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.
Stroke patients, irrespective of subtype, are better off with statins
Do statins increase bleeding risk in patients with history of ischemic stroke (IS) or even hemorrhagic stroke (ICH)? This systematic review and meta-analysis examined the existing evidence collected in observational as well as randomized controlled studies comparing active statin treatment with placebo/no therapy. Patients had a history of ICH or IS. In total 42 studies encompassing 317 291 patients were included. Patients that suffered an ICH, were not at risk for a recurrent cerebral bleed when using statins; RR 1.04 (0.86-1.25; N=23 695). Statin use was associated with significant reduced mortality RR 0.49 (0.36-0.76; N=89 976), and less chance for a poor functional outcome RR 0.71 (0.67-0.75; N=9113). On a similar note patient with a history of IS experienced a non-significant increase in ICH, RR 1.36 (0.96-1.91; N=103 525). Statin use did significantly lower their risk of recurrent IS RR 0.74 (0.66 -0.83; N=53 162), any stroke RR 0.82 (0.67-0.99; n=55 260), mortality RR 0.68, (0.50-0.92; n=74 648) and poor functional outcome (RR 0.83 (0.76 to 0.91; N=34 700). The evidence from this meta-analysis confirms that statin use by patients that suffered an ICH was not associated with an increased risk for recurrence, but in IS patient there was a non-significant trend towards increased risk for a recurrent ICH, but this was overshadowed by substantial improvement in mortality and functional outcomes.
Ziff OJ, Banerjee G, Ambler G, Werring DJ. Statins and the risk of intracerebral haemorrhage inpatients withstroke:systematic review and meta-analysis.Journal of neurology, neurosurgery, and psychiatry 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30150320
TG’s predict outcomes in high risk diabetic patients
Risk prediction as well as risk management in diabetic patients has focused on glycemic parameters blood pressure control and LDL-cholesterol targets. In this post hoc analysis of the standard versus intEnsive statin therapy for hypercholesteroleMic Patients with diabetic retinopaTHY (EMPATHY) study. The aim was to determine the impact of triglycerides on cardiovascular outcomes. In this 3-year, recently published study, a standard treatment was compared to a more intensive strategy aiming for an LDL-c target < 70 mg/dl. Using a Cox-regression hazard model, adjusted for sex, hypertension, current smoking. LDL-c and BMI. Higher TG’s were associated with increased risk for MACE HR 1.021/10 mg/dl (1.007-1.035; P=0.0025) as well as CVD HR 1.023/10 mg/dl (1.013-1.034; P=0.0000077). When comparing the top quintile (>185 mg/dl) to the lowest quintile (79 mg/dl) the MACE HR increased to 1.89 (1.03-2.80; P=0.04), the CVD HR 1.90 (1.18-3.07; P=0.007). when examining a possible interaction between statin intensity plus triglycerides on both outcomes; For MACE P-trend=0.33 and CVD P-trend-0.62), no correlation was observed. The authors concluded that serum TG’s predicted CVD events in high-risk Japanese hypercholesterolemic diabetics with retinopathy.
