Statin Loading Before Percutaneous Coronary Intervention to Reduce Periprocedural Myocardial Infarction

Norris, Davena M. PharmD*; Anderson, Joe R. PharmD†‡

doi: 10.1097/CRD.0b013e31826db7ff
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Periprocedural myocardial infarction (PMI) is a common complication associated with percutaneous coronary intervention (PCI), occurring in approximately 15% to 20% of patients undergoing the procedure. The established diagnostic criteria for PMI is an increase in cardiac biomarkers, specifically creatine kinase-MB levels > 3 times the upper limit of normal. As PMI has been associated with an increased risk of mortality after PCI, investigative efforts have been directed at therapies that can potentially decrease PMI. One such therapy is the use of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) administered as a loading dose before PCI. Multiple small, randomized, controlled trials have demonstrated significant reductions in the incidence of PMI with statin loading before PCI. The risk reduction was seen in patients with stable and unstable coronary artery disease, as well in statin-naive patients or those on chronic statin therapy. Potential mechanisms for the rapid benefits of statin loading include: anti-inflammatory effects, reversal of endothelial dysfunction, decrease in oxidative stress, and inhibition of the thrombotic system. None of the current studies were of sufficient power or duration to detect benefits on mortality, though a recent meta-analysis did demonstrate a reduction in major adverse cardiovascular events. In addition to long-term effects, several additional questions remain with regard to statin loading, such as statin type, dose, and optimal timing of administration. However, given the current evidence of benefit and the low risk of adverse events, it can be recommended that all patients undergoing PCI be considered for statin loading before the procedure.

From the *Department of Pharmacy, Southern Arizona VA Health Care System, Tucson, Arizona; and Departments of Pharmacy and Internal Medicine, University of New Mexico College of Pharmacy and School of Medicine, Albuquerque, NM.

Disclosure: The authors declare no conflict of interest.

Correspondence: Joe R. Anderson, PharmD, College of Pharmacy, MSC09 5360 1, University of New Mexico, Albuquerque, NM 87131. E-mail: janderson@salud.unm.edu.

Article Outline
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REQUEST

Should all patients undergoing percutaneous coronary intervention (PCI) receive a statin-loading dose?

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RESPONSE

Periprocedural myocardial infarction (PMI) is a common complication associated with PCI.1 PMI is assessed by elevations in cardiac biomarkers, including creatine kinase-MB (CK-MB), troponin I, and troponin T, and has been reported to occur in as high as 69% of patients undergoing PCI.1,2 This elevation in cardiac enzymes is indicative of necrosis and should be labeled as myocardial infarction (MI).3 According to Joint European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force for the Redefinition of Myocardial Infarction, the cutoff for PMI after PCI is a CK-MB elevation of > 3 times the upper limit of normal (ULN).3

Most patients who have PMI remain asymptomatic with no changes in cardiac function.4 However, PMI has been associated with increased short- and long-term mortality.5–8 A meta-analysis conducted by Ioannidis et al5 showed that even a small increase in CK-MB is associated with a greater risk of mortality during follow-up, and there is a dose–response relationship between CK-MB levels and the risk of death. A report from the Evaluation of Drug Eluting Stents and Ischemic Events registry of 5961 patients undergoing PCI found that after multivariable adjustment, PMI (defined as peak CK-MB >3 times ULN) was independently associated with an increased 1-year mortality (adjusted hazard ratio, 1.84; 95% confidence interval (CI), 1.17–2.89; P = 0.009).6

Antiplatelet agents, beta blockers, and statins have long-term benefits when used for secondary prevention in patients with coronary artery disease (CAD).9 As a result, many of these treatments have also been studied for the prevention of PMI.10–13 The benefits of statins in acute coronary syndromes (ACS) are seen early, before substantial lipid lowering has occurred. This suggests that pleiotropic effects of statins, not lipid-lowering effects, are responsible for these early benefits. These pleiotropic effects may include improvement in endothelial function, anti-inflammatory effects, decrease in oxidative stress, vasodilation of coronary microvessels, and inhibition of thrombogenic response.4 Observational studies have suggested that treatment with statin therapy, before and at the time of PCI, might reduce the incidence of PMI after PCI, and have mortality benefits.14–16

Recent evidence-based guidelines for PCI recommend the use of high-dose statin loading before PCI, a class IIa recommendation, indicating that it is “reasonable” to administer treatment because the benefits outweigh the risks.9 The objective of this article is to review the available literature (Table 1) to answer the question, “Should all patients undergoing PCI receive a statin-loading dose?”

