Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).

[1]  Nian-Hua Deng,et al.  Statin's role on blood pressure levels: Meta‐analysis based on randomized controlled trials , 2023, Journal of clinical hypertension.

[2]  M. Clemons,et al.  Attitudes towards open‐label versus placebo‐control designs in oncology randomized trials: A survey of medical oncologists , 2022, Journal of evaluation in clinical practice.

[3]  Yingxian Sun,et al.  Hyperlipidemia and hypertension have synergistic interaction on ischemic stroke: insights from a general population survey in China , 2022, BMC Cardiovascular Disorders.

[4]  L. Kasselman,et al.  Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target , 2021, Metabolites.

[5]  A. Khera,et al.  Lp(a) (Lipoprotein[a]) Concentrations and Incident Atherosclerotic Cardiovascular Disease , 2020, Arteriosclerosis, thrombosis, and vascular biology.

[6]  Yi-Wei Kao,et al.  Fixed‐dose combination of amlodipine and atorvastatin improves clinical outcomes in patients with concomitant hypertension and dyslipidemia , 2020, Journal of clinical hypertension.

[7]  H. Predel,et al.  Single Pill Regimen Leads to Better Adherence and Clinical Outcome in Daily Practice in Patients Suffering from Hypertension and/or Dyslipidemia: Results of a Meta-Analysis , 2020, High Blood Pressure & Cardiovascular Prevention.

[8]  Y. Ahn,et al.  A randomized, double‐blind clinical trial to evaluate the efficacy and safety of a fixed‐dose combination of amlodipine/rosuvastatin in patients with dyslipidemia and hypertension , 2020, Journal of clinical hypertension.

[9]  G. Hindricks,et al.  2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. , 2019, Atherosclerosis.

[10]  M. Pletcher,et al.  Associations of Blood Pressure and Cholesterol Levels During Young Adulthood With Later Cardiovascular Events , 2019, Journal of the American College of Cardiology.

[11]  Daniel E Forman,et al.  2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. , 2019, Journal of the American College of Cardiology.

[12]  P. Barter,et al.  Variability of low-density lipoprotein cholesterol response with different doses of atorvastatin, rosuvastatin, and simvastatin: results from VOYAGER. , 2016, European heart journal. Cardiovascular pharmacotherapy.

[13]  J. DiNicolantonio,et al.  Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes , 2016, Open Heart.

[14]  D. Waters,et al.  2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis? , 2016, The American journal of medicine.

[15]  D. Prabhakaran,et al.  Effectiveness of fixed dose combination medication ('polypills') compared with usual care in patients with cardiovascular disease or at high risk: A prospective, individual patient data meta-analysis of 3140 patients in six countries. , 2016, International journal of cardiology.

[16]  S. Adams,et al.  Lipid lowering efficacy of atorvastatin. , 2012, The Cochrane database of systematic reviews.

[17]  Børge G Nordestgaard,et al.  Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. , 2009, JAMA.

[18]  D. Sullivan,et al.  Comparison of benefits and risks of rosuvastatin versus atorvastatin from a meta-analysis of head-to-head randomized controlled trials. , 2008, The American journal of cardiology.

[19]  Joel E Dimsdale,et al.  Reduction in blood pressure with statins: results from the UCSD Statin Study, a randomized trial. , 2008, Archives of internal medicine.

[20]  J. Jukema,et al.  A Randomized, Placebo‐Controlled Trial to Evaluate the Efficacy, Safety, and Pharmacodynamic Interaction of Coadministered Amlodipine and Atorvastatin in 1660 Patients With Concomitant Hypertension and Dyslipidemia: The Respond Trial , 2007, Journal of clinical pharmacology.

[21]  S. Bangalore,et al.  Fixed-dose combinations improve medication compliance: a meta-analysis. , 2007, The American journal of medicine.

[22]  J. Amerena,et al.  Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia – Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR) , 2006, Trials.

[23]  M. Jeong,et al.  ORIGINAL ARTICLE DOI: 10.3904/kjim.2010.25.1.27 Comparative Study of Low Doses of Rosuvastatin and Atorvastatin on Lipid and Glycemic Control in Patients with Metabolic Syndrome and Hypercholesterolemia , 2022 .

[24]  C. Aguilar-Salinas,et al.  Single-pill amlodipine/atorvastatin helps patients of diverse ethnicity attain recommended goals for blood pressure and lipids (the Gemini-AALA study) , 2009, Journal of Human Hypertension.

[25]  J. Mckenney,et al.  Comparison of the efficacy and safety of atorvastatin initiated at different starting doses in patients with dyslipidemia. , 2005, American heart journal.

[26]  U. Laufs,et al.  Pleiotropic effects of statins. - Basic research and clinical perspectives -. , 2010, Circulation journal : official journal of the Japanese Circulation Society.