New warnings required for nonaspirin NSAIDs

The FDA issued a safety alert last week regarding cardiovascular warnings for nonaspirin NSAIDs.

Prescription NSAIDs have carried warnings about heart attack and stroke risk since 2005. After reviewing new safety information, the FDA decided to strengthen the existing warning and require that all labels for prescription NSAIDs include the following information:

• The risk of heart attack or stroke can occur as early as the first weeks of NSAID use; it may increase with longer use and appears to be greater at higher doses.
• All NSAIDs were previously thought to have a similar risk for heart attack or stroke. Newer information makes this less clear but is not sufficient for the FDA to determine that any particular NSAID definitely has a higher or lower risk than any other.
• NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or heart disease risk factors.
• In general, patients with heart disease or risk factors for heart disease have a greater likelihood of heart attack or stroke after NSAID use than patients without these risk factors because their baseline risk is higher.
• Patients treated with NSAIDs after a first heart attack were more likely to die in the first year afterward than those who were not treated with NSAIDs after their first heart attack.
• Heart failure risk is increased with NSAID use.

The agency is also requesting that these changes be made to the labels of over-the-counter nonaspirin NSAIDs.

The FDA recommended that patients and health care professionals remain alert for heart-related side effects the entire time NSAIDs are taken. Patients who are taking NSAIDs should seek medical attention immediately if they experience such symptoms as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech, the FDA said.

The safety alert, which was issued July 9, is available online. 

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ACE inhibitors, ARBs most effective against ESRD in patients with diabetes, kidney disease

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) appear most effective in preventing end-stage renal disease (ESRD) in patients with diabetes and kidney disease, although no regimen to lower blood pressure seems to prolong survival, a recent analysis has found.

Researchers performed a network meta-analysis of randomized trials comparing the effects of oral blood pressure-lowering agents in adults who had diabetic kidney disease. The primary outcomes were all-cause mortality and ESRD; secondary safety and cardiovascular outcomes were also assessed. All drug regimens were ranked comparatively against placebo. The study results were published online on May 23 by The Lancet. 

Overall, 157 studies involving 43,256 patients were included in the meta-analysis. The mean patient age was 52.5 years. The drug classes compared with placebo or standard treatment were ACE inhibitors, ARBs, aldosterone antagonists, beta-blockers, calcium-channel blockers, endothelin inhibitors, and renin inhibitors. None of the drug regimens examined appeared to be more effective in reducing all-cause mortality. ESRD was significantly less likely in patients treated with an ARB and an ACE inhibitor (odds ratio, 0.62; 95% CI, 0.43 to 0.90) and in those treated with only an ARB (odds ratio, 0.77; 95% CI, 0.65 to 0.92) versus those treated with placebo.

Hyperkalemia and acute kidney injury did not appear to increase significantly with any regimen (calcium-channel blocker, beta-blocker, ACE inhibitor plus diuretic, endothelin inhibitor, diuretic, renin inhibitor, ARB, ACE inhibitor, aldosterone antagonist, and ACE inhibitor plus ARB for hyperkalemia; ACE inhibitor plus calcium-channel blocker, calcium-channel blocker, ACE inhibitor, renin inhibitor, endothelin inhibitor, ARB, aldosterone antagonist, and ACE inhibitor plus ARB for acute kidney injury). However, the authors noted that ACE inhibitor plus ARB was the regimen with the highest odds ratios for these 2 outcomes (odds ratios, 2.69 [95% CI, 0.97 to 7.47] and 2.69 [95% CI, 0.98 to 7.38]).

The authors noted that their study had limited primary data, that data for the ESRD outcome came mainly from patients with macroalbuminuria and patients with type 2 diabetes, and that acute kidney injury was not well defined, among other limitations. They concluded that based on available evidence, lowering blood pressure in adults with diabetes and kidney disease does not appear to improve survival but that ACE inhibitors and ARBs, together or alone, appear most effective in preventing ESRD in this population.

