Prescribing statins for patients with ACS? No need to wait

Illustrative case

A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia, and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well-known for their cholesterol-lowering effect, they also have benefits that are independent of their effects on lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, patients with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk of coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time for starting statins in patients with ACS.

STUDY SUMMARY: Meta-analysis of 20 RCTs shows
 statins before PCI cuts risk of MI

Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) vs those who received low-dose statins or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8750 patients. Four studies enrolled only patients with ST elevation MI, 8 were restricted to NSTEMI, and the remaining 8 studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 ± 0.42 days before. For those started after PCI, the average time to administration was 3.18 ± 3.56 days after.

Administering statins before PCI resulted
 in a greater reduction in the odds of MI than starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3621) in the statins group and 5% (179 of 3577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat=62.5), and a reduction of the odds of MI by 33% (odds ratio [OR]=0.67; 95% confidence interval [CI], 0.53-0.84; P=.0007). There was also a trend toward reduced mortality in the statin group (OR=0.66; 95% CI, 0.43-1.02; P=.06).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR=0.38; 95% CI, 0.24-0.59; P<.0001) than starting them post-PCI (OR=0.85; 95% CI, 0.64-1.13; P=.28) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant (P=.002). These findings persisted past 30 days (P=.06).

WHAT'S NEW: Early statin administration 
is most effective

According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk of subsequent MI.

CAVEATS: Benefits might vary
 with different statins


The studies evaluated in this meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION: No barriers 
to starting statins earlier


Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the risks of taking a statin are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative case

A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia, and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well-known for their cholesterol-lowering effect, they also have benefits that are independent of their effects on lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, patients with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk of coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time for starting statins in patients with ACS.

STUDY SUMMARY: Meta-analysis of 20 RCTs shows
 statins before PCI cuts risk of MI

Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) vs those who received low-dose statins or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8750 patients. Four studies enrolled only patients with ST elevation MI, 8 were restricted to NSTEMI, and the remaining 8 studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 ± 0.42 days before. For those started after PCI, the average time to administration was 3.18 ± 3.56 days after.

Administering statins before PCI resulted
 in a greater reduction in the odds of MI than starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3621) in the statins group and 5% (179 of 3577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat=62.5), and a reduction of the odds of MI by 33% (odds ratio [OR]=0.67; 95% confidence interval [CI], 0.53-0.84; P=.0007). There was also a trend toward reduced mortality in the statin group (OR=0.66; 95% CI, 0.43-1.02; P=.06).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR=0.38; 95% CI, 0.24-0.59; P<.0001) than starting them post-PCI (OR=0.85; 95% CI, 0.64-1.13; P=.28) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant (P=.002). These findings persisted past 30 days (P=.06).

WHAT'S NEW: Early statin administration 
is most effective

According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk of subsequent MI.

CAVEATS: Benefits might vary
 with different statins


The studies evaluated in this meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION: No barriers 
to starting statins earlier


Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the risks of taking a statin are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative case

A 48-year-old man comes to the emergency department with chest pain and is diagnosed with ACS. He is scheduled to have PCI within the next 24 hours. When should you start him on a statin?

Statins are the mainstay pharmaceutical treatment for hyperlipidemia, and are used for primary and secondary prevention of coronary artery disease and stroke.^2,3 Well-known for their cholesterol-lowering effect, they also have benefits that are independent of their effects on lipids, including improving endothelial function, decreasing oxidative stress, and decreasing vascular inflammation.^4-6

Compared to patients with stable angina, patients with ACS experience markedly higher rates of coronary events, especially immediately before and after PCI and during the subsequent 30 days.¹ American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST elevation myocardial infarction (NSTEMI) advocate starting statins before patients are discharged from the hospital, but they don’t specify precisely when.⁷

Considering the higher risk of coronary events before and after PCI and statins’ pleiotropic effects, it is reasonable to investigate the optimal time for starting statins in patients with ACS.

STUDY SUMMARY: Meta-analysis of 20 RCTs shows
 statins before PCI cuts risk of MI

Navarese et al¹ performed a systematic review and meta-analysis of studies comparing the clinical outcomes of patients with ACS who received statins before or after PCI (statins group) vs those who received low-dose statins or no statins (control group). The authors searched PubMed, Cochrane, Google Scholar, and CINAHL databases as well as key conference proceedings for studies published before November 2013. Using reasonable inclusion and exclusion criteria and appropriate statistical methods, they analyzed the results of 20 randomized controlled trials that included 8750 patients. Four studies enrolled only patients with ST elevation MI, 8 were restricted to NSTEMI, and the remaining 8 studies enrolled patients with any type of MI or unstable angina.

For patients who were started on a statin before PCI, the mean timing of administration was 0.53 ± 0.42 days before. For those started after PCI, the average time to administration was 3.18 ± 3.56 days after.

Administering statins before PCI resulted
 in a greater reduction in the odds of MI than starting them afterward. Whether administered before or after PCI, statins reduced the incidence of MIs. The overall 30-day incidence of MIs was 3.4% (123 of 3621) in the statins group and 5% (179 of 3577) in the control group. This resulted in an absolute risk reduction of 1.6% (number needed to treat=62.5), and a reduction of the odds of MI by 33% (odds ratio [OR]=0.67; 95% confidence interval [CI], 0.53-0.84; P=.0007). There was also a trend toward reduced mortality in the statin group (OR=0.66; 95% CI, 0.43-1.02; P=.06).

In addition, administering statins before PCI resulted in a greater reduction in the odds of MI at 30 days (OR=0.38; 95% CI, 0.24-0.59; P<.0001) than starting them post-PCI (OR=0.85; 95% CI, 0.64-1.13; P=.28) when compared to the controls. The difference between the pre-PCI OR and the post-PCI OR was statistically significant (P=.002). These findings persisted past 30 days (P=.06).

WHAT'S NEW: Early statin administration 
is most effective

According to ACC/AHA guidelines, all patients with ACS should be receiving a statin by the time they are discharged. However, when to start the statin is not specified. This meta-analysis is the first report to show that administering a statin before PCI can significantly reduce the risk of subsequent MI.

CAVEATS: Benefits might vary
 with different statins


The studies evaluated in this meta-analysis used various statins and dosing regimens, which could have affected the results. However, sensitivity analyses found similar benefits across different types of statins. In addition, most of the included trials used high doses of statins, which minimized the potential discrepancy in outcomes from various dosing regimens. And while the included studies were not perfect, Navarese et al¹ used reasonable methods to identify potential biases.

CHALLENGES TO IMPLEMENTATION: No barriers 
to starting statins earlier


Implementing this intervention may be as simple as editing a standard order. This meta-analysis also suggests that the earlier the intervention, the greater the benefit, which may be an argument for starting a statin when a patient first presents for evaluation for ACS, since the risks of taking a statin are quite low. We believe it would be beneficial if the next update of the ACC/AHA guidelines⁷ included this recommendation.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.