Saturday, August 31, 2013

Novel Oral Agent Improves Pulmonary HTN

Medpage link:

Novel Oral Agent Improves Pulmonary HTN

Published: Aug 28, 2013 | Updated: Aug 29, 2013

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The novel dual endothelin-receptor antagonist macitentan (Opsumit) improved clinical outcomes in pulmonary arterial hypertension (PAH), the SERAPHIN trial showed.

Action Points

  • The novel dual endothelin-receptor antagonist macitentan (Opsumit) improved clinical outcomes in pulmonary arterial hypertension (PAH).
  • Point out that the beneficial effect was driven by fewer cases of worsening PAH but came with generally good tolerability.

The oral agent reduced the composite risk of death, atrial septostomy, lung transplantation, starting IV or subcutaneous prostanoids, or worsening PAH by 30% at the 3-mg dose and by 45% at the 10-mg dose compared with placebo, Tomás Pulido, MD, of the National Heart Institute in Mexico City, Mexico, and colleagues found.

The effect was driven by fewer cases of worsening PAH but came with generally good tolerability, the group reported in the Aug. 29 issue of the New England Journal of Medicine, mirroring results initially presented at a conference.

"We now have proof that oral medications do indeed reduce morbidity and mortality in PAH and we don't always have to rely on the more invasive IV medications to accomplish this endpoint," commentedRaymond L. Benza, MD, director of the pulmonary hypertension program at Pittsburgh's Allegheny General Hospital.

He called it a landmark trial as the first powered for a hard clinical endpoint instead of just change in functional class or 6 minute walk distance.

However, the 6 minute walk results were less impressive, noted Brett Fenster, MD, a cardiologist at National Jewish Health in Denver.

The gain over placebo was 17 m with the low macitentan dose and 22 m with the higher dose. While both met statistical significance, most studies with PAH treatments have shown changes of more than 30 m, Fenster explained in an interview with MedPage Today.

Also, the improvement in WHO functional class on either dose of the drug was modest compared with placebo (20% and 22% versus 13%), though again significant.

"So one concern is that this drug really isn't improving the functional capacity of patients the way we would normally see it," Fenster said. "However, one argument has been made that a lot of patients in this group were functional class 2; that is, relatively healthier patients. And in general it's hard to make a healthy patient healthier."

The more important limitation was that the study wasn't powered for and didn't show a significant reduction in all-cause or PAH-related mortality, he noted.

"However, designing a study to reach that endpoint is incredibly difficult, especially in a rare disease that's often progressive," Fenster acknowledged. "And probably this drug alone, even in combinations of drugs, is unlikely to ever achieve that."

The Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) trial did show areduction in PAH hospitalizations, with rates of 19% on the higher macitentan dose and 22% on the lower dose compared with 32% on placebo.

The combined endpoint of PAH-related hospitalization or death from PAH did come out significantly lower with the novel oral agent, with a 50% relative risk reduction on the 10-mg dose and 33% relative risk reduction on the lower dose compared with placebo (P=0.01 andP<0.001, respectively).

That's an important consideration in this era of focus on cost savings and efficiency, Benza added.

Also, the analysis counted only the first event, and clinical deterioration usually precedes death in this progressive disease, the researchers pointed out.

The 742-patient trial didn't show a difference in treatment effect by whether patients were on other therapies for PAH at baseline.

Overall, the primary composite endpoint occurred in 38% of patients randomized to once-daily 3-mg macitentan and 31% randomized to the higher drug dose compared with 46% on the placebo (P=0.01 and P<0.001, respectively).

Adverse events associated with macitentan more frequently than with placebo were headache, nasopharyngitis, and anemia. Liver enzyme elevations were uncommon across treatment groups. Peripheral edema on macitentan didn't differ from placebo.

Limitations included the lack of an active comparator control arm and that patients who discontinued treatment before a primary endpoint event weren't followed out to the end of the trial.

