Statins Abstracts 4

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Low-dose statin treatment increases prostate cancer aggressiveness.
            (Caro-Maldonado et al., 2018)  Download
Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that in vivo simvastatin administration alone increases prostate cancer aggressiveness. In vitro cell line systems supported the notion that this phenomenon occurs, at least in part, through the direct action on cancer cells of low doses of statins, in range of what is observed in human plasma. In sum, our results reveal a prostate cancer experimental system where statins exhibit an undesirable effect, and warrant further research to address the relevance and implications of this observation in human prostate cancer.

Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series.
            (Cham et al., 2016)  Download
Psychiatric adverse drug reactions (ADRs) have been reported with statin use, but the literature regarding statin-associated mood/behavioral changes remains limited. We sought to elicit information germane to natural history and characteristics of central nervous system/behavioral changes in apparent connection with statin and/or cholesterol-lowering drug use, and delineate mechanisms that may bear on an association. Participants (and/or proxies) self-referred with behavioral and/or mood changes in apparent association with statins completed a survey eliciting cholesterol-lowering drug history, character and impact of behavioral/mood effect, time-course of onset and recovery in relation to drug use/modification, co-occurrence of recognized statin-associated ADRs, and factors relevant to ADR causality determination. Naranjo presumptive ADR causality criteria were assessed. Participants (n = 12) reported mood/behavior change that commenced following statin initiation and persisted or progressed with continued use. Reported problems included violent ideation, irritability, depression, and suicide. Problems resolved with drug discontinuation and recurred with rechallenge where attempted. Eight met presumptive criteria for "probable" or "definite" causality; others had additional factors not considered in Naranjo criteria that bear on casual likelihood. (1) Simvastatin 80 mg was followed in 5 days by irritability/depression culminating in suicide in a man in his 40s (Naranjo criteria: possible causality). (2) Simvastatin 10 mg was followed within 2 weeks by depression in a woman in her 50s (probable causality). (3) Atorvastatin 20 mg was followed in ~1 month by depression and irritability/aggression in a male in his 50s (probable causality). (4) Atorvastatin 10 mg was followed in several months by aggression/irritability and depression culminating in suicide in a man in his 40s (possible causality). (5) Fenofibrate + rosuvastatin (unknown dose), later combined with atorvastatin were followed in 1 month by aggression/irritability in a male in his 30s (probable causality). (6) Lovastatin (unknown dose and time-course to reaction) was followed by depression, dyscontrol of bipolar disorder, and suicide attempts in a male in his 40s (possible causality). (7) Atorvastatin 20 mg was followed within 2 weeks by cognitive compromise, and nightmares, depression, and anxiety culminating in suicide in a man in his teens (definite causality). (8) Simvastatin 10 mg was followed (time-course not recalled) by depression, aggression/irritability culminating in suicide in a man in his 60s (possible causality). (9) Simvastatin 20 mg then atorvastatin 10 mg were followed (time-course not provided) by irritability/aggression in a man in his 60s (definite causality). (10) Atorvastatin 10 then 20 then 40 mg were followed shortly after the dose increase by violent ideation and anxiety in a man in his 30s (probable causality). (11) Atorvastatin 20 mg and then simvastatin 20 mg were followed in 2 weeks by aggression/irritability in a man in his 50s (definite causality). (12) Lovastatin, rosuvastatin, atorvastatin, and simvastatin at varying doses were followed as quickly as 1 day by aggression, irritability, and violent ideation in a man in his 40s (definite causality). Most had risk factors for statin ADRs, and co-occurrence of other, recognized statin ADRs. ADRs had implications for marriages, careers, and safety of self and others. These observations support the potential for adverse mood and behavioral change in some individuals with statin use, extend the limited literature on such effects, and provide impetus for further investigation into these presumptive ADRs. Potential mechanisms are reviewed, including hypothesized mechanisms related to oxidative stress and bioenergetics.

