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Update - Week 25,  2017 
 
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

Can statins promote sedentary behavior?
Statins use could have a negative impact on preventive lifestyle actions in patients that presume the statin pill will take care of reducing, even eliminating their CVD risk, and no need for personal efforts in terms of physical activity or healthier food choices are deemed necessary. The Polish Norwegian Study (PONS) prospective community based investigation of risk factors for chronic diseases in 12,754 participants, from south-east Poland; age 45 to 64 years in 2010–11 was queried for this analysis. Statin use was reported in 1728 (13.5%) of the participants and 628 (36.34%) had cardiovascular diseases. Patients using statins watched more TV (≥21 h/week) compared to the non-users. Respectively 29.72% compared to 23.10%) in the non-users. After adjusting for age, sex, education, smoking, chronic obstructive pulmonary disease and other chronic diseases, prevalence remained 15% higher (OR 1.15; 1.06 -1.25). No difference for those with or without CVD was observed.  Physical health status was cited more often as a reason for their sedentary behavior in statin users than nonusers (14.72% vs. 8.29%) (OR 1.78, CI 1.56-2.03). However, after adjusting for age, sex, prevalent CVD, COPD and other chronic diseases the relationship remained: OR 1.16 (1.01-1.33). Lack of time was less frequently invoked in statin users (19.9% vs. 27.7%) and “no mood to exercise” (45%) or lack of perceived need (7.7%) was similar in both groups. Intriguingly poor AHA diet was found in 33.7% of statin users and 41.2% of non-users. As well as the prevalence of smoking was reported less frequently in statin users, 16.6% and 20.6% among non-users. The aim of this study was to document the prevalence of prolonged TV-viewing among statin users and non-users, and not to explain this behavior. The authors concluded that in order to change this observed increase of sedentary behavior of statin users, innovative interventions and counseling strategies are needed.
Vaidean GD, Vansal SS, Manczuk M. Television viewing time among statin users and non-users. The Polish Norwegian Study (PONS). Preventive medicine reports 2017; 7:106-109. http://www.ncbi.nlm.nih.gov/pubmed/?term=28626626
 
In SATURN, Lp(a), at baseline and on-trial, did not correlate with regression or progression
In this sub-analysis of the Study of coronary atheroma by intravascular ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) study, Lp(a) levels were measured in 915 of the 1039 SATURN participants. Changes in percent atheroma volume (DPAV) were correlated with observed Lp(a) concentrations at baseline and follow-up. At baseline Lp(a) levels <50 mg/dL [median Lp(a) of 10.9 mg/dL] was observed in 676 patients.  Lp(a) levels > 50 mg/dL [median Lp(a) of 83.2 mg/dL] in 239 patients. Lp(a) concentrations or changes did not correlate with plaque modifications. The authors concluded that in coronary artery disease patients prescribed long-term maximally intensive statin therapy with low on-treatment LDL-C levels, Lp(a) levels, at baseline and on-trial were unable to predict coronary atheroma progression or regression.
Puri R, Ballantyne CM, Hoogeveen RC et al. Lipoprotein(a) and coronary atheroma progression rates during long-term high-intensity statin therapy: Insights from SATURN. Atherosclerosis 2017; 263:137-144. http://www.ncbi.nlm.nih.gov/pubmed/?term=28641153
 
Optimal CVD risk control in patients with DM2 and CVD?
The TECOS trial was a multi-national, double-blind randomized placebo-controlled study of
sitagliptin versus placebo in adults with type 2 diabetes and CVD. Participants (N=13 616) were recruited form 38 countries in Western Europe, Eastern Europe, North America, Asia Pacific and Latin America, with a mean follow up of 3 years. In this retrospective secondary analysis of the intention to treat TECOS cohort, attainment of 5 secondary prevention parameters—aspirin use, lipid control (LDL-C <70 mg/dL or statin therapy), blood pressure control (<140 mmHg systolic, <90 mmHg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and non-smoking status was evaluated. Achieving all 5 secondary prevention parameters was observed in 29.9% of the participants. Overall 71.8% achieved 4 out of 5 targets. Blood pressure control proved to be the biggest challenge 57.9% were able to reach the guideline dictated goals. Non-smoking status was observed in 89% of the participants, this was the highest score of the 5 parameters. Patients that were able to achieve all 5 targets had a 40% lower risk compared with individuals that only managed to control ≤2; adjusted HR 0.60 [95% CI 0.47-0.77]. The authors concluded that significant opportunities exist to improve the care of diabetic patients with CVD and, within a relatively short time frame, would generate an impressive reduced risk of CVD events.
