Who has benefit and who not – or less?
Who will derive benefit (of statins) and who does not! That is the million-dollar question the authors attempted to address in this study. CHD Patients (N=84) treated with a statin and that had serial optical coherence tomography (OCT) evaluations (median interval 6.3 months) were included in this analysis. Thin-cap area (TCA) was measured at baseline and re-evaluated during the study. LDL-C was lowered from 92.9 (±30.1) mg/dL) to 76.3 (±23.3) mg/dL; P<0.001. Overall TCA measurements improved during follow-up. At baseline: 2.852 mm2 (25th–75th percentile, 1.023–6.157 mm2). At follow up: 1.210 mm2 (25th–75th percentile, 0.250–3.192 mm2); P<0.001. In patients with chronic kidney disease patients these improvements were mitigated, regression coefficient b, 1.691 mm2; (0.350–3.033 mm2); P=0.013. Improved changes were observed in ACS patients; regression coefficient b, -1.535 mm2; (-2.561 to -0.509 mm2); P=0.003. The authors concluded in patients with CKD statins had less TCA improving effects while ACS patients derived a more robust benefit.
Minami Y, Wang Z, Aguirre AD et al. Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study. J Am Heart Assoc 2017; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=29092845
Acute pancreatitis patients start or stop a statin?
The role of statins as an anti-inflammatory agent are explored in this interesting study of acute pancreatitis patients admitted to single US hospital. Between 2007 and 2014, 1097 patients presented with an acute pancreatitis in the Cleveland Clinic Health system. A propensity score 1:1 matching resulted in 210 patients that were using statins and 210 that were not, at admission. Outcomes included pancreatitis severity, multi systems organ failure, acute necrosis and death. Surrogate markers severity was hospital length of stay, Bedside Index of Severity of Acute Pancreatitis (BISAP), and presence of SIRS. Baseline clinical characteristics were well matched. For patients using a statin at the time of hospital admission the risk of MSOF, sever AP and necrosis were reduced; OR 0.18 (0.05-0.60) and OR 0.41 (0.20-0.82) respectively. Mortality was lower in statin users as well but not statistically significant; 2% vs 4% (P=0.38). Based on their findings, the authors concluded that baseline statin use resulted in improved outcome in acute pancreatitis patients. If statins should be started on admission needs to be re-evaluated in a properly designed prospective randomised controlled trial.
Lee PJ, Modha K, Chua T et al. Association of Statins With Decreased Acute Pancreatitis Severity: A Propensity Score Analysis. Journal of clinical gastroenterology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29095423
Statins as an antibiotic adjuvant?
This systematic review discusses the potential role of statin as antibiotic adjuvant. In order to break antimicrobial resistance (AMR), by direct antimicrobial activity as well stimulating the immune system, statins could enhance the effectiveness of commonly used antibiotics.
An extensive literature search resulted in 793 articles of which 16 relevant articles were selected for this systematic review. Statins interfere with bacterial cell regulatory functions via binding and disrupting cell surface structures such as wall teichoic acids, lipoteichoic acids, lipopolysaccharides, and/or surface proteins. In contrast with these findings statins could also promote AMR by their wide spread use. this could result in resistance by means of sub lethal plasma concentrations in bacteremic patients and promotion of dysbiosis of the gut microbiome. For Gram-positive bacteria, simvastatin possesses the greatest antibacterial activities, when compared with atorvastatin, rosuvastatin and fluvastatin. Atorvastatin exerted similar or slightly superior activity for Gram-negative bacteria as simvastatin. Both were superior when compared to fluvastatin and rosuvastatin. The authors conclude that simvastatin appeared to be the best suited statin for antibiotic adjuvant use. The available data favors statins as AMR breakers but their role as AMC makers needs to be investigated more thoroughly. They emphasize that the mechanism of antibacterial activity of statins is the most relevant knowledge gap that needs to be addressed.
Ko HHT, Lareu RR, Dix BR, Hughes JD. Statins: antimicrobial resistance breakers or makers? PeerJ 2017; 5:e3952. http://www.ncbi.nlm.nih.gov/pubmed/?term=29085751
Statins associated with prolonged recurrence free survival in HCC patients after initial liver resection
The interest in the potential protective effect of statins in chronic liver disease is gaining momentum. In NASH and NAFLD patients statins seem to not only safeguard them from CVD complications, but their underlying liver disease respond favourably as well. In this Japanese study patients treated for hepatocellular carcinoma (HCC) were retrospectively evaluated. From 2003 -2013, 734 patients with HCC underwent a n initial liver resection. Patients were grouped in statin users (n=34/4.2%) and no-statin users (N=703/98,8%) at the time of diagnosis/surgery. Statin users were only adjucated if patients used statins >90 days. The proportions of patients with hepatitis B surface antigen (HBsAg) positivity and hepatitis C virus antibody (HCVAb) positivity were significantly lower in the statin than non-statin group; HBsAg, 6.5% vs. 22.8%, P = 0.032; HCVAb, 19.4% vs. 45.0%, P = 0.005. Recurrence free survival (RFS) improved significantly in the patients on statins. The 1-, 3-, and 5- year RFS rates were 87.1%, 76.7%, and 76.7%, respectively, in the statin group, and 65.3%, 40.6%, and 32.9%, respectively, in the non-statin group (P < 0.001). No significant difference could be detected for overall survival (OS). The 1-, 3, and 5- year OS rates were 96.7%, 93.1%, and 85.3%, respectively, in the statin group, and 94.2%, 87.1%, and 70.2%, respectively, in the non-statin group (P = 0.142). The authors concluded that statins provided a significant improvement of RFS in HCC patent that had an initial liver resection. To provide a definite answer if statins should be added as a standard adjuvant therapy for patients that are diagnosed with HCC, needs to be addressed in a prospective randomized trial.