"Because pulmonary arterial hypertension is a chronic life-threatening disease, data from long-term outcome studies are required to assess the effect of therapy on disease progression," the researchers added.

CORRECTION: This article, which was originally published Aug. 28, 2013, at 6:55 p.m., has been corrected. There were 742 patients in the trial, not 250.

The study was funded by Actelion Pharmaceuticals, which provided study oversight and statistical support.

Pulido reported serving on a macitentan advisory board for which he received consulting fees or honoraria, travel support, and fees for serving as a member of a scientific board, all from Actelion.

He also reported consulting for Actelion, Pfizer, Eli Lilly, and Bayer; receiving grant funds from Actelion, Bayer, United Therapeutics, and Gilead; receiving payment for speaking from Actelion, Bayer, and Eli Lilly; and getting grant funds to his institution from the National Heart Institute.

Three co-authors were Actelion employees.

From the American Heart Association:

Certain Fruits May Be Linked to Lower Risk of Type 2 Diabetes

Bloomberg News reports that research published in BMJ suggests that “eating more blueberries, apples and grapes” may be linked to a reduced risk of “type 2 diabetes.” However, “increased consumption of fruit juice was linked to a higher risk.”

Friday, August 30, 2013

Kidney Donors Show Some Signs of Mild CKD 6 Months After Donation

In a prospective study comparing 203 kidney donors with 201 controls, donors had 28% lower GFR at 6 months (67.6 vs. 94.6 mL/min/1.73 m²), 23% higher parathyroid hormone (52.7 vs. 42.8 pg/mL), and 5.4% lower serum phosphate (3.3 vs. 3.5. mg/dL). They also had 3.7% lower hemoglobin (13.1 vs. 13.6 g/dL), 8.2% higher uric acid (5.3 vs. 4.9 mg/dL), 24% higher homocysteine (1.5 vs. 1.2 mg/L), and 1.5% lower HDL cholesterol (54.1 vs. 54.9 mg/dL) levels. The American Journal of Kidney Diseases study found no significant difference between donors and controls in albumin-creatinine ratios, office blood pressure levels, or glucose homeostasisin.

Wednesday, August 28, 2013

Procalcitonin can help guide antibiotic therapy in ICU patients

Procalcitonin can help guide antibiotic management, including when to discontinue therapy, in ICU patients, a new meta-analysis found.

Researchers searched MEDLINE, EMBASE, the Cochrane Controlled Trials register, and others for comparative studies and systematic reviews on using procalcitonin-guided antibiotic therapy in patients with infections. Specifically, they sought data from randomized, controlled trials that compared using procalcitonin versus clinical criteria to guide initiation, intensification or discontinuation of antibiotic therapy. Outcomes were antibiotic usage, morbidity and mortality. The results were published online August 17 by the Journal of Hospital Medicine.

Data from the 18 qualified studies were pooled into five clinically similar groups. In adult ICU patients, using procalcitonin to guide antibiotic discontinuation lowered the duration of antibiotic use by 2.05 days (95% CI, −2.59 to −1.52) without increasing morbidity or mortality. However, using procalcitonin as an indicator of need for antibiotic intensification led to greater antibiotic usage and morbidity, including longer length of stay and more days on mechanical ventilation. In adults with respiratory tract infections, guidance with procalcitonin significantly reduced antibiotic duration by 2.35 days (95% CI, −4.38 to −0.33) and antibiotic prescription rate by 22% (95% CI, −41% to −4%); it also decreased total antibiotic exposure and didn't affect morbidity or mortality.

The authors noted that, despite some differences between this and previous reviews, the conclusion is the same: Procalcitonin-guided decision making reduces use of antibiotics without changing morbidity and mortality, as compared to clinical criteria-guided decision making. However, procalcitonin shouldn't be used to guide intensification of antibiotics in adult ICU patients, they added, and there's not enough evidence to recommend procalcitonin-guided therapy in postoperative patients at risk for infection.

