Statin Therapy in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention (from the Evaluation of Drug Eluting Stents and Ischemic Events Registry) Tarun W. Dasari, MD, MPHa,*, David J. Cohen, MD, MScb, Neal S. Kleiman, MDc, Michelle J. Keyes, PhDd, Chen-Hsing Yen, MSd, Elias B. Hanna, MDa, and Jorge F. Saucedo, MDe 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 b blockers and angiotensin-converting enzyme inhibitors. Outcomes were assessed from discharge through 1-year follow-up. Oneyear 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. Ó 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;-:-e-) 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.1e4 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.1e4 Moreover, statins have proven to be beneficial in both primary and secondary prevention settings.5e14 However, patients with chronic kidney disease (CKD) have generally been excluded from such trials.15,16 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) a Department of Internal Medicine, Cardiology Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; bDepartment of Internal Medicine, Cardiology Section, St Luke’s Mid America Heart Institute, Kansas City, Kansas; cDepartment of Internal Medicine, Cardiology Section, Methodist DeBakey Heart & Vascular Center, Houston, Texas; dHarvard Clinical Research Institute, Boston, Massachusetts; and eNorthShore University Health System, Evanston, Illinois. Manuscript received September 27, 2013; revised manuscript received and accepted November 4, 2013. See page 4 for disclosure information. *Corresponding author: Tel: (405) 271-4742x44754; fax: (405) 2712960. E-mail address: [email protected] (T.W. Dasari).

0002-9149/13/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2013.11.006

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.17 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), noneST 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 www.ajconline.org

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Table 1 Baseline demographic and clinical characteristics of the study population

Table 3 Medication prescription pattern stratified by the statin use at discharge

Characteristic

Medication

Statin Therapy

p Value

Yes (n ¼ 1,833), No (n ¼ 473), % % Age (yrs), mean  SD Men Body mass index (mean  SD) Diabetes mellitus Hypertension Current smoker Renal dialysis Previous stroke Heart failure Peripheral arterial disease Previous MI Previous PCI Previous coronary bypass MI within 7 days Number of narrowed coronary arteries 1 2 3

74  10 54 27  5

75  10 48 26  5

0.16 0.01 0.12

36 87 14 7 14 18 17 41 39 30 16

37 82 13 7 18 20 19 36 36 25 11

0.66 0.004 0.59 0.58 0.07 0.36 0.45 0.06 0.36 0.06 0.002 0.26

43 30 27

46 29 25

Statin Therapy

p Value

Yes (n ¼ 1,833), No (n ¼ 473), % % Indication for PCI ST-segment elevation MI PosteST-segment elevation MI ACS Chronic stable angina or positive stress test Other Ejection fraction 50 Unknown Canadian classification system angina class No angina I II III IV Unknown

0.05 4 1

2 2

40 48

37 51

7

9

3 9 22 46 19

6 9 19 47 19

0.03