Pagidipati NJ, Navar AM, Pieper KS et al. Secondary Prevention of Cardiovascular Disease in Patients with Type 2 Diabetes: International Insights from the TECOS Trial. Circulation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28626088
 
Genetic polymorphisms in SCLO2B1 affect Rosuvastatin efficacy
in this study, genetic polymorphisms in the solute carrier organic anion transporter 2B1 (SLCO2B1) were evaluated to differentiate the lipid lowering response of 18 volunteers with LDL-C >130 mg/dl, that received rosuvastatin 20 mg for 8 weeks. Single nucleotide polymorphisms (SNPs) of SLCO2B1 (c.935G>A and c.1457C>T), SLCO1B1 (c.521C>T, c.388A>G, and c.-11187G>A) and ABCG2 (c.421C>A) were determined. In participants carrying the SLCO2B1 c.935G>A (rs12422149) variant, rosuvastatin was less effective at lowering LDL (mean % decrease: GG 62.8% GA 50.6% AA 49.3%, p=0.012) and apolipoprotein B (mean % decrease: GG 52.1% GA 42.8% AA 42.8%, p=0.036. Although the trough concentrations were not significantly different between volunteers with wild-type and those with variant genotypes, in one volunteer with SLCO1B1 *17/*17 a trough concentration of 18.8 ng/mL was observed, which was 6.3-fold and 4.9-fold higher than those of wild-type and heterogeneous variant volunteers. The authors conclude that due to small number of volunteers a larger study with a greater sample size is warranted to confirm these first findings.
Kim TE, Shin DS, Gu N et al. The Effect of Genetic Polymorphisms in SLCO2B1 on the Lipid-lowering Efficacy of Rosuvastatin in Healthy Adults with Elevated Low-density Lipoprotein. Basic & clinical pharmacology & toxicology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28627804
 
Patients scheduled carotid stenting suffer less complications if (high dose) statins “on board”
Pretreatment of coronary PTCA has been well documented and established an evidenced based intervention. For carotid stenting data on the benefits of statin pretreatment is sparse or non-existent. In this retrospective study, patients from the Korean prospective CAS registry was used. Patients admitted to one of two tertiary university hospitals, between July 2003 and June 2013, were analyzed. Overall 397 symptomatic carotid stenosis (≥50% stenosis) and treated with carotid stenting were included. Statin pre-treatment was portioned into 3 categories: non statin (n=158; 39.8%), standard dose (<40 mg of atorvastatin, n=155; 39.0%), and high dose (≥40 mg of Atorvastatin; n=84; 21.2%). The periprocedural complication rates amounted to 12.0%, 4.5%, and 1.2% respectively. This translated to a periprocedural complication odds ratio of standard-dose statin: OR 0.24 (0.07−0.8) and high-dose statin: OR 0.11; (0.01−0.96); P for trend=0.01). Antiplatelet drugs reduced periprocedural complications as well OR 0.10 (0.05−0.69). The authors concluded that in patients with symptomatic carotid artery stenting pretreatment with a statin significantly reduced periprocedural complications in a dose dependent manner.
