Tag: antihypertensives

Common Hypertension Drug Extends Lifespan in Animal Studies

Old man
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Researchers have found that, in animal studies, the hypertension drug rilmenidine can extend lifespan and slow ageing. Published in Aging Cell, the findings show that animals treated with rilmenidine at young and older ages increases lifespan and improves health markers by mimicking the effects of caloric restriction.

They also demonstrate that the healthspan and lifespan benefits of rilmenidine treatment in the roundworm C. elegans are mediated by the I1-imidazoline receptor nish-1, identifying this receptor as a potential longevity target.

With side-effects being rare and non-severe, unlike other drugs previously studied for this purpose by the researchers, the widely-prescribed antihypertensive has potential for future translatability.

A caloric restriction diet has thus far proved to be the most robust anti-ageing intervention, promoting longevity across species. However, studies of caloric restriction in humans have had mixed results and side effects, meaning finding medications like rilmenidine that can mimic the benefits of caloric restriction is the most reasonable anti-ageing strategy.

Professor João Pedro Magalhães, who led the research whilst at the University of Liverpool and is now based at the University of Birmingham, said: “With a global ageing population, the benefits of delaying ageing, even if slightly, are immense. Repurposing drugs capable of extending lifespan and healthspan has a huge untapped potential in translational geroscience. For the first time, we have been able to show in animals that rilmenidine can increase lifespan. We are now keen to explore if rilmenidine may have other clinical applications.”

Source: University of Liverpool

A Trend of Prescribing Oral Minoxidil Off-label for Baldness

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The New York Times reports that low oral doses of the cheap antihypertensive drug minoxidil – a key ingredient in many hair-loss treatments such as Rogaine – is now being widely used as an off-label prescription for male and female hair loss.

Since the accidental discovery of minoxidil’s topical efficacy in treating hair loss in the 1980s, it had became a staple in `Rogaine for male and female patients. However, applying the foam or lotion onto scalps is time-consuming and uncomfortable for many – as well as expensive.

There is not much in the way of clinical evidence as to its efficacy. A 2019 study in the Journal of the American Academy of Dermatology is so far the only randomised open study to compare 1mg oral minoxidil against 5% topical minoxidil for hair loss in female patients.

The oral minoxidil was not inferior to the topical version, and indeed trend analysis suggested it might be more effective.

According to the Times, the off-label designation might scare off some, but such drugs are widely used in practice.

Dermatologist Robert Swerlick, of the Emory University School of Medicine, noted that “most things we [dermatologists] do are off-label because there is nothing on-label.”

Brett King, a Yale School of Medicine dermatologist, told the Times that it would likely stay off-label because there wasn’t a financial incentive for Big Pharma to invest in proper trials.

“Oral minoxidil costs pennies a day,” King told the Times. “There is no incentive to spend tens of millions of dollars to test it in a clinical trial. That study truly is never, ever going to be done.”

Until researchers have the motivation and funding to conduct randomised controlled trials into low-dose oral minoxidil as a baldness treatment, the situation is likely to remain unchanged even if it is growing in popularity with certain dermatologists.

Gut Bacteria can Reduce Effectiveness of Antihypertensive Drugs

A new study published this month in the journal Hypertension has shown gut bacteria can reduce the effectiveness of certain antihypertensive drugs. The research provides the first clues into why some people not respond well to medication.

Among those with hypertension, an estimated 20% have resistant hypertension, where their blood pressure remains high despite aggressive treatment.

“The only thing doctors can really do in these patients is adding or switching medications and increasing the dose with the hope they can find something that works,” said Dr Tao Yang, an assistant professor at University of Toledo and the study’s first and lead author. “Until now, we haven’t had any clear indication what the mechanism is for resistant hypertension. Our research could provide a first step toward identifying new ways to effectively overcome treatment-resistant hypertension.”

Recent research has focused on the link between blood pressure and the gut microbiome. That work has helped to unravel potential causes of hypertension beyond diet and exercise. However, Dr Yang’s research is the first to examine the impact of gut bacteria on blood pressure medication itself.

In the study, UToledo scientists compared the effectiveness of the antihypertensive drug quinapril in rats with normal gut bacteria against those with gut microbiota depleted by high doses of antibiotics.

Researchers found a clear difference between the two, with animals that were given antibiotics first responding much better to quinapril.

Analysis of the gut bacteria composition in the animals identified the bacteria Coprococcus as the culprit. Laboratory experiments proved that Coprococcus comes, a dominant bacteria species in this genus, can break down quinapril and ramipril, resulting in the compromised blood pressure-lowering effects.