"However, we must consider the potential harms of these treatments in individual patients," the authors wrote. "Surveillance for treatment-related acute kidney injury and hyperkalaemia is important, as is better standardisation of the definitions of these adverse events and improved understanding of their outcomes, particularly in the context of future trials." They also noted that their results don't support the use of beta-blockers, calcium-channel blockers, renin inhibitors, or diuretic monotherapy in this patient population.

The authors of an accompanying comment said that the results "reignite the debate" about the utility of dual renin-angiotensin-aldosterone system (RAAS) blockade and said that the findings will help researchers design future trials examining this question. The comment authors pointed out that preventive treatments for end-stage kidney failure are urgently needed in diabetic patients.

"Screening for albuminuria and prompt initiation of lifestyle and pharmacological interventions is likely to prevent progression of chronic kidney disease and cardiovascular disease," they wrote. "Addition of dual ACE inhibitor and ARB treatment to this multifactorial management approach—if confirmed to be efficacious and cost effective—might further improve patients' outcomes in regions of the world where careful selection of patients and close monitoring are possible."

Power Down in May for National High Blood Pressure Education Month

http://www.cdc.gov/Features/HighBloodPressure/

Reducing high blood pressure can lower your risk for stroke and heart attack.

Less is better in some things, including in blood pressure. About 1 of 3 US adults—67 million people—have high blood pressure.1High blood pressure makes your heart work too hard and increases your risk of heart disease and stroke.

You can have high blood pressure and not know it. That is why it is called the silent killer. It is also why it is so important to have your blood pressure checked. If you know family or friends who haven't had their blood pressure checked recently, make it a point to ask them to do it in May, National High Blood Pressure Education Month.

It is easy to check blood pressure and it is painless. It can be checked by your doctor, and many pharmacies have free screenings.

Caution! Arteries Under Pressure

Blood pressure is the force of blood on the walls of your blood vessels as blood flows through them. This pressure naturally rises and falls during the day, but when it is consistently too high, it is considered high blood pressure. The medical term is hypertension.

Like the pipes in your house, your arteries can fail if they are under too much pressure. The video, "High Blood Pressure Basics," illustrates the concept of high blood pressure.

More than 360,000 American deaths in 2010 included high blood pressure as a primary or contributing cause.2 That's 1,000 deaths each day.

Blood pressure has two numbers, systolic and diastolic, and is measured in millimeters of mercury (mmHg). Systolic pressure (the top number) is the force on the blood vessel walls when the heart beats and pumps blood out of the heart. Diastolic pressure (the bottom number) is the force that occurs when the heart relaxes in between beats.

If your blood pressure is less than 120 systolic and less than 80 diastolic, then your blood pressure is normal; between 120 and 139 systolic and 80–89 diastolic, you have prehypertension. Systolic of 140 or greater, or diastolic that is 90 or greater, is hypertension.

What Is Your Risk?

Men and women are about equally likely to develop high blood pressure over their lifetimes, but their risks vary at different ages. The condition affects more men than women before 64 years of age. For people aged 65 years or older, more women than men have high blood pressure.

Age	Men (%)	Women (%)
20–34	9.1	6.7
35–44	24.4	17.6
45–54	37.7	37.7
55–64	52.0	52.0
65–74	63.9	70.8
75+	72.1	80.1

Data in this table are from the 2014 AHA Statistical Update, using 2007-2010 NHANES

African Americans develop high blood pressure more often, and at an earlier age, than whites and Hispanics do. More black women than men have high blood pressure.3

Racial or Ethnic Group	Men (%)	Women (%)
Blacks	40.5	44.3
Mexican Americans	28.6	27.8
Whites	31.1	28.1
All	31.3	29.6

Data in this table are from Health US 2012, using 2007-2010 NHANES

African American men are disproportionately affected by cardiovascular disease (CVD). One of the reasons for this has to do with the rates of uncontrolled high blood pressure among African American men. Uncontrolled high blood pressure among African American men aged 20 years and older is 59.7%; compared to 47.0% of white men. Uncontrolled hypertension among African American women is 47.3% compared to 43.2% for white women.2

Eliminating health disparities among various segments of the population is a CDC priority and a Healthy People 2010 goal.

Keep It Down in There!

