Statin use alone or with metformin may increase survival in high-risk prostate cancer patients

In continuation of my update on metformin

Among high-risk prostate cancer patients - those with high PSA and Gleason scores of 8 or more - many will develop a difficult-to-treat disease. Preliminary research suggests that two commonly prescribed medications, cholesterol-lowering statins and the diabetes therapy metformin may have anticancer effects. However, it is unclear which of these two medications - commonly prescribed together -- contributes the most and whether they can impact high-risk prostate cancer. New research shows that statins, alone or with metformin, increase survival in men with high-risk prostate cancer.

"Both metformin and statins have been associated with longer life in prostate cancer patients, yet because they are commonly prescribed together, no study we know of has looked at these two medications separately," says senior author Grace Lu-Yao, PhD, associate director of Population Science at the Sidney Kimmel Cancer Center--Jefferson Health, one of only eight NCI-designated cancer centers nationwide with a prostate cancer program of excellence.

The study, published in Cancer Medicine on Feb 8th, looked at a number of statin therapies, and metformin, an anti-diabetic medication, in high-risk prostate cancer populations.

Using data from the Surveillance, Epidemiology and End Results (SEER-18) database linked with Medicare files, Dr. Lu-Yao and colleagues looked at patients diagnosed with cancer from 2007 through to 2011. Based on 12,700 patients, the researchers observed that statins alone or in combination with metformin was significantly associated with reduced mortality from all causes.

Dr. Lu-Yao and colleagues saw the highest median survival of 3.9 months in men who took both metformin and statins, 3.6 with statins alone and 3.1 years with metformin alone. The median survival for those who did not use either drug was also 3.1 years.

With respect to prostate mortality, metformin plus statin was associated with a 36% reduction in risk of death followed by statins alone. Those taking metformin alone were relatively rare, and there was no significant association with all-cause mortality."

Interestingly, the study revealed that men who took atorvastatin, pravastatin, or rosuvastatin - but not lovastatin - demonstrated a reduction in mortality compared with non-users, which is consistent with the findings from a recent population-based cohort study using Taiwan National Health Insurance Research Data. The Taiwanese research showed that these three statins are more effective at lowering triglycerides and low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol than other statins in patients with hypercholesterolemia.

Of the three statins studied, men on atorvastatin did have a longer median time to progression on androgen deprivation therapy compared to those who weren't treated with statins. "Although the exact mechanisms remain unknown, it is worth noting that atorvastatin exhibits a potent lipid-lowering effect per dose of any statin, and has the greatest bioavailability and one of the longest half-lives," says to Dr. Lu-Yao.

The data presented in the current study provide crucial insight for the design of future randomized clinical trials of statin for high-risk patients with prostate cancer. Based on the existing evidence, a well-designed clinical trial is warranted to investigate the roles of statins and combination statins/metformin to reduce the mortality cancer of the prostate.

"Our study showed that the effects were more pronounced in patients taking statins after the diagnosis of prostate cancer, 54% reduction in PCA mortality among patients with high-risk prostate cancer," says Lu-Yao. "This magnitude of reduction is comparable to the results of men treated with androgen signaling inhibitors." Statins are relatively inexpensive with good safety records. Further studies to understand the mechanisms of the observed association and its potential clinical utility are warranted.

https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.2862

Statins May Protect Heart From Chemo for Early Breast Cancer

In continuation of my update on statins 

For women with early breast cancer treated with anthracyclines, statin exposure is associated with a lower risk for hospital presentation for heart failure, according to a study published online Jan. 6 in the Journal of the American Heart Association.

Husam Abdel-Qadir, M.D., Ph.D., from the Women's College Hospital in Toronto, and colleagues conducted a retrospective cohort study involving women aged 66 years and older without prior heart failure who received anthracyclines or trastuzumab for newly diagnosed early breast cancer. Using propensity scores, statin-exposed and unexposed women were matched in a 1:1 ratio. Data were included for 666 statin-discordant pairs of anthracycline-treated women and 390 pairs of trastuzumab-treated women.

The researchers found that the five-year cumulative incidence of heart failure hospital presentations after anthracyclines was 1.2 percent (95 percent confidence interval [CI], 0.5 to 2.6 percent) and 2.9 percent (95 percent CI, 1.7 to 4.6 percent) in statin-exposed and unexposed women, respectively (P = 0.01). In the anthracycline cohort, the cause-specific hazard ratio associated with statins was 0.45 (95 percent CI, 0.24 to 0.85; P = 0.01). The five-year cumulative incidence of heart failure hospital presentations after trastuzumab was 2.7 percent (95 percent CI, 1.2 to 5.2 percent) and 3.7 percent (95 percent CI, 2.0 to 6.2 percent) in statin-exposed and unexposed women, respectively (P = 0.09), with a cause-specific hazard ratio associated with statins of 0.46 (95 percent CI, 0.20 to 1.07; P = 0.07).

