Effect of Preprocedural Statin Use on Procedural Myocardial
Infarction and Major Cardiac Adverse Events in Percutaneous
Corona

Multiple primary and secondary prevention trials demonstrate a significant reduction in adverse cardiovascular outcomes in patients with, or at risk of, coronary artery disease as a result of statin therapy.^1–6 Furthermore, there is increasing evidence that early and aggressive statin therapy in patients with acute coronary syndromes (ACS) can decrease untoward cardiovascular events.^{7, 8}
A number of studies have investigated the link between preprocedural statin use and early reduction in death or myocardial infarction (MI) after percutaneous coronary intervention (PCI). The purpose of our current study is to determine whether statin use prior to elective PCI is associated with lower procedural MI and major adverse cardiovascular events (MACE) in the form of a meta-analysis of published trials.^9–15

Methods
Using the terms “statin”, “percutaneous coronary intervention” and “angioplasty”, a literature search of Medline and the Cochrane Controlled Trials Register was performed to identify all prospective trials published in the last 20 years that compared statin administration to placebo prior to PCI. In addition, a limited search of the scientific sessions abstracts of the American Heart Association, the American College of Cardiology, the European Society of Cardiology, the Society of Cardiovascular Angiography and Interventions and the Transcatheter Therapeutics Meetings was performed. The reference lists of identified trials and reviews were also checked for relevant studies. Trials were eligible for inclusion if they included patients who received a statin prior to PCI and if appropriate documentation of procedural MI was performed. For each trial, the results immediately post intervention and at the longest follow up (up to 12 months) were extracted and analyzed based on an intention-to-treat principle. Procedural MI was defined by elevation of CK-MB of at least more than twice the normal limits. Nonfatal MI was defined by the elevation of the aforementioned biomarkers at any visit post intervention. Emergent revascularization was defined as the need for either repeat PCI or coronary artery bypass graft surgery (CABG) within 24 hours of the index PCI. Major cardiac endpoints (MACE) were defined as the combined endpoint of death, nonfatal MI or target vessel revascularization up to 12 months after PCI.
Two authors independently identified trials for inclusion and extracted information on demographics, interventions and outcomes. When later publications added more information to original publications of randomized trials, only the updated trial was included. Absolute risks and risk differences were computed. The random effects model of DerSimonian and Laird were used to compute the estimated pooled MACE or MI risk difference across studies and its corresponding 95% confidence interval as well as a chi-square statistic for testing that the overall risk difference is zero.¹⁶

Results
Six trials^9–14 (Table 1) involving 2,996 subjects who met the inclusion criteria for procedural MI were included in the analysis. Three trials involving 6,723 subjects had appropriate follow up and were analyzed for MACE.^12,13,15

Baseline characteristics (Table 2) were similar between the 2 groups. When the 6 trials included in the main analysis were combined, statin use preprocedurally was associated with a mean absolute reduction of -5.44% (95% CI -8.2% to -2.7% [p < 0.0001]) in procedural MI from 9.17% for the control to 3.73% for patients treated with statins. There was no evidence of heterogeneity between trials (p = 0.66). The relative risk reduction was 59.3% (95% CI -8.2% to -2.7% [p < 0.0001]). Sensitivity analysis did not alter this finding (Figure 1).

Table 3 depicts the individual studies that evaluated MACE. In each of these trials, the MACE rate was lower in the statin group as opposed to the control group; the overall MACE rates were 19.5% and 15.5% in the control and statin groups, respectively. The overall MACE absolute risk difference was -4.0%, (95% CI -11.4% to +3.4% [p = 0.2900]). The corresponding overall relative risk reduction (RRR) was 20.5% (Figure 2).

Discussion
This meta-analysis demonstrates that statin administration prior to PCI is associated with a significant decrease in the number of procedural MIs and a trend toward a reduction in MACE for up to 12 months. The effect of statins was large, with a relative risk reduction of 59.3% in procedural MIs. Furthermore, there was a trend toward a reduction in MACE for up to 12 months, with a relative reduction of 21%. This beneficial effect was seen regardless of the type of statin used in the studies analyzed.
Several randomized trials have shown that statins have beneficial effects on the incidence of long-term cardiovascular events in subjects with hypercholesterolemia, coronary artery disease and in patients who underwent PCI. The exact mode of action of statins in preventing procedural adverse events is not well understood. In addition to plaque stabilization due to a reduction of matrix metalloproteinase secretion, statins can reduce adhesion molecule expression in endothelial cells via interactions with the nitric oxide pathway.¹⁸ Some studies have demonstrated antiplatelet properties of statins.¹³ In addition, statins have been shown to reduce inflammatory markers such as C-reactive protein (CRP). These combined effects may explain the reduction of thromboembolic events and inflammatory cascade in a vessel that has just recently undergone PCI.^14,19,20
With respect to study limitations, many of the trials in this analysis were retrospective in design, with dissimilar definitions for MI. Although all studies measured the cardiac markers approximately 3 times in 24 hours post procedure, the timings were not exactly the same. Furthermore, the follow-up period and methodology were not uniform between the trials. Such variability may alter the final interpretation of the results of this pooled analysis. Further prospective clinical trials with uniform methodology are therefore warranted to confirm the findings of this meta-analysis.

Conclusion
Based on the results of this meta-analysis, treatment with statins before elective PCI is associated with a significant reduction in procedural MI and a positive trend, though not significant reduction in MACE. Although further prospective, randomized, placebo-controlled trials would help to validate these findings, the ease of administration of statins as well as their generalized safety and tolerability supports their routine preprocedural use in patients undergoing PCI.

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