Tada H, Kawashiri MA, Nomura A et al.Serum triglycerides predict first cardiovascular events in diabetic patients with hypercholesterolemia and retinopathy.Eur J Prev Cardiol 2018:2047487318796989. http://www.ncbi.nlm.nih.gov/pubmed/?term=30160521
Plaque changes predicted by DPB not SBP, in statin treated CAD patients
The Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids (HEARTS) trial was a randomized, single-center study that assessed the effects of 3.36 g daily of EPA and DHA to no EPA and DHA on coronary artery plaque volume. In this retrospective cross-sectional baseline analysis, the impact of blood pressure (systolic and diastolic) on coronary plaque characteristics was evaluated in patients that were well treated with statins. Plaque characteristics were measured by CT-Coronary Angiography. Participants were stable CAD patients (N=285) aged 63.1 (±7.7) years LDL-c 78.7 (±28.5) mg/dl. Patients with the lowest DBP (<68 mmHg) compared with the highest DBP (>76 mmHg) showed more favorable plaque features. Fatty plaque: 10.0 vs. 7.7mm3/mm, (p trend = 0.042), fibrous plaque: 19.6 vs. 13.8mm3/mm (p trend = 0.011), non-calcified plaque:29.7 vs. 22.5mm3/mm (p trend = 0.017) and total plaque: 37.8 vs. 25.1mm3/mm (p trend = 0.010). Plaque features were not influenced by differences in SBP (comparing the lowest to the highest tertile). When adjusting of DBP as a continuous variable, the following plaque changes were noted for each increased of 1 mmHg DBP. Fibrous plaque increased 0.128mm3/mm (p = 0.022), noncalcified plaque increased 0.176mm3/mm (p = 0.045), calcified plaque increased 0.096mm3/mm (p = 0.001) and total plaque increased 0.249mm3/mm (p + 0.019). Changes in SBP ranging from 95 to 154 mmHg did not predict plaque volume. The authors concluded that in patients with optimally treated LDL-c (<80 mg/dl) not SBP but DBP predicted plaque changes. The lowest DBP tertile (< 68mmHg) was associated with the least amount of coronary plaque.
In Saleh M, Alfaddagh A, Elajami TK et al.Diastolic blood pressure predicts coronary plaque volume in patients with coronary artery disease.Atherosclerosis 2018; 277:34-41. http://www.ncbi.nlm.nih.gov/pubmed/?term=30170222
Managing statin associated muscle complaints by alternate day dosing
In developing economies managing CVD risk factors in general and LDL-cholesterol in particular, is challenging but can be improved by simple dosing regimens. A descriptive cross-sectional study was conducted in a single tertiary hospital in Karachi, Pakistan. Patients included (N=400) had been taking statins >6 months and were equally divided in two groups. Each group received simvastatin 40 mg, but one group every day (EDD) and the second group every other day (ADD). Age of the patients was between 40 -70 years. Reported myalgic complaints was significantly higher in the EDD group (N=20 / 10%) compared to the ADD (N=8 / 4%), P=0.02. From the 28 patients that developed myalgia, half started to experience symptoms (cramps and weakness) in the first 4 weeks. Only 3 patients graded their symptoms as severe. The most common trigger for myalgia was physical exercise and the majority of patients (6 fold increase) experienced intermittent and not continuous muscle complaints. Vitamin D levels were low in 13 (6.5%) patients of the EDD vs 6 (3%) in the ADD group. The nature of the statin associated muscle complaints such as the time of onset, nature, severity, type, or location of myalgia were similar in both groups. The authors suggested that ADD is an attractive strategy to address statin associated muscle complaints.
Riaz R, Merchant AZ, Ul Haq MS et al.Statins everyday versus alternate days: Is there a difference in myalgia rates?Indian Heart J 2018; 70:492-496. http://www.ncbi.nlm.nih.gov/pubmed/?term=30170642
ASCOT study 16 year follow up!
In the ASCOT study, hypertensive patients received a blood pressure lowering regime (amlodipine-based vs atenolol-based). Patients with a total cholesterol ≤6.5 mmol/l and no previous lipid lowering treatment were also randomized to atorvastatin or placebo (Lipid lowering arm of the ASCOT study) remaining patients formed the non-lipid lowering arm. In late 2002 the trial was stopped prematurely after 3.3 years follow up because of substantial benefits in the patients using atorvastatin. In this post-hoc analysis the 8 580 UK participants were followed for a total period of approximately 16 years. Almost half of the patients, 3282 (38.4%) died during this period; 1640/4275 (38.4%) in the atenolol group and 1624/4305 (37.3%) in the amlodipine arm. The patients assigned to the lipid lowering arm, 1768/4605 (39.5%) did not survive the 16-year follow-up; placebo users: 903/2288 (39.5%) and 865/2317 (37.3%) of the atorvastatin assigned patients. No interaction between BPLA and in the LLA could be discerned, but in the 3975 patients in the non-LLA group, less CVD deaths were observed, adjusted HR 0·79 (0·67–0·93, p=0·0046). Among those assigned to amlodipine-based treatment, compared to atenolol-based treatment (p=0·022 for the test for interaction between the two blood pressure treatments and allocation to LLA or not), in the LLA, significantly fewer cardiovascular deaths (HR 0·85, 0·72–0·99, p=0·0395) occurred among patients assigned to atorvastatin than among those assigned placebos. The authors concluded that after almost 16 years follow up, the ASCOT study showed that blood pressure and cholesterol lowering translated in long term reductions of cardiovascular complications. Amlodipine use was associated with fewer stroke deaths compared to atenolol-based treatments and patients on atorvastatin experienced fewer cardiovascular deaths.
