Intensive Lipid Lowering in ACS Patients Undergoing PCI
Intensive Lipid Lowering in ACS Patients Undergoing PCI
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco Dr. Boyle reports no financial relationships relevant to this field of study. This article originally appeared in the February 2010 issue of Clinical Cardiology Alert. It was edited by Michael H. Crawford, MD, and peer reviewed by Ethan Weiss, MD. Dr. Crawford is Professor of Medicine, Chief of Cardiology, University of California, San Francisco, and Dr. Weiss is Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer, and Dr. Weiss reports no financial relationships relevant to this field of study.
Source: Gibson CM, et al. Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome PCI-PROVE IT: A PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) Substudy. J Am Coll Cardiol. 2009;54:2290-2295.
Intensive lipid lowering with statin therapy (atorvastatin 80 mg) in patients presenting with acute coronary syndromes (ACS) resulted in improved outcomes compared to treatment with moderate lipid lowering (pravastatin 40 mg) in the PROVE-IT TIMI-22 study (Cannon et al. N Engl J Med. 2004;350:1495-1504), which included patients treated conservatively, as well as those treated with percutaneous coronary intervention (PCI). Whether this effect holds true in patients treated with PCI is unknown. Therefore, Gibson et al performed a post-hoc analysis of the PROVE-IT TIMI 22 study and analyzed the outcomes of those patients who had PCI during the index hospitalization for ACS.
Patients presenting with ACS (myocardial infarction [MI] or high-risk unstable angina) were screened for total cholesterol 240 mg/dL if statin-naïve or 200 mg/dL if they were already taking statins. Within 10 days of presentation, they were randomized 1:1 in a double-blind fashion to receive atorvastatin 80 mg daily or pravastatin 40 mg daily. If low-density lipoprotein (LDL) remained 125 mg/dL, the pravastatin could be increased to 80 mg daily. The main outcome measure of this analysis was time to the occurrence of one of the components of the primary endpoint of PROVE-IT TIMI 22: death, MI, unstable angina requiring hospitalization and revascularization at least 30 days after randomization, and stroke. Additional outcome measures included target vessel revascularization (TVR) and non-target vessel revascularization (non-TVR). Patients were followed for two years.
Results: Of the 4,162 patients enrolled in the trial, 2,868 underwent PCI during the initial hospitalization and were eligible for this analysis. Among this PCI cohort, the baseline characteristics between those randomized to atorvastatin 80 mg and those randomized to pravastatin 40 mg were similar, with the exception of peripheral arterial disease being more prevalent in the pravastatin group. Baseline LDL was 106 mg/dL in both groups. This dropped to 89 mg/dL in the pravastatin group and 57 mg/dL in the atorvastatin group at 30 days (p < 0.001). Baseline C-reactive protein (CRP) was 13.2 mg/dL, and dropped to 2.14 mg/dL in the pravastatin group and 1.55 in the atorvastatin group (p < 0.001). Patients treated with intensive lipid-lowering therapy exhibited significant reductions in the primary composite endpoint (death, MI, stroke or unstable angina requiring hospitalization, and revascularization) compared to patients treated with moderate lipid-lowering therapy (21.5% vs. 26.5% in the atorvastatin 80 mg and the pravastatin 40 mg groups, respectively; p = 0.001). Several secondary endpoints were also significantly reduced in the intensive lipid-lowering group: recurrent ischemia (13.0% vs. 17.1%; p < 0.001), rehospitalization for unstable angina (3.3% vs. 4.7%; p < 0.001), and revascularization 30 days after randomization (16.6% vs. 21.0%; p = 0.002) in the atorvastatin 80 mg and pravastatin 40 mg groups, respectively. In addition, there were non-significant trends favoring the intensive lipid-lowering group in all-cause mortality (1.5% vs. 2.5%, p = 0.057) and MI (5.8% vs. 7.7%, p = 0.052). Intensive lipid-lowering therapy resulted in lower rates of TVR (11.4% vs. 15.4%, p < 0.001) and non-TVR (8.0% vs. 10.5%, p < 0.001) than moderate lipid-lowering therapy. However, after adjustment for on-treatment LDL and CRP levels, only the reduction in TVR remained significant. Interestingly, the cohort from the original study that was treated medically, instead of with PCI, did not appear to benefit from intensive over moderate lipid-lowering therapy. Gibson et al conclude that among patients with ACS who undergo PCI, intensive statin therapy reduces major adverse cardiac events compared with moderate-dose statin therapy.
Intensive statin therapy improves outcomes following hospitalization for ACS. Gibson et al asked whether this held true in patients who had PCI during their ACS hospitalization and found, somewhat unexpectedly, that this only held true in the PCI patients. Patients treated medically had no statistically significant improvement in the primary outcome in this post-hoc analysis of PROVE-IT TIMI 22 (24.5% vs. 25.2%, p = 0.779) when treated with intensive lipid-lowering therapy. Their data are consistent with several recent studies demonstrating the benefits of high-dose statin therapy immediately prior to PCI. In this study, statin therapy was commenced after the PCI procedure, suggesting there may be incremental benefit in high-dose statins before PCI and then continued for two years thereafter. Importantly, their data were collected during the time of bare-metal stents and may, therefore, not apply to patients receiving drug-eluting stents and prolonged dual anti-platelet therapy. It is not clear if the achieved LDL level or the change in LDL correlated with the occurrence of the primary outcome in this substudy. Thus, we do not know if the observed effects are due to more effective lipid lowering or to the pleiotropic effects of statins. Regardless, this study reinforces the need for aggressive lipid-lowering therapy in patients undergoing PCI for ACS.Intensive lipid lowering with statin therapy (atorvastatin 80 mg) in patients presenting with acute coronary syndromes (ACS) resulted in improved outcomes compared to treatment with moderate lipid lowering (pravastatin 40 mg) in the PROVE-IT TIMI-22 study (Cannon et al. N Engl J Med. 2004;350:1495-1504), which included patients treated conservatively, as well as those treated with percutaneous coronary intervention (PCI).
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