Statins and Stents 

Abstract & Commentary

The significance of periprocedural myocardial injury in the context of coronary stenting, while sometimes referred to by euphemisms such as "enzyme leak," "infarctlet," or "coronet," should not be underestimated. In fact, "enzyme leaks" of sufficient magnitude have been shown to be associated with adverse clinical outcomes, including higher mortality rates, in several clinical trials. Many of these trials have also demonstrated the cardioprotective effects of glycoprotein IIb-IIIa inhibitors in reducing ischemic complications of percutaneous coronary interventions (PCI). The "pleiotropic" (nonlipid lowering) cardioprotective effects of HMG coenzyme-A reductase inhibitors (statins) have also been demonstrated in a growing number of clinical trials of primary and secondary coronary artery disease prevention. Within the last year, the benefits of statin therapy and the adverse effects of statin withdrawal in patients undergoing coronary PCI have been described by several investigators. One recent report1 demonstrated improved long-term outcomes (30-day and 6-month all-cause mortality) in patients receiving statin therapy at the time of PCI, and this was discussed by Dr. Abrams in the April 2002 issue of Clinical Cardiology Alert. Another study,2 discussed in the February issue of this publication, showed that pre-PCI statin therapy was associated with a reduction in major adverse cardiac events and angiographic restenosis, particularly among patients with elevated C-reactive protein (CRP) levels "abrogating the increased risk associated with elevated CRP."

The present study by Herrmann and colleagues was designed to test the hypothesis that preprocedural statin treatment might be associated with a reduction in periprocedural myocardial injury. This analysis included 296 consecutive patients undergoing successful stenting of a de novo lesion. Of these patients, 229 (statin treated) had received a statin for more than 1 week prior to the index PCI, and the remaining 67 patients (controls) had not. Additional exclusion criteria included pre-PCI elevation of creatine kinase (CK) or troponin T (cTnT), myocardial infarction (MI) in the 4 weeks prior to PCI, the use of periprocedural glycoprotein IIb-IIIa inhibition, or any contraindication to antiplatelet therapy. All patients received ASA and a thienopyridine for 4 weeks. Serum CK, CKMB (if CK elevated), and cTnT were measured before, and 6, 12, and 24 hours after PCI. Clinical end points included death and MI, defined as CK > 2 ´ upper limit of normal (ULN) or development of new Q-waves.


Baseline demographic characteristics differed between the 2 groups in that, as expected, there was a higher incidence of history of hyperlipidemia in the statin-treated patients (100% vs 66%; P < 0.001). In addition, the statin-treated patients had a higher incidence of previous PCI (48% vs 24%; P = 0.001) and multivessel disease (79% vs 54%; P < 0.001) suggesting a higher vascular disease burden in the statin-treated patients. The groups were well matched in terms of angina severity, with the majority of patients in both groups presenting with CCS Class = 2. There were no differences between the groups with regard to baseline serum parameters, including total cholesterol, HDL-cholesterol, LDL cholesterol, or triglycerides. Of interest, there was a nonsignificant trend toward lower baseline CRP levels in the statin treated group (0.5 ± 0.9 vs 0.8 ± 1.4 mg/dL; P = 0.09). There were no differences between the groups in term of angiographic or procedural variables.

The overall incidence of any degree of CK or cTnT elevation was somewhat lower in the statin-treated patients (14.4% vs 20.9%, P = 0.03; and 17.9% vs 22.4%, P = 0.5, respectively). However, the incidence of large CK elevation (3 ´ ULN) was more than 90% lower in the statin-treated patients (0.4% vs 6.0%; P = 0.01). Furthermore, statin therapy was the only independent negative predictor of large postprocedural CK elevation. Clinical data were available for 90.2% of patients for a follow-up period of 13 ± 7 months, which revealed slightly, but not significantly, improved MI-free survival in statin-treated patients

Herrmann et al acknowledge that the study was limited by its small size, as well as its retrospective and nonrandomized design, but conclude that statin pretreatment resulted in a substantial reduction in the extent, rather than the overall incidence, of MI after coronary stenting. In addition, they suggest that the trend toward lower baseline CRP levels among statin-treated patients supports the hypothesis that reduced vascular inflammation may play a role in improved outcomes in these patients (Herrmann J, et al. Circulation. 2002;106:2180-2183).

Comment by Sarah M. Vernon, MD

The "inflammatory hypothesis" and the putative pleiotropic effects of statin therapy have certainly gained the spotlight in recent months, and for good reason. It seems the more we learn about the vascular biology of atherosclerosis and thrombosis, the more we learn about the links between the vessel wall, the platelet, and inflammatory modulators. High-sensitivity CRP is rising to the surface as an important marker, not only for inflammation, but also for the presence of vascular disease and the risk of adverse ischemic outcomes. This study adds to the growing body of largely observational data, suggesting that statins might contribute to improved outcomes, in frequency or in magnitude, after PCI (or ACS or MI) by mechanisms independent from their lipid-lowering effects. In his April 2002 commentary, Dr. Abrams cautions us not to blindly take the "leap of faith" from the results of randomized long-term prevention trials such as 4S, CARE and LIPID, to MIRACL (which did not demonstrate reduced mortality or MI after ACS), to the results from many observational "data sets" that have recently been reported. Nonetheless, these studies, including the recent report from Herrmann et al, are intriguing (or, as Dr. Abrams says, "hypothesis generating") and in toto, beg for a randomized clinical trial with long-term clinical follow-up to more definitively address the relationship between statins, CRP, and outcomes in patients receiving coronary stents. While we wait for definitive randomized data, we can’t forget to "Get With the Guidelines" and miss an opportunity for aggressive secondary prevention in each and every patient who undergoes PCI.

Dr. Vernon is Assistant Professor of Medicine, Director, VAMC Cardiac Catheterization Laboratory University of New Mexico Health Sciences Center, Albuquerque, NM.


1. Chan AW, et al. Circulation. 2002;105:691-696.

2. Walter DH, et al. J Am Coll Cardiol. 2001;38: 2006-2012.