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Effectiveness and Safety of Atorvastatin vs. Rosuvastatin
Quick Takes
- Compared with atorvastatin, whether for primary or secondary prevention, rosuvastatin initiation had lower risk for all-cause mortality and MACE in both the Chinese and UK databases.
- The number needed to treat to demonstrate the additional value of rosuvastatin over atorvastatin was 97 in the Chinese cohort.
- The dose of each statin was low in primary and intermediate in secondary prevention, which may have biased the results.
Study Questions:
What is the real-world effectiveness and safety comparing rosuvastatin and atorvastatin?
Methods:
The authors conducted a real-world cohort study of >8 million Chinese patients and 500,000 UK patients. The China Renal Data System (CRDS) and UK Biobank (UKB) databases were utilized for an active comparative cohort study using target trial emulation in adults newly prescribed rosuvastatin or atorvastatin. The primary outcome was all-cause mortality. Cox proportional hazards regressions were used after 1:1 multilevel propensity score matching. Other endpoints included major adverse cardiovascular events (MACE), major adverse liver outcomes (MALO), development of chronic kidney disease (CKD), development of type 2 diabetes mellitus (T2DM), and other statin-related adverse events.
Results:
Among the 285,680 participants in both databases, 6-year all-cause mortality was lower for rosuvastatin than for atorvastatin (2.57 vs. 2.83 per 100 person-years in the CRDS database and 0.66 vs. 0.90 per 100 person-years in the UKB database), with differences in cumulative incidence of -1.03% (95% confidence interval [CI], -1.44% to -0.46%) in the CRDS database and -1.38% (CI, -2.50% to -0.21%) in the UKB database. For secondary outcomes in both databases, rosuvastatin conferred lower risks for MACE and MALO. In the UKB database, the risk for development of T2DM was higher with rosuvastatin, and the two medications carried similar risks for development of CKD and other statin-related adverse effects.
Conclusions:
The authors conclude that rosuvastatin might be associated with cardiovascular and mortality benefits that need to be weighed against the risk for development of T2DM. The differences were relatively small, and many did not meet traditional standards for statistical significance. Further research is warranted to understand whether these findings can be used with confidence in clinical practice.
Perspective:
Target trial emulation is a research method that uses real-world observational data to evaluate causal risk-benefit of interventions that mimic a hypothetical randomized trial. The cost of further research to compare the two very effective statins would not seem prudent. Clinical trials have demonstrated the increase in fasting blood sugar or glycemic hemoglobin (HgA1c) occurs in those with pre-diabetes and diabetes and is proportionate to the low-density lipoprotein cholesterol (LDL-C) dose response (Laakso M, Silva LF. Front Endocrinol 2023;14:1239335).
I personally prefer rosuvastatin over atorvastatin because of potency mg/mg decrease in LDL-C, which may explain the slight increase in T2DM and small rise in HgA1c in diabetics. Most importantly, as referenced in this article, rosuvastatin has a lower likelihood of drug interactions than atorvastatin, greater reduction in the inflammatory markers associated with coronary plaque progression, and greater decrease in levels of C-reactive protein. An alternative to high-dose rosuvastatin particular for persons with or prone to diabetes is low-dose rosuvastatin plus generic ezetimibe, which is neutral regarding glucose metabolism and has anti-inflammatory effects.
Clinical Topics: Prevention
Keywords: Diabetes Mellitus, Type 2, Primary Prevention, Secondary Prevention, Statins
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