"This study does not conclusively prove statins are protective," Abdel-Qadir said in a statement. "However, this study builds on the body of evidence suggesting that they may have benefits."

AHA: Adding Omega-3 Fatty Acids Does Not Cut High CV Risk

In continuation of my update on omega-3 fatty acids

A carboxylic acid formulation of eicosapentaenoic acid and docosahexaenoic acid (omega-3 CA) does not improve outcomes among statin-treated patients at high cardiovascular risk, according to a study published online Nov. 15 in the Journal of the American Medical Association to coincide with the American Heart Association Scientific Sessions 2020, held virtually from Nov. 13 to 17.

Stephen J. Nicholls, M.B.B.S., Ph.D., from Monash University in Melbourne, Australia, and colleagues conducted a double-blind trial comparing omega-3 CA to corn oil in 13,078 statin-treated patients with high cardiovascular risk, hypertriglyceridemia, and low high-density lipoprotein cholesterol from 675 academic and community hospitals in 22 countries. Participants were randomly assigned in a 1:1 ratio to either 4 g/day omega-3 CA or corn oil (6,539 to each) in addition to usual background therapies, including statins.

The trial was halted prematurely based on an interim analysis indicating low probability of clinical benefit of omega-3 CA, when 1,384 patients had experienced a primary end-point event. The researchers found that the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization) occurred in 12.0 and 12.2 percent of those treated with omega-3 CA and corn oil, respectively (hazard ratio, 0.99; 95 percent confidence interval, 0.90 to 1.09; P = 0.84).

"These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including AstraZeneca, which funded the study.

AHA: Adding Omega-3 Fatty Acids Does Not Cut High CV Risk  

Aspirin May No Longer Have Effect in Primary CVD Prevention

Aspirin may not be effective for primary prevention of cardiovascular disease and cancer mortality, according to research published online Nov. 21 in Family Practice.

Frank Moriarty, Ph.D., from the Royal College of Surgeons in Dublin, and Mark H. Ebell, M.D., from the University of Georgia in Athens, compared the benefits and harms of aspirin for primary prevention before (1978 to 2002) and after (2005 onward) widespread use of statins and screening for colorectal cancer.

The researchers found that for older versus newer studies, the relative risks for vascular outcomes were 0.89 (95 percent confidence interval [CI], 0.83 to 0.95) versus 0.93 (0.86 to 0.99) for major adverse cardiovascular events; 1.73 (1.11 to 2.72) versus 1.06 (0.66 to 1.70) for fatal hemorrhagic stroke; 0.86 (0.74 to 1.00) versus 0.86 (0.75 to 0.98) for any ischemic stroke; 0.84 (0.77 to 0.92) versus 0.88 (0.77 to 1.00) for any myocardial infarction; and 0.79 (0.71 to 0.88) versus 0.94 (0.83 to 1.08) for nonfatal myocardial infarction. In newer studies, there was no significant decrease observed for cancer mortality (relative risk, 1.11; 95 percent CI, 0.92 to 1.34). Significant increases were seen in major hemorrhage (older studies, relative risk, 1.48 [95 percent CI, 1.25 to 1.76] versus newer studies, relative risk, 1.37 [95 percent CI, 1.24 to 1.53]).

"In a modern era characterized by widespread statin use and population-wide cancer screening, aspirin no longer reduces the absolute risk of cancer death or myocardial infarction when given as primary prevention," the authors write.

https://academic.oup.com/fampra/advance-article/doi/10.1093/fampra/cmz080/5637484

Statin Use Associated With Higher Incidence of Diabetes

In continuation of my update on statins

There may be a dose-dependent relationship between statin therapy and new-onset diabetes across the duration of statin use, according to a study recently published in Diabetes Metabolism Research and Reviews.

Victoria A. Zigmont, Ph.D., from The Ohio State University in Columbus, and colleagues used medical records to retrospectively assess the risk of dysglycemia and new-onset diabetes among 7,064 individuals with indications for statin use. At baseline, participants were candidates for statins based on heart disease risk but had not started taking the drugs; 755 patients were eventually prescribed statins during the study period (2011 to 2014).