The Effects of Melatonin on Elevated Liver Enzymes during Statin Treatment.
            (Chojnacki et al., 2017)  Download
Taking statins can cause increase in the level of aspartate and alanine aminotransferase. The aim of this study was to assess the usefulness of melatonin in counteracting the adverse hepatic events from statins. Methods. The research program included 60 patients (aged 47-65 years, 41 women and 19 men) with hyperlipidemia taking atorvastatin or rosuvastatin at a dose of 20-40 mg daily. The patients were randomly allocated in two groups. Group I (n = 30) was recommended to take the same statin at a standardized daily dose of 20 mg together with melatonin at a dose of 2 × 5 mg. Group II (n = 30) patients took statin with placebo at the same dose and time of the day. Follow-up laboratory tests (AST, ALT, GGT, and ALP) were evaluated after 2, 4, and 6 months of treatment. Results. In Group I the levels of all enzymes decreased after 6 months, particularly AST, 97,2 ± 19,1 U/L versus 52,8 ± 12,3 U/L (p < 0,001); ALT, 87,4 ± 15,6 U/L versus 49,8 ± 14,5 U/L (p < 0,001); and GGT, 84,1 ± 14,8 U/L versus 59,6 U/L (p < 0,001). Conclusion. Melatonin exerts a hepatoprotective effect in patients taking statins.

Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.
            (Cicero et al., 2017)  Download
A large number of nutraceuticals have been tested in available trials, demonstrating their lipid-lowering effects. It is, however, important to once again emphasize that nutraceuticals cannot replace lipid-lowering therapy but might essentially help to optimize it (reducing CV residual risk).

Statin wars: have we been misled about the evidence? A narrative review.
            (Demasi, 2018)  Download
Statins are the most widely prescribed, cholesterol-lowering drugs in the world. Despite the expiration of their patents, revenue for statins is expected to rise, with total sales on track to reach an estimated US$1 trillion by 2020. A bitter dispute has erupted among doctors over suggestions that statins should be prescribed to millions of healthy people at low risk of heart disease. There are concerns that the benefits have been exaggerated and the risks have been underplayed. Also, the raw data on the efficacy and safety of statins are being kept secret and have not been subjected to scrutiny by other scientists. This lack of transparency has led to an erosion of public confidence. Doctors and patients are being misled about the true benefits and harms of statins, and it is now a matter of urgency that the raw data from the clinical trials are released.

Does Adjuvant Treatment With Ginkgo Biloba to Statins Have Additional Benefits in Patients With Dyslipidemia
            (Fan et al., 2018)  Download
Objective: Ginkgo biloba are widely used alone or in combination with other lipid-lowering agents in the treatment of dyslipidemia in China. We conducted this meta-analysis to investigate whether adjuvant treatment with ginkgo biloba leaves to statins has incremental benefits in patients with dyslipidemia. Methods: Potential studies were searched from PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang database up to October 2017. Only randomized controlled trials (RCTs) comparing the efficacy and safety of ginkgo biloba leaves plus statins versus statins alone in patients with dyslipidemia were included. Results: Eight RCTs involving 664 patients were included. Compared with statins therapy alone, combination of statins and ginkgo biloba leaves therapy achieved greater reductions in triglycerides [mean difference (MD) -0.32 mmol/L; 95% confidence interval (CI) -0.43 to -0.20], total cholesterol (MD -0.61 mmol/L; 95% CI -0.90 to -0.33), or low-density lipoprotein cholesterol (LDL-C) (MD -0.32 mmol/L; 95% CI -0.48 to -0.16), and a greater increment in high-density lipoprotein cholesterol (MD 0.26 mmol/L; 95% CI 0.15 to 0.37). Subgroup analyses showed that ginkgo biloba leaves plus simvastatin appeared to achieve a greater reduction in serum levels of triglycerides, total cholesterol, and LDL-C than in combination with atorvastatin therapy. Conclusion: This meta-analysis suggests that adjuvant treatment with ginkgo biloba leaves appears to improve blood lipid parameters than statins therapy alone. More well-designed RCTs are needed to investigate the benefits of the combination of statins and ginkgo biloba leaves.

Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial.
            (Golomb et al., 2012)  Download
A total of 1016 subjects (692 men 20 years or older and 324 nonprocreative women, with screening low-density lipoprotein cholesterol levels 115–190 mg/dL [to convert to millimoles per liter, multiply by 0.0259] and no cardiovascular disease or diabetes) were randomized equally to 20-mg simvastatin (lipophilic statin), 40-mg pravastatin (hydrophilic statin), or microcrystalline-cellulose placebo, to be taken at bedtime in identical blinding capsules for 6 months. To our knowledge, this is the first randomized evidence affirming unfavorable statin effects on energy and exertional fatigue. Effects were seen in a generally healthy sample given modest statin doses, and both simvastatin and pravastatin contributed to the significant adverse effect of statins on energy and fatigue with exertion. Particularly for women, these unfavorable effects were not uncommon.

