Meta-analysis of Time-related Benefits of Statin Therapy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Eliano Pio Navarese, MD, PhD Mariusz Kowalewski, MD Felicita Andreotti, MD,PhD Marleen van Wely, MD Cyril Camaro, MD Michalina Kolodziejczak, MD Bartosz Gorny, MD Jeffrey Wirianta, MD Jacek Kubica, MD, PhD Malte Kelm, MD Menko-Jan de Boer, MD Harry Suryapranata, MD, PhD

Abstract

Patients with acute coronary syndromes (ACS) still experience high rates of recurrent coronary events, particularly early in their presentation. Statins yield substantial cardiovascular benefits but the optimal timing of their administration, before or after coronary intervention (PCI), remains unclear.

We aimed to perform a meta-analysis of randomized controlled trials (RCTs) of statin administration before or after PCI vs no statin/low dose statin in patients with ACS. Primary endpoints were 30-day all-cause mortality and 30-day myocardial infarction (MI) stratified by pre- and post-PCI statin administration. Secondary endpoints were major adverse-cardiac (MACE) or -cardiac and cerebrovascular (MACCE) events. Long term analysis beyond 30 days was also performed.

Twenty RCTs enrolling 8750 patients were included. At 30 days, the rate of MI was significantly lower in the statin group (OR [95% CI] = 0.67 [0.53-0.84], p=0.0007) with a trend towards reduced mortality (p=0.06) and significant reductions in MACE and MACCE compared with no/low-dose statin. The 30-day incidence of MI was markedly lower when statins were administered before PCI (OR [95% CI] = 0.38 [0.24-0.59], p<0.0001) rather than after PCI (p=0.28). The direction and magnitude of the estimates for pre- and post-PCI vs no statin/low dose statin were sustained at long term, not reaching statistical significance for MI (OR [95% CI] = 0.81 [0.65-1.01], p=0.06) but with significant reductions in MACE (p=0.0002). By meta-regression, earlier statin administration correlated significantly with lower risk of MI, MACE and MACCE at 30 days. In conclusion, the present meta-analysis indicates a time-related impact of statin therapy on clinical outcomes of ACS patients undergoing PCI: the earlier the administration before PCI the greater the benefits.