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LITERATURE REVIEW

Prospective Randomized Controlled Trials

Briguori and colleagues17 conducted an open-label, prospective, randomized study to assess whether treatment with a statin before elective PCI is effective in preventing elevation of cardiac biomarkers of myocardial injury. A total of 451 statin-naive patients, predominantly with stable angina (84%), were randomized to receive statin before PCI or no statin. The type and dose of statin were left to the discretion of the treating physician, and were as follows: atorvastatin, 29% of cases (mean dose 22 ± 9 mg/day); pravastatin, 29% of cases (mean dose 32 ± 10 mg/day); simvastatin, 39% of cases (mean dose 24 ± 9 mg/day); and fluvastatin, 3% of cases (80 mg/day). Statin therapy was started at least 3 days before PCI, with a mean of 17 ± 8 days and range of 3 to 31 days. All patients received aspirin 325 mg and ticlopidine 250 mg twice daily or clopidogrel 75 mg daily for at least 3 days before initiation of a statin. The primary endpoint was the rate of a large non-Q-wave MI, defined as a CK-MB elevation > 5 times the ULN alone or associated with chest pain or ST segment or T-wave abnormalities. CK-MB and troponin I levels were measured before PCI and at 6 and 12 hours after. The primary endpoint occurred in 18 (8%) patients in the statin group compared with 35 (15.6%) patients in the control group (odds ratio [OR], 0.47; 95% CI, 0.26–0.86; P = 0.012). However, the rate of CK-MB elevation > 3 times the ULN was not significantly different between the statin-treated patients and controls, 13.7% versus 16.4%, respectively. The rate of CK-MB elevation did not differ based on type of statin (atorvastatin 6%, pravastatin 6.2%, simvastatin 10%, and fluvastatin 0%; P = 0.53). In addition, the length of statin therapy before PCI was not statistically different between patients with and without cardiac enzyme elevation.

A prospective randomized trial by Yun and colleagues18 analyzed the effect of a high loading dose of rosuvastatin before PCI on the rate of PMI (defined by CK-MB elevation > 2 times ULN) and the 30-day incidence of major adverse cardiac events (MACE), which included death, Q-wave MI, target vessel revascularization (TVR), and ischemic stroke. A total of 445 statin-naive patients with non-ST segment elevation MI (NSTEMI) and unstable angina were randomly assigned to a rosuvastatin 40 mg loading dose administered 7 to 25 hours before PCI or to no statin. All patients were loaded with 300 mg of aspirin and 300 mg of clopidogrel, and after PCI received aspirin (200 mg/day), clopidogrel (75 mg/day) and rosuvastatin (10 mg/day). Cardiac enzymes were measured before PCI, at 6 hours and the next morning after PCI. PMI was detected after PCI in 5.8% of patients in the rosuvastatin group and in 11.4% of the placebo group (P = 0.035). The incidence of 30-day MACE was 6.7% and 15.9% for the rosuvastatin and control groups, respectively (P = 0.002). The difference in MACE between groups was primarily the result of the lower incidence of PMI in rosuvastatin-treated patients. In addition, the incidences of postprocedural elevation of troponin T, CK-MB, and highly sensitive C-reactive protein were higher in the control group than in the rosuvastatin group. The investigators reported that there were no serious adverse effects with rosuvastatin loading.

