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Update - Week 13, 2019
 
Curated by Peter Lansberg,
a Dutch lipidologist and educator, and
reviewed by prof. Philip Barter, Past President of the
International Atherosclerosis Society.
The IAS Statin Newsletter will keep you up-to-date with all recent statin publications, using a curated approach to select relevant articles.

Key publications

Statins are the same?
Statins are a well-established therapeutic strategy for CVD prevention. Despite their different pharmacokinetic and dynamic differences, they are referred to as a common and comparable group of LDL-cholesterol lowering drug class,. Very few clinical trials have compared equipotent dosages of different statins in a single study. The authors of this network meta-analysis compared 9 RCT’s using different statins in patients (N=10 741) with ischemic stroke and/or TIA’s; none of the included trials were direct comparisons. Median follow-up time was relatively short, 2.5 years. All-cause and stroke mortality were not significantly improved. Overall benefits were observed for ischemic stroke, OR: 0.81 (0.70-0.93); absolute risk difference, ARD: − 1.6% (− 2.6 to − 0.6%), ischemic stroke or TIA, OR: 0.75 (0.64 to 0.87); ARD: − 4.2% (− 6.2 to − 2.1%], and cardiovascular event, OR: 0.75 (0.69 to 0.83); ARD: − 5.4% (− 6.8 to − 3.6%). Differences between statins were qualified as modest, highest dosages (atorvastatin 80 mg and simvastatin 40 mg) were associated with the greatest benefits. An increased risk for hemorrhagic stroke was absent after exclusion of the SPARCL study, OR: 1.35 (0.78 to 2.33).  The data presented in this meta-analysis supports the association of statin use with an absolute risk reduction of ischemic strokes and CV events and indicating therapeutic equivalence. However potential differences between statins cannot be dismissed.
Tramacere I, Boncoraglio GB, Banzi R et al. Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis. BMC Med 2019; 17:67. http://www.ncbi.nlm.nih.gov/pubmed/?term=30914063
 
SPRINT study, combining statins and BP target < 120 mmHg
Renal disease is associated with serious CVD complications and optimal management of established CV risk factors such as blood pressure and plasma LDL-cholesterol is crucial. In this retrospective analysis of 2 646 CKD patients (e-GFR<60ml/min/1,73m2) that participated in the systolic blood pressure (SBP) Intervention Trial (SPRINT), the ASCVD modifying effects of statins combined with lower SBP targets, were evaluated. In SPRINT patients were randomized to a systolic BP target of <120 mm Hg vs <140 mmHg. Statin use was noted in 1 273 vs 1 354 patients no using statins. After 3.6 years of follow-up, the primary endpoints, all-cause mortality and CVD mortality were significantly improved in patients that used statins. In the statin group, an SBP < 120 mm Hg compared to < 140 mm was associated with reduced all-cause mortality, aHR: 0.44 (0.28–0.71); event rates 1.16 vs.2.5 per 100 patient-years. As well as an improved CV mortality, aHR: 0.29 (0.12–0.74); event rates 0.28 vs. 0.92 per 100 patient-years. In patients not using statins, evaluating the same endpoints were not significantly different in both SBP goal arms. All-cause mortality, aHR: 1.07 (0.69–1.66); event rates 2.01 vs. 1.94 per 100 patient-years and CV mortality, aHR: 1.42 (0.56–3.59]); event rates 0.52 vs. 0.41 per 100 patient-years). The authors concluded that intensive SBP treatment only when combined with statin use, resulted in a significantly improved survival of hypertensive CKD patients.
Rivera M, Tamariz L, Suarez M, Contreras G. Modifying Effect of Statins on Fatal Outcomes in Chronic Kidney Disease Patients in the Systolic Blood Pressure Intervention Trial: A Post Hoc Analysis. Am J Nephrol 2019; 49:297-306. http://www.ncbi.nlm.nih.gov/pubmed/?term=30917364
 
