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Update - Week 24, 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 reduce Lp(a)?
A retrospective analysis of a Chinese single institute registry the Case Collection and Scientific reSearch System for Clinical Cardiology (CCSSSCC) database (N= 40 000) was queried to observe the effects of statins on Lp(a) when used short term (median 39 days), medium term (median 219 days) and long term (median 677 days). All patients had manifest CAD and were included in the registry between 1-1-2010 and 31-12-2013. After exclusions of non-eligible patients 1369 individuals were analyzed. No effects on Lp(a) were observed in patients that used statins for a short or medium time interval. Statin used were simvastatin 40 mg (n=454), atorvastatin 20 mg, (n=546), Fluvastatin 40 mg (N=16), and rosuvastatin 10 mg (N=74) Patients using statins for a longer period had significantly lower Lp(a). When analyzing the efficacy of different statins, only long-term use of simvastatin showed a statistical significant lower Lp(a); Atorvastatin, Fluvastatin and Rosuvastatin showed a trend towards lower Lp(a) levels but this did not reach statistical significance. Patients with LDL-C mid tertile ranges (2.18-3.03 mmol/L) showed increases of Lp(a) ∼10% in all treatment durations. The study design was very complicated and the number of patients in the created subgroups quite small. Limitations in the design, including the observational nature, makes it impossible to come to a definite conclusion. However, looking at long term effects of Statins on Lp(a) as well as the analysis of different statins and different baseline levels of LDL-c is intriguing. Future explorations of larger registries, where Lp(a) data and statins use including statin dosage are available, to replicate the effects observed in this analysis, should be considered.  
Xu MX, Liu C, He YM et al. Long-term statin therapy could be efficacious in reducing the lipoprotein (a) levels in patients with coronary artery disease modified by some traditional risk factors. J Thorac Dis 2017; 9:1322-1332. http://www.ncbi.nlm.nih.gov/pubmed/?term=28616285
 
Can we forget cognitive impairment and statins?
A retrospective analysis of 3,500 adult patient’s medical records in one US suburban internal medicine outpatient clinic, between July 1 and December 31, 2015. Patients using statins: 720 (20.6%). In this group dementia or cognitive impairment was more frequently encountered in the statin group (7.9%) compared patients in the non-statin group (3.1%; P < 0.001). However, in the statin group the prevalence of co-morbidities and CV risk factors was significantly higher: hyperlipidemia (86.3%), hypertension (69.6%), diabetes mellitus (36.0%), osteoarthritis (31.5%), coronary artery disease (26.1%), hypothyroidism (21.5%) and depression (19.3%) compared to the non-statin group (P < 0.001). Among the patients with cognitive deficit or dementia + statin use, lipophilic statin such as atorvastatin and simvastatin (79%) were used more frequently than hydrophilic statins such as rosuvastatin and pravastatin (21%). Other factors that showed a correlation with cognitive impairment (OR): year increase in age (1.3), in women (2.2), African American race (2.7), non-consumption of moderate amount of alcohol (2.0), diabetes mellitus (1.6), hypothyroidism (1.7), cerebrovascular accident (3.2), and other rheumatological diseases (1.8). Although the authors postulate a direct effect of statins on cognitive dysfunction, the observational design of this study plus the significant heterogeneity between the two groups prohibit this. Only a long term randomized prospective follow-up study could provide the definite answer, however the by definition increased CVD risk of patients participating in such a trial would prohibit assigning patients to a placebo.
Roy S, Weinstock JL, Ishino AS et al. Association of Cognitive Impairment in Patients on 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitors. Journal of clinical medicine research 2017; 9:638-649. http://www.ncbi.nlm.nih.gov/pubmed/?term=28611866
 