A 12-month follow-up of this trial was conducted to analyze long-term effects.19 Patients were followed at 3-month intervals through direct contact or telephone investigation. The investigators found that the total incidence of MACE, defined as a composite of cardiac death, nonfatal MI, nonfatal stroke, and any ischemia-driven revascularizations, occurred in 9.8% of patients in the rosuvastatin group and 20.5% of patients in the control group (hazard ratio, 2.23; 95% CI, 1.34–3.72; P = 0.002). Unlike what has been seen with the 30-day MACE, the difference in MACE over a 12-month follow-up period was largely because of higher rates of revascularization in the control group (6.2% rosuvastatin versus 11.4% control; P = 0.055). The incidence of death and nonfatal MI was also significantly greater in the control group (hazard ratio, 3.71; 95% CI, 1.22–11.27; P = 0.021). A multivariate analysis showed that rosuvastatin loading was an independent predictor of a reduction in the risk of MACE at 12 months (OR, 0.5; 95% CI, 0.3–0.8; P = 0.006).

Cay et al20 also evaluated the effect of a single, high loading dose of rosuvastatin on PMI, defined as CK-MB elevation > 3 times ULN. A total of 299 statin-naive patients with stable angina were randomized to rosuvastatin 40 mg 24 hours before PCI (n = 153) or no statin (n = 146). All patients were loaded with clopidogrel 300 mg at least 12 hours before PCI. CK-MB and troponin I levels were measured before and 12 hours after the procedure. There were no significant differences in baseline characteristics. The rosuvastatin group significantly reduced the incidence of PMI compared with the control group (0.7% vs. 11%, P < 0.001). Similarly, the incidence of troponin I elevation > 3 times ULN was significantly lower in the rosuvastatin group versus the control group (10.5% vs. 39%, P < 0.001).

The Novel Approaches for Preventing or Limiting Events (NAPLES) II trial evaluated the effect of a single, high loading dose of atorvastatin before elective PCI in 2 centers in Italy.21 A total of 668 statin-naive patients with predominantly stable angina were randomized to receive atorvastatin 80 mg or no statin within 24 hours of PCI. All patients received aspirin 100 mg/day and clopidogrel 300 mg on the day before PCI, and then long-term statin treatment on atorvastatin 20 mg/day and aspirin 325 mg/day and clopidogrel 75 mg/day for at least the month after PCI. The primary endpoint was the rate of PMI, defined as a CK-MB elevation of > 3 times ULN alone or associated with chest pain or ST-segment or T-wave abnormalities, which matches the current definition of MI.2 CK-MB and troponin I levels were assessed before PCI and at 6 and 12 hours after. The incidence of PMI was 9.5% in the atorvastatin group and 15.8% in the control group (OR, 0.56; 95% CI, 0.35–0.89; P = 0.014). The incidence of troponin I elevation > 3 times ULN was 26.6% and 39.1% for the atorvastatin and control groups, respectively (OR, 0.56; 95% CI, 0.4–0.78, P < 0.001). In addition, peak concentrations of both CK-MB and troponin I were significantly lower in the atorvastatin-treated group. A post hoc analysis of the NAPLES II trial found that the cardioprotective effect of atorvastatin was more pronounced in patients with high C-reactive protein (CRP) (> 6 mg/L) at baseline. The incidence of PMI in the subgroup with high CRP levels at baseline was 4.6% and 16.5% in the atorvastatin loading and control groups, respectively (P = 0.016) as compared with 11.1% and 15% with normal CRP levels (P = 0.18).

A single-center, prospective, randomized trial conducted by Veselka et al22 did not find a benefit to statin administration before PCI. This study investigated the effect of 2-day atorvastatin therapy on the incidence of PMI in patients with chronic stable angina, undergoing elective PCI. A total of 200 statin-naive patients who had been referred for PCI were randomized to receive a 2-day treatment of atorvastatin 80 mg followed by PCI or no statin pretreatment with immediate PCI. All patients were loaded with aspirin 100 mg/day and clopidogrel 300 mg before PCI, and then received maintenance therapy with aspirin, clopidogrel, and a statin. The primary endpoint was the occurrence of PMI, as defined by troponin I and CK-MB levels > 3 times the ULN. Levels were drawn before and at 16 and 24 hours after PCI. Baseline characteristics were similar except older patients and fewer men were randomized to the atorvastatin group (P < 0.01). The incidence of PMI did not differ between the atorvastatin and control groups (10% vs. 12%, respectively. P = 0.65). A multivariate analysis showed that patient age was the only significant predictor of PMI.