Kawaguchi Y, Sakamoto Y, Ito D et al. Statin use is associated with a reduced risk of hepatocellular carcinoma recurrence after initial liver resection. Bioscience trends 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29081488
In prediabetics statins increase risk for NODM
Statins have been shown to increase the risk for developing new onset diabetes (NODM). The exact mechanism for these effects remains blurred, but risk factors associated with developing diabetes increased this risk significantly in Jupiter and TNT. The statin trials where the NODM effects of statins were analyzed, most participants had a relatively low risk for developing diabetes and this diagnosis was mostly self-reported. In the Diabetes Prevention Program (DPP) study 3 234 patients were randomized to metformin lifestyle and placebo at risk for developing diabetes, and were followed for ± 3.2 years. At the end of the study participants were invited to enroll in the Prevention Program Outcomes (DPPO) study. In this study, all patients were recommended to follow quarterly lifestyle sessions. Patients that had used metformin in the DPP now received open label metformin and participants in the lifestyle section were invited for two additional lifestyle educational programs. NODM was assessed by annual 75 g oral glucose tolerance testing and semiannual fasting glucose measurements. Participants in the DPPO study were monitored for an additional 10 years. Statins were used, before the NODM manifested, in 33-37% of the participants in the three randomized treatment arms (P=0.36). Statin users were found to have an increased risk for developing diabetes, irrespective of the treatment protocol, HR 1.36 (1.17-1.58). No effects could be seen for potential statin initiation confounders or by adjusting for baseline diabetes risk factors. A decline of insulin secretion was observed in the statin-users that progressed to diabetes. No difference between the three intervention arms was noted in the participants that became diabetic. Based on these observations the authors concluded that in patients at risk for diabetes, statins increase the risk for NODM. Therefore, pre-diabetic patients should be carefully monitored after statins are started. The observed and relatively modest NODM risk increase, should be balanced against the rugged benefits that statins provide in terms of CVD risk diminution, particular in diabetic patients.
Crandall JP, Mather K, Rajpathak SN et al. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ open diabetes research & care 2017; 5:e000438. http://www.ncbi.nlm.nih.gov/pubmed/?term=29081977
Ticagrelor and atorvastatin do not always match!
The omnipresent use of statina in a very large, and still growing, number of patients warrants up-to date expertise on potential drug-drug interactions. In this case report, a 58-year-old male patient started with ticagrelor 90 mg twice daily after a successful stent placement. At a follow-up visit 3 months later CPK levels were elevated (2360 IU/L). Muscle complaints could not be properly evaluated due to a prior stroke that resulted in musculoskeletal deficits. Other causes for the CPK increase were eliminated and atorvastatin was stopped considering he had been using this drug with ease for >10 years. After 3 days CK levels decreased to 834 IU/L. Later atorvastatin was re-started at his initial dose of 40 mg/day but ticagrelor was replaced by clopidogrel 75 mg. CK measurements were repeated two weeks later and normalised to 54 IU/L. the author recalls that in earlier pharmacokinetic studies the combination of ticagrelor and atorvastatin 80 mg increased the AUC of atorvastatin by 32-67%; this difference was not statistically significant and deemed as clinically irrelevant. Studies comparing younger and elderly with this combination showed a higher AUC of ± 17% and also males were discovered to have a 11% higher AUC compared to women. One other case report presented a 62-year old woman that developed rhabdomyolysis after combining atorvastatin 80 mg with ticagrelor 90 mg twice daily. She was switched to a lower dose statin and Clopidogrel that resulted in an uneventful follow-up and normalization of her CPK’s. Ticagrelor, in contrast with clopidogrel and prasurgel, acts as weak CYP450-3A4 and P-gp inhibitor; enzymes that play role in the metabolism of atorvastatin as well. The author suggests that, although this interaction seems to clinically irrelevant in most patients, if someone presents with muscle related side effects when using atorvastatin + ticagrelor, the latter can successfully be replaced with a suitable alternative.
Beavers JC. Elevated Creatine Kinase due to Potential Drug Interaction With Ticagrelor and Atorvastatin. Journal of pharmacy practice 2017:897190017740282. http://www.ncbi.nlm.nih.gov/pubmed/?term=29096571