If you have high blood pressure, there are steps you can take to get it under control, including—

• Ask your doctor what your blood pressure should be.Set a goal to lower your pressure with your doctor and then discuss how you can reach your goal. Work with your health care team to make sure you meet that goal.
• Take your blood pressure medication as directed. If you are having trouble, ask your doctor what you can do to make it easier. For example, you may want to discuss your medication schedule with your doctor if you are taking multiple drugs at different times of the day. Or you may want to discuss side effects you are feeling, or the cost of your medicine.
• Quit smoking—and if you don't smoke, don't start.You can find tips and resources at CDC's Smoking and Tobacco Web site or Be Tobacco Free Web site.
• Reduce sodium. Most Americans consume too much sodium, and it raises blood pressure in most people. Learn about tips to reduce your sodium.

There are other healthy habits, that can help keep your blood pressure under control—

• Achieve and maintain a healthy body weight.
• Participate in 30 minutes of moderate physical activity on most days of the week.
• Eat a healthy diet that is high in fruits and vegetables and low in sodium, saturated fats, trans fat, and cholesterol.
• Manage stress.
• Limit the amount of alcohol you drink (no more than one drink each day for women and two for men).
• If you have high blood pressure and are prescribed medication, take it as directed.
• If you have a family member who has high blood pressure, you can help by taking many of the steps listed above with them. Go for walks together or cook meals with lower sodium. Make it a family affair!
• Check your blood pressure regularly.

Resources

The Dietary Approaches to Stop Hypertension (DASH) can help control high blood pressure through a healthy diet.

"I can do it!" is the message of the My Blood Pressure Wallet Card that helps patients monitor their blood pressure readings, remember to take their medications, and keep up the lifestyle changes that will help lower their blood pressure.

Million Hearts® is a national initiative to prevent 1 million heart attacks and strokes in the United States by 2017. Launched by the US Department of Health and Human Services (HHS), it aligns existing efforts and creates new programs to help Americans live longer, more productive lives. The CDC and Centers for Medicare and Medicaid Services, co-leaders of Million Hearts™ within HHS, are working alongside other federal agencies and private-sector organizations to make a long-lasting impact against cardiovascular disease.

References

1. CDC. Vital signs: awareness and treatment of uncontrolled hypertension among adults—United States, 2003–2010. MMWR. 2012;61:703-9.
2. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics-2014 update: a report from the American Heart Association. Circulation.2014;129:e28-e292.
3. CDC. Health, United States, 2012: With Special Feature on Emergency Care. Atlanta, GA: US Department of Health and Human Services; 2013.
4. CDC. A Closer Look at African American Men and High Blood Pressure Control: A Review of Psychosocial Factors and Systems-Level Interventions. Atlanta, GA: US Department of Health and Human Services; 2010.

PE recurrence same with vena cava filter plus anticoagulation as anticoagulation alone

Adding an inferior vena cava filter did not reduce the risk of recurrent pulmonary embolism (PE) compared to anticoagulation alone, according to a recent study of French patients hospitalized with PE.

The open-label trial included patients who were hospitalized with acute, symptomatic PE associated with lower-limb venous thrombosis and who met at least 1 criterion for severity between 2006 and 2012. The patients were randomized to retrievable inferior vena cava filter implantation plus anticoagulation (n=200) or anticoagulation alone (n=199) and were followed for 6 months. Patients with a contraindication to anticoagulation therapy and those with recurrence despite adequate anticoagulation were excluded. Results were published in the April 28 Journal of the American Medical Association. 

Filters were successfully inserted in 193 patients, and they were retrieved, at 3 months after placement, in 153 of the 164 patients in whom retrieval was attempted. By 3 months, 6 patients in the filter group had a recurrent PE (3.0% of the group, all were fatal), compared to 3 patients in the anticoagulation-only group (1.5% of the group; 2 fatal; P=0.50 for PE recurrence). The groups also had similar rates of recurrence within 6 months, symptomatic deep venous thrombosis, major bleeding, and mortality within 3 or 6 months. Filter thrombosis occurred in 3 patients. One patient died of cardiac arrest during filter insertion.