The Efficacy of High-Dose AtorvaSTATIN Loading Before Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction (STATIN STEMI) trial, is the only study to evaluate the effect of high-dose statin loading before primary PCI in patients presenting with an STEMI.23 A total of 171 STEMI patients from 4 Korean institutions were randomized to receive an 80-mg atorvastatin- or 10-mg atorvastatin-loading dose before PCI. A placebo group was not used for comparison, but unlike the studies discussed thus far, in this study the physicians performing the procedure and follow-up assessments were blinded to the randomization assignment. Patients with current or previous statin use within the last 3 months were excluded. All patients were loaded with aspirin 200 mg and clopidogrel 600 mg. After PCI, all patients received atorvastatin 10 mg/day, aspirin 100 mg/day, and clopidogrel 75 mg/day. The primary endpoint was the 30-day incidence of MACE (death, nonfatal MI including PMI, TVR). There was a decreased incidence of MACE in the patients assigned atorvastatin 80 mg; however, the difference was not statistically significant (5.8% vs. 10.6% in the 80 mg and 10 mg atorvastatin groups, respectively; P = 0.26). In addition, MACE-free survival at 9 months was no different between the 80-mg and 10-mg groups (91% vs. 86% respectively; P = 0.32). The incidence of clinical events in both groups was lower than the investigators’ original estimates, which resulted in an insufficient sample size to detect a statistically significant difference. However, the 80-mg atorvastatin dose showed a statistically significant benefit in the corrected “thrombolysis in MI” frame, myocardial blush grade, and ST-segment resolution, suggesting that high-dose atorvastatin loading may improve coronary perfusion.

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Randomized, Double-Blind, Placebo-Controlled Trials

The Atorvastatin for Reduction of Myocardial Damage during Angioplasty (ARMYDA) trial was the first randomized, double-blind, placebo-controlled trial that analyzed the effect of pretreatment with a statin before PCI.24 In this trial 153 statin-naive patients with chronic stable angina and scheduled for PCI were randomized to receive atorvastatin 40 mg/day or placebo 7 days before the procedure. All patients received atorvastatin 40 mg/day after PCI, regardless of initial randomization assignment. Unless contraindicated, all patients were pretreated with aspirin 100 mg/day and ticlopidine 250 mg twice daily at least 3 days or clopidogrel at least 6 hours before the procedure.

The primary endpoint was the occurrence of PMI, defined as a postprocedural increase of CK-MB > 2 times the ULN. Secondary endpoints included (1) incidence of any postprocedural increases and mean peak values of CK-MB, troponin I, and myoglobin measured at baseline and at 8 and 24 hours after procedure and (2) the 30-day incidence of MACE (death, MI, or need for unplanned revascularization). The primary endpoint of PMI was detected after PCI in 5% of patients in the statin group and in 18% of the placebo group (P = 0.025). Peak values of all biomarkers were significantly lower in the statin group compared with the placebo group: CK-MB 2.9 ± 3 versus 7.5 ± 18 ng/mL (P = 0.007), TnI 0.09 ± 0.2 versus 0.47 ± 1.3 ng/mL (P = 0.0008), and myoglobin 58 ± 36 versus 81 ± 49 ng/mL (P = 0.0002), respectively. Because there were no cardiac events at the 1-month follow-up, the MACE composite depended entirely on PMI and was reduced with statin therapy versus placebo (5% vs. 18%, P = 0.025).

