Blood Pressure Drug Linked with Increased Risk of Bowel Condition

Kate Wighton wrote . . . . . . . . .

A type of blood pressure lowering medication, called a calcium-channel blocker, may be linked with increased risk of bowel condition diverticulosis.

This condition causes small bulges or pouches to appear in the lining of the intestine. Particularly affecting the elderly (as many as 65 per cent of over 85s may be affected), diverticulosis can in some cases can lead to a medical emergency if the pouches become infected or burst.

The new early-stage research finding comes from a team of scientists led by Imperial College London, who investigated the effectiveness and side effects of three common blood pressure medications: ACE-inhibitors, beta-blockers and calcium channel blockers.

High blood pressure affects one in ten adults across the globe, and increases the risk of heart attack and stroke. The most common treatments for high blood pressure are lifestyle changes and medications.

However, despite the three main medications being taken by millions, investigating their potential side effects (as well as studying their effectiveness for treating other diseases), can be difficult and often involves lengthy and expensive clinical trials.

Genetic clues

To overcome this problem, the research team, led by Imperial’s School of Public Health, used genetic analyses to study the effects of the drugs.

By investigating versions of genes that mimic the effects of these drugs, the team were able to study the drugs’ effectiveness – and their potential side effects.

First, the researchers, who published their work in the journal Circulation, identified the proteins targeted by the drugs, and which help lower blood pressure. Next, they analysed genetic data from around 750,000 people and identified the so-called genetic variants that code for these proteins.

The team, who included researchers from LMU Munich, then studied whether these gene variants – which cause increased production of these proteins – were linked to an increased or decreased risk of other diseases.

The good news was that, as expected, these so-called genetic variants (which coded for proteins involved in lowering blood pressure) were linked to lower heart disease and stroke risk.

Increased risk

However after assessing the risk of around 900 different diseases – using data from the UK Biobank study – the team found that the versions of genes related to the effects of a particular type of calcium channel blocker – the non-dihydropyridine class, were linked to an increased the risk of a bowel condition called diverticulosis.

The team compared their findings with further genetic data, and supported the potential link with an increased risk of the bowel condition.

The link now needs further investigation with larger trials, explains Dr Dipender Gill, co-lead author of the research from Imperial’s School of Public Health: “This is the first time that this class of blood pressure drug has been associated with diverticulosis. We’re not sure of the underlying mechanism – although it may relate to effects on the function of intestine muscles, which perform contractions to transport food through the gut.”

Dr Joanna Tzoulaki, senior author from Imperial’s School of Public Health added: “The study of genetic variants that mimic the effect of drugs is evolving as a powerful concept to help prioritise clinical trials and design clinical trials more likely to be successful”.

Dr Gill cautions the findings should not change current prescribing guidelines and that people should not stop taking their medication unless first consulting their doctor.

He added: “These findings should not change clinical practice, but instead should act as a catalyst for further research.”

Source: Imperial College London

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FDA Approves Drug for Loss of Sexual Desire in Women

Saumya Joseph wrote . . . . . . . . .

The U.S. drug regulator on Friday approved Palatin Technologies and Amag Pharmaceuticals’ drug to restore sexual desire in premenopausal women, the latest attempt to come up with a therapy that some have dubbed as “female Viagra”.

The therapy, Vyleesi, will compete in a market which has seen previous attempts fail. Analysts have said that a drug that safely and effectively treats loss of sexual desire in women could eventually reach annual sales of about $1 billion.

Vyleesi, chemically known as bremelanotide, activates pathways in the brain involved in sexual desire, helping premenopausal women with hypoactive sexual desire disorder (HSDD).

The drug will compete with Sprout Pharmaceuticals’ Addyi, a once-daily pill that was approved for HSDD in 2015 with a warning restricting alcohol use when on the medication. It will be available from September through select pharmacies.

Addyi was approved under intense pressure from advocacy groups despite a review by scientists at the Food and Drug Administration (FDA) that deemed it minimally effective and possibly unsafe.

Vyleesi, which does not restrict alcohol use, is seen as having several advantages over Addyi, including tolerable side effects, rapid-acting nature and not having to take it every day, according to analysts.

Side effects reported during clinical trials included mild to moderate nausea lasting no more than two hours and mostly occurred over the first three doses, Amag said. About 40% of patients in clinical trials experienced nausea.

The drug is administered as a shot into the abdomen or thigh using an auto-injector at least 45 minutes before anticipated sexual activity, with the FDA recommending patients not to take more than one dose within 24 hours or more than eight doses per month.

