CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 5, November/December 2023 AFRICA 265 Evidence from large-scale, prospective, double-blind, randomised clinical trials clearly indicates a rate reduction in total and cardiovascular morbidity and mortality with statins, initially for pravastatin,6,7 and shortly followed by evidence for simvastatin.8,9 An average reduction in LDL-C of about 1 mmol/l, maintained for approximately five years, produced a reduction in non-fatal myocardial infarction and coronary death in about one-quarter of the study populations.9 Although the concept of aggressive treatment of raised LDL-C level is now well entrenched, the cost of long-term treatment is often seen as prohibitive by third-party funders, especially in lower-risk individuals, therefore the increase in entry threshold of treatment. The introduction of multisource generic products has however, eroded this objection but introduced yet another from the prescriber and that is distrust in the equivalence of products. In order to investigate whether the distrust is founded on evidence, it was decided to retrospectively investigate the impact of the introduction of a multisource product into public-sector (government funded) lipid clinics by evaluating LDL-C values over time, before and after introduction. The primary aim of this real-world study was, therefore, to assess the efficacy of a generic formulation of simvastatin (Simvotin®, Ranbaxy, a Sun Pharma company) compared to a non-generic (originator) formulation of simvastatin (Zocor®, MSD South Africa) in patients with hyperlipidaemia, by assessing the maintenance of lipid control after the switch of medication from Zocor® to Simvotin®. Methods The analysis was performed as a multi-centre, retrospective study at three sites in South Africa (one each in Gauteng, Free State and KwaZulu Natal provinces). A retrospective, short review of patient files was done with no administration of study treatment. Ethics committee approval was obtained for retrospective chart review at each centre prior to initiation of the study and data collection. Patients received their normal care and medication at these public lipid or cardiology clinics. The study focused on a time period from 2005 to 2007, during which the simvastatin dispensed to patients at these clinics changed from the original drug (Zocor®) to the generic drug (Simvotin®). The time points for data collection assessed is illustrated in Fig. 1. The patients included in this study were male and female between the ages of 18 and 80 years who had been on treatment with the originator drug (Zocor®) for at least six months on the same dosage, before being switched to the generic drug (Simvotin®), and where the dose had been unchanged for the period until the second evaluation, which was at least six months after the switch. Patients were excluded from the study if they had been taking any other lipid-lowering agents in addition to the simvastatin. Demographics of the patients are presented in Table 1. This study was a retrospective chart review of patients’ files and therefore required no study-related administration of treatment. The lipid-lowering agents in treatment that were evaluated were simvastatin oral tablets, namely Zocor® and Simvotin® tablets that were used in a once-daily dosing regimen. No formal sample size estimation was done. A sample of 205 patients from three sites was enrolled into the study. These individuals formed the total number of patients who fulfilled the stated criteria and had pathology reports on lipid profiles on file. Patient were excluded if the lipid profiles were not available, or if they were taking other lipid-lowering agents, or were non-compliant (missed more than one script fill in a six-month period). All patients had to switch from originator to generic multisource product to be included in the study. With a sample size of 205 patients switched from Zocor® to Simvotin®, a two-sided 95% confidence interval for the true proportion (percentage) of patients controlled (the control rate) after the switch, using the large sample normal approximation of the binomial distribution, will extend to approximately 0.03 (3%) from the observed proportion (percentage) to be calculated from the sample, if the expected proportion (percentage) of controlled patients (after the switch) is between 0.85 and 0.90 (85 to 90%). The primary outcome of the study was to assess the efficacy of the generic formulation Simvotin® tablets in controlling the total cholesterol level in patients in relation to baseline (visit 1) after being switched from Zocor® tablets. All lipid levels available were recorded and analysed as secondary outcomes. They are displayed in Table 2. Statistical analysis All statistical procedures were performed on SAS®, release 9.1, run under Microsoft® Windows® for a personal computer, and p-values ≤ 0.05 were considered significant. Results The charts of 205 patients who fulfilled the inclusion criteria were included for review in the study. Of the 205 patients enrolled, 118 patients had the same strength of simvastatin administered at all three data-collection points (visit 1, 2 and 3), which means they had been prescribed the same strength of statin even after the switch from Zocor® to Simvotin® tablets (Table 2). These 118 patients would then not have a dosedifferent effect on cholesterol levels, which will then be used to demonstrate similarity. Dose continuity was a requirement for therapeutic equivalence. Table 1. Patient demographics Parameters Number (%) of patients Male 87 (42.4) Female 118 (57.6) Total 205 (100) Non-smoker 156 (76.1) Smoker 39 (19.0) Ex-smoker 10 (4.9) Total 205 (100) Visit 1 Visit 2 Visit 3 Assessment of lipid profile before initiation of therapy with Zocor® Assess lipid control rate on Zocor® before switch from Zocor® to Simvotin® Assess lipid control rate on Simvotin® >6 months on treatment with Zocor® >6 months on treatment with Simvotin® Fig. 1. Data-collection time points.
RkJQdWJsaXNoZXIy NDIzNzc=