Do ischemic stroke patients, using lipophilic statins run a risk of hemorrhagic stroke?
In this nested case- control study conducted in Ontario, Canada between April 1, 2001 and March 31, 2015 patients 66 years or older and diagnosed with ischemic stroke (IS) and receiving a statin within 100 days preceding an intracranial hemorrhage complication (IH). Each case was matched with up to four controls. Overall 2766 post IS patients developed an IH during statin therapy as well as 11,060 matched controls. No increased risk for IH was observed in patients using a lipophilic statin compared to patients on hydrophilic statins (pravastatin and rosuvastatin), OR: 1.07 (0.97–1.19). The authors concluded that statin lipophilicity does not increase the risk for IH in IS patients.
Quinn KL, Macdonald EM, Mamdani MM et al. Lipophilic Statins and the Risk of Intracranial Hemorrhage Following Ischemic Stroke: A Population-Based Study. Drug Saf 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28620871
 
Reduced risk of delirium in ICU patients on statins
In this single institute retrospective propensity-matched cohort analysis was conducted between September 1, 2012, to September 30, 2015 .  A total of 6 664 consecutive patients admitted to the ICU in the Hartford Hospital, Hartford, CT were assessed and 1475 statin users + 1 475 matched controls were used in the final analysis. Statin users had a significant reduced risk of developing delirium; OR 0.47 (0.38–0.56). This protective effect was observed for all statins studied but did not reach statistical significance for rosuvastatin due to limited number of patients (N= 74). The authors concluded that statin use was associated with a significant decreased risk of delirium in ICU patients, due to the observational design of this analysis, confirmation in prospective randomized trials is urgently needed.
Mather JF, Corradi JP, Waszynski C et al. Statin and Its Association With Delirium in the Medical ICU. Critical care medicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28622167
 
“All Hands on Deck” for Statins on board
Patients with AMI and taking statins are less likely to present with risk full plaque features.
Using data collected in the optical coherence tomography (OCT)-Formidable registry (9 European centers) to evaluate the effects of statins “on board” in 285 consecutive ACS patients that were evaluated with OCT. Statins were used by 150 (52.6%) patients presenting with AMI, they were older, more frequently female and presented a higher prevalence of CV risk factors (except smoking). Beta-blockers, angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) and aspirin were more frequently used by statin users. Non-STEMI was observed more frequently in statin users; 111 patients (74%); No pre-statin use resulted in a higher risk of developing a STEMI. Primary endpoint of the trial was ruptured plaque. In patients with statins this was less frequently observed OR 0.375 (0.185-0.759; P=0.006). a ruptured plaque was recognized as the culprit lesion in 186 (65.3%) cases and TCFA without signs of rupture in 22 (7.7%). Plaque rupture was associated with a higher prevalence of TCFA at any site, a thinner minimum fibrous cap thickness and other features of higher risk plaques. The secondary endpoint: thin-cap fibro-atheroma (TCFA) at any site was again less frequently observed in patients using statins OR 0.432 (0.213-0.848; P=0.014). No difference in the secondary endpoint of not-ruptured TCFA as the culprit lesion could be determined. In Non-STEMI patients there was a trend towards less plaque rupture and a significant reduction in TCFA, but not for patients presenting with STEMI. The authors make a strong case by showing the benefits of statins, even when unable to prevent the acute event! Chronic treatment with statins is associated with reduced incidence of plaque rupture detected by OCT in patients presenting with ACS, with a potentially more marked effect in patients with NSTE-ACS.
Gili S, Iannaccone M, Colombo F et al. Effects of statins on plaque rupture assessed by optical coherence tomography in patients presenting with acute coronary syndromes: insights from the optical coherence tomography (OCT)-FORMIDABLE registry. European heart journal cardiovascular Imaging 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28605473
 