Source: Reuters

Hypertension Drug May Hold Promise for Alzheimer’s Disease

Seeking new treatments to slow the progression of Alzheimer’s disease, researchers found the blood pressure drug nilvadipine increased blood flow to the brain’s memory and learning center among people with Alzheimer’s disease without affecting other parts of the brain, according to new research in the American Heart Association’s journal Hypertension.

These findings indicate that the known decrease in cerebral blood flow in patients with Alzheimer’s can be reversed in some regions. However, an important question is whether this observed increase in cerebral blood flow translates to clinical benefits, the authors note.

Alzheimer’s disease is the most common form of dementia. The risk for the disease increases with age and the causes are largely unknown. Previous research has shown that blood flow to the brain declines in early Alzheimer’s disease.

Nilvadipine is a calcium channel blocker used to treat high blood pressure. Researchers sought to discover whether nilvadipine could help treat Alzheimer’s disease by comparing the use of nilvadipine and a placebo among people with mild to moderate Alzheimer’s disease. Researchers randomly assigned 44 participants to receive either nilvadipine or a placebo for six months. Neither researchers nor the participants knew who received the drug or the placebo that was evenly divided among the two groups. At the study’s start and after six months, researchers measured blood flow to specific regions of the brain using a unique magnetic resonance imaging (MRI) technique.

Results showed that blood flow to the hippocampus – the brain’s memory and learning center – increased by 20% among the nilvadipine group compared to the placebo group. Blood flow to other regions of the brain was unchanged in both groups.

“This high blood pressure treatment holds promise as it doesn’t appear to decrease blood flow to the brain, which could cause more harm than benefit,” said study lead author Jurgen Claassen, M.D., Ph.D., associate professor at Radboud University Medical Center in Nijmegen, the Netherlands. “Even though no medical treatment is without risk, getting treatment for high blood pressure could be important to maintain brain health in patients with Alzheimer’s disease.”

Researchers note that sample sizes were too small and follow-up time too short to reliably study the effects of this cerebral blood flow increase on structural brain measures and cognitive measures.

Study participants were screened between 2013 and 2015 as part of a larger research project comparing nilvadipine to placebo among more than 500 people with mild to moderate Alzheimer’s disease (average age 73, more than half female and most were Caucasian).

In that larger project, effects on cerebral blood flow were not measured. Overall, no clinical benefit was noted with use of nilvadipine. However, a subgroup of patients with only mild symptoms of disease did show benefit, in the sense of a slower decline in memory.

Previous studies have hinted that high blood pressure treatment could reduce the risk of developing dementia. The authors think that beneficial effects on brain blood flow could explain part of this effect.

The study is one of a few to use this MRI technique to probe the effects of treatment on cerebral blood flow, making additional research critical. In addition, the small number of participants of similar race and ethnicity mean that the results may not apply to other populations.

“In the future, we need to find out whether the improvement in blood flow, especially in the hippocampus, can be used as a supportive treatment to slow down progression of Alzheimer’s disease, especially in earlier stages of disease,” Claassen said.

Source: American Heart Association


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Anti-hypertensive Drug Was Associated with a Decreased Dementia Risk

Various clinical trials indicate what effects can be expected from standardized intervention programs on the basis of existing evidence. Little is known about the way in which such programs can be implemented in actual care practice. However, it may be possible to use data from clinical practice to estimate the potential of drug prescriptions to delay or reduce the development of dementia.

The goal of the present study, which will be published in the next issue of Journal of Alzheimer’s Disease, was to investigate the relationship between antihypertensive drug use and dementia in elderly persons followed in general practices in Germany.

“After another setback for the anti-amyloid strategy, dementia prevention is increasingly becoming an area of interest,” explains Dr. Jens Bohlken, MD, PhD, from the Institute of Social Medicine, Occupational Health and Public Health (ISAP) from the Medical Faculty of the University of Leipzig. “In view of this, our most important task is to find existing therapies that are associated with a reduction in dementia risk or at least an extension of the time to dementia onset.”

This study was based on data from the Disease Analyzer database (IQVIA), which compiles drug prescriptions, diagnoses, and basic medical and demographic data obtained directly and in anonymous format from computer systems used in the practices of general practitioners and specialists. This study included patients with documented blood pressure values and an initial diagnosis of all-cause dementia in 739 general practices in Germany between January 2013 and December 2017 (index date). Inclusion criteria were as follows: age 60 years at the index date, observation time of at least 12 months prior to the index date, and hypertension diagnosis prior to the index date. After applying similar inclusion criteria, dementia cases were matched to non-dementia controls using propensity scores based on age, sex, index year, and co-diagnoses (i.e. diabetes mellitus, hyperlipidemia, stroke including transient ischemic attack, coronary heart disease, depression, intracranial injury, Parkinson’s disease, osteoporosis, and epilepsy). For the controls, the index date was that of a randomly selected visit between January 2013 and December 2017.