Although the ARMYDA study included patients with stable angina24, the ARMYDA-ACS trial evaluated the effect of pretreatment with statins in patients with NSTEMI or unstable angina.25 ARMYDA-ACS was a randomized, double-blind trial performed in 3 Italian institutions. A total of 171 statin-naive patients sent to early PCI (< 48 hours from diagnosis) were randomized to receive placebo or atorvastatin 80 mg 12 hours before plus 40 mg approximately 2 hours before PCI. All patients were loaded with 600 mg of clopidogrel and 100 mg of aspirin and received long-term atorvastatin 40 mg/day treatment after PCI. The primary endpoint was the 30-day incidence of MACE (death, MI, unplanned revascularization). PMI was defined as a postprocedural increase in CK-MB > 2 times ULN. Cardiac enzymes were measured before PCI and at 8 and 24 hours after PCI, and later if the patient had symptoms suggestive of MI. MACE occurred in 5% of patients treated with atorvastatin and in 17% of patients treated with placebo (P = 0.01), which was mostly driven by a reduction of PMI incidence (5% versus 15%, P = 0.04). Multivariable analysis showed that pretreatment with atorvastatin was a predictor of decreased risk of MACE at 30 days (OR, 0.12; 95% CI, 0.05–0.5; P = 0.004).

In a smaller study, Yu and colleagues26 also investigated the effects of atorvastatin loading in statin-naive patients with NSTEMI and unstable angina. A total of 81 patients were randomized to placebo or pretreatment with atorvastatin 80 mg 12 hours prior and an additional 40 mg 2 hours before PCI. All patients were loaded with aspirin 100 mg/day and clopidogrel 300 mg at least 6 hours before the procedure, and then received clopidogrel 75 mg/day for at least 1 month, aspirin 100 mg/day indefinitely, and atorvastatin 20 mg/day. Blood samples were collected before and at 8 and 24 hours after PCI to assay CK-MB and troponin I levels. The primary endpoint was the 30-day incidence of MACE (cardiac death, nonfatal MI, TVR), which occurred in 2.4% of patients in the atorvastatin and 22.5% in the placebo group (P = 0.0161). This was mostly driven by a reduction in PMI (2.4 vs. 20%, P = 0.0307). One patient in the placebo group required revascularization the day after the procedure because of an abrupt vessel closure induced by coronary dissection. There was no significant difference in adverse events between the groups.

All studies discussed thus far were performed in statin-naive patients. The Efficacy of Atorvastatin Reload in Patients on Chronic Statin Therapy Undergoing Percutaneous Coronary Intervention (ARMYDA-RECAPTURE) trial was designed to investigate whether an acute reload of a statin before PCI in patients on chronic statin therapy reduces periprocedural myocardial damage.27 A total of 383 patients with stable angina (53%) or non-ST segment elevation ACS (47%) who had been on statin therapy for at least 1 month were randomized to atorvastatin reload (80 mg 12 hours before PCI and 40 mg about 2 hours before PCI) or placebo. All patients received long-term statin therapy thereafter with atorvastatin 40 mg/day. In addition, all patients received a loading dose of clopidogrel 600 mg and aspirin 100 mg/day at least 3 hours before PCI, followed by daily maintenance therapy with both medications. The primary endpoint was 30-day incidence of MACE (cardiac death, revascularization, and MI defined as postprocedural increases in troponin or CK-MB > 3 times the ULN). Blood samples were drawn before and at 8 and 24 hours after PCI, and later if symptoms were suggestive of MI. MACE occurred in 3.7% of patients treated with atorvastatin reload compared with 9.4% of the placebo group (P = 0.037). As with previous studies, the benefits of statin loading were largely caused by a reduction in PMI. Patients with ACS had a significant benefit with atorvastatin reload (MACE incidence: 3.3% vs. 14.8% in placebo; P = 0.015); however, patients with stable angina did not appear to benefit (MACE incidence: 4% vs. 4.9% in placebo; P = 0.98). On multivariate analysis, atorvastatin reload was identified as a predictor of a decreased risk of MACE.

