Secondary prevention trials have demonstrated the efficacy of statins in reducing cardiovascular morbidity and mortality in patients with coronary artery disease and events after percutaneous coronary intervention (PCI). However, there are few data describing the clinical value of statins in patients with coronary artery disease and chronic kidney disease (CKD) undergoing PCI. Of 10,148 patients who entered into Evaluation of Drug Eluting Stents and Ischemic Events, a multicenter registry of unselected patients undergoing PCI from July 2004 to December 2007, we studied 2,306 patients with CKD (estimated glomerular filtration rate ≤60 ml/min based on the Modified Diet in Renal Disease calculation). Patients were stratified into those receiving statins at discharge (n = 1,833, 79%) or not (n = 473, 21%). Patients in the statin group had a greater prevalence of hypertension, recent myocardial infarction (MI), and use of β blockers and angiotensin-converting enzyme inhibitors. Outcomes were assessed from discharge through 1-year follow-up. One-year all-cause mortality was 5.7% in statin group versus 8.7% in the no statin group (adjusted hazard ratio 0.55, 95% confidence interval 0.34 to 0.88). The composite of death, MI, and repeat revascularization was lower in statin group (adjusted hazard ratio 0.71, 95% confidence interval 0.51 to 0.99). In conclusion, among patients with CKD undergoing PCI, the prescription of statins at hospital discharge was associated with a significant improvement in subsequent outcomes including mortality and composite end point of death, MI, and repeat revascularization.
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) are the mainstay of lipid-lowering therapy in patients with chronic coronary artery disease (CAD) and acute coronary syndromes (ACSs) as well as those at high risk for atherosclerotic heart disease. Over the last 2 decades, randomized clinical trials have demonstrated the efficacy of statin therapy in improving cardiovascular outcomes in both stable CAD and ACS populations. Moreover, statins have proven to be beneficial in both primary and secondary prevention settings. However, patients with chronic kidney disease (CKD) have generally been excluded from such trials. We used data from Evaluation of Drug Eluting Stents and Ischemic Events (EVENT), a prospective multicenter registry of the practice and outcomes of percutaneous coronary intervention (PCI) in the United States to examine the benefits of statins in patients with CKD. We hypothesized that the statin use in patients after PCI would be associated with a reduction in adverse cardiovascular outcomes at 1 year.
Methods
A detailed description of the patient population and the design of the EVENT registry have been published. Briefly, EVENT is a multicenter registry that prospectively enrolled unselected patients undergoing PCI with attempted stent implantation at 50 US centers. Enrollment occurred in discrete “waves” of approximately 2,500 patients at approximately yearly intervals. Patients in whom stent implantation was not attempted during PCI or who had undergone PCI or cardiac surgery within the preceding 4 weeks were excluded. Patients underwent PCI for a variety of clinical indications, including ST-segment elevation myocardial infarction (MI), non–ST elevation ACS, and chronic CAD. The present analysis includes patients enrolled in the 4 waves of the registry (2004 to 2007). Study population consisted of patients who were successfully discharged after index hospitalization. In-hospital deaths and periprocedural MI were excluded from the analysis. Data concerning patient characteristics, presentation, and treatment were collected prospectively on standardized case report forms and submitted to the data-coordinating center. The institutional review board of each hospital approved participation in the EVENT registry; informed consent was obtained from each participating patient. Telephone follow-up was performed at 30 days and 6 and 12 months after the PCI to ascertain the occurrence of major cardiovascular events, which were subsequently source verified by the local study coordinator. Serum creatinine levels were recorded at baseline for all patients. CKD was defined as an estimated glomerular filtration rate (eGFR) ≤60 ml/min based on the Modified Diet in Renal Disease calculation. Patients for whom baseline GFR could not be calculated (because of ≥1 missing data elements) were excluded.
All end points were from discharge through 1-year follow-up. Postdischarge out-of-hospital MI was site reported. Target lesion revascularization was defined as any repeat PCI or bypass surgery to treat recurrent stenosis of the original target lesion. The primary end points for this study included all-cause mortality. Secondary end points included MI, death or MI, and a composite of death, MI, and repeat revascularization.
For baseline demographic and clinical characteristics, continuous variables are described as mean ± 1 SD, and the p value was based on a 2-sample t test for differences in continuous outcomes. For dichotomous or categorical outcomes, percentages are displayed, and the p value was reported for chi-square test and Wilcoxon rank-sum test. Clinical outcome and follow-up medication variables are reported as percentages. End point comparisons were performed using multivariate Cox proportional hazards models with adjustment for age, gender, hypertension, recent MI (within 7 days), ejection fraction, New York Heart Association class, warfarin, β blockers, and angiotensin-converting enzyme inhibitors. Results of these analyses are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). All analyses were performed using SAS software, version 9.1 (SAS Institute, Cary, North Carolina).
Results
Among the 10,148 patients included in the EVENT registry, a total of 2,306 had CKD (eGFR ≤60 ml/min) and constituted the primary analytical cohort for this analysis. Patients were stratified into those receiving statins at discharge (statin group; n = 1,833, 79%) or not (no statin group; n = 473, 21%).