The researchers found that a higher prevalence of elevated hemoglobin A1c occurred among incident statin users without diabetes. Statin users also had a higher risk of developing new-onset diabetes (adjusted hazard ratio, 2.20). The greatest risk of developing new-onset diabetes was seen among those taking statins for two years or longer (adjusted hazard ratio, 3.33), with no differences seen by statin class or intensity of dose.

"As lifestyle programs like the Diabetes Prevention Program are promoted in primary care settings, we hope physicians will integrate and insurers support healthy lifestyle strategies as part of the optimal management of individuals at risk for both new-onset diabetes and cardiovascular disease," the authors write.

https://medlineplus.gov/statins.html

Statins Help the Heart, No Matter What Your Age

Cholesterol-lowering statins are already known to help cut heart risks for seniors and the middle-aged. Now, research confirms the meds can also help people aged 75 and older.

"Statin therapy has been shown to prevent cardiovascular disease in a wide range of people, but there has been uncertainty about its efficacy and safety among older people," said lead investigator Anthony Keech. He's a professor of medicine, cardiology and epidemiology at the University of Sydney in Australia.

He and colleagues at the University of Oxford in England analyzed the findings of 28 large clinical trials of statins. The trials involved nearly 187,000 people in six age groups: younger than 55; 55 to 60; 60 to 65; 65 to 70; 70 to 75; and older than 75.

"Our study summarized all the available evidence from major trials to help clarify this issue. We found that there were significant reductions in major vascular events in each of the six age groups considered, including patients [who were] aged over 75 at the start of treatment," Keech said in an Oxford news release.

Major vascular events included heart attack, stroke and procedures to clear clogged arteries.

"Statin therapy appears to be just as effective in people aged over 75 years as it is in younger people," study co-investigator Jordan Fulcher said in the news release. Fulcher is a cardiovascular research fellow at the University of Sydney.

"We have definitive evidence that statins benefit older people who have suffered a heart attack or stroke. Fewer healthy older people were represented in these trials, so more information in this group of people would help confirm the same benefits that we see in our overall trials population," he said.

Fulcher noted that a new randomized trial in Australia is exploring whether statins prolong disability-free survival in a healthy population.

The risk of heart attacks and strokes rises sharply with age, yet statins are not used as widely in older people as they should be, study co-investigator Colin Baigent said in the news release. He's director of Oxford's Medical Research Council Population Health Research Unit.

"Since the risk of heart attack and stroke increases with age, the potential benefits are likely to be even greater for older people," he said.

"Therefore, there is a need to ensure that patients at risk of cardiovascular disease due to their age are offered statin therapy where there is good reason to believe that it will be beneficial," Baigent said.

Anyone with concerns about whether statin therapy is right for them should discuss it with their health care provider, he added.

Two anticlotting medicines better at reducing bleeding risk than triple therapy

A major international study has found that the combination of two drugs - rivaroxaban and aspirin -- is superior to aspirin alone in preventing further heart complications in people with vascular disease.

The study of 27,400 people with stable coronary or peripheral artery disease from 33 countries worldwide will be published today, and results show that the combination of 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily was significantly better than only aspirin or only rivaroxaban in preventing heart attacks, strokes, and death. Rivaroxaban, often known by the brand name Xarelto, is an anticoagulant, aspirin is an antiplatelet drug, and both are blood thinners.

  rivaroxaban   Aspirin

The results will be presented today at the Congress of the European Society of Cardiology (ESC) in Barcelona, Spain, and the overall results will be published in the New England Journal of Medicine.

The study, called COMPASS, is led by the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences (HHS) in Hamilton, Canada. The study is funded by Bayer AG.

The findings are significant because there are about 300 million people around the world living with cardiovascular disease, and every year as many as five to 10 per cent have a stroke or heart attack. Although aspirin reduces the risk of major cardiovascular events by 19 per cent, a more effective antithrombotic strategy could have major benefits for the large population of patients with stable cardiovascular disease.

The clear result of this clinical study - that the combination reduced strokes, heart attacks and cardiovascular death by practically 25 per cent compared to either drug alone in both patients with stable coronary or peripheral artery disease - caused the clinical trial to be stopped early, after 23 months, in February 2017.

The researchers report that the drug combination does increase the chance of a major bleeding. These bleeds were mainly gastroenterological, and not in critical organs such as the brain nor fatal.

