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Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence

  • Pharmacoepidemiology and Prescription
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

We aimed to summarize current evidence regarding the impact of a high-dose statin loading before percutaneous coronary intervention (PCI) on short-term outcomes in patients presenting with the acute coronary syndrome (ACS).

Methods

This meta-analysis was based on a search of the MEDLINE, Cochrane Central Register of Controlled Trials, Ovid Journals, and SCOPUS for randomized controlled trials that compared high-dose atorvastatin or rosuvastatin with no or low-dose statin administered before planned PCI in statin-naive patients with ACS. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and all-cause mortality at 30 days. Prespecified subanalyses were performed with respect to statin and ACS type.

Results

A total of eleven trials enrolling 6291 patients were included, of which 75.4% received PCI. High-dose statin loading was associated with an overall 43% relative risk (RR) reduction in MACCE at 30 days (RR 0.57, 95% CI 0.41–0.77) in whole ACS population. This effect was primarily driven by the 39% reduction in the occurrence of MI (RR 0.61, 95% CI 0.46–0.80). No significant effect on all-cause mortality reduction was observed (RR 0.92, 95% CI 0.67–1.26). In the setting of ST-elevation myocardial infarction (STEMI), atorvastatin loading was associated with a 33% reduction in MACCE (RR 0.67, 95% CI 0.48–0.94), while in non-ST-elevation myocardial infarction ACS (NSTE-ACS), rosuvastatin loading was associated with 52% reduction in MACCE at 30 days (RR 0.48, 95% CI 0.34–0.66). The level of evidence as qualified with GRADE was low to high, depending on the outcome.

Conclusion

A high-dose loading of statins before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days. Atorvastatin reduces MACCE in STEMI while rosuvastatin reduces MACCE in NSTE-ACS at 30 days.

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Availability of data and material

The data that supports the findings of this study are available in the article and the supplementary material of this article.

Code availability

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Acknowledgements

The authors would wish to express gratitude to an independent methodology consultant Tina Poklepovic Pericic (T.P.P.), DMD, PhD, from Cochrane Croatia, for participating in risk of bias assessment performed for this study and help with manuscript preparation.

Author information

Authors and Affiliations

  1. Department of Pathophysiology, School of Medicine, University of Split, Split, Croatia

    Josip A. Borovac, Mette Leth-Olsen, Marko Kumric & Josko Bozic

  2. Clinic for Heart and Cardiovascular Diseases, University Hospital of Split (KBC Split), Split, Croatia

    Josip A. Borovac & Duska Glavas

  3. Department of Cardiovascular and Thoracic Sciences, IRCCS Fondazione Policlinico A. Gemelli, Universita Cattolica Sacro Cuore, Rome, Italy

    Domenico D’Amario

  4. Department of Internal Medicine 3, Karl Landsteiner University of Health Sciences, University Hospital St, Pölten, Krems, Austria

    Konstantin Schwarz

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  1. Josip A. Borovac
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Contributions

J.A.B. concieved the study and wrote the first original draft of the manuscript in its entirety. J.A.B., M.L.O., and M.K. performed research, data collection, and manuscript preparation. All authors (J.A.B., M.L.O., M.K., D.D., K.S., D.G., and J.B.) commented on the original draft and contributed to the writing of manuscript. All authors participated in the manuscript revision process. All authors read and approved the final version of the manuscript.

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Correspondence to Josip A. Borovac.

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Key points

• Early loading of high-dose statins in patients with the acute coronary syndrome (ACS) naive to statin treatment and before percutaneous coronary intervention was associated with a reduction in major adverse cardiovascular and cerebrovascular events during the 30 days.

• This effect was primarily driven by the reduction in recurrent myocardial infarctions with no impact on all cause mortality. These effects were observed for the rosuvastatin use in the setting of non-ST-elevation ACS and atorvastatin in ST-elevation ACS.

• Caution in interpreting these findings should be exercised due to the possibility of publication and geographical bias as well as the small sample size of the most of included trials.

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Borovac, J.A., Leth-Olsen, M., Kumric, M. et al. Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence. Eur J Clin Pharmacol 78, 111–126 (2022). https://doi.org/10.1007/s00228-021-03196-9

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