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Meta-Analysis

Zhang and colleagues4 conducted a meta-analysis to evaluate the beneficial effects of statins given before PCI, on preventing PMI. The studies included in the meta-analysis were conducted in statin-naive patients and compared the administration of preprocedural statins to placebo or to a no-treatment control group. A total of 6 trials involving 2088 patients were selected from the 751 potentially relevant articles initially screened. These trials included the ARMYDA24, ARMYDA-ACS25, NAPLES II,21 Briguori et al,17 Yun et al,18 Veselka et al,22 all of which have been discussed previously. The definition of PMI, type of statin, and dosing regimen varied among trials, and the investigators of the meta-analysis did not attempt to retrospectively recategorize them. The results showed that 7.7% of the statin pretreatment group developed PMI compared with 14.2% of patients randomized to the control group (OR, 0.51; CI 95%, 0.38–0.67; P < 0.001). There was no significant heterogeneity among the trials (P = 0.55). The incidence of 30-day MACE (cardiac death, MI, or revascularization) was reported in 8% of the patients pretreated with statins and in 15.3% of patients in the control group (OR, 0.48; 95% CI, 0.36–0.64; P < 0.001). This was driven by a reduction in the incidence of PMI. Only 4 deaths (1 in the statin and 3 in the control groups), 7 nonperiprocedural Q-wave MIs (2 in the statin and 5 in the control groups), and 4 revascularizations (all in the control group) were reported.

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DISCUSSION

The majority of the studies analyzed found that the administration of a statin before PCI significantly reduces the incidence of PMI and MACE (Tables 1 and 2). However, 3 studies did not show a significant difference between placebo or control.22,23,27 A potential explanation for the discordant results from the study by Vaselka et al22 is that the cardiac enzymes were sampled at a later time point (18–24 hours post PCI) than the other studies (8–12 hours), which may have been outside the time window to identify PMI. In addition, participants assigned to atorvastatin were significantly older, and on multivariate analysis, older age was associated with an increased risk of PMI (OR, 1.09; 95% CI, 1.026–1.159; P = 0.006).

The ARMYDA-RECAPTURE study was the only study that examined statin preloading in patients already receiving chronic statin therapy.27 Though the study did not demonstrate a significant reduction in PMI overall, the subgroup of patients presenting with ACS did derive a significant reduction in PMI and an impressive 82% relative risk reduction in MACE at 30 days (P = 0.027), whereas those undergoing PCI with stable angina demonstrated a 26% reduction in MACE (P = 0.70). Given the low event rate in those with stable angina assigned to placebo, the study was likely underpowered to determine the true benefit of reloading in this population. The STATIN-STEMI trial was the only trial to assess statin loading in patients undergoing immediate PCI as a result of a STEMI.23 Given the active comparator group, this study was likely of insufficient power to be able to determine a significant difference in PMI between high-dose atorvastatin and low-dose atorvastatin. However, STEMI is characterized by increased inflammation, and the NAPLES II trial showed that patients with high baseline C-reactive protein derived a much greater benefit in reduction of PMI.21 It is likely that patients with STEMI would derive a benefit from a statin loading dose, but it cannot be confirmed based on the available evidence.

Few adverse effects were reported in the studies. One patient in the atorvastatin treatment groups in both the ARMYDA24 and ARMYDA-ACS25 trials experienced an increase beyond the ULN of an increase beyond the ULN of the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes after the procedure, and 1 patient in the Yun et al18 study experienced myalgia without elevation of muscle enzyme upon rosuvastatin loading. Yu and colleagues18 reported the highest incidence of AST/ALT and CK elevations; however, these incidences were similar between statin and placebo groups.26 The remainder of the studies either did not report or stated that no adverse effects attributable to statins were seen.