Co-principal investigator Dr. John Eikelboom and his team compared rivaroxaban at doses of 2.5 mg twice-daily combined with 100 mg of aspirin once-daily to rivaroxaban 5 mg twice-daily or to aspirin 100 mg once-daily. In the randomized clinical trial, patients were seen at one and six months, and then every six months.

They found the drug combination reduces cardiovascular outcomes, increases bleeding and improves survival in stable coronary or peripheral artery disease.

"Efforts to improve aspirin have focused primarily on combining aspirin with another antiplatelet drug or replacing aspirin with another antiplatelet drug, but this has had only limited success," said Eikelboom. He is a principal investigator of the PHRI, an associate professor of medicine at McMaster and a hematologist at HHS.

Fenofibrate drug may reduce risk of cardiovascular events in patients with type 2 diabetes

In continuation of my update on Fenofibrate

A new study shows that the drug fenofibrate might reduce the risk of cardiovascular events in patients with type 2 diabetes who have high levels of triglycerides and low levels of "good" cholesterol, despite being treated with statins. The study, funded by the National Heart, Lung, and Blood Institute (NHLBI), appears in the December 28 issue of JAMA Cardiology.

Fenofibrate is primarily used to help reduce elevated levels of triglycerides, or fat, in the blood. But the researchers wanted to know if the drug, when combined with statin treatment, could also reduce the risk of heart disease in people with type 2 diabetes. People with type 2 diabetes are at high risk of cardiovascular-related events, such as heart attacks, stroke, and even death, often because their levels of triglycerides are so high, and their high-density lipoprotein (HDL) cholesterol levels are low.

To answer their question, the researchers followed 4,640 participants from the NHLBI-funded Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study for five years after the conclusion of the trial in 2009. The findings suggest that fenofibrate therapy may be beneficial in the way the researchers hoped: by reducing cardiovascular events in patients with type 2 diabetes who take statins but still have especially high triglycerides levels and low HDL cholesterol levels. However, a randomized study is needed to confirm these findings, according to the authors.

In addition to NHBLI, the study received funding from the NIH's National Institute of Diabetes and Digestive and Kidney Disease, the National Institute of Aging, and the National Eye Institute.

WHO: Jerome Fleg, MD and Yves Rosenberg, MD, M.P.H., Division of Cardiovascular Sciences, NHLBI, NIH, are available to comment on the findings and implications of this research.

New research shows how cholesterol medicine has beneficial effect on immune defence system

In continuation of my update on simvastatin,  

The cholesterol medicine simvastatin, which is one of the most commonly used pharmaceuticals in the world, also has a beneficial effect on the immune defence system with regard to diseases such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis. Danish researchers have now explored why this is so, and their findings may result in improved treatment.

New research from Aarhus University has demonstrated how simvastatin, one of the most commonly used medicines in the world - typically prescribed to reduce cholesterol - also has a direct effect on the immune defence system. This discovery opens up new opportunities for treating chronic inflammatory diseases.

Sought-after explanation of unexpected effect

The immune defence system, which normally protects the body against infections and foreign bodies, sometimes attacks the body's own tissue. This error in the immune system - whose cause is unknown - results in a chronic state of inflammation which breaks down the tissue. This, in turn, triggers diseases such as rheumatoid arthritis, multiple sclerosis and type 1 diabetes.

In the case of multiple sclerosis, the immune defence system destroys the central nervous system, while the inflammation affects the kidneys, eyes and sense of touch in both type 1 and type 2 diabetes, leading to a variety of complications. However, simvastatin has been shown to reduce the level of inflammation in these diseases, even though it sometimes has to be administered in high concentrations to have any effect. The reason why it does so has eluded researchers thus far.

"Simvastatin - and statins in general - are not designed to have this effect. We have now identified a new mechanism that forms the basis for the effect, and this opens up new opportunities for developing a better substance to combat these inflammatory diseases. It's an interesting line to pursue because a great many people can take statins without significant side effects," relates Thomas Vorup-Jensen, Professor at the Department of Biomedicine at Aarhus University.

The reason for the positive effect is that the pharmaceutical acts as a 'plug' in the proteins that retain the immune cells in the inflammation zones. With the plug in place, the immune cells can no longer contribute to the inflammation, which is therefore reduced, leaving the patient feeling better. In the case of diabetes, for example, it can help reduce the risk of patients developing complications.

"We initially observed this mechanism in the laboratory. Of course, we now need to establish whether it works in the same way in vivo, but we think it's likely," says Thomas Vorup-Jensen.