While the study was confined to animal models and lab experiments, researchers did find at least one intriguing case study that seems to support the notion that this could be applicable to humans.

That 2015 report, published in the International Journal of Cardiology, described a woman with a long history of treatment-resistant hypertension whose blood pressure was controlled without any antihypertensive medication for the two weeks she was taking antibiotics for a post-surgical infection. Her blood pressure was able to be controlled with only one medication for six months after stopping antibiotics, before again becoming treatment-resistant.

“This is just one report and more research is needed. However, this suggests that gut bacteria can play a very real and very important role in regulating the efficacy of blood pressure medication,” Dr Yang said.

The research group intends to further explore the interaction between additional blood pressure medications and other common types of gut bacteria.

Though long-term use of antibiotics isn’t a realistic strategy for addressing treatment-resistant hypertension, Dr Yang said it should be possible for someone to alter their microbiota through probiotics, prebiotics and changes in diet.

“The ultimate goal of my research is to identify ways we can specifically target the bacteria in an individual’s gut to improve drug efficacy,” he said. “This has the potential to benefit a lot of people.”

Source: University of Toledo

Hypertension Drugs Linked to Psoriasis

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A review of studies has found an association with the use of antihypertensive medications and the development of psoriasis.

Psoriasis is a chronic inflammatory skin disease that, when inflicted, can be detrimental to the individual’s overall quality of life. The prevalence rate of psoriasis is 0.1–11%, more common in Caucasian and Scandinavian populations, and also more common in older people and in high-income countries as well.

In the analysis, which is published in the British Journal of Clinical Pharmacology, data from 13 studies indicated that angiotensin-converting-enzyme inhibitors, beta- blockers, calcium-channel blockers, and thiazide diuretics may increase the risk of psoriasis. However, there was no greater increase of any of the drugs relative to the others.

The authors of the analysis propose several mechanisms by which blood pressure medications may affect an individual’s risk of developing skin conditions.

“Our findings indicate that patients who take antihypertensive drugs should be carefully monitored for psoriasis,” said senior author Hye Sun Gwak, PharmD, PhD, of Ewha Womans University, in Seoul.

Source: Wiley

Some Meds May be Raising Blood Pressure Unnecessarily

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New research has found that nearly a fifth of adults with high blood pressure are taking a drug that may be raising their blood pressure further.

The findings presented at the American College of Cardiology’s 70th Annual Scientific Session. The results highlight the need for patients to regularly review all of the medications they take with their care team, including over-the counter drugs, to ensure none might interfere with blood pressure lowering efforts.

The research found that three most common culprits were antidepressants; nonsteroidal anti-inflammatory drugs (NSAIDs) that include ibuprofen and naproxen; and oral steroids used to treat conditions such as gout, lupus, rheumatoid arthritis or after an organ transplant. These drugs were reported by 9%, 7% and 2% of participants, respectively. Other drugs associated with blood pressure elevation included antipsychotics, certain oral contraceptives and popular decongestants.

Researchers said these findings raise concerns, especially as nearly half of Americans diagnosed with high blood pressure do not have it sufficiently controlled. Dr. Vitarello explained the goal blood pressure for hypertension patients is a reading of less than 130 mmHg over 80 mmHg, based on the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.

“These are medications that we commonly take—both over-the-counter and prescribed medications—that may have the unintended side effect of raising blood pressure and could have adverse effects on our heart health,” said John Vitarello, MD, an internal medicine resident at Beth Israel Deaconess Medical Center in Boston and the study’s lead author. “We know that high blood pressure leads to cardiovascular disease, stroke and death and even small increases in blood pressure can have meaningful impacts on cardiovascular disease. Based on our findings, we need to be more aware of polypharmacy (the use of multiple medications by a single patient) in older adults who also have the highest burden of high blood pressure.”

The study examined data from 27 599 participants in the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018. About half of the participants (49%) had hypertension (average age 55 years, 48% female), defined in the study as a blood pressure reading of ≥ 130 mmHg (systolic) or ≥80 mmHg (diastolic) or ever having been told they have high blood pressure. Researchers identified medications associated with blood pressure elevation based on those listed in the ACC/AHA guideline and examined use of these medications by hypertensive adults

Among hypertensive participants, 19% reported using one or more blood pressure raising medications and 4% reported using multiple. Nearly one-quarter (24%) of women with high blood pressure reported using a blood pressure raising medication compared with 14% of men. Older adults were more likely to be using blood pressure raising medications than younger adults (19% of participants over age 65 vs. 18% of participants under age 65).