Hong JH, Sohn SI, Kwak J et al. Dose-Dependent Effect of Statin Pretreatment on Preventing the Periprocedural Complications of Carotid Artery Stenting. Stroke 2017; 48:1890-1894. http://www.ncbi.nlm.nih.gov/pubmed/?term=28626049
 
Calcium score identifies patients most likely to benefit from statins
In this analysis, the authors compare statin eligibility based on the evidence from primary prevention statin trials to using a calcium score cut off to optimize selecting patients that would benefit from statins. Using data from MESA (Multi-Ethnic Study of Atherosclerosis) with 5,600 men and women, 45 to 84 years of age, and free of clinical ASCVD and lipid-lowering therapy. After 10 years follow-up, 354 ASCVD and 219 hard coronary heart disease (CHD) events occurred. Almost 73% of MESA participants (91% of those >55 years of age) would be eligible for statin therapy, based on the enrollment criteria for 7 RCTs of statin therapy in primary prevention. A CAC score of 0% was observed in 44% of the MESA individuals and this reflected a very low ASCVD and CHD event rate (3.9 and 1.7, respectively, per 1,000 person-years). A CAC score >100 was found in 27% of participants with ASCVD and CHD event rates of 18.9 and 12.7, respectively. This resulted in a 10-year NNT to prevent 1 ASCVD event of 87 for CAC = 0 and 19 for CAC >100. NNT’s to prevent 1 CHD event were 197 for CAC = 0 and 28 for CAC >100. The authors suggest that a CAC score could help guide physicians in shared decision making to target evidence-based statins to those who are likely to benefit the most.
Mortensen MB, Falk E, Li D et al. Statin Trials, Cardiovascular Events, and Coronary Artery Calcification: Implications for a Trial-Based Approach to Statin Therapy in MESA. JACC. Cardiovascular imaging 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28624395 Blumenthal RS, Aslam MI, McEvoy JW. Using Trial Eligibility to Personalize Statin Therapy Appears No More Accurate Than a Coin Flip in Determining High-Risk Status. JACC. Cardiovascular imaging 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28624410
McClelland RL, Blaha MJ. Incorporating Coronary Artery Calcium into Global Risk Scoring. JACC. Cardiovascular imaging 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28624403
Relevant publications
  1. Waite LH, Phan YL, Spinler SA. Translating Guidelines Into Practice: Interpreting the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. The Annals of pharmacotherapy 2017:1060028017714003. http://www.ncbi.nlm.nih.gov/pubmed/?term=28627235
  2. Suzumura EA, Ribeiro RA, Kawano-Dourado L et al. Effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery: protocol for a systematic review, meta-analysis, and trial sequential analysis. Systematic reviews 2017; 6:116. http://www.ncbi.nlm.nih.gov/pubmed/?term=28629445
  3. Stoekenbroek RM, Kastelein JJP. Dyslipidaemia: Statin-associated muscle symptoms - really all in the mind? Nat Rev Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28631752
  4. Mortensen MB, Budoff MJ, Li D et al. High Quality Statin Trials Support the 2013 ACC/AHA Cholesterol Guidelines After HOPE-3: The Multi-Ethnic Study of Atherosclerosis. Circulation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28634218
  5. Zhang X, Zhou Y, Zhang S et al. Cerebral blood flow evaluation of intensive rosuvastatin therapy in stroke/transient ischemic attack patients with intracranial arterial atherosclerotic stenosis study: Rationale and design. Brain and behavior 2017; 7:e00689. http://www.ncbi.nlm.nih.gov/pubmed/?term=28638702
  6. Ballantyne CM, Shah S, Sapre A et al. A Multiregional, Randomized Evaluation of the Lipid-Modifying Efficacy and Tolerability of Anacetrapib Added to Ongoing Statin Therapy in Patients With Hypercholesterolemia or Low High-Density Lipoprotein Cholesterol. Am J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28624096
  7. Zhang K, Zhai S, Li K et al. Effect of Atorvastatin on lower extremity function of patients with hypertension and peripheral arterial disease. Pak J Pharm Sci 2017; 30:325-327. http://www.ncbi.nlm.nih.gov/pubmed/?term=28625961