Review FDC atorvastatin + ezetimibe
Fixed-dose combinations (FDC) are commonly used for blood pressure management, in lipid management this therapeutic strategy is gaining prominence. This review explored the pharmacokinetics, pharmacodynamics and clinical efficacy of the components and the combination of ezetimibe and atorvastatin. The IMPROVE-IT was the only randomized controlled clinical endpoint trial that successfully evaluated the combined effects of simvastatin + ezetimibe vs simvastatin monotherapy. For the combination of atorvastatin and ezetimibe, only lipoprotein changes were studied. The LDL-c lowering efficacy of adding ezetimibe 10 mg proved to be more superior as compeered to doubling the atorvastatin dosage. The lower LDL-c targets reached with the combination of atorvastatin and ezetimibe are expected to provide improved protection from ASCVD complications, were well tolerated and could improve adherence. In patients unable to reach LDL-c targets with maximally tolerated (ator)vastatin therapy, the addition of ezetimibe is a well-accepted next step. The FDC combination provides a practical and effective means of achieving lower LDL-c targets.
Ma YB, Chan P, Zhang Y et al. Evaluating the efficacy and safety of atorvastatin + ezetimibe in a fixed-dose combination for the treatment of hypercholesterolemia. Expert Opin Pharmacother 2019:1-12. http://www.ncbi.nlm.nih.gov/pubmed/?term=30908086
 
A patients perspective on statin used in the PALM registry
The PALM (Patient and Provider Assessment of Lipid Management) registry was a cross-sectional registry in the United States designed to evaluate lipid management practices and
patient and provider beliefs about cholesterol, statin therapy, and heart disease. In this sub-analysis, patient-reported reasons for not using statins were explored. Out of the 7938 patients, 5693 participants were deemed suitable for guideline-recommended statins. Over one quarter (1511 - 26.5%) were not using them. In over half of the eligible patients, not taking statins,  894 (59.2%), statins were not offered; however, their willingness to take statins was high, 67.7%. There were 153 patients (10.1%) that declined statins; statins were stopped by 464 (30.7%) patients, fear of side effects was the most commonly reported reason in this group, however, 59.7% were willing to retry statins. Statin users that continued were more likely to believe that statins were safe (70.4%) and effective (86.3%) this was less often the case with patients that declined statins and those that stopped statins; safe: 36.9% and 37.4%; effective: 67.4% and 69.1% respectively. Females, un-insured and blacks more often reported that they were not offered statins; RR 1.22; 1.48 and 1.38 respectively. The observed lack of statin prescriptions in a majority of high CVD risk patients underlines the need for a more pro-active approach for health care providers;, especially in women un-insured and black patients. The voiced willingness to start or re-start statins by patients that were not offered statins or that stopped statins, seem to be underestimated and are underused opportunities that healthcare professionals need to be made aware of.
Bradley CK, Wang TY, Li S et al. Patient-Reported Reasons for Declining or Discontinuing Statin Therapy: Insights From the PALM Registry. J Am Heart Assoc 2019; 8:e011765. http://www.ncbi.nlm.nih.gov/pubmed/?term=30913959
 
Who is prone to develop NODM with statins?
Statins and new onset diabetes (NODM) is a recurring topic that deserves a better understanding. In this single hospital retros,pective observational analysis 1241 consecutive Greek adults that attended an outpatient Lipid Clinic of the University hospital of Ioannina Greece were followed. After excluding 166 diabetics and 193 patients that were already using lipid-lowering medication, 882 patients remained for the final analysis. During a median follow-up time of 6 years (IQR: 4-10), 94 patients (11%) developed diabetes. The risk of developing NODM were independently  associated with age, OR: 1.05 (1.02–1.08; p < 0.01); family history of diabetes, OR: 3.58 (1.86–6.91, p < 0.01), IFG,OR: 6.56 (3.53–12.12, p < 0.01);  overweight/obesity, OR: 2.65 (1.39–5.05, p < 0.01); atherogenic dyslipidemia, OR: 3.27 (1.50–7.15, p < 0.01), and using high-intensity statins, OR: 3.51 (CI: 1.89–6.51, p < 0.01). A separate analysis was performed in statin treated IFG patients in whom atherogenic dyslipidemia, OR: 3.44 (1.31–9.04, p = 0.01) and overweight/obesity, OR: 2.54 (1.14–5.66, p < 0.05) independently increased the risk of NODM. Finally, statin use in overweight/obese patients was associated with NODM in patients that presented with atherogenic dyslipidemia at baseline OR 5.60 (2.19-14.30, p<0.01). the authors suggested that when high intensity-high dose statins need to be prescribed, strategies aimed at reducing the modifiable risk factors associated with NODM should be implemented to avoid compromising glycemic control.
Barkas F, Elisaf M, Liberopoulos E et al. Atherogenic dyslipidemia increases the risk of incident diabetes in statin-treated patients with impaired fasting glucose or obesity. J Cardiol 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30910387
 
