Hypertension Drug Letairis Gets New Boxed Warning: No Monthly Liver Enyme Test Required

Monthly liver enzyme tests are no longer required for those taking Letairis tablets (ambrisentan), according to the U.S. Food and Drug Administration (FDA). The drug is used to treat high blood pressure in the vessels that carry blood to the lungs (pulmonary arterial hypertension, or PAH).

Citing data from clinical trials and post-market reports, the FDA said that the drug poses only a low risk of liver injury. Information related to potential serious liver injury and the need to monitor for such serious injury is being removed from the drug’s boxed warning. [Read more…]

New Drug, Edarbi, Approved to Treat High Blood Pressure (Hypertension)

The U.S. Food and Drug Administration today approved Edarbi tablets (azilsartan medoxomil) to treat high blood pressure (hypertension) in adults.

Data from clinical studies showed Edarbi to be more effective in lowering 24-hour blood pressure compared with two other FDA-approved hypertension drugs, Diovan (valsartan) and Benicar (olmesartan). [Read more…]

Generic Versions of Cozaar and Hyzaar Tablets Approved for Hypertension Treatment

The U.S. Food and Drug Administration approved today the first generic versions of two drugs used for the treatment of hypertension. Losartan potassium tablets and losartan potassium and hydrochlorothiazide tablets (a combination drug) are the generic equivalents of Cozaar and Hyzaar tablets, respectively.

Cozaar and Hyzaar tablets are widely-used antihypertensive drugs. Both generic losartan products will carry the same safety warnings as their brand counterparts. These warnings include a boxed warning against the use of these products during the second and third trimesters of pregnancy.

Losartan potassium tablets are approved in 25 milligram, 50 mg, and 100 mg strengths, and Losartan potassium and hydrochlorothiazide tablets are approved in 50 mg/12.5 mg, 100mg/12.5 mg, and 100 mg/25 mg strengths. Both products are manufactured by TEVA Pharmaceuticals USA in North Wales, Pa.

In related actions, the FDA also approved applications from several other companies for losartan potassium and hydrochlorothiazide tablets for the 100 mg/12.5 mg strength only. These companies include Mylan Pharmaceuticals Inc., Roxane Laboratories Inc., and Torrent Pharmaceuticals Ltd.

Source: FDA, April 7, 2010

Controversial Recommendation to Consider Statins for Kids with High Cholesterol

The American Academy of Pediatrics has issued new cholesterol screening and treatment recommendations for children that suggest cholesterol screening, and possible use of statins for certain children.

The policy statement, “Lipid Screening and Cardiovascular Health in Childhood,” recommends cholesterol screening of children and adolescents with a family history of high cholesterol or heart disease. It also recommends screening patients whose family history is unknown or those who have other factors for heart disease including obesity, high blood pressure or diabetes.

The AAP suggests that screening should take place after age two, but no later than age 10. The best method for testing, according to the organization’s policy statement, is a fasting lipid profile. If a child has values within the normal range, testing should be repeated in three to five years.

The American Academy of Pedatrics suggests that for children who are more than eight years old and who have high LDL concentrations, cholesterol-reducing medications should be considered. Younger patients with elevated cholesterol readings should focus on weight reduction and increased activity while receiving nutritional counseling.

The policy statement also recommends the use of reduced-fat dairy products, such as two percent milk, for children as young as one year of age for whom overweight or obesity is a concern.

Source: American Academy of Pediatrics, July 7, 2008

Study Shows Obesity Is a Major Risk for Heart Failure

The results of the Multiethnic Study of Atherosclerosis (MESA) identifies "the biological effects of obesity on the heart" as a serious reason for 72 million overweight Americans to worry about their health.

Senior study investigator Joao Lima, M.D., says "Even if obese people feel otherwise healthy, there are measurable and early chemical signs of damage to their heart, beyond the well-known implications for diabetes and high blood pressure. Now there is even more reason for them to lose weight, increase their physical activity and improve their eating habits."

The development of heart failure of some 7,000 mean and women, aged 45 to 84 was followed by researchers conducting the MESA study, which started in 2000. To date, of the 79 participants who developed congestive heart failure 44% were obese with a body mass index (BMI) of 30 or more. They were also found to have higher blood levels of interleukin 6, C-reactive protein and fibrinogen, key immune system proteins involved in inflammation, than non-obese adults. An 84% greater risk of developing heart failure was accounted for by a near doubling of average interleukin 6 levels.

The links between inflammation and the combination of risk factors known as the metabolic syndrome alarmed the researchers from 5 U.S. universities.

