Dyslipidaemia is defined as abnormal levels of one or more of the following in the blood: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).1
Dyslipidaemia is defined as abnormal levels of one or more of the following in the blood: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).1
While the precise causes of dislipidaemia are not fully understood, research shows that it can be caused by metabolic disorders such as obesity, hypertension, and diabetes.1
The cornerstone of dyslipidaemia treatment is lifestyle management, which includes dietary changes, increased physical activity, and weight loss if necessary. Alongside these lifestyle adjustments, dyslipidaemia can also be treated with pharmacotherapy.1
The updated consensus guidelines for managing dyslipidaemia in South Africa (2018) recommend statin therapy for all patients at risk for CVD, including those with diabetes and familial hypercholesterolaemia.1
How effective are statins in reducing cholesterol levels?
Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that effectively lower total and LDL-C levels. Large randomised controlled trials have consistently shown that reducing LDL-C - especially with statins - significantly decreases the risk of CV events and mortality.2
The reduction in CV events resulting from the use of statins is directly proportional to the decrease in LDL-C levels. The Cholesterol Treatment Trialists' Collaborators' meta-analysis demonstrated that a 1mmol/L decrease in LDL-C correlates with a 20% reduction in CV risk. This benefit was also supported by the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese study, which showed a 33% reduction in CV events.2
Are all statins equally effective?
The Study to Evaluate the Long-term Lipid-lowering Efficacy and Safety of Rosuvastatin study demonstrated that rosuvastatin is the most potent statin. After six weeks of treatment, rosuvastatin at doses of 10mg-40mg reduced LDL-C levels by 46%-55%.3
In comparison, atorvastatin 10mg-80mg reduced LDL-C by 37%-51%, simvastatin 10mg-40mg by 28%-39%, and pravastatin 10mg-40mg by 20%–30%.3
Rosuvastatin also significantly increased HDL-C by 8%-10%, compared to 2%-6% with atorvastatin, 5% with simvastatin, and 3%-6% with pravastatin. Additionally, rosuvastatin decreased TG levels by 20%-26%, whereas atorvastatin reduced triglycerides by 20%-28%, simvastatin by 12%-15%, and pravastatin by 8%-13%.3
These findings were corroborated by the Vascular Outcomes in Young Adults with Elevated Risk study, which pooled data from 32,258 individual patients across various trials comparing rosuvastatin with atorvastatin or simvastatin. Furthermore, a meta-analysis, which included 50 studies and 51,956 patients, confirmed rosuvastatin's superior efficacy in reducing LDL-C levels compared to other statins.3
In South Africa, rosuvastatin is indicated for adult patients at increased risk of atherosclerotic CVD (ASCVD), who present with risk factors such as elevated high-sensitivity C-reactive protein (hsCRP) levels, advanced age, hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease. In these patients, rosuvastatin reduce the risk of non-fatal stroke, non-fatal myocardial infarction (MI), and the need for arterial revascularisation.4
For individuals living with hypercholesterolaemia, rosuvastatin is indicated for managing primary hypercholesterolaemia, mixed dyslipidaemia, and isolated hypertriglyceridaemia, including conditions classified under Fredrickson Type IIa, IIb, and IV, as well as heterozygous familial and non-familial hypercholesterolaemia.4
In paediatric patients aged 10- to 17-years living with heterozygous familial hypercholesterolaemia, rosuvastatin is indicated for lowering TC, LDL-C, and Apo B levels.4
Role of rosuvastatin in primary and secondary prevention of CVD
Primary prevention of CVD
The Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial evaluated rosuvastatin's impact on a group of apparently healthy participants (n=17,802) with normal LDL-C but high hsCRP.2
Results indicated that rosuvastatin reduced median LDL-C by 50%, hsCRP by 37%, and TG by 17%, leading to a 44% reduction in major CV events, including MI and stroke. Importantly, rosuvastatin's benefits were consistent across various demographics and risk levels.2
Further analyses revealed that rosuvastatin provided incremental benefits in intermediate-risk patients compared to those with low or high risk. When combined with low hsCRP levels, rosuvastatin's impact on reducing residual CV risk was particularly notable.2
Secondary prevention of CVD
A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-derived Coronary Atheroma Burden found that rosuvastatin 40mg led to significant reductions in LDL-C and atheroma volume, contributing to plaque regression in 78% of participants.2
In acute coronary syndrome, intensive statin therapy is recommended. Studies including Comparison of the Effects Noted in The ApoB ratio Using Rosuvastatin or Atorvastatin in Patients with Acute Coronary Syndrome and the Secondary Prevention of Acute Coronary Events - Reduction of Cholesterol to Key European Targets Trial highlighted the efficacy of LDL-C lowering and potential for achieving optimal treatment goals in patients diagnosed with acute coronary syndrome.2
Despite the efficacy of statins, why do patients fail to meet targets?