Misinterpretation of trial evidence on statin adverse effects may harm patients.
            (Golomb, 2015)  Download
Finegold et al.,1 in their article, interpret the absence of average difference in rates of published adverse effects (AEs) for statins vs placebo in industry-funded randomized controlled trials (RCTs) as meaning that statins have approximately no side effects. This shows a lack of understanding of critical issues of effect modification, selection bias, and selective publication that have repeatedly contributed to underappreciation of drug AEs. The resulting flawed conclusion is likely to cause serious harm to patients.


 

Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial.
            (Golomb et al., 2015)  Download
BACKGROUND:  Low/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized. METHODS:  1016 adults (692 men, 324 postmenopausal women) underwent double-blind sex-stratified randomization to placebo, simvastatin 20mg, or pravastatin 40mg (6 months). The Overt-Aggression-Scale-Modified-Aggression-Subscale (OASMa) assessed behavioral aggression. A significant sex-statin interaction was deemed to dictate sex-stratified analysis. Exploratory analyses assessed the influence of baseline-aggression, testosterone-change (men), sleep and age. RESULTS:  The sex-statin interaction was significant (P=0.008). In men, statins tended to decrease aggression, significantly so on pravastatin: difference=-1.0(SE=0.49)P=0.038. Three marked outliers (OASMa-change ≥40 points) offset otherwise strong significance-vs-placebo: statins:-1.3(SE=0.38)P=0.0007; simvastatin:-1.4(SE=0.43)P=0.0011; pravastatin:-1.2(SE=0.45)P=0.0083. Age≤40 predicted greater aggression-decline on statins: difference=-1.4(SE=0.64)P=0.026. Aggression-protection was emphasized in those with low baseline aggression: age<40-and-low-baseline-aggression (N=40) statin-difference-vs-placebo=-2.4(SE=0.71)P=0.0016. Statins (especially simvastatin) lowered testosterone, and increased sleep problems. Testosterone-drop on statins predicted aggression-decline: β=0.64(SE=0.30)P=0.034, particularly on simvastatin: β=1.29(SE=0.49)P=0.009. Sleep-worsening on statins significantly predicted aggression-increase: β=2.2(SE=0.55)P<0.001, particularly on simvastatin (potentially explaining two of the outliers): β=3.3(SE=0.83)P<0.001. Among (postmenopausal) women, a borderline aggression-increase on statins became significant with exclusion of one younger, surgically-menopausal woman (N=310) β=0.70(SE=0.34)P=0.039. The increase was significant, without exclusions, for women of more typical postmenopausal age (≥45): (N=304) β=0.68(SE=0.34)P=0.048 - retaining significance with modified age-cutoffs (≥50 or ≥55). Significance was observed separately for simvastatin. The aggression-increase in women on statins was stronger in those with low baseline aggression (N=175) β=0.84(SE=0.30)P=0.006. No statin effect on whole blood serotonin was observed; and serotonin-change did not predict aggression-change. CONCLUSION:  Statin effects on aggression differed by sex and age: Statins generally decreased aggression in men; and generally increased aggression in women. Both findings were selectively prominent in participants with low baseline aggression - bearing lower change-variance, rendering an effect more readily evident. TRIAL REGISTRATION:  Clinicaltrials.gov NCT00330980.


