Is alternating statins (HMG-CoA reductase inhibitors) with fibrates or using statins every other day an effective and evidence-based approach for lipid-lowering treatment in patients with dyslipidemia?

From the Guidelines

Alternating statins with fibrates or using statins every other day is not recommended as a standard approach for treating dyslipidemia, as the most evidence-based strategy is daily statin therapy at appropriate doses based on cardiovascular risk. The rationale for daily statin use relates to their mechanism of action in inhibiting cholesterol synthesis and upregulating LDL receptors, processes that work optimally with consistent drug levels 1. For patients who cannot tolerate standard statin regimens due to side effects, alternative approaches include using lower doses of high-intensity statins, switching to a different statin, or trying twice-weekly dosing with long-acting statins like rosuvastatin or atorvastatin.

Some key points to consider in the management of dyslipidemia include:

• The importance of assessing cardiovascular risk and tailoring statin therapy accordingly 1
• The use of statins as first-line pharmacologic therapy for LDL lowering, with fibrates considered for patients with low HDL 1
• The need for careful monitoring when combining statins with fibrates due to the increased risk of muscle toxicity 1
• The consideration of non-statin options like ezetimibe, bile acid sequestrants, or PCSK9 inhibitors for truly statin-intolerant patients 1

In terms of specific lipid targets, guidelines recommend lowering LDL cholesterol to <100 mg/dl, with further titration to <70 mg/dl considered for high-risk patients 1. Additionally, therapeutic options to reduce non-HDL-C are recommended, including more intense LDL-C-lowering therapy 1.

Overall, the evidence supports the use of daily statin therapy as the primary approach for managing dyslipidemia, with alternative strategies considered on a case-by-case basis for patients who cannot tolerate standard regimens.

From the Research

Alternating Statins with Fibrates or Using Statins Every Other Day

There is limited evidence to support the practice of alternating statins with fibrates or using statins every other day for lipid-lowering treatment in patients with dyslipidemia.

• The provided studies do not directly address the effectiveness of alternating statins with fibrates or using statins every other day 2, 3, 4, 5, 6.
• However, studies suggest that statins, ezetimibe, and PCSK9 inhibitors are effective in reducing LDL-C levels and ameliorating the risk of atherosclerotic cardiovascular disease (ASCVD) 2, 3, 4, 6.
• The optimal time of day for statin administration has been reviewed, and the current limited evidence suggests that short-acting statins should be given in the evening, whereas long-acting statins could be given at any time of the day 5.
• PCSK9 inhibitors have been shown to be effective in lowering LDL-C levels in patients not receiving statins, including those who are statin intolerant 6.

Evidence for Lipid-Lowering Therapies

• Statins, ezetimibe, and PCSK9 inhibitors are well-established lipid-lowering therapies that have been shown to reduce the risk of ASCVD 2, 3, 4, 6.
• Angiopoietin-like 3 (ANGPTL3) is a potential target for the treatment of dyslipidemia and atherosclerosis, with monoclonal antibodies and antisense oligonucleotides being investigated in clinical trials 4.
• The 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias include the use of PCSK9 inhibitors in very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 2.

Links to References

No direct links to references are provided, but the study details are as follows:

• 2: Statins and PCSK9 inhibitors: A new lipid-lowering therapy. European journal of pharmacology, 2020.
• 3: Do we need new lipid-lowering agents in the era of PCSK9 inhibitors? Recent advances. Kardiologia polska, 2022.
• 4: Targeting angiopoietin-like 3 in atherosclerosis: From bench to bedside. Diabetes, obesity & metabolism, 2021.
• 5: The optimal time of day for statin administration: a review of current evidence. Current opinion in lipidology, 2018.
• 6: PCSK9 Inhibitors and Ezetimibe Monotherapy in Patients Not Receiving Statins: A Meta-Analysis of Randomized Trials. Current vascular pharmacology, 2021.