There are some limitations to the available evidence. Six of the randomized trials analyzed were not blinded or placebo controlled.17–22 This introduces the possibility for reporting bias by the investigators; however, the PMI outcome measure is objective (based on cardiac enzyme levels), which should minimize the potential for bias. The studies included in the meta-analysis by Zhang and colleagues4 used different statins, doses, and administration times, and the definition of PMI varied between studies from a CK-MB elevation of > 2 to 5 times the ULN. Despite these differences, the investigators reported no significant heterogeneity among trials. The studies in this analysis provide extensive evidence that statin loading before PCI reduces PMI. In addition, statin loading seems to reduce MACE upon 30-day follow-up (Table 2). Although there is little evidence of long-term clinical outcomes, previous studies have demonstrated an association between PMI and mortality,5–8 and 1 study with 12-month follow-up demonstrated significant improvement in clinical outcomes.19

Upon review of the evidence, several questions remain regarding the administration of statin-loading doses before PCI:

1. Is there a preferred statin? The majority of trials used atorvastatin;21–27 however, 2 trials that used rosuvastatin demonstrated positive benefits.18–20 A separate study used 1 of 4 statins and did not demonstrate any differences in benefit among the 4.17 So there does not seem to be a preferred statin, though the amount of evidence is greatest with atorvastatin and rosuvastatin.

2. What is the optimal timing of administration? Statin loading demonstrated benefit when pretreatment was initiated from 7 days to immediately before PCI. Without a clinical trial to determine the optimal timing of statin administration, the timing of initiation should be based on acuity. Patients with ACS should be initiated on statin therapy within 24 hours of PCI; whereas, those with stable angina can likely be loaded at any point within the preceding 7 days of the procedure.

3. What is the optimal dose of statin therapy? The majority of the trials used high-dose statin therapy (atorvastatin 80 mg and rosuvastatin 40 mg) for loading and moderate-dose statin therapy for maintenance therapy. Studies of statin therapy post-ACS, such as Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22, have demonstrated the superiority of high-dose statin therapy as compared with moderate-dose statin treatment.28 A recent study assessed 4 different loading doses of atorvastatin administered before PCI.29 The results demonstrated a dose–response relationship between the incidence of PMI and increasing loading dose. The highest loading dose (atorvastatin 80 mg 12 hours before and 60 mg 2–4 hours before PCI) was associated with the lowest incidence of PMI (0 of 20 patients or 0%), whereas the control group (atorvastatin 40 mg once daily for up to 3 days before PCI) showed the highest rate of PMI (8 of 20 patients; P < 0.007 vs. high loading dose). In addition, a dose–response was seen in relation to anti-inflammatory activity as determined by change in levels of high sensitivity C-reactive protein. Given this information, it seems that high loading doses of statins, particularly atorvastatin and rosuvastatin, should be administered before PCI. A remaining question is what dose of statin should be administered for maintenance? As described, the majority of studies used moderate doses of statins after PCI. However, should patients be continued on high-dose statin therapy after PCI, based on the Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22 study results? Or does the administration of statin loading before PCI abrogate the need for high-intensity statin maintenance dosing? Given the lack of data, maintenance statin therapy after PCI should follow recommendations from secondary prevention guidelines.30

4. Are there additional benefits associated with statin loading before PCI? A recent study demonstrated that statin loading before PCI reduced the incidence of contrast-induced nephropathy.31 In addition, a meta-analysis demonstrated that statin-loading administered before coronary artery bypass graft surgery resulted in a decreased incidence of atrial fibrillation; however, none of the available studies have assessed atrial fibrillation in patients undergoing PCI.32

On the basis of the available evidence, all statin-naive patients (both ACS and stable angina) should be strongly recommended to receive statin-loading doses before PCI to reduce the incidence of PMI.17–21,24–26 For patients on chronic statin therapy before PCI, strong consideration should be given to reload with statins, particularly if they present with ACS.27 There is less evidence for patients on chronic statin therapy presenting with stable angina; however, because of the low risk associated with statin loading, it is reasonable to reload all patients on chronic statin therapy. Future research should be directed at determination of the optimal loading dose of statin, the timing of administration for stable and unstable ACS, and the long-term maintenance dose requirements after ACS.

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hydroxymethylglutaryl-coenzyme A reductase inhibitors; statins; percutaneous coronary intervention; periprocedural myocardial infarction

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