 

Amyotrophic Lateral Sclerosis Associated with Statin Use: A Disproportionality Analysis of the FDA's Adverse Event Reporting System.
            (Golomb et al., 2018)  Download
INTRODUCTION:  Apparent elevations in reporting of amyotrophic lateral sclerosis (ALS)-like conditions associated with statin use have been previously described from data obtained via US and European databases. OBJECTIVE:  The aim of this study was to examine US FDA Adverse Event Reporting System (FAERS) data to compare reporting odds ratios (RORs) of ALS and ALS-like conditions between statins and other drugs, for each statin agent. METHODS:  We assessed for disproportional rates of reported ALS and ALS-related conditions for each statin agent separately by using the ROR formula. FAERS data were analyzed through September 2015. RESULTS:  RORs for ALS were elevated for all statins, with elevations possibly stronger for lipophilic statins. RORs ranged from 9.09 (6.57-12.6) and 16.2 (9.56-27.5) for rosuvastatin and pravastatin (hydrophilic) to 17.0 (14.1-20.4), 23.0 (18.3-29.1), and 107 (68.5-167) for atorvastatin, simvastatin, and lovastatin (lipophilic), respectively. For simvastatin, an ROR of 57.1 (39.5-82.7) was separately present for motor neuron disease. CONCLUSION:  These findings extend previous evidence showing that significantly elevated ALS reporting extends to individual statin agents, and add to concerns about potential elevated occurrence of ALS-like conditions in association with statin usage.

Statins and cognitive impairment.
            (Gracias et al., 2014)  Download
Evidence indicates statins do not prevent, treat, or cause cognitive impairment or dementia. The US Food and Drug Administration warning is based on case reports that might reflect idiosyncratic, short- term, “fuzzy” thinking. Decisions to prescribe statins should not be altered.

Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate.
            (Hobbs et al., 2016)  Download
The most prescribed medications in the world are statins, lipid modifiers that have been available for over 25 years and amongst the most investigated of all drug classes. With over a million patient years of trial data and publications in the most prestigious medical journals, it is remarkable that quite so much debate remains as to their place in healthcare. They have had a bittersweet passage, with vocal concerns over their possible risks, from suicide to cancer, and allegations that they do not work in women or the elderly, to statements that the whole published dataset, on over 200,000 patients consenting to enter trials, was fatally compromised by being industry-funded by and large. On the other side, there have been billions of dollars spent on generating their evidence base followed by promotion which has returned that investment many times over in profits, and a powerful scientific lobby that argue they are wonder drugs and that continued nihilism on their value risks patient lives. So who is right

Does Googling lead to statin intolerance
            (Khan et al., 2018)  Download
BACKGROUND:  The nocebo effect, where patients with expectations of adverse effects are more likely to experience them, may contribute to the high rate of statin intolerance found in observational studies. Information that patients read on the internet may be a precipitant of this effect. The objective of the study was to establish whether the number of websites about statin side effects found using Google is associated with the prevalence of statin intolerance. METHODS:  The prevalence of statin intolerance in 13 countries across 5 continents was established in a recent study via a web-based survey of primary care physicians and specialists. Using the Google search engine for each country, the number of websites about statin side effects was determined, and standardized to the number of websites about statins overall. Searches were restricted to pages in the native language, and were conducted after connecting to each country using a virtual private network (VPN). RESULTS:  English-speaking countries (Australia, Canada, UK, USA) had the highest prevalence of statin intolerance and also had the largest standardized number of websites about statin side effects. The sample Pearson correlation coefficient between these two variables was 0.868. CONCLUSIONS:  Countries where patients using Google are more likely to find websites about statin side effects have greater levels of statin intolerance. The nocebo effect driven by online information may be contributing to statin intolerance.

Statins increase the risk of herpes zoster: A propensity score-matched analysis.
            (Kim et al., 2018)  Download
OBJECTIVES:  Statins, which are lipid-lowering agents, have anti-inflammatory and immunomodulatory properties that may affect the occurrence of various infectious diseases. We assessed whether statins increase the risk of herpes zoster (HZ) with propensity score-matching. METHODS:  The study was based on the National Health Insurance database and its subset database of the "medical check-up" population of South Korea. These cohorts consist of about one million and 570,000 people, respectively, representative of the entire population of South Korea. We identified 103,930 statin users and 430,685 non-statin users. After propensity score-matching, 25,726 statin users and the same number of non-statin users were finally analyzed. The development of HZ was monitored in these matched pairs over the 11 years from 2003 to 2013. RESULTS:  Statin users had a significantly higher risk of HZ than non-statin users: hazard ratio (HR) 1.25 (95% CI, 1.15 to 1.37) (p < .0001). The risk of HZ associated with statins was especially high in the elderly: HR 1.39 (95% CI, 1.12 to 1.73) in the over 70-year-olds (p = 0.003) and HR 1.18 (95% CI, 1.00 to 1.39) in the 60-to-69-year-olds (p = 0.056). Furthermore, there was a significant p for trend in terms of cumulative dose effect between the risk of HZ and the duration of statin use (p < .0001). CONCLUSIONS:  These epidemiologic findings provide strong evidence for an association between HZ and statin use, and suggest that unnecessary statins should be avoided.