Statins may shield unborn babies from mother's stress, study suggests

In continuation of my update on statins

Scientists have discovered that the widely-prescribed drugs help to counteract the negative impact of stress hormones on fetal growth and heart development in mice.

The therapy could lower the chances of babies being born underweight and reduce their risk of health problems in later life, including heart disease, researchers say.

Further studies are needed to assess the long-term effects of statins in pregnancy, but the drugs are already used occasionally in pregnant women and should be suitable for clinical trials, the team says.

Babies that are exposed to excessive stress hormones in the womb are often born underweight and have a greater risk of heart disease in later life.

Normally, the unborn baby is protected by a key enzyme produced by the placenta that breaks down stress hormones and greatly limits the amount of active hormones that reach the baby's blood supply.

When the expectant mother is stressed, they produce less of this enzyme and the baby is less well protected.

Scientists at the University of Edinburgh studied mice that cannot produce the enzyme as a model of maternal stress.

They found that stress hormones stop the placenta from developing normal blood vessels, which cuts back the blood supply to the growing fetus.

The developing fetus does not grow to full size as a result, and its heart function does not develop normally.

Treating the mother with a type of statin triggers production of a molecule called VEGF, which stimulates the development of blood vessels in the placenta.

By re-establishing the blood supply, the treatment promotes normal development of the heart and helps the baby to grow to a healthy birthweight, the team showed.

Around 2.5 million people in the UK take statins to lower high cholesterol.

The study is published in the journal Proceedings of the National Academy of Sciences and was funded by the Wellcome Trust. The research also received funding from the Raine Medical Research Foundation, University of Western Australia.

Professor Megan Holmes, of the University of Edinburgh's British Heart Foundation Centre for Cardiovascular Sciences, said: "These are very exciting results suggesting that there may finally be a potential therapy for women whose placenta is unable to maintain the normal growth of her baby.

"At present there is no treatment and babies may be born prematurely or small, and will be at greater risk of developing cardiovascular disease, diabetes and even psychiatric disorders later in life. Although more work needs to be done to show statins are safe in human pregnancy, these results show a new way forward for the major unmet need of fetal growth retardation."

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: "Low birthweight has been associated with maternal stress, and babies with low birthweights may be more prone to cardiovascular complications later in life.

"In this study the researchers have discovered that a drug called Pravastatin may counteract the consequences of increased levels of the stress hormone corticosterone within the placentas of mice. How Pravastatin counteracts the stress hormone is not yet understood, therefore more research is needed to see whether the drug will have the same effect in humans."

Ref : http://www.pnas.org/content/early/2016/05/10/1520356113

High fruit intake during adolescence linked with lower breast cancer risk: But increasing alcohol intake in later life associated with higher risk

The first study reports that high fruit consumption during adolescence may be associated with lower breast cancer risk, while the second study finds that increasing alcohol intake in later life is associated with an increased risk of breast cancer.

Fruit and vegetables are thought to protect against breast cancer, but the evidence is conflicting. Most studies have assessed intakes during midlife and later, which may be after the period when breast tissue is most vulnerable to carcinogenic influences.

So a team of US researchers wanted to see whether fruit and vegetable consumption might affect subsequent breast cancer risk. They followed 90,000 nurses for over 20 years who reported their diet in early adulthood, of whom half also recalled their usual diet during adolescence.

They found that high fruit consumption during adolescence (2.9 v 0.5 servings per day) was associated with a roughly 25% lower risk of breast cancer diagnosed in middle age.

In particular, greater consumption of apple, banana and grapes during adolescence, as well as oranges and kale during early adulthood was significantly associated with a reduced breast cancer risk. But there was no link between intake of fruit juice in either adolescence or early adulthood and risk.

The authors say their findings are in line with cancer prevention advice to eat more fruits and vegetables, and suggest that food choices during adolescence may be particularly important.

In a linked editorial, University of Oxford researchers say "much more evidence is needed before we can draw conclusions on the reported protective association between adolescent fruit intake and breast cancer risk." But that these foods "have well known beneficial effects on health, and efforts should continue to increase intake of both fruit and vegetables at all ages."

In the second study, a team of Danish researchers wanted to test the effect of a change in alcohol intake on the risk of breast cancer and heart disease. Alcohol is responsible for about 11% of female breast cancers in the UK.

They followed the health of nearly 22,000 post-menopausal women in Denmark and found that women who increased their alcohol intake by two drinks per day over five years had around a 30% increased risk of breast cancer but around a 20% decreased risk of coronary heart disease, compared with women with a stable alcohol intake.