  8. Wium-Andersen IK, Wium-Andersen MK, Jorgensen MB, Osler M. Anti-inflammatory treatment and risk for depression after first-time stroke in a cohort of 147 487 Danish patients. Journal of psychiatry & neuroscience : JPN 2017; 42:160244. http://www.ncbi.nlm.nih.gov/pubmed/?term=28632121
  9. Wang J, Ai XB, Wang F et al. Efficacy of ezetimibe combined with atorvastatin in treatment of carotid artery plaque in patients with type 2 diabetes mellitus complicated with coronary heart disease. International angiology : a journal of the International Union of Angiology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28641407
  10. Teramoto T, Kondo A, Kiyosue A et al. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale. Lipids Health Dis 2017; 16:121. http://www.ncbi.nlm.nih.gov/pubmed/?term=28623954
  11. Tani S, Nagao K, Kawauchi K et al. The Ratio of Eicosapentaenoic Acid (EPA) to Arachidonic Acid may be a Residual Risk Marker in Stable Coronary Artery Disease Patients Receiving Treatment with Statin Following EPA Therapy. Am J Cardiovasc Drugs 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28634822
  12. Song MK, Shin BS, Ha CS, Park WY. Would Lipophilic Statin Therapy as a Prognostic Factor Improve Survival in Patients With Uterine Cervical Cancer? International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28644162
  13. Seaman KL, Sanfilippo FM, Roughead EE et al. Impact of consumer copayments for subsidised medicines on health services use and outcomes: a protocol using linked administrative data from Western Australia. BMJ Open 2017; 7:e013691. http://www.ncbi.nlm.nih.gov/pubmed/?term=28637723
  14. Santos TRA, Silveira EA, Pereira LV et al. Potential drug-drug interactions in older adults: A population-based study. Geriatrics & gerontology international 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28635169
  15. Sahebkar A, Banach M. Response letter: Management of statin-induced myopathies: Much demands and still (almost) empty hands! Journal of cachexia, sarcopenia and muscle 2017; 8:514-515. http://www.ncbi.nlm.nih.gov/pubmed/?term=28631417
  16. Richman JS, Graham LA, DeRussy A et al. Perioperative beta blockers and statins for noncardiac surgery patients with coronary stents. American journal of surgery 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28641862
  17. Pecin I, Hartgers ML, Hovingh GK et al. Prevention of cardiovascular disease in patients with familial hypercholesterolaemia: The role of PCSK9 inhibitors. Eur J Prev Cardiol 2017:2047487317717346. http://www.ncbi.nlm.nih.gov/pubmed/?term=28644091
  18. Mezian K, Vacek J, Navratil L, Ozcakar L. Bilateral Rectus Femoris Muscle Rupture Following Statin Medication. American journal of physical medicine & rehabilitation 2017; 96:e138. http://www.ncbi.nlm.nih.gov/pubmed/?term=28628543
  19. King P, Nicholls SJ. PCSK9 Inhibitors: Treating the Right Patients in Daily Practice. Current cardiology reports 2017; 19:66. http://www.ncbi.nlm.nih.gov/pubmed/?term=28643240
  20. Janko M, Moore R, Kim AH et al. Carotid occlusion is associated with more frequent neurovascular events than moderately severe carotid stenosis. Journal of vascular surgery 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28625670
  21. Heine GH, Rogacev KS, Weingartner O, Marsche G. Still a reasonable goal: Targeting cholesterol in dialysis and advanced chronic kidney disease patients. Semin Dial 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28628255
  22. Guemara R, Lazarou I, Guerne IA. Drug-induced myopathies. Revue medicale suisse 2017; 13:1013-1017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28627846
  23. Durairaj A, Sabates A, Nieves J et al. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and Its Inhibitors: a Review of Physiology, Biology, and Clinical Data. Current treatment options in cardiovascular medicine 2017; 19:58. http://www.ncbi.nlm.nih.gov/pubmed/?term=28639183
  24. Chojnacki C, Blonska A, Chojnacki J. The Effects of Melatonin on Elevated Liver Enzymes during Statin Treatment. BioMed research international 2017; 2017:3204504. http://www.ncbi.nlm.nih.gov/pubmed/?term=28630863