The researchers from five universities across the United States also found alarming links between inflammation and the dangerous mix of heart disease risk factors known as the metabolic syndrome. Its combined risk factors for heart disease and diabetes—high blood pressure, elevated blood glucose levels, excess abdominal fat and abnormal cholesterol levels, and particularly obesity—double a person’s chances of developing heart failure.

"More practically, physicians need to monitor their obese patients for early signs of inflammation in the heart and to use this information in determining how aggressively to treat the condition," says Lima, a professor of medicine and radiology at the Johns Hopkins University School of Medicine and its Heart Institute. "Our results showed that when the effects of other known disease risk factors—including race, age, sex, diabetes, high blood pressure, smoking, family history and blood cholesterol levels—were statistically removed from the analysis, inflammatory chemicals in the blood of obese participants stood out as key predictors of who got heart failure," says Lima.

The study found that higher levels of interleukin 6 and a tripling of average levels of C-reactive protein in study subjects increased the possibility of heart failure by 36%.

What this tells us is that both obesity and the inflammatory markers are closely tied to each other and to heart failure," says lead researcher Hossein Bahrami, M.D., M.P.H. Bahrami, a senior cardiology research fellow at Hopkins, says "the basic evidence is building the case that inflammation may be the chemical route by which obesity targets the heart, and that inflammation may play an important role in the increased risk of heart failure in obese people, especially those with the metabolic syndrome."

Each year, nearly 300,000 Americans die from heart failure.

Source: Journal of the American College of Cardiology, May 6, 2008

Calcium-Channel Blockers No Better Than Diuretics for Treating Hypertension

Diuretics are just as effective as calcium-channel blockers, alpha-blockers or angiotensin-converting enzymes (ACE) inhibitors when treating hypertension among patients with metabolic syndrome, according to a report in the Archives of Internal Medicine.

Metabolic syndrome is defined as hypertension with at least two of the following factors: high glyceride levels, diabetes, a body mass index (BMI) of at least 30, and low levels of "good cholesterol." Patients with metabolic syndrome are at high risk for complications of cardiovascular disease.

While some alpha-blockers, ACE inhibitors and calcium channel blockers have more favorable short-term effects on blood glucose or blood cholesterol levels, they have been promoted over beta-blockers and diuretics to treat patients with metabolic syndrome.

Researchers at Case Western Reserve University, Cleveland, analyzed data from the Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). 42,418 hypertension patients with at least one other risk factor for heart disease were randomly picked to take either a diuretic (chlorthalidone -15,255 patients), a calcium channel blocker (doxazosin mesylate – 9,061 patients), or an ACE inhibitor (lisinopril – 9,054 patients).

Other drugs could be added if necessary to control blood pressure, and patients were checked for an average of 4.9 years for all drugs administered except the alpha-blocker. Followup of this drug was discontinued after 3.2 years, because increased rates of cardiovascular disease were noted, including nearly twice the rate of heart failure, compared with the group taking diuretics. A total of 23,077 ALLHAT participants (54.4%) met criteria for metabolic syndrome.

"No differences were noted among the four treatment groups, regardless of race or metabolic syndrome status for the primary end point (non-fatal myocardial infarction [heart attack] and fatal coronary heart disease)," the authors write.

Among patients with the metabolic syndrome (7,327 black and 15,750 white patients), the calcium channel blocker, ACE inhibitor and alpha-blocker had higher rates of heart failure compared with the diuretic; the ACE inhibitor and the alpha-blocker also had an increased risk of combined cardiovascular disease.

"The lack of benefit of the agents with the most favorable metabolic profile (i.e., ACE inhibitors and alpha-blockers) was especially marked in the black participants with metabolic syndrome," the authors write. "The magnitude of the excess risk of end-stage renal disease (70 percent), heart failure (49 percent) and stroke (37 percent) and the increased risk of combined cardiovascular disease and combined coronary heart disease strongly argue against the preference of ACE inhibitors over diuretics as the initial therapy in black patients with metabolic syndrome. Similar higher risk was noted for those randomized to the alpha-blocker vs. the diuretic."

"These findings fail to provide support for the selection of alpha-blockers, ACE inhibitors, or calcium channel blockers over thiazide-type diuretics to prevent cardiovascular or renal outcomes in patients with metabolic syndrome, despite their more favorable metabolic profiles," the authors conclude.

This study was supported by a contract from the National Heart, Lung, and Blood Institute and by Pfizer Inc. (ALLHAT).

Source: Arch Intern Med. 2008;168[2]:207-217.