Patients in the statin group had a greater prevalence of hypertension or recent (within 7 days) MI ( Table 1 ). The most common indication for PCI was either chronic stable angina or a positive stress study in both groups followed by non–ST elevation ACS. The proportion of patients undergoing PCI for ST-segment elevation MI was low in both the statin and no statin groups (4.3% vs 2.3%; Table 2 ).
| Characteristic | Statin Therapy | p Value | |
|---|---|---|---|
| Yes (n = 1,833), % | No (n = 473), % | ||
| Age (yrs), mean ± SD | 74 ± 10 | 75 ± 10 | 0.16 |
| Men | 54 | 48 | 0.01 |
| Body mass index (mean ± SD) | 27 ± 5 | 26 ± 5 | 0.12 |
| Diabetes mellitus | 36 | 37 | 0.66 |
| Hypertension | 87 | 82 | 0.004 |
| Current smoker | 14 | 13 | 0.59 |
| Renal dialysis | 7 | 7 | 0.58 |
| Previous stroke | 14 | 18 | 0.07 |
| Heart failure | 18 | 20 | 0.36 |
| Peripheral arterial disease | 17 | 19 | 0.45 |
| Previous MI | 41 | 36 | 0.06 |
| Previous PCI | 39 | 36 | 0.36 |
| Previous coronary bypass | 30 | 25 | 0.06 |
| MI within 7 days | 16 | 11 | 0.002 |
| Number of narrowed coronary arteries | 0.26 | ||
| 1 | 43 | 46 | |
| 2 | 30 | 29 | |
| 3 | 27 | 25 | |
| Variable | Statin Therapy | p Value | |
|---|---|---|---|
| Yes (n = 1,833), % | No (n = 473), % | ||
| Indication for PCI | 0.05 | ||
| ST-segment elevation MI | 4 | 2 | |
| Post–ST-segment elevation MI | 1 | 2 | |
| ACS | 40 | 37 | |
| Chronic stable angina or positive stress test | 48 | 51 | |
| Other | 7 | 9 | |
| Ejection fraction | 0.03 | ||
| <25 | 3 | 6 | |
| 25–35 | 9 | 9 | |
| 36–50 | 22 | 19 | |
| >50 | 46 | 47 | |
| Unknown | 19 | 19 | |
| Canadian classification system angina class | <0.001 | ||
| No angina | 14 | 20 | |
| I | 9 | 14 | |
| II | 25 | 21 | |
| III | 20 | 21 | |
| IV | 18 | 12 | |
| Unknown | 14 | 13 | |
Medication prescription patterns were similar in both groups at the time of discharge. However, patients not receiving statins at discharge were also less likely to be prescribed β blockers, warfarin, or angiotensin-converting enzyme inhibitors. Nonstatin lipid-lowering therapy was greater among patients not receiving statins (22% vs 12%, p <0.001; Table 3 ). During the follow-up, a greater proportion of patients in both groups were prescribed statins at 6 and 12 months (p <0.0001; Supplementary Table 1 ).
| Medication | Statin Therapy | p Value | |
|---|---|---|---|
| Yes (n = 1,833), % | No (n = 473), % | ||
| Aspirin | 97 | 96 | 0.25 |
| Clopidogrel | 96 | 96 | 0.88 |
| β Blocker | 81 | 69 | <0.001 |
| Angiotensin-converting enzyme inhibitor | 47 | 40 | 0.007 |
| Angiotensin receptor blocker | 16 | 17 | 0.46 |
| Calcium channel blocker | 24 | 24 | 0.98 |
| Nonstatin lipid lowering | 12 | 22 | <0.001 |
| Long-acting nitrates | 21 | 20 | 0.52 |
| Warfarin | 9 | 6 | 0.03 |
| Ranolazine (wave 4 only) | 1 | 2 | 0.33 |
One-year all-cause mortality was 5.7% in the statin group versus 8.7% in the no statin group (unadjusted HR 0.64, 95% CI 0.44 to 0.93, adjusted HR 0.55, 95% CI 0.34 to 0.88). The adjusted composite of death, MI, and repeat revascularization was also lower in statin group (15% vs 18%, unadjusted HR 0.87, 95% CI 0.70 to 1.07, adjusted HR 0.71, 95% CI 0.51 to 0.99; Table 4 and Figures 1 and 2 ). In the dialysis subgroup, the end point of death or composite of death, MI, and repeat revascularization was not significantly different (HR 0.82, 95% CI 0.64 to 1.05 and HR 0.50, 95% CI 0.15 to 1.75, respectively).
| 1-yr Outcome Among Patients With CKD With eGFR ≤60 ml/min | Statin Therapy | Adjusted HR ∗ (95% CI) | Adjusted p Value | |
|---|---|---|---|---|
| Yes (n = 1,833), % | No (n = 473), % | |||
| Death | 6 | 9 | 0.55 (0.34–0.88) | 0.01 |
| MI | 3 | 2 | 1.49 (0.44–5.04) | 0.52 |
| Death/MI | 8 | 10 | 0.65 (0.42–1.01) | 0.06 |
| Any repeat revascularization | 7 | 9 | 0.73 (0.44–1.20) | 0.21 |
| TVR | 5 | 6 | 0.87 (0.47–1.59) | 0.64 |
| TVR/Non-TLR | 2 | 2 | 0.69 (0.25–1.91) | 0.47 |
| Death/MI/any repeat revascularization | 15 | 18 | 0.71 (0.51–0.99) | 0.04 |
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