Relevant publications
  1. Zarei B, Mousavi M, Mehdizadeh S et al. Early Effects of Atorvastatin on Vitamin D and Parathyroid Hormone Serum Levels Following Acute Myocardial Infarction. Journal of research in pharmacy practice 2019; 8:7-12. http://www.ncbi.nlm.nih.gov/pubmed/?term=30911557
  2. Tonelli M, Lloyd AM, Bello AK et al. Statin use and the risk of acute kidney injury in older adults. BMC Nephrol 2019; 20:103. http://www.ncbi.nlm.nih.gov/pubmed/?term=30909872
  3. Stralberg T, Nordenskjold A, Cao Y et al. Proprotein convertase subtilisin/kexin type 9 and mortality in patients starting hemodialysis. European journal of clinical investigation 2019:e13113. http://www.ncbi.nlm.nih.gov/pubmed/?term=30921469
  4. Stasinopoulou M, Kadoglou NPE, Christodoulou E et al. Statins' Withdrawal Induces Atherosclerotic Plaque Destabilization in Animal Model-A "Rebound" Stimulation of Inflammation. Journal of cardiovascular pharmacology and therapeutics 2019:1074248419838499. http://www.ncbi.nlm.nih.gov/pubmed/?term=30905179
  5. Ramanan B, Jeon-Slaughter H, Chen X et al. Comparison of open and endovascular procedures in patients with critical limb ischemia on dialysis. Journal of vascular surgery 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30922740
  6. Mahabadi AA, Nasir K, Rassaf T. Routine CAC-scoring prior to initiation of statin therapy - a European perspective. Eur J Prev Cardiol 2019:2047487319839188. http://www.ncbi.nlm.nih.gov/pubmed/?term=30913900
  7. Park J, Lee JH, Kim KA et al. Effects of Preoperative Statin on Acute Kidney Injury After Off-Pump Coronary Artery Bypass Grafting. J Am Heart Assoc 2019; 8:e010892. http://www.ncbi.nlm.nih.gov/pubmed/?term=30905260
  8. Pappa E, Rizos CV, Filippatos TD, Elisaf MS. Emerging Fixed-Dose Combination Treatments for Hyperlipidemia. Journal of cardiovascular pharmacology and therapeutics 2019:1074248419838506. http://www.ncbi.nlm.nih.gov/pubmed/?term=30909733
  9. Neal D, Beck AW, Eslami M et al. Validation of a preoperative prediction model for mortality within 1 year after endovascular aortic aneurysm repair of intact aneurysms. Journal of vascular surgery 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30922759
  10. Miao XY, Liu HZ, Jin MM et al. A comparative meta-analysis of the efficacy of statin-ezetimibe co-therapy versus statin monotherapy in reducing cardiovascular and cerebrovascular adverse events in patients with type 2 diabetes mellitus. Eur Rev Med Pharmacol Sci 2019; 23:2302-2310. http://www.ncbi.nlm.nih.gov/pubmed/?term=30915779
  11. Loubser L, Weider KI, Drake SM. Acute liver injury induced by red yeast rice supplement. BMJ case reports 2019; 12. http://www.ncbi.nlm.nih.gov/pubmed/?term=30910808
  12. Laufs U, Banach M, Mancini GBJ et al. Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc 2019; 8:e011662. http://www.ncbi.nlm.nih.gov/pubmed/?term=30922146
  13. Kim TS, Rha SW, Kim SY et al. Efficacy and Tolerability of Telmisartan/Amlodipine and Rosuvastatin Coadministration in Hypertensive Patients with Hyperlipidemia: A Phase III, Multicenter, Randomized, Double-blind Study. Clinical therapeutics 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30904178
  14. Kim K, Kwak A, Choi CU et al. Differences in preventing new-onset cardiovascular events with statin therapy in seniors aged 75 years and over: a cohort study in the South Korean National Health Insurance Database. Basic & clinical pharmacology & toxicology 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30924261
  15. Kawada T. Statin use and pancreatic cancer: A risk assessment. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30926286
  16. Jia X, Virani SS. CLEAR Serenity Trial: More Clarity for the Future of Bempedoic Acid in Patients Unable to Take Statins? J Am Heart Assoc 2019; 8:e012352. http://www.ncbi.nlm.nih.gov/pubmed/?term=30922156
  17. Esper RJ, Nordaby RA. Cardiovascular events, diabetes and guidelines: the virtue of simplicity. Cardiovascular diabetology 2019; 18:42. http://www.ncbi.nlm.nih.gov/pubmed/?term=30922303
  18. De La Cruz JA, Mihos CG, Horvath SA, Santana O. The Pleiotropic Effects of Statins in Endocrine Disorders. Endocrine, metabolic & immune disorders drug targets 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30924424
  19. Braun LT. Life-Saving Medications: The Urgent Need for Guideline Adherence and Patient Acceptance. J Am Heart Assoc 2019; 8:e012348. http://www.ncbi.nlm.nih.gov/pubmed/?term=30913935
  20. Bowles EJA, Yu O, Ziebell R et al. Cardiovascular medication use and risks of colon cancer recurrences and additional cancer events: a cohort study. BMC Cancer 2019; 19:270. http://www.ncbi.nlm.nih.gov/pubmed/?term=30917783
  21. Bogsrud MP, Graesdal A, Johansen D et al. LDL-cholesterol goal achievement, cardiovascular disease, and attributed risk of Lp(a) in a large cohort of predominantly genetically verified familial hypercholesterolemia. J Clin Lipidol 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30910667
  22. Archibugi L, Arcidiacono PG, Capurso G. Statin use and pancreatic cancer: a risk assessment. Authors? reply. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30926285
  23. Shaw-Gallagher M, Boyle R, Zuber K. Longitudinal survey of clinician behavior change in CKD management. JAAPA : official journal of the American Academy of Physician Assistants 2019; 32:39-43. http://www.ncbi.nlm.nih.gov/pubmed/?term=30913148
  24. Nguyen CA, Gilstrap LG, Chernew ME et al. Social Risk Adjustment of Quality Measures for Diabetes and Cardiovascular Disease in a Commercially Insured US Population. JAMA network open 2019; 2:e190838. http://www.ncbi.nlm.nih.gov/pubmed/?term=30924891
  25. Nakao K, Yasuda S, Nishimura K et al. Prescription Rates of Guideline-Directed Medications Are Associated With In-Hospital Mortality Among Japanese Patients With Acute Myocardial Infarction: A Report From JROAD - DPC Study. J Am Heart Assoc 2019; 8:e009692. http://www.ncbi.nlm.nih.gov/pubmed/?term=30909774
  26. Lim S. (Retraction Request) Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia. Circulation journal : official journal of the Japanese Circulation Society 2019; 83:948. http://www.ncbi.nlm.nih.gov/pubmed/?term=30905909
  27. Kim H, Seol YM, Choi YJ et al. HMG CoA reductase expression as a prognostic factor in Korean patients with breast cancer: A retrospective study. Medicine (Baltimore) 2019; 98:e14968. http://www.ncbi.nlm.nih.gov/pubmed/?term=30921201
Basic Science publications
 