Monday, August 26, 2013

Megachurch epicenter of Texas measles outbreak.

USA Today (8/23, Szabo, 5.82M) reported the measles outbreak in Texas which has sickened 25 so far, has been tied to the members of Eagle Mountain International Church in Newark, Texas, after exposure to the virus from a church visitor “who had recently traveled to a country where measles remains common.” The infected “include nine children and six adults, ranging in age from 4 months old to 44 years old,” many of whom were not fully immunized, and some with no vaccination record. In a statement, Eagle Mountain pastor Terri Pearsons, “said she still has some reservations about vaccines,” and recommended “that her congregants take vitamin D to fortify their immune systems,” in addition to obtaining the measles vaccine.

        Forbes (8/24, Willingham, 5.76M) reported that the church’s leader, Kenneth Copeland, has “reportedly...warned followers away from vaccines, advocating for faith healing and pushing the debunked notion that vaccines cause autism.” Public health officials in neighboring counties and states are on alert due to the highly infectious nature of measles.

Saturday, August 24, 2013

Study: Flu Shots May Help Prevent Heart Attacks

Bloomberg News (8/22, Gale) reported that research published online in Heart suggests that flu vaccines may help to prevent heart attacks, a finding that “suggests flu vaccination programs targeting the elderly should be extended to include younger adults, especially those with coronary artery disease.” Investigators found that “immunization against the respiratory illness lowered the probability of heart attack by 45 percent.”

QT Prolongation Common in Patients Taken to Hospital with Severe Hypoglycemia

MedPage Today (8/17, Fiore) reported that research published online in Diabetes Care suggests that individuals with diabetes who are “taken to the hospital for severe hypoglycemia have a high prevalence of QT prolongation.” Researchers found, “in a retrospective study at a single center in Tokyo, 50% of patients with type 1 diabetes and 59.9% of those with type 2 disease had a prolonged QT interval during hospitalization for severe hypoglycemia.”

Protein-Based Urine Test May Predict Kidney Transplant Outcomes

Low urinary levels of the protein CXCL9 could identify kidney transplant recipients with a low risk of developing kidney injury and a high probability of having stable long-term kidney function in a recent American Journal of Transplantation study. Researchers periodically collected urine samples from 280 adult and child kidney transplant recipients for 2 years after transplantation. Urinary CXCL9 levels began to increase up to 30 days before clinical signs of kidney injury, which could help doctors intervene early to potentially prevent rejection-associated kidney damage. The protein levels began to drop after treatment for rejection.

Friday, August 23, 2013

Exercise Can Safely Help Patients with Moderate CKD Become Fitter and Lose Weight

In a study of 83 patients with moderate CKD, those who participated in a structured exercise and lifestyle program for 12 months became significantly fitter—with an 11% increase in their maximal aerobic capacity compared with a 1% decrease in patients receiving usual care. Patients in the program also achieved a small but significant amount of weight loss and heart function improved. The CJASN findingssuggest that exercise can be safe in patients with kidney disease even if they have various other medical problems.

Small changes in your diet like limiting salt and fat can make a big impact on your health

Tips for Healthy Living

Eat a diet low in salt and fat
Be physically active
Keep a healthy weight
Control your cholesterol
Take medicines as directed
Limit alcohol
Avoid tobacco

Eat a diet low in salt and fat

Eating healthy can help prevent or control diabeteshigh blood pressure and kidney disease.  A healthy diet has a balance of fruits, vegetables, whole grains, dairy products, lean meats and beans.  Even small changes like limiting salt (sodium) and fat, can make a big difference in your health.

Limit salt

  • Do not add salt to your food when cooking or eating.  Try cooking with fresh herbs, lemon juice or other spices.
  • Choose fresh or frozen vegetables instead of canned vegetables.  If you do use canned vegetables, rinse them before eating or cooking with them to remove extra salt.
  • Shop for items that say “reduced-sodium” or “low-sodium.”
  • Avoid processed foods like frozen dinners and lunch meats.
  • Limit fast food and salty snacks, like chips, pretzels and salted nuts.

