Should lipid-lowering therapy be intensified after acute coronary syndrome (ACS) in high-risk patients, considering the current regimen of Rosuvastatin (rosuvastatin) 20mg daily?

From the Guidelines

**Yes, lipid-lowering therapy should be intensified after acute coronary syndrome (ACS) in high-risk patients, considering the current regimen of Rosuvastatin 20mg daily, by increasing the dose to 40mg daily to achieve an LDL-C reduction of >50% from baseline and an LDL-C goal <1.4 mmol/L (<55 mg/dL) as recommended by the 2020 ESC guidelines for the management of acute coronary syndromes 1.** The goal of lipid-lowering therapy in high-risk patients after ACS is to reduce the risk of recurrent cardiovascular events and mortality. The 2020 ESC guidelines recommend that statins are used in all NSTE-ACS patients, with the aim of reducing LDL-C by >50% from baseline and achieving an LDL-C level <1.4 mmol/L (<55 mg/dL) 1.

• Key considerations for intensifying lipid-lowering therapy include:
  • The patient's current regimen of Rosuvastatin 20mg daily may not be sufficient to achieve the recommended LDL-C goal
  • Increasing the dose of Rosuvastatin to 40mg daily can provide more potent LDL lowering and help achieve the recommended LDL-C goal
  • Monitoring liver function tests and creatine kinase is necessary if muscle symptoms develop
  • If the patient experiences side effects on 40mg, reducing the dose to 20mg and considering adding ezetimibe 10mg daily may be necessary
  • Reassessing lipid levels 4-6 weeks after discharge is crucial to evaluate treatment efficacy and adjust therapy if needed The 2021 study provides the most recent and highest quality evidence for the management of acute coronary syndromes, and its recommendations should be prioritized over older studies such as the 2013 ACCF/AHA focused update 1.
• The benefits of early aggressive lipid lowering after ACS include:
  • Stabilizing plaque
  • Reducing inflammation
  • Improving endothelial function
  • Providing immediate benefits beyond just LDL reduction Overall, intensifying lipid-lowering therapy after ACS in high-risk patients is crucial to reduce the risk of recurrent cardiovascular events and mortality, and the 2020 ESC guidelines provide the most recent and highest quality evidence to guide this management.

From the FDA Drug Label

The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects The primary end point was a composite end point consisting of the time-to-first occurrence of any of the following major CV events: CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina or an arterial revascularization procedure. Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0. 001) relative risk reduction of 44% and absolute risk reduction of 1. 2%

The current regimen of Rosuvastatin (rosuvastatin) 20mg daily has been shown to be effective in reducing the risk of major CV events. However, the decision to intensify lipid-lowering therapy after acute coronary syndrome (ACS) in high-risk patients should be based on individual patient factors and clinical judgment.

• Key considerations:
  • The patient's current lipid profile and response to the current regimen
  • The presence of other cardiovascular risk factors
  • The patient's overall health status and ability to tolerate more intensive therapy
• Clinical decision: Intensification of lipid-lowering therapy may be considered in high-risk patients after ACS, but the FDA drug label does not provide direct guidance on this specific scenario 2, 2.

From the Research

Lipid-Lowering Therapy Intensification after Acute Coronary Syndrome (ACS)

• The current regimen of Rosuvastatin 20mg daily may not be sufficient for high-risk patients after ACS, as studies suggest that high-intensity statins, in combination with ezetimibe, should be used to achieve target LDL-C levels 3, 4.
• The French expert panel recommends early use of high-intensity statins, in combination with ezetimibe, for patients with LDL-C above 100 mg/dL at baseline, and PCSK9 inhibitors should be rapidly added in high-risk patients with residual LDL-C above 70 mg/dL despite maximal tolerated dose statin and ezetimibe 3.
• The European Society of Cardiology (ESC) suggests an early treatment with a well-defined target value of LDL-C level, which should be achieved during follow-up, and innovative lipid-lowering therapies, such as monoclonal antibodies targeting human PCSK9, may become a new opportunity in ACS patients 4.
• Studies have shown that early and intensive treatment with statins after an ACS event decreases recurrent adverse cardiovascular events, and the combination of statin + ezetimibe is superior to statin alone in preventing cardiovascular death, non-fatal myocardial infarction, and other cardiovascular events 4, 5.
• Expert consensus, as seen in the BEST consensus, supports the use of combination lipid-lowering therapies, including high-dose/intensity statin + ezetimibe and PCSK9 inhibitors, to achieve early and robust lipid reduction in post-ACS patients 6.

Considerations for High-Risk Patients

• High-risk patients, such as those with diabetes, recent ACS, recurrent ischemic events, multivessel coronary disease, and polyvascular disease, may require more intensive lipid-lowering therapy, including the addition of PCSK9 inhibitors 3, 4.
• The use of icosapent ethyl (EPA) may also be considered in patients with clinical atherosclerotic cardiovascular disease or those already on high-intensity or maximally tolerated statin therapy with fasting triglycerides 135-499 mg/dL 3.
• The goal of lipid-lowering therapy should be to achieve target LDL-C levels as quickly and safely as possible, and combination therapies may be necessary to achieve this goal 3, 6.