According to international guidelines, patients do not meet targets because statins are often prescribed at the lowest dose and not adequately up-titrated to achieve treatment goals.5
Most statins, except for rosuvastatin, which is available in dosage strengths from 5mg to 40mg, are available in four dosage strengths - mostly 10mg, 20mg, 40mg and 80mg.6
Most patients are prescribed the two lowest doses, while the highest doses are rarely used. Furthermore, healthcare professionals tend to maintain low initial doses and seldom opt to prescribe higher doses, which highlights the need for intermediate options.5,6
Another challenge is that treatment adherence over the long term is poor, with >33% of patients stopping their statin treatment within a year. As a result, these patients are not getting the maximum benefit of this preventive strategy. They remain at an increased risk for the development and/or progression of CVD despite receiving treatment.5
To address these gaps, Pharma Dynamics recently introduced generic rosuvastatin at 15mg and 30mg dosages. The wide range of dosage strengths of rosuvastatin allows treatment to be adjusted to the requirements of individual patients and increases the percentage of patients that reach their target lipid levels.5,6
Are the new dosages safe and effective?
According to Brus and Barbič-Žagar, <3% of participants in their study experienced side effects. Furthermore, post-authorisation studies involving ~7,000 participants demonstrated good tolerability and confirmed the expected efficacy of rosuvastatin, including the new 15mg and 30mg dosage strengths.6
The efficacy and safety of 15mg and 30mg rosuvastatin were shown in two sub-analyses of the ROSUvastatin dose titration in the treatment of PATients with Hyperlipidemia trial. The first sub-analysis evaluated the efficacy and safety of higher doses of rosuvastatin (15mg and 30mg), while the second analysed the efficacy and safety of rosuvastatin 15mg compared to 10mg.7,8
In the first sub-analysis, LDL-C goal achievement with rosuvastatin 10mg and 30mg was evaluated across different risk categories (moderate, high, very-high). Those at moderate, high, and very-high CV risk achieved LDL-C goals with success rates of 83.4%, 66.7%, and 33.0%, respectively. Among very-high risk patients, 55.7% reached the target LDL-C goal of <1.8mmol/l with ≥50% reduction from baseline. Moderate and high-risk patients generally met their LDL-C targets, whereas very-high risk patients required higher doses for optimal results.7
In the second sub-analysis, participants were randomised to either a standard titration arm (10mg, 20mg, 40mg) or an alternative titration arm (15mg, 30mg, 40mg). Lipid levels and safety parameters were measured at baseline and during three follow-up visits (weeks four, eight, and 12).8
Participants in the alternative titration arm experienced a significantly greater reduction in LDL-C levels compared to those in the standard arm. At week four, a higher proportion of patients on rosuvastatin 15mg achieved target lipid levels compared to those on 10mg (81% vs 67%). The safety and tolerance of both doses were comparable.8
The authors concluded that rosuvastatin 15mg was a more effective initial dose compared to 10mg, with significantly more patients reaching target LDL-C levels and fewer dose adjustments needed.8
Conclusion
The introduction of new 15mg and 30mg rosuvastatin dosages marks a significant advancement in the treatment of dyslipidaemia, particularly for patients at varying CV risk levels. These intermediate dosages offer a personalised approach to therapy, enhancing the likelihood of achieving target LDL-C levels. Studies have shown that these new dosages improve lipid profile outcomes and reduce the need for frequent dose adjustments, providing an effective and safe option for initial treatment.
References
- Masilela C, Adeniyi OV, Benjeddou M. Prevalence, patterns and determinants of dyslipidaemia among South African adults with comorbidities. Sci Rep, 2022.
- Luvai A, Mbagaya W, Hall AS, Barth JH. Rosuvastatin: A Review of the Pharmacology and Clinical Effectiveness in Cardiovascular Disease. Clinical Medicine Insights: Cardiology, 2012.
- Mostaza JM, Escobar C. Rosuvastatin-Based Lipid-Lowering Therapy for the Control of LDL Cholesterol in Patients at High Vascular Risk. J Clin Med, 2024.
- Professional information. Crevas. [Internet]. Available at: https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2023/07/Final_PI_Crevas15mg30mgpreregcl_Applicant.pdf
- Milovanovič Jarh D, Grošelj M, Barbič-Žagar B. Evidence-based therapy with Krka’s rosuvastatin in primary and secondary prevention of cardiovascular disease. Cardiol Croat, 2017.
- Brus S, Barbič-Žagar B. Clinical evidence of the effi cacy of Krka’s rosuvastatin in the Treatment of Hyperlipidemia with Focus on Additional Dosage Strengths. Cardiol Croat, 2014.
- Cevc M, Shlyakhto E, Dan GA, et al. Evaluation of target LDL-C levels attainment in patients at different cardiovascular risk: analysis of the ROSU-PATH trial. European Heart Journal, 2016.
- Vrablik M, Cevc M, Dan GA, et al. Comparison of efficacy and safety of rosuvastatin 15 mg vs. 10 mg: subanalysis of the ROSU-PATH trial.
- European Heart Journal, 2016.