However, results for women who decreased their alcohol intake over the five year period were not significantly associated with risk of breast cancer or coronary heart disease.

Altogether, the authors say their findings support the hypothesis that alcohol is associated with breast cancer and coronary heart disease in opposite directions.

The results for breast cancer are in line with previous research, but the true effect of alcohol on risk of ischaemic heart disease remains uncertain, say the editorial authors.

"There may be some benefit with low to moderate intakes of alcohol, but this could be outweighed by an increased risk of breast cancer and other morbidities," they explain. "Furthermore, risk of ischaemic heart disease can be reduced substantially by other lifestyle changes, as well as by drugs such as statins shown to be effective in primary prevention."

Both studies are observational, so their interpretation needs to consider the potential impact of other factors before any firm conclusions can be drawn about cause and effect, they add.

REF : http://www.bmj.com/content/353/bmj.i2314

Evolocumab could be more effective than ezetimibe in lowering cholesterol in statin-intolerant patients

 

Ezetimibe                                                                                                           atorvastatin

In the first major trial of its kind, Cleveland Clinic researchers used a blinded rechallenge with atorvastatin or placebo to objectively confirm the presence of muscle-related symptoms in patients with a history of intolerance to multiple statins and found that evolocumab (a PCSK9 inhibitor) was a more effective option to lower cholesterol than ezetimibe in these patients.

The double-blinded, placebo-controlled clinical trial was designed with two stages:

• In Phase A, patients were assigned to two groups. Each group was treated for 10 weeks with atorvastatin or placebo in a blinded fashion, then crossed over to the alternate therapy for another 10 weeks. Patients were asked to report any muscle pain or weakness.
• Patients who reported intolerable muscle symptoms on atorvastatin, but not placebo, moved to Phase B. In this 24-week phase, patients with confirmed statin intolerance were administered two alternative non-statin therapies, ezetimibe vs. evolocumab.
• The research is being presented at the American College of Cardiology's 65th Annual Scientific Session and simultaneously published online in the Journal of the American Medical Association.
  "Statin intolerance has been a very challenging clinical problem," said Steven Nissen, M.D., chairman of Cardiovascular Medicine at Cleveland Clinic. "The study showed that PCSK9 inhibitors can significantly lower cholesterol in patients with documented statin intolerance, providing an effective treatment for these difficult to manage patients."
  The GAUSS-3 trial enrolled 511 patients with very high levels of LDL cholesterol - averaging more than 210 mg/dL ¬¬- and with a history of muscle-related statin intolerance. More than 80% of participants had previously reported intolerance to three or more statins. The study showed that 42.6 percent of these patients reported muscle pain or weakness on atorvastatin, but not placebo, and 26.5 percent on the placebo, but not atorvastatin.

Evolocumab could be more effective than ezetimibe in lowering cholesterol in statin-intolerant patients

Cholesterol-lowering statin drugs could delay prostate cancer growth in patients receiving ADT

In a study published online today by JAMA Oncology, the researchers report that men who had been taking statins since the start of androgen deprivation therapy (ADT) went a median of 27.5 months before their disease began to worsen, compared to 17.4 months for men who didn't take statins. The trial involved 926 patients, 70 percent of whom had their disease progress during a six-year period.

"This median 10-month benefit in delaying disease progression suggests that statins could be a valuable addition to our current therapies for prostate cancer," says the study's first author, Lauren Harshman, MD, medical oncologist at the Lank Center for Genitourinary Oncology at Dana-Farber. "These results are supported by multiple prior epidemiologic studies demonstrating that statin use may be associated with improved outcomes in prostate cancer, but require validation."

The trial grew out of laboratory studies that suggested statins could delay prostate cancer growth in patients receiving ADT. (ADT reduces the amount of androgen in the body, preventing prostate cancer cells from using it to fuel their growth. For many years, it has been the frontline treatment for patients with hormone-sensitive prostate cancer that has spread beyond the prostate gland.)

The laboratory phase of the research focused on a protein called SLCO2B1, which helps a variety of drugs and hormones enter cells. One of these immigrants to the cell is dehydro-epiandrosterone  sulfate (DHEAS), a precursor of testosterone, the hormone that spurs prostate cancer cell growth. Statin drugs, too, rely on SLCO2B1 to gain entry to cells.