Vitarello said the findings suggest that there may be opportunities to treat hypertension by switching out the drugs raising blood pressure rather than adding more anti-hypertensives. Some drugs may have the same benefit but impact on blood pressure less. Still, some patients may not have another medication option, so monitoring and talking to their care team is advised over stopping medications.

The researchers also estimated that if half of hypertensive US adults taking blood pressure raising drugs were to discontinue one of them, 560 000 to 2.2 million patients could be able to reach blood pressure goals without additional drugs. But Vitarello cautioned that this is only a preliminary analysis, and individual responses to stopping blood pressure drugs are variable, so the real-world benefit and tradeoffs of stopping these medications need to be further studied.

The study is limited in that it relies on participants’ self-report of having high blood pressure and an accurate accounting of all the medications they take. The study was funded by the National Institute on Aging and an ACC Fellows Career Development Award.

Source: American College of Cardiology

Antihypertensive Drugs Not Linked to Cancer Risk

A review of 33 clinical studies  showed that antihypertensive drugs did not have a consistent association with cancer risk.

Patients treated with any of five different classes of antihypertensive drugs had essentially the same cancer risk as those receiving placebo. Comparisons of each antihypertensive class against all the others showed no association with an increased risk of cancer, save for calcium channel blockers (CCBs), which had only a modestly higher risk versus the other drug classes (HR 1.06, 95% CI 1.01-1.11).

The data do not conclude the issue, since some comparisons had insufficient data to exclude the possibility of excess cancer risk, reported Kazem Rahimi, DM, of the University of Oxford in England, and colleagues in Lancet Oncology.

“Our study has addressed an ongoing controversy about the safety of blood pressure-lowering medication with respect to cancer risk, using the largest sample of individual-level randomized evidence on blood pressure-lowering treatment to date, to our knowledge,” they wrote. “The main implication of our study is that patients using antihypertensive medication should continue to take their medications because concerns about increased cancer risk seem to be unfounded.”

The author of an accompanying commentary noted that the findings could have been due to chance. The number of trials per drug class varied greatly, and small sample sizes were used in analyses by type of cancer.

“Taken together, these limitations raise a more fundamental question about how the findings of randomised controlled trials should be interpreted,” wrote Laurent Azoulay, PhD, of McGill University in Montreal.

Randomised trials are the “gold standard” for assessing drug efficacy, but are not typically designed to assess safety, he continued. This is especially important for outcomes like cancer, which have a delayed onset. Since the median follow-up was only 4.2 years , “a potential association between cancer and the long-term use of antihypertensive drugs cannot be ruled out.”

“Such analyses are necessary to understand the short-term effects of these drugs on cancer incidence,” Azoulay concluded. “However, moving forward, these studies will need to be complemented with well-designed, real-world studies in heterogeneous patient populations who are followed up for extended periods of time to fully understand their carcinogenic potential.”

Several meta-analyses have yielded conflicting evidence, Rahimi and colleagues stated. The Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) is the world’s largest individual patient-level data on blood pressure-lowering trials, and data from this formed the basis for the meta-analysis.

The authors identified 33 trials for inclusion in the meta-analysis, which comprised 260 447 patients with available data on cancer outcomes. CCBs were the antihypertensive class most commonly represented in the trials (n=19), followed by ACE inhibitors (15), angiotensin-receptor blockers (ARBs, 11), thiazide diuretics (six), and beta-blockers (five). Median follow-up ranged from 4 to 5 years across the trials, grouped by drug class.

Patient age ranged between 64 and 68 by drug class, and pretreatment systolic blood pressure ranged from 147mm Hg (ACE inhibitors) to 166mm Hg (beta-blockers).

Across the five classes of antihypertensive drugs, individual comparisons for cancer risk versus the other drug classes yielded only a maximum hazard ratio of 1.06 for CCBs.

“We found no consistent evidence that antihypertensive medication use had any effect on cancer risk,” the authors stated.

Source: MedPage Today

Journal information 1: Copland E, et al “Antihypertensive treatment and risk of cancer: An individual participant data meta-analysis” Lancet Oncol 2021; DOI: 10.1016/S1470-2045(21)00033-4.

Journal information 2: Azoulay L “Elucidating the association between antihypertensive drugs and cancer: A need for real-world studies” Lancet Oncol 2021; DOI: 10.1016/S1470-2045(21)00085-1.