Limit fat

  • Choose lean meats or fish.  Remove the skin and trim the fat off your meats before you cook them.
  • Bake, grill or broil your foods instead of frying them.
  • Shop for fat-free and low-fat dairy products, salad dressing and mayonnaise.
  • Try olive oil or canola oil instead of vegetable oil.
  • Choose egg whites or egg substitute rather than whole eggs.

Choosing healthy foods is a great start, but eating too much of healthy foods can also be a problem.  The other part of a healthy diet is portion control (watching how much you eat).  To help control your portions, you might:

  • Eat slowly and stop eating when you are not hungry anymore.  It takes about 20 minutes for your stomach to tell your brain that you are full.
  • Check nutrition facts to learn the true serving size of a food.  For example, a 20-ounce bottle of soda is really two and a half servings.
  • Do not eat directly from the bag or box.  Take out one serving and put the box or bag away.
  • Avoid eating when watching TV or driving.
  • Be mindful of your portions even when you do not have a measuring cup, spoon or scale.

Get more information about kidney friendly diets here.

Be physically active

Exercise can help you stay healthy.  To get the most benefit, exercise for at least 30 minutes, 5 days of the week.  If that seems like too much, start out slow and work your way up.  Look for fun activities that you enjoy.  Try walking with a friend, dancing, swimming or playing a sport.  Adding just a little more activity to your routine can help.  Exercise can also help relieve stress, another common cause of high blood pressure.

Keep a healthy weight

Keeping a healthy weight can help you manage your blood sugar, control your blood pressure, and lower your risk for kidney disease.  Being overweight puts you more at risk for diabetes and high blood pressure.  Talk to your doctor about how much you should weigh.  If you are overweight, losing just a few pounds can make a big difference.

Control your cholesterol

Having high cholesterol, especially if you have diabetes, puts you more at risk for kidney disease, heart disease and stroke.  It can also cause diabetic kidney disease to get worse faster.

For most people, normal cholesterol levels are:

  • Total Cholesterol: Less than 200
  • HDL (“good” cholesterol): More than 40
  • LDL (“bad” cholesterol): Less than 100

Your triglycerides are also important.  People with high triglycerides are more at risk for kidney disease, heart disease and stroke.  For most people, a healthy triglyceride level is less than 150.

If your total cholesterol, LDL or triglycerides are high, or if your HDL is low, talk to your doctor.  Your doctor may suggest exercise, diet changes or medicines to help you get to a healthy cholesterol level.

Take medicines as directed

To help protect your kidneys, take medicines as directed. 

Some medicines may help you manage conditions that can damage your kidneys, like diabetes or high blood pressure. Ask your doctor how to take any medicines he or she prescribes.  Make sure to take the medicines just how your doctor tells you.  This may mean taking some medicines, like blood pressure medicines, even when you feel fine.
Other medicines can harm your kidneys if you take them too much.  For example, even over-the-counter pain medicines can damage your kidneys over time.  Follow the label directions for any medicines you take.  Share with your doctor a list of all of your medicines (even over-the-counter medicines and vitamins) to help make sure that you are not taking anything that may harm your kidneys.

Limit alcohol

Drinking alcohol in large amounts can cause your blood pressure to rise.  Limiting how much alcohol you drink can help you keep a healthy blood pressure.  Have no more than two drinks per day if you’re a man and no more than one drink per day if you’re a woman.

Avoid tobacco

Using tobacco (smoking or chewing) puts you more at risk for high blood pressure, kidney disease and many other health problems.  If you already have kidney disease, using tobacco can make it get worse faster.

If you use tobacco, quitting can help lower your chances of getting kidney disease or help slow the disease down if you already have it.