  25. Bea AM, Perez-Calahorra S, Marco-Benedi V et al. Effect of intensive LDL cholesterol lowering with PCSK9 monoclonal antibodies on tendon xanthoma regression in familial hypercholesterolemia. Atherosclerosis 2017; 263:92-96. http://www.ncbi.nlm.nih.gov/pubmed/?term=28623742
  26. Batais MA, Khan AR, Bin Abdulhak AA. The Use of Statins and Risk of Community-Acquired Pneumonia. Current infectious disease reports 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28639080
  27. Banakh I, Haji K, Kung R et al. Severe Rhabdomyolysis due to Presumed Drug Interactions between Atorvastatin with Amlodipine and Ticagrelor. Case reports in critical care 2017; 2017:3801819. http://www.ncbi.nlm.nih.gov/pubmed/?term=28630772
  28. Abdel Magid AM, Abbassi MM, Iskander EEM et al. Randomized comparative efficacy and safety study of intermittent simvastatin versus fenofibrate in hemodialysis. Journal of comparative effectiveness research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28627930
Miscellaneous publications
  1. Yu IC, Kuo PC, Yen JH et al. A Combination of Three Repurposed Drugs Administered at Reperfusion as a Promising Therapy for Postischemic Brain Injury. Translational stroke research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28624878
  2. Wilkinson EL, Sidaway JE, Cross MJ. Statin Regulated ERK5 Stimulates Tight Junction Formation and Reduces Permeability in Human Cardiac Endothelial Cells. Journal of cellular physiology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28639275
  3. Wang L, Yao X, Li Q, Sun S. Effect of Simvastatin on Lipid Accumulation and the Expression of CXCL16 and Nephrin in Podocyte Induced by Oxidized LDL. Journal of investigative surgery : the official journal of the Academy of Surgical Research 2017:1-6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28635512
  4. Taylor HS, Alderman M, D'Hooghe TM et al. Effect of Simvastatin on Baboon Endometriosis. Biology of reproduction 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28637327
  5. Lin Z, Jiang Z, Huang X et al. Preventive treatment with atorvastatin ameliorates endothelial dysfunction of small pulmonary arteries in monocrotaline-induced pulmonary hypertensive rats. Clinical and experimental hypertension (New York, N.Y. : 1993) 2017:1-7. http://www.ncbi.nlm.nih.gov/pubmed/?term=28628347
  6. Lin CH, Hsu KW, Chen CH et al. Differential changes in the pharmacokinetics of statins in collagen-induced arthritis rats. Biochem Pharmacol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28636885
  7. Kokilambigai KS, Seetharaman R, Lakshmi KS. Critical review on the analytical techniques for the determination of the oldest statin-atorvastatin-in bulk, pharmaceutical formulations and biological fluids. Critical reviews in analytical chemistry 2017:0. http://www.ncbi.nlm.nih.gov/pubmed/?term=28644038
  8. Kirzioglu FY, Tozum Bulut M, Dogan B et al. Anti-inflammatory effect of rosuvastatin decreases alveolar bone loss in experimental periodontitis. Journal of oral science 2017; 59:247-255. http://www.ncbi.nlm.nih.gov/pubmed/?term=28637984
  9. Ishola IO, Tijani HK, Dosumu OO et al. Atorvastatin attenuates testosterone induced benign prostatic hyperplasia in rats: role of peroxisome proliferator activated receptor-gamma and cyclo-oxygenase-2. Fundamental & clinical pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28636803
  10. Gidal BE, Mintzer S, Schwab M et al. Evidence for a pharmacokinetic interaction between eslicarbazepine and rosuvastatin: Potential effects on xenobiotic transporters. Epilepsy research 2017; 135:64-70. http://www.ncbi.nlm.nih.gov/pubmed/?term=28624574
  11. Chu YT, Zhu XY, Zhang YY et al. [Hemostatic Effect of Spleen-invigorating, Qi-replenishing and Blood-containing Formula on Simvastatin-induced Zebrafish Hemorrhage Model]. Zhongguo shi yan xue ye xue za zhi 2017; 25:853-859. http://www.ncbi.nlm.nih.gov/pubmed/?term=28641649
  12. Basak S, Mondal S, Dey S et al. Fabrication of beta-cyclodextrin-mediated single bimolecular inclusion complex: characterization, molecular docking, in-vitro release and bioavailability studies for gefitinib and simvastatin conjugate. The Journal of pharmacy and pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28631808
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