Physicians' Experiences as Patients with Statin Side Effects: A Case Series.
            (Koslik et al., 2017)  Download
Physicians are among those prescribed statins and therefore, subject to potential statin adverse effects (AEs). There is little information on the impact of statin AEs on physicians affected by them. We sought to assess the character and impact of statin AEs occurring in physicians and retired physicians, and to ascertain whether/how personal experience of AEs moderated physicians' attitude toward statin use. Seven active or retired physicians from the United States communicated with the Statin Effects Study group regarding their personal experience of statin AEs. AE characteristics, experience with (their own) physicians, and impact of AE was ascertained. We inquired whether or how their experience altered their own attitude toward statins or statin AEs. Patient A: Atorvastatin 40 then 80 mg was followed by cognitive problems, neuropathy, and glucose intolerance in a Radiologist in his 50s (Naranjo criteria: probable causality). Patient B: Atorvastatin 10 mg was followed in 2 months by muscle weakness and myalgia in an Internist in his 40s (probable causality). Patient C: Atorvastatin, ezetimibe/simvastatin, rosuvastatin at varying doses was followed shortly after by irritability, myalgia, and fatigue in a Cardiac Surgeon in his 40s (probable causality). Patient D: Simvastatin 20 then 40 mg was followed in 4 years by mitochondriopathy, myopathy, neuropathy, and exercise intolerance in an Emergency Medicine physician in his 50s (definite causality). Patient E: Simvastatin 20 mg and niacin 1000 mg was followed in one month by muscle weakness and myalgia in a Physical Medicine and Rehabilitation physician in his 50s (probable causality). Patient F: Lovastatin 20 mg then simvastatin 20 mg, atorvastatin 20 mg, rosuvastatin 5 mg, niacin 20 mg and ezetimbe 10 mg was followed by muscle weakness and myalgia in an Obstetrician/Gynecologist in his 70s (definite causality). Patient G: Ezetimibe/simvastatin and atorvastatin (dose unavailable) was followed shortly after by cognitive problems in a Radiologist in her 80s (probable causality). Thus AEs affected multiple quality-of-life relevant domains, often in combination, encompassing muscle (N = 5), fatigue (N = 2), peripheral neuropathy (N = 2), cognitive (N = 2), dysglycemia (N = 1) and behavioral manifestations (N = 1). In five, the AEs affected the physician professionally. Five physicians experienced dismissive attitudes in some of their own healthcare encounters. One noted that his experience helped not only his own attention to statin AEs, but that of other physicians in his community. Several stated that their experience altered their understanding of and/or attitude toward statin AEs, and/or their view of settings in which statin use is warranted. Statin AEs can have profound impact in high functioning professionals with implications to the individual, their professional life, and those whom they serve professionally.

Prevalence and Management of Symptoms Associated With Statin Therapy in Community Practice: Insights From the PALM (Patient and Provider Assessment of Lipid Management) Registry.
            (Navar et al., 2018)  Download
When compared against placebo in randomized trials, statins are extremely well tolerated, causing muscle-related side effects in 1% or fewer of treated patients.1 Yet in routine practice, patients often report having symptoms which are misattributed to their statin.2–4 Using data from the PALM Registry, we examined patient-reported rates of statin intolerance, characteristics of patients with perceived side effects, and response to perceived statin intolerance in contemporary practice.

