% ⁎ | 37% ⁎ † | 63% † |
| 2 | 27% | 36% | 23% |
| 3 | 18% | 26% † | 14% † |
| Lesion type | |||
| A | 15% | 7% | 10% |
| B1 | 29% | 36% | 35% |
| B2 | 38% | 36% | 40% |
| C | 18% | 20% | 15% |
| Stenosis before percutaneous coronary intervention | 82 ± 8 | 82 ± 9 | 84 ± 10 |
| Stenosis after percutaneous coronary intervention | 3 ± 10 | 3 ± 8 | 3 ± 12 |
| Intracoronary thrombosis | 1% | 3% | 2% |
| Mean number of treated lesions | 1.2 ± 0.1 | 1.2 ± 0.4 | 1.1 ± 0.1 |
| Stents per patient | 1.1 | 1.1 | 1.1 |
| Mean stent length (mm) | 18 ± 9 | 17 ± 9 | 17 ± 8 |
| Complete revascularization | 74% | 66% † | 82% † |
| Inflation time (seconds) | 20 (10–30) | 15 (10–26) | 18 (10–30) |
| Mean fluoroscopic time (minutes) | 6.9 ± 4.4 | 6.3 ± 5.1 | 6.7 ± 4.8 |
| Angiographic success | 99% | 99% | 97% |
| Troponin I before percutaneous coronary intervention (ng/ml) | 0.100 (0.015–0.100) | 0.100 (0.100–0.100) † | 0.100 (0.010–0.100) † |
| Troponin I (ng/ml) 24 hours after percutaneous coronary intervention | 0.100 (0.096–0.385) | 0.100 (0.100–0.295) | 0.100 (0.060–0.262) |
| Periprocedural myocardial infarction (%) | 17 | 13 | 16 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