More : http://oncology.jamanetwork.com/article.aspx?articleid=2288665

Cholesterol-lowering statin drugs could delay prostate cancer growth in patients receiving ADT

Cholesterol Drug Vytorin Linked to Reduced Heart Attack Risk

We know that, Ezetimibe/simvastatin  is a drug combination used for the treatment of dyslipidemia. It is a combination of ezetimibe (known as Zetia in the United States and Ezetrol elsewhere) and the statin drug simvastatin (known as Zocor in the U.S.). The combination preparation is marketed by Merck & Co. under the trade names Vytorin and Inegy. Ezetimibe reduces blood cholesterol by acting at the brush border of the small intestine and inhibiting the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.

Simvastatin is an HMG-CoA reductase inhibitor or statin. It works by blocking an enzyme that is necessary for the body to make cholesterol.

Cholesterol-fighting statins inhibit uterine fibroid tumors that account for 50% of hysterectomies...

In continuation of my update on simvastatin

Researchers at the University of Texas Medical Branch at Galveston, in collaboration with The University of Texas Health Science Center at Houston (UTHealth), Baylor College of Medicine and the Georgia Regents University, report for the first time that the cholesterol-lowering drug simvastatin inhibits the growth of human uterine fibroid tumors. These new data are published online and scheduled to appear in the January print edition of the Journal of Biological Chemistry.

Statins, such as simvastatin, are commonly prescribed to lower high cholesterol levels. Statins work by blocking an early step in cholesterol production.

Beyond these well-known cholesterol-lowering abilities, statins also combat certain tumors. Statins have previously been shown to have anti-tumor effects on breast, ovarian, prostate, colon, leukemia and lung cancers. The effect of statins on uterine fibroids was unknown.

"Non-cancerous uterine fibroids are the most common type of tumor in the female reproductive system, accounting for half of the 600,000 hysterectomies done annually in the U.S. Their estimated annual cost is up to $34 billion in the U.S. alone," said UTMB's Dr. Mostafa Borahay, assistant professor in the department of obstetrics and gynecology and lead author. "Despite this, the exact cause of these tumors is not well understood, as there are several genetic, familial and hormonal abnormalities linked with their development."

Cholesterol-fighting statins inhibit uterine fibroid tumors that account for 50% of hysterectomies

Rosuvastatin promotes bone growth in mice with achondroplasia symptoms

Skeletal dysplasia is a group of rare diseases that afflict skeletal growth through abnormalities in bone and cartilage. Its onset hits at the fetal stage and is caused by genetic mutations. A mutation in the gene encoding fibroblast growth factor receptor 3 (FGFR3) has been associated with two types of skeletal dysplasia, thanatophoric dysplasia (TD), a skeletal dysplasia that cause serious respiratory problems at birth and is often lethal, and achondroplasia (ACH), which causes stunted growth and other complications throughout life. Several experimental treatments have been considered, but none are commercially available.

The need for new drug compounds that can combat skeletal dysplasia has led the Noriyuki Tsumaki group at CiRA, Kyoto University, to consider iPS cell technology. In a joint study with Associate Professor Hideaki Sawai of Hyogo College of Medicine and Team Leader Shiro Ikegawa of RIKEN, Professor Tsumaki's team screened molecules based on their ability to rescue TD-iPSCs from degraded cartilage. Molecules known to affect FGFR3 signaling and/or the metabolism of chondrocytes, the cells responsible for growing cartilage, were identified as good candidates. More importantly, so too were statins, a class of drugs renown for their action against cholesterol and investigated because they have anabolic and protective effects on chondrocytes.

The authors used iPS cells generated from the fibroblasts of both healthy individuals (WT-iPSC) and TD patients (TD-iPSC). Chondrocytes differentiated from TD-iPSC produced less cartilage than those from WT-iPSC and also had a lower proliferation rate and greater apoptosis, properties that were attributed to a gain of function by the mutated FGFR3. Adding statin recovered the cartilage formation in TD-iPSC and increased the proliferation rate. Coincidently, the group observed increased expressions of SOX9, a chondrocytic transcription factor, and of COL2A1 and ACAN, two cartilage extracellular components, all of which are down-regulated in TD patients. Moreover, statin treatment was found to accelerate the degradation of the FGFR3 protein in chondrogenically differentiated TD-iPSC, a process inhibited in TD cases.

Read more at :https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/140918-110738.html

Rosuvastatin promotes bone growth in mice with achondroplasia symptoms

Statins could ease coughing in lung disease patients, study finds -- ScienceDaily

In continuation of my update on Statins

Common cholesterol-lowering drugs could provide relief to patients suffering from a chronic lung disease, a study has shown. The drugs -- known as statins -- were found to help alleviate the chronic coughing associated with the disease for some patients.

