Rosuvastatin, atorvastatin: similar effectiveness in LODESTAR, some different signals

Among people with coronary artery disease, rosuvastatin and atorvastatin are both effective in reducing all-cause death, MI, stroke or any coronary revascularization over 3 years, analysis shows secondary study of the LODESTAR trial. Notably, although the former was associated with lower LDL cholesterol levels, it was also linked to higher risks of developing diabetes and cataract surgery.

Presented at the 2023 American College of Cardiology Meeting, the main conclusions of LODESTAR demonstrated that a targeted treatment approach regarding statins is not inferior to the guideline-recommended high-intensity strategy with respect to reducing the risk of major adverse cardiovascular events.

This secondary analysis of the trial focusing on statin type will be useful not only to physicians in optimizing their practice in dyslipidemia management, but also to the general population by providing information on regular blood glucose monitoring, HbA1c and cataracts. [that] should be considered when taking high-potency statins, said lead author Myeong-Ki Hong, MD, PhD (Yonsei University College of Medicine, Seoul, Republic of Korea), in an e- email to TCTMD.

Previous marketing of these drugs before they became generic likely led some to believe that rosuvastatin is better than atorvastatin, according to Derek Connolly, MBChB, PhD (Birmingham City Hospital, England), who commented on the study on the TCTMD. However, I think the LODESTAR studies tell us that there is probably no major difference between them, he said.

Secondary analysis results

For the new analysis, published yesterday in the BMJ, Yong-Joon Lee, MD (Yonsei University College of Medicine), Hong, and colleagues included 4,341 Korean patients from the initial trial (mean age 65 years; 27.9% women) who were randomized to receive atorvastatin or rosuvastatin.

At 3 years, the average daily dose was higher in the rosuvastatin group than in those taking atorvastatin (17.1 versus 36.0 mg; P. < 0.001). Additionally, fewer patients in the rosuvastatin group were also taking ezetimibe.

The primary combined outcome of all-cause death, MI, stroke, or any coronary revascularization at 3 years was not different between agents, occurring in 8.7% of the rosuvastatin cohort and 8.2 % in the atorvastatin arm (HR 1.06; 95% CI 0.86). -1h30). There were no differences between study groups for any of these endpoints, individually.

Mean LDL cholesterol was lower in patients treated with rosuvastatin than in those taking atorvastatin (1.8 vs. 1.9 mmol/L; P. < 0.001), but more former patients reported both new-onset diabetes requiring antidiabetic medications (7.2% vs. 5.3%; HR 1.39; 95% CI 1. 03-1.87) and cataract surgery (2.5% versus 1.5%; HR 1.66; 95). % CI 1.07-2.58). There were no differences between study groups for all other safety parameters.

Finally, a post hoc analysis using a definition of new-onset diabetes incorporating a hemoglobin A1c level of at least 6.5% during the study period consistently showed a higher incidence in people treated with rosuvastatin versus atorvastatin (9.5% versus 7.7%; HR 1.25). ; 95% CI 1.02-1.53).

Hong called all the results surprising given the lack of randomized clinical data in this space. The primary result of comparable cardiovascular benefits between the two types of statins and the secondary results of a [slight] difference in LDL cholesterol levels [achieved]the need for high-intensity statins or ezetimibe, the onset of diabetes requiring medication, and cataract surgery are all important findings that could affect our clinical practice, he said.

Hong said he takes all of these into account to optimize my dyslipidemia management practice by considering the risk factors for each patient. For example, if the patient surely needs more intensive reduction of LDL cholesterol levels, certain types of statins may be preferred. On the other hand, if patients’ LDL levels are well managed, but their fasting blood sugar is impaired, the other type of statin may be preferred.

Although the data may be considered for future iterations of the cholesterol guidelines, Hong said he believes more data will be needed to modify the guidelines.

Statins are just one building block

Additionally, although there may be subtle differences between medications, the statin monotherapy strategy is no longer the preferred approach, Connolly argued: citing data support the benefits of combination therapy, including medications like bempedoic acid (Nexletol; Esperion), ezetimibe, PCSK9 inhibitors, and inclisiran (Leqvio; Novartis). Statins are just one of the basics, and I think that’s not really emphasized in the [LODESTAR] papers, he said.

The bottom line, though, is that it’s not a surprising try, Connolly said. [It] will likely lead most clinicians to choose atorvastatin over rosuvastatin, even if there are minimal differences. This won’t change my practice at all, because I was already in favor of atorvastatin, and I and most of the rest of the country were in favor of atorvastatin. [already] Doing this.