 
  1. Wu P, Liu Z, Zhao T et al. Lovastatin attenuates angiotensin II induced cardiovascular fibrosis through the suppression of YAP/TAZ signaling. Biochem Biophys Res Commun 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30926167
  2. Nishiya M, Yasuhira S, Shibazaki M et al. Fluvastatin exerts an antitumor effect in vemurafenib-resistant melanoma cells. Anticancer Drugs 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30920401
  3. Lu D, Shen L, Mai H et al. HMG-CoA Reductase Inhibitors Attenuate Neuronal Damage by Suppressing Oxygen Glucose Deprivation-Induced Activated Microglial Cells. Neural plasticity 2019; 2019:7675496. http://www.ncbi.nlm.nih.gov/pubmed/?term=30911291
  4. Liu C, Guo Y, Sun L et al. Six types of tea reduce high-fat-diet-induced fat accumulation in mice by increasing lipid metabolism and suppressing inflammation. Food & function 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30907897
  5. Lee YP, Cho Y, Kim EJ et al. Reduced expression of pyruvate kinase in kidney proximal tubule cells is a potential mechanism of pravastatin altered glucose metabolism. Scientific reports 2019; 9:5318. http://www.ncbi.nlm.nih.gov/pubmed/?term=30926836
  6. Kim MJ, Bible KL, Regnier M et al. Simvastatin provides long-term improvement of left ventricular function and prevents cardiac fibrosis in muscular dystrophy. Physiological reports 2019; 7:e14018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30912308
  7. Karazniewicz-Lada M, Baba K, Dolatowski F et al. The polymorphism of statins and its effect on their physicochemical properties. Polimery w medycynie 2018; 48:77-82. http://www.ncbi.nlm.nih.gov/pubmed/?term=30916495
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