Statins could ease coughing in lung disease patients, study finds 

New Cholesterol-Lowering Drug, ALN-PCS Shows Early Promise

An experimental drug that lowers LDL "bad" cholesterol by helping sweep it from the bloodstream appears to be both safe and effective in its first human trial.

The drug known as ALN-PCS reduced cholesterol an average of 40 percent in the small, early study, and, if proven to work in large trials, potentially could replace or complement statins, the researchers said.

Currently, statin drugs such as Lipitor, Crestor and Zocor are widely used to control cholesterol. One heart doctor not involved with the new study said another class of drugs might be useful.

"Cardiovascular disease remains the leading cause of death of men and women globally and reduction of LDL cholesterol with statin medications has been demonstrated to substantially reduce the risk of first or recurrent cardiovascular events," said Dr. Gregg Fonarow, a professor of cardiology at the University of California, Los Angeles.

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61914-5/abstract

New Cholesterol-Lowering Drug Shows Early Promise - Drugs.com MedNews

Common cholesterol-lowering drug may help protect against cerebral malaria

In continuation of my update lovastatin

Researchers have discovered that adding lovastatin, a widely used cholesterol-lowering drug, to traditional antimalarial treatment decreases neuroinflammation and protects against cognitive impairment in a mouse model of cerebral malaria. Although there are differences between mouse models of cerebral malaria and human disease, these new findings indicate that statins are worthy of consideration in clinical trials of cerebral malaria. 

Statins, a class of drugs best known for their ability to lower cholesterol, have also been shown to be active in modulating a variety of immune system responses. In their research, Zimmerman and his Brazilian colleagues evaluated the effect of statins in a mouse model of cerebral malaria. The researchers found that adding a drug called lovastatin to traditional antimalarial therapy prevented cognitive dysfunction in mice infected with cerebral malaria. They discovered that addition of lovastatin decreased white blood cell accumulation and leakiness in blood vessels in the brain. Lovastatin also reduced production of damaging oxygen-containing molecules and other factors that promote inflammation.

"The molecular mechanisms that give rise to cerebral malaria and subsequent cognitive dysfunction are not yet known," says Zimmerman. "However, the fact that statin treatment decreases both injurious blood vessel inflammation and cognitive dysfunction suggests that a combination of vascular and inflammatory triggers leads to cerebral pathology and intellectual deficits."

Ref : http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003099

Common cholesterol-lowering drug may help protect against cerebral malaria

New medication lomitapide, shows promise as lipid-lowering therapy for rare cholesterol disorder

Penn researchers have found that,   lomitapide (see structure)  a first-in-class microsomal triglyceride transfer protein (MTP) inhibitor, substantially and stably reduced LDL cholesterol (the "bad" cholesterol) in patients with the orphan disease homozygous familial hypercholesterolemia (HoFH). Lomitapide works by inhibiting MTP, which is required for the production of VLDL,  the precursor to LDL.

The current study was an open-label trial that comprised a six-month phase designed to assess the efficacy of lomitapide when added to standard of care and an additional year-long phase to assess safety and tolerability. Twenty-nine adult HoFH patients from across the world were enrolled, with 23 patients completing both the efficacy and the safety phases. All of the patients received lomitapide along with conventional lipid-lowering therapies including statins and, in some cases, apheresis. The lomitapide dose was gradually increased from 5 mg to a maximum tolerated dose of up to 60 mg per day. Median dose was 40 mg per day. At the end of the efficacy phase, LDL-C levels were reduced by an average of 50 percent from baseline. Approximately one-third of the patients experienced levels of LDL-C that were less than 100 mg/dl -- close to the recommended therapeutic goals -- at some point during the study, and concomitant lipid-lowering therapy was modified in a subset of these patients during the safety phase. Despite these changes in treatment, patients' mean LDL-C levels were still reduced by 38 percent at the end of the study.

"The magnitude of this reduction in LDL-C and the fact that some patients reached or approached the LDL-C therapeutic goals is truly remarkable for this high risk population that historically doesn't respond to lipid-lowering drugs," said the study's lead author, Marina Cuchel, MD, PhD, research assistant professor of Medicine at Penn. "A reduction in LDL-C of this magnitude is certainly expected to favorably alter the clinical course of this devastating disease."

Ref : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61731-0/fulltext

New medication shows promise as lipid-lowering therapy for rare cholesterol disorder