Reporting bias in the literature on the associations of health-related behaviors and statins with cardiovascular disease and all-cause mortality.
            (Rezende et al., 2018)  Download
Reporting bias in the literature occurs when there is selective revealing or suppression of results, influenced by the direction of findings. We assessed the risk of reporting bias in the epidemiological literature on health-related behavior (tobacco, alcohol, diet, physical activity, and sedentary behavior) and cardiovascular disease mortality and all-cause mortality and provided a comparative assessment of reporting bias between health-related behavior and statin (in primary prevention) meta-analyses. We searched Medline, Embase, Cochrane Methodology Register Database, and Web of Science for systematic reviews synthesizing the associations of health-related behavior and statins with cardiovascular disease mortality and all-cause mortality published between 2010 and 2016. Risk of bias in systematic reviews was assessed using the ROBIS tool. Reporting bias in the literature was evaluated via small-study effect and excess significance tests. We included 49 systematic reviews in our study. The majority of these reviews exhibited a high overall risk of bias, with a higher extent in health-related behavior reviews, relative to statins. We reperformed 111 meta-analyses conducted across these reviews, of which 65% had statistically significant results (P < 0.05). Around 22% of health-related behavior meta-analyses showed small-study effect, as compared to none of statin meta-analyses. Physical activity and the smoking research areas had more than 40% of meta-analyses with small-study effect. We found evidence of excess significance in 26% of health-related behavior meta-analyses, as compared to none of statin meta-analyses. Half of the meta-analyses from physical activity, 26% from diet, 18% from sedentary behavior, 14% for smoking, and 12% from alcohol showed evidence of excess significance bias. These biases may be distorting the body of evidence available by providing inaccurate estimates of preventive effects on cardiovascular and all-cause mortality.

Curcumin: An effective adjunct in patients with statin-associated muscle symptoms
            (Sahebkar et al., 2017)  Download
In spite of the unequivocal efficacy of statins in reducing primary and secondary cardiovascular events, the use of these drugs in a considerable number of patients is limited because of statin intolerance, mainly statin-associated muscle symptoms (SAMS). SAMS encompass a broad spectrum of clinical presentations, including mild muscular aching and other types of myalgias, myopathy with the significant elevation of creatine kinase, and the rare but life-threatening rhabdomyolysis. Among several pathophysiologic mechanisms of SAMS, mitochondrial dysfunction is thought to be one of the main one. Curcumin is the polyphenolic ingredient of Curcuma longa L., which has various pharmacological properties against a vast range of diseases. Curcumin has several mechanisms of actions relevant to the treatment of SAMS. These effects include the capacity to prevent and reduce delayed onset muscle soreness by blocking the nuclear factor inflammatory pathway, attenuation of muscular atrophy, enhancement of muscle fibre regeneration following injury, and analgesic and antioxidant effects. Curcumin can also increase the levels of cyclic adenosine monophosphate, which leads to an increase in the number of mitochondrial DNA duplicates in skeletal muscle cells. Finally, owing to its essential lipid-modifying properties, curcumin might serve as an adjunct to statin therapy in patients with SAMS, allowing for effective lowering of low-density lipoprotein cholesterol and possibly for statin dose reduction. Owing to the paucity of effective treatments, and the safety of curcumin in clinical practice, proof-of-concept trials are recommended to assess the potential benefit of this phytochemical in the treatment of SAMS.

Statin medications and the risk of gynecomastia.
            (Skeldon et al., 2018)  Download
OBJECTIVE:  Case reports have suggested an increased risk of gynecomastia with HMG-CoA reductase inhibitors (ie, statins). A recent meta-analysis also found that statins decrease circulating testosterone levels in men. We investigated whether statin use was associated with an increased risk of gynecomastia. DESIGN:  Case-control study. PATIENTS:  A cohort of patients from a random sample of 9 053 240 US subjects from the PharMetrics Plus MEASUREMENTS:  New cases of gynecomastia requiring at least two ICD-9 codes were identified from the cohort and matched to 10 controls by follow-up time and age using density-based sampling. Rate ratios (RRs) for users of statins were computed using conditional logistic regression adjusting for alcoholic cirrhosis, hyperthyroidism, testicular cancer, Klinefelter syndrome, obesity, hypogonadism, hyperprolactinemia and use of spironolactone, ketoconazole, H RESULTS:  Our cohort included 6147 cases of gynecomastia and 61 470 corresponding matched controls. The adjusted RR for current, recent and past statin use with respect to gynecomastia was 1.19 (1.04-1.36), 1.38 (1.15-1.65) and 1.20 (1.03-1.40), respectively. CONCLUSIONS:  Statin use is associated with an increased risk of developing gynecomastia. Clinicians should be cognizant of this effect and educate patients accordingly.