 
RCT with simvastatin shows improved quality of life in MS patients
The first report of the 24-month MS-STAT phase 2 trial showed that high-dose simvastatin significantly reduced the annualized rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). The MS-STAT cognitive sub-study evaluated the effect of simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures. MS-STAT phase 2 trial was a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centers in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). Patients were assessed at baseline, 12 months and 24 months with multiple cognitive and HRQoL assessment tests. At baseline 60 (45%) of 133 patients showed impairments on the test of frontal lobe function (FAB). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group as well as a 2·5 points better score in the mean physical component evaluation. No treatment benefits were noted for any other outcomes. The authors concluded that the observed potential benefits of Simvastatin on frontal lobe function and a physical quality-of-life measure warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials.
Chan D, Binks S, Nicholas JM et al. Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Lancet neurology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28600189
Filippi M, Editorial: Rocca MA. Simvastatin and cognition in multiple sclerosis. Lancet neurology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28600188

Relevant publications
  1. Zhang J, Long M, Yu Y. The effects of additional ezetimibe treatment to baseline rosuvastatin on circulating PCSK9 among patients with stable angina. J Thorac Dis 2017; 9:1226-1233. http://www.ncbi.nlm.nih.gov/pubmed/?term=28616272
  2. Sinning D, Landmesser U. Effective low-density lipoprotein-lowering therapy: Implementation in clinical practice. Eur J Prev Cardiol 2017; 24:71-76. http://www.ncbi.nlm.nih.gov/pubmed/?term=28618905
  3. Schiele F, Ecarnot F, Chopard R. Coronary artery disease: Risk stratification and patient selection for more aggressive secondary prevention. Eur J Prev Cardiol 2017; 24:88-100. http://www.ncbi.nlm.nih.gov/pubmed/?term=28618915
  4. Dai YY, Zhang HS, Zhang XG et al. Statin-ezetimibe versus statin lipid-lowering therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention. J Thorac Dis 2017; 9:1345-1352. http://www.ncbi.nlm.nih.gov/pubmed/?term=28616287
  5. Xu D, Hu J, Wu Q et al. Efficacy and safety of zhibitai in combination with atorvastatin for lipid lowering in patients with coronary heart disease. Oncotarget 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28611309
  6. Ursoniu S, Mikhailidis DP, Serban MC et al. The effect of statins on cardiovascular outcomes by smoking status: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2017; 122:105-117. http://www.ncbi.nlm.nih.gov/pubmed/?term=28602797
  7. Sijbrands EJ. Xanthomas and atheromas. Atherosclerosis 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28606368
  8. Schreml J, Gouni-Berthold I. Role of anti-PCSK9 antibodies in the treatment of patients with statin intolerance. Curr Med Chem 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28618994
  9. Sanada S, Miyasaka Y, Kanno A et al. Efficacy of statin on vascular access patency in diabetic hemodialysis patients. The journal of vascular access 2017:0. http://www.ncbi.nlm.nih.gov/pubmed/?term=28604988
  10. Pinto X, Trias Vilagut F, Rius Taruella J, Mairal Sallan E. [Dyslipidemia management in patients with high cardiovascular risk in Spain. ALMA study]. Atencion primaria / Sociedad Espanola de Medicina de Familia y Comunitaria 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28619533
  11. Nash DM, Brimble S, Markle-Reid M et al. Quality of Care for Patients With Chronic Kidney Disease in the Primary Care Setting: A Retrospective Cohort Study From Ontario, Canada. Canadian journal of kidney health and disease 2017; 4:2054358117703059. http://www.ncbi.nlm.nih.gov/pubmed/?term=28616249
