Impact of treatment with rosuvastatin and atorvastatin on cardiovascular outcomes: evidence from the Archimedes-simulated clinical trials

Furio Colivicchi,1 Catarina Sternhufvud,2 Sanjay K Gandhi3 1Cardiology Division, Emergency Department, San Filippo Neri Hospital, ASL Roma E, Rome, Italy; 2Global Payer Evidence and Pricing, AstraZeneca R&D, Mölndal, Sweden; 3Global Health Economics and Outcomes Research, TEVA Pharmaceuticals, Frazer, PA, United States Objective: No clinical trials have been conducted to directly compare the effect of the two high-intensity statins, rosuvastatin and atorvastatin, on cardiovascular outcomes. However, three such trials have been computer-simulated using the Archimedes model, an individual-based simulation of human physiology and behaviors, treatment interventions, and health care systems. The results are reviewed here.Methods: The first simulated trial assessed clinical outcomes in patients receiving available doses of the two drugs. The second assessed the impact of initial treatment decisions, while the third assessed the effect of switching from rosuvastatin to atorvastatin.Results: In the first simulated trial, treatment with rosuvastatin was estimated to result in greater reductions than treatment with atorvastatin in major adverse cardiac event (MACE) rates at 5 years and 20 years at all doses examined (relative risk [RR]: 0.897, 0.888, and 0.930 at 5 years for rosuvastatin 20 mg vs atorvastatin 40 mg, rosuvastatin 40 mg vs atorvastatin 80 mg, and rosuvastatin 20 mg vs atorvastatin 80 mg, respectively; all P<0.05). In the second simulated trial, outcomes were significantly better in patients initially prescribed rosuvastatin than in those initially prescribed atorvastatin (RR of MACE at 5 years: 0.918; P<0.001). In the third simulated trial, risk of MACE was significantly greater in patients switching from rosuvastatin to atorvastatin than in those remaining on rosuvastatin (RR at 5 years: 1.109; P<0.001).Conclusion: The results of these simulated clinical trials suggest improved outcomes among patients receiving rosuvastatin relative to patients receiving atorvastatin in various clinical settings.Keywords: statins, rosuvastatin, atorvastatin, simulated clinical trials, outcome assessmen

Network meta-analysis of treatments for type 2 diabetes mellitus following failure with metformin plus sulfonylurea

<p><b>Aims</b> The efficacy and safety of sodium–glucose linked transporters (SGLT2s) plus metformin and a sulfonylurea (MET + SU) for the treatment of type 2 diabetes mellitus (T2DM) in patients who fail to achieve glycemic control with MET + SU, relative to other triple therapies licensed in the EU, were estimated.</p> <p><b>Methods</b> A systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) involving anti-diabetes treatments added to MET + SU were conducted.</p> <p><b>Results:</b> Of 2236 abstracts identified through a systematic literature review, 30 RCTs published between 2003 and 2013 were included. RCTs ranged from 12 to 52 weeks in duration, included 28 to 1274 patients, were of parallel design, and most were open-label. Comparators included placebo (reference treatment), SGLT2 inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), alpha-glucosidase inhibitors (AGIs), meglitinides, glucagon-like peptide 1 (GLP-1) analogues, and basal, bolus, and biphasic insulin, all added on to MET + SU, as well as basal and biphasic insulin added to MET and monotherapy. The mean change (%) in HbA1c levels compared to placebo was -0.86 for SGLT2 inhibitors, −0.68 for DPP-4 inhibitors, −0.93 for TZDs, and −1.07 for GLP-1 analogues, respectively. Only SGLT2 inhibitors and GLP-1 analogues led to a weight loss (−1.71 kg and −1.14 kg, respectively) and decrease in systolic blood pressure (SBP; −3.73 mmHg and −2.90 mmHg, respectively), while all other treatments showed either an increase or no changes in weight or SBP.</p> <p><b>Conclusion</b> SGLT2 inhibitors are at least as effective as other classes of antidiabetic agents at controlling HbA1c levels, while providing the additional benefits of weight loss and reducing SBP. Additionally, since the risk of hypoglycemia is similar or reduced with SGLT2 inhibitors, patients do not have to trade off efficacy for tolerability. Similar findings were observed for GLP-1 analogues.</p