Statins for primary prevention in people with a 10% 10-year cardiovascular risk: too much medicine too soon
            (Yerrakalva and Griffin, 2017)  Download
Perhaps we should worry less about side effects if statins allow us to live longer, as side effects are rarely fatal. However, if statins do not extend life in those at lower CVD risk then the balance of risks and benefits becomes more important.

 


References

Caro-Maldonado, A, et al. (2018), ‘Low-dose statin treatment increases prostate cancer aggressiveness.’, Oncotarget, 9 (2), 1494-504. PubMed: 29416709
Cham, S, HJ Koslik, and BA Golomb (2016), ‘Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series.’, Drug Saf Case Rep, 3 (1), 1. PubMed: 27747681
Chojnacki, C, A Błońska, and J Chojnacki (2017), ‘The Effects of Melatonin on Elevated Liver Enzymes during Statin Treatment.’, Biomed Res Int, 2017 3204504. PubMed: 28630863
Cicero, AFG, et al. (2017), ‘Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.’, Arch Med Sci, 13 (5), 965-1005. PubMed: 28883839
Demasi, M (2018), ‘Statin wars: have we been misled about the evidence? A narrative review.’, Br J Sports Med, 52 (14), 905-9. PubMed: 29353811
Fan, Y, et al. (2018), ‘Does Adjuvant Treatment With Ginkgo Biloba to Statins Have Additional Benefits in Patients With Dyslipidemia’, Front Pharmacol, 9 659. PubMed: 29988404
Golomb, BA, et al. (2012), ‘Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial.’, Arch Intern Med, 172 (15), 1180-82. PubMed: 22688574
Golomb, BA, et al. (2015), ‘Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial.’, PLoS One, 10 (7), e0124451. PubMed: 26132393
Golomb, BA (2015), ‘Misinterpretation of trial evidence on statin adverse effects may harm patients.’, Eur J Prev Cardiol, 22 (4), 492-93. PubMed: 24770566
Golomb, BA, et al. (2018), ‘Amyotrophic Lateral Sclerosis Associated with Statin Use: A Disproportionality Analysis of the FDA’s Adverse Event Reporting System.’, Drug Saf, 41 (4), 403-13. PubMed: 29427042
Gracias, G, S Garrison, and GM Allan (2014), ‘Statins and cognitive impairment.’, Can Fam Physician, 60 (8), e391. PubMed: 25122828
Hobbs, FD, et al. (2016), ‘Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate.’, BMC Med, 14 4. PubMed: 26769594
Khan, S, A Holbrook, and BR Shah (2018), ‘Does Googling lead to statin intolerance’, Int J Cardiol, 262 25-27. PubMed: 29706390
Kim, MC, et al. (2018), ‘Statins increase the risk of herpes zoster: A propensity score-matched analysis.’, PLoS One, 13 (6), e0198263. PubMed: 29902266
Koslik, HJ, AH Meskimen, and BA Golomb (2017), ‘Physicians’ Experiences as Patients with Statin Side Effects: A Case Series.’, Drug Saf Case Rep, 4 (1), 3. PubMed: 28217821
Navar, AM, et al. (2018), ‘Prevalence and Management of Symptoms Associated With Statin Therapy in Community Practice: Insights From the PALM (Patient and Provider Assessment of Lipid Management) Registry.’, Circ Cardiovasc Qual Outcomes, 11 (3), e004249. PubMed: 29545393
Rezende, LFM, et al. (2018), ‘Reporting bias in the literature on the associations of health-related behaviors and statins with cardiovascular disease and all-cause mortality.’, PLoS Biol, 16 (6), e2005761. PubMed: 29912869
Sahebkar, A, et al. (2017), ‘Curcumin: An effective adjunct in patients with statin-associated muscle symptoms’, J Cachexia Sarcopenia Muscle, 8 (1), 19-24. PubMed: 27897416
Skeldon, SC, et al. (2018), ‘Statin medications and the risk of gynecomastia.’, Clin Endocrinol (Oxf), 89 (4), 470-73. PubMed: 29923212
Yerrakalva, D and SJ Griffin (2017), ‘Statins for primary prevention in people with a 10% 10-year cardiovascular risk: too much medicine too soon’, Br J Gen Pract, 67 (654), 40-41. PubMed: 28034950