Gupta A, Mackay J, Whitehouse A et al.Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomised factorial trial.Lancet 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30158072
Yang N, Song Y, Dong B et al.Elevated Interleukin-38 Level Associates with Clinical Response to Atorvastatin in Patients with Hyperlipidemia.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2018; 49:653-661. http://www.ncbi.nlm.nih.gov/pubmed/?term=30165364
Dobrzycka M, Spychalski P, Lachinski AJ et al.Statins and Colorectal Cancer - A Systematic Review.Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30149418
Carvalho AAS, Silva VGD, Vieira TF et al.Proposed cut-off for reactivity of anti-HMGCR and anti-SRP antibodies in patients statin-exposed and statin-unexposed.Medicine (Baltimore) 2018; 97:e11858. http://www.ncbi.nlm.nih.gov/pubmed/?term=30170376
Salem MM, Maragkos GA, Enriquez-Marulanda A et al.Statin Therapy and Diabetes Do Not Affect Aneurysm Occlusion or Clinical Outcomes Following Pipeline Embolization Device Treatment: a Preliminary Study.World neurosurgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30149155
Rozani V, Gurevich T, Giladi N et al.Higher serum cholesterol and decreased Parkinson's disease risk: A statin-free cohort study.Movement disorders : official journal of the Movement Disorder Society 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30145829
Krysiak R, Szkrobka W, Okopien B. The Relationship Between Statin Action On Thyroid Autoimmunity And Vitamin D Status: A Pilot Study.Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30149415
Bergt S, Grub A, Wagner S et al.Pravastatin But Not Simvastatin Improves Survival and Neurofunctional Outcome After Cardiac Arrest and Cardiopulmonary Resuscitation.JACC. Basic to translational science 2017; 2:149-159. http://www.ncbi.nlm.nih.gov/pubmed/?term=30167563
Martinez-Jimenez C, Cruz-Angeles J, Videa M, Martinez LM. Co-Amorphous Simvastatin-Nifedipine with Enhanced Solubility for Possible Use in Combination Therapy of Hypertension and Hypercholesterolemia.Molecules (Basel, Switzerland) 2018; 23. http://www.ncbi.nlm.nih.gov/pubmed/?term=30154310
Godoy JC, Niesman IR, Busija AR et al.Atorvastatin, but not pravastatin, inhibits cardiac Akt/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2018:fj201800876R. http://www.ncbi.nlm.nih.gov/pubmed/?term=30169110
Xiao H, Hwang JE, Wu R. Mass spectrometric analysis of the N-glycoproteome in statin-treated liver cells with two lectin-independent chemical enrichment methods.International journal of mass spectrometry 2018; 429:66-75. http://www.ncbi.nlm.nih.gov/pubmed/?term=30147434
Mirzaei-Kalar Z. In vitro binding interaction of atorvastatin with calf thymus DNA: multispectroscopic, gel electrophoresis and molecular docking studies.Journal of pharmaceutical and biomedical analysis 2018; 161:101-109. http://www.ncbi.nlm.nih.gov/pubmed/?term=30145447
Alqudah MAY, Mansour HT, Mhaidat N. Simvastatin enhances irinotecan-induced apoptosis in prostate cancer via inhibition of MCL-1.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 2018; 26:191-197. http://www.ncbi.nlm.nih.gov/pubmed/?term=30166915
Ahmadi M, Madrakian T, Ghavami S. Preparation and Characterization of Simvastatin Nanocapsules: Encapsulation of Hydrophobic Drugs in Calcium Alginate.Methods in molecular biology (Clifton, N.J.) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30159829