Elevated Blood Pressure May Result in Mild Cognitive Impairment

A report in the December, 2007 issue of Archives of Neurology claims that high blood pressure can increase the risk of mild cognitive impairment, affecting the ability to thinking and learning.

About 9.9 of every 1000 elderly people who do not have dementia develop mild cognitive impairment early, and of these, 10%-12% develop Alzheimer’s disease. compared with 1%-2% of the general population. Dr. Christiane Reitz, M.D., Ph.D., and colleagues at the Columbia University Medical Center, New York, monitored 918 Medicare patients with an average age of 76.3 years, starting in 1992 through 1994. None had any mild cognitive impairment. Participants were then checked every 18 months, for an average of 4.7 years. People with mild cognitive impairment registered low cognitive scores and a defective memory, but were not diagnosed with dementia.

334 people developed mild cognitive impairment during the follow-up phase— including 160 cases of amnestic mild cognitive impairment, and 174 cases of non-amnestic mild cognitive impairment. High Blood pressure was connected with an increased risk of all types of mild cognitive impairment that was mostly associated with an increased risk of non-amnestic mild cognitive impairment. Hypertension was not associated with amnestic mild cognitive impairment, or a change in memory and language

"The mechanisms by which blood pressure affects the risk of cognitive impairment or dementia remain unclear," the authors write. "Hypertension may cause cognitive impairment through cerebrovascular disease. Hypertension is a risk factor for subcortical white matter lesions found commonly in Alzheimer’s disease. Hypertension may also contribute to a blood-brain barrier dysfunction, which has been suggested to be involved in the cause of Alzheimer’s disease. Other possible explanations for the association are shared risk factors," including the formation of cell-damaging compounds known as free radicals.

The authors believe that their findings support the hypothesis that hypertension increases the risk of incident mild cognitive impairment, especially non-amnestic mild cognitive impairment They conclude that preventing and treating hypertension may be important in lowering the risk of cognitive impairment.

Source: American Medical Association (AMA)

Some Hypertension Drugs May Also Treat Alzheimer’s

Recent research points to the possibility that patients being treated with hypertension drugs may also benefit from the drug’s ability to treat or even prevent Alzheimer’s disease.

"If we can deliver certain anti-hypertensive drugs to patients at high risk to develop Alzheimer’s disease, at doses that do not affect blood pressure, these drugs could be made available for all members of the geriatric population identified as being at high
risk for developing Alzheimer’s disease", says Dr. Giulio Maria Pasinetti of Mount Sinai School of Medicine.

Under Dr. Pasinetti’s supervision, more than 1,500 drugs used to treat other disorders have been screened for their potential in treating Alzheimer’s disease, and 7 out of 55 drugs prescribed for the treatment of hypertension have been identified as significantly preventing beta-amyloid production, which plays a key role in Alzheimer’s disease pathogenesis.

Valsartan, an anti-hypertensive agent, was found to pharmacologically prevent beta-amyloid production in the brains of test mice even when administered to Alzheimer’s disease mice at 3-4 times lower than the minimal equivalent dose prescribed for the treatment of hypertension in humans.

Other hypertension drugs with positive results included Propranol HCI, Carvedilol, Losartan, Nicardipine HCI, Amiloride HCI and Hydralazine HCI.

"The use of these drugs for their potential anti-Alzheimer’s disease role is still highly experimental," said Dr. Pasinetti, "and at this stage we have no clinical data beyond phenomenological observation in humans. We need to complete preventive and therapeutic clinical trials in the near future if we are to identify certain anti-hypertensive drugs with anti beta-amyloid antiligomeric activities, which will need to be prescribed at dosages that do not interfere with blood pressure in normotensive Alzheimer’s patients."

The research was conducted by Dr.Giulio Maria Pasinetti, MD, Ph.D., Professor of Psychiatry and Neuroscience, Geriatrics and Adult Development , and Director of the Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer’s Disease at Mount Sinai School of Medicine, and published in the November, 2007 issue of the The Journal of Clinical Investigation.

Novartis Combination Hypertension Drug May Be Unsafe

According to a U.K. medical journal, Novartis AG’s two hypertension drugs made by combining Diovan and Tekturna although more effective in lowering blood pressure, may have some life-threatening side effects.

A recent study found that these drugs when taken in combination, at the maximum recommended doses, are more beneficial than when taken separately. However, the combination drug may cause a life-threatening side effect of high blood potassium.

Novartis has disputed these results by claiming that these drugs are no more likely to increase blood potassium levels than when either of the two drugs is taken alone.