The main outcome of the study was the incidence of dementia as a function of the use of antihypertensive drugs (i.e. diuretics, beta blockers, calcium channel blockers, angiotensin-converting enzyme [ACE] inhibitors, and angiotensin II receptor blockers).

Three logistic regression models were conducted to study the association between the use of antihypertensive drugs and dementia incidence after adjusting for blood pressure (first model: ever versus never use; second model: 3 versus less than 3 years of therapy; third model: 5 versus less than 5 years of therapy).

The present study included 12,405 patients with dementia and 12,405 patients without dementia (mean age: 80.6 years; 61.3% women). The use of angiotensin II receptor blockers (odds ratios [ORs] ranging from 0.74 to 0.79), ACE inhibitors (ORs ranging from 0.85 to 0.88), calcium channel blockers (ORs ranging from 0.82 to 0.89), and beta blockers (OR=0.88) was associated with a decrease in dementia incidence. In patients treated with calcium channel blockers, increasing the duration of treatment decreased the incidence of dementia.

"Antihypertensive therapy alone cannot guarantee that dementia will never occur," noted corresponding author Prof. Karel Kostev, PhD, from the Epidemiology Department of IQVIA (Germany), "However, these findings highlight the importance of the prescription of antihypertensive drugs in the context of preventing hypertension-associated cognitive decline."

The authors of the study also note that: "further studies are needed to gain a better understanding of the medications associated with a decreased risk of dementia. We plan to investigate the role of lipid-lowering drugs, antidepressants, and further medications in the future."

The study is subject to some limitations, as the patients in the study were 60 or older, and this inclusion criterion was necessary for identifying dementia. However, previous research has shown that it is important for a life course-related prevention strategy to initiate hypertension treatment at a younger age. Moreover, data on patients' lifestyle factors, including smoking and physical activity, education, and job, were also lacking. The strengths of this study are the number of patients available for analysis, which allowed the use of a case-control design, and the use of real-world data, with different diagnoses and medications available for analysis.

Source: Science Daily


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Study: Antibiotics that Dentists Prescribe Are Unnecessary 81% of the Time

Antibiotics prescribed by dentists as a preemptive strike against infection are unnecessary 81% of the time, according to a study published today in JAMA Network Open.

The findings are important because dentists are responsible for 10% of all antibiotic prescriptions written in the United States.

Antibiotics prescribed when not warranted expose patients to the risk of side effects unnecessarily and also contribute to the problem of antibiotic resistance – bacteria evolving to make the drugs ineffective.

Antibiotics are recommended as a prophylactic prior to some dental procedures for patients with certain types of heart conditions.

Researchers including Jessina McGregor of Oregon State University used a national health care claims database to examine nearly 170,000 dentist-written antibiotic prescriptions from 2011 to 2015.

The prescriptions involved more than 90,000 patients, 57 percent female, with a median age of 63.

Greater than 90 percent of the patients underwent a procedure that possibly warranted taking an antibiotic ahead of time. However, less than 21 percent of those people had a cardiac condition that made an antibiotic prescription recommended under medical guidelines.

“Preventive antibiotics in these patients gave them risks that outweighed the benefits,” said McGregor, an associate professor in the OSU College of Pharmacy.

Led by corresponding author Katie Suda of the University of Illinois at Chicago College of Pharmacy, the researchers also looked at the prescriptions regionally and found unnecessary prescriptions to be most prevalent, on a percentage basis, in the West; 11,601 of the 13,735 prescriptions written, or 85%, were out of sync with the guidelines.

The other regional percentages were 78% for the Northeast, 83% for the Midwest, and 80% for the South.

Eighty-two percent of the unnecessary prescriptions were written in urban population centers, 79% in rural areas.

Among patients who filled prescriptions for unnecessary antibiotics, clindamycin was the most common drug, and joint implants were the most typical reason they were prescribed.

“Dental providers are very thoughtful when they develop care plans for their patients and there are many factors that inform dentists’ recommendations, but this study shows that there is an opportunity for dentists to reevaluate if necessary,” said Susan Rowan of the UIC College of Dentistry. “I think dental providers should view this study, which is the first to look at preventive antibiotic prescribing for dental procedures, as a powerful call to action, not a rebuke.”

The study was limited to patients with commercial dental insurance and the analysis used a broad definition of high-risk cardiac patients, suggesting the findings may underestimate the unnecessary prescribing of antibiotics.

Five other researchers from UIC and one from Northwestern University also collaborated on the study, which was funded by the Agency for Healthcare Research and Quality.

Source: Oregon State University


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