  12. Meltzer AJ, Sedrakyan A, Connolly PH et al. Risk factors for sub-optimal utilization of statins and antiplatelet therapy in patients undergoing revascularization for symptomatic peripheral arterial disease. Annals of vascular surgery 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28602895
  13. Lissaker CT, Wallert J, Held C, Olsson E. Emotional distress as a predictor of statin non-adherence among Swedish first-time myocardial infarction patients, 2006-2013. Journal of psychosomatic research 2017; 97:30-37. http://www.ncbi.nlm.nih.gov/pubmed/?term=28606496
  14. Kulik A, Abreu AM, Boronat V, Ruel M. Intensive versus moderate atorvastatin therapy and one-year graft patency after CABG: Rationale and design of the ACTIVE (Aggressive Cholesterol Therapy to Inhibit Vein Graft Events) randomized controlled trial (NCT01528709). Contemporary clinical trials 2017; 59:98-104. http://www.ncbi.nlm.nih.gov/pubmed/?term=28611006
  15. Kabel AM, Elkhoely AA. Targeting proinflammatory cytokines, oxidative stress, TGF-beta1 and STAT-3 by rosuvastatin and ubiquinone to ameliorate trastuzumab cardiotoxicity. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017; 93:17-26. http://www.ncbi.nlm.nih.gov/pubmed/?term=28622591
  16. Hussenbux A, Hofer M, Steuer A. Statin-induced necrotizing autoimmune myopathy: importance of early recognition. British journal of hospital medicine (London, England : 2005) 2017; 78:352-353. http://www.ncbi.nlm.nih.gov/pubmed/?term=28614015
  17. Hong YJ, Jeong MH, Bae JH et al. Efficacy and safety of pitavastatins in patients with acute myocardial infarction: Livalo in Acute Myocardial Infarction Study (LAMIS) II. The Korean journal of internal medicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28618772
  18. Doyle M, Bhimji S. Statin Medications. In: StatPearls. Treasure Island (FL): StatPearls Publishing StatPearls Publishing LLC.; 2017.
  19. Gossman W, Siddique M. Atorvastatin. In: StatPearls. Treasure Island (FL): StatPearls Publishing StatPearls Publishing LLC.; 2017.
  20. Gossman W, Bhimji S. Fluvastatin. In: StatPearls. Treasure Island (FL): StatPearls Publishing StatPearls Publishing LLC.; 2017.
  21. E JY, Lu SE, Lin Y et al. Differential and joint effects of metformin and statins on overall survival of elderly patients with pancreatic adenocarcinoma: a large population-based study. Cancer Epidemiol Biomarkers Prev 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28619830
  22. Dujovne CA. Red yeast rice preparations: are they suitable substitutions for statins? Am J Med 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28601545
  23. Chapman SR, Fitzpatrick RW, Aladul MI. Has cost inhibited the uptake of more potent statins in England? Pharmacoepidemiol Drug Saf 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28612964
  24. Blackburn R, Osborn D, Walters K et al. Statin prescribing for prevention of cardiovascular disease amongst people with severe mental illness: Cohort study in UK primary care. Schizophrenia research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28599749
  25. Bahls M, Gross S, Ittermann T et al. Statins are related to impaired exercise capacity in males but not females. PLoS One 2017; 12:e0179534. http://www.ncbi.nlm.nih.gov/pubmed/?term=28617869
  26. Akershoek JJ, Brouwer KM, Vlig M et al. Differential effects of Losartan and Atorvastatin in partial and full thickness burn wounds. PLoS One 2017; 12:e0179350. http://www.ncbi.nlm.nih.gov/pubmed/?term=28614412

Miscellaneous publications
  1. Mitsuhashi T, Uemoto R, Ishikawa K et al. Endothelial Nitric Oxide Synthase-Independent Pleiotropic Effects of Pitavastatin Against Atherogenesis and Limb Ischemia in Mice. J Atheroscler Thromb 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28592707
  2. Lee YJ, Kim MJ, Yoon YS et al. Simvastatin treatment boosts benefits of apoptotic cell infusion in murine lung fibrosis. Cell death & disease 2017; 8:e2860. http://www.ncbi.nlm.nih.gov/pubmed/?term=28594406
  3. Fafilek B, Hampl M, Ricankova N et al. Statins do not inhibit the FGFR signaling in chondrocytes. Osteoarthritis and cartilage 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=2858389

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