Implantation of the filters did not reduce risk of symptomatic PE recurrence, and thus the study's results do not support use of inferior vena cava filters in PE patients who can be treated with anticoagulation, the study authors concluded. The rate of PE recurrence in the study was less than expected, but this shows that "modern management with full-dose anticoagulation is likely very effective even in patients usually considered to be at high risk for recurrence," the authors wrote.

The study was limited by its open-label design and its small size, and the results do not exclude the possibility of benefit from filters in certain subgroups of patients with venous thromboembolism, such as those with PE and hemodynamic instability. The study used the ALN brand of filter (provided by the manufacturer for the study), but given existing evidence of similarities among retrievable filter models, the results are probably applicable to other retrievable filters, the authors said.

Fecal transplants for recurrent C. diff may resolve symptoms with few adverse events

Low-strength evidence shows fecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infections (CDIs), with few short-term adverse events, a review found.

Researchers conducted a literature search to find 2 randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports (included only for reporting harms) assessing FMT. Results of their analysis, which was funded by the Department of Veterans Affairs, appeared in the May 5 Annals of Internal Medicine. 

Across all studies of FMT for recurrent CDI, symptom resolution was seen in 85% of cases. In the 2 RCTs, totaling 36 patients with recurrent CDI, 27 (75%) had resolution of CDI symptoms without recurrence. One RCT comparing FMT with 2 control groups reported resolution of symptoms in 81% of patients who received FMT, 31% of patients who received vancomycin, and 23% of patients who received vancomycin plus bowel lavage (P<0.001 for both control groups vs. FMT). An RCT comparing different FMT routes of administration for CDI recurrence reported no difference between groups (60% had their symptoms resolved in the nasogastric tube group, as did 80% in the colonoscopy group; P=0.63). Among the 480 patients in 21 case-series studies who received FMT for recurrent CDI, 85% had resolution of symptoms without recurrence.

There were 7 studies reporting on patients with refractory CDI treated with FMT, and they used various methods and did not compared FMT with standard therapy. Reported resolution of symptoms ranged widely (0% to 100%; overall resolution rate, 55%).

Case-series studies included 7 patients treated with FMT for initial CDI, with mixed results. Six cases were part of a series of 14 patients with refractory CDI, and 1 case was part of a series of 4 patients. Among the 6 cases, 1 was cured after FMT. The other, single case received FMT as initial treatment of an episode of postantibiotic-associated colitis and had symptom resolution within 48 hours.

"[L]ow-strength evidence supports FMT as having a substantial effect and few short-term adverse events for adults with recurrent CDI," the authors wrote. "There is insufficient evidence about FMT for patients with refractory CDI or for initial treatment of CDI. Evidence is insufficient about whether treatment effects vary by FMT donor, preparation, or delivery method."

The author of an accompanying editorial stated that FMT is effective, provides durable cures, and can result in a cost savings of $17,000 per patient in recurrent cases. Remaining issues include the need for regulations to standardize the treatment, which is currently considered a biologic by the FDA, and the potential effects of transplanting a microbiome from one patient to another.

"The excitement about FMT is justified given its high efficacy in treating recurrent CDI, relative availability and simplicity, and favorable cost profile compared with other therapies," the editorial stated.

Restrictive vs. liberal transfusion strategies may not matter after cardiac surgery

Restrictive transfusion thresholds after cardiac surgery didn't improve outcomes compared to liberal ones, a study found.

The Transfusion Indication Threshold Reduction (TITRe2), a multicenter, parallel-group trial, recruited patients age 16 and older undergoing nonemergency cardiac surgery at 17 British centers. Patients with a postoperative hemoglobin level of less than 9 g/dL were randomly assigned to a restrictive transfusion threshold of hemoglobin level <7.5 g/dL (n=1,000) or a liberal transfusion threshold of <9 g/dL (n=1,003). In the liberal-threshold group, patients received 1 unit of red cells immediately after randomization and received another unit if the hemoglobin level remained or dropped below 9 g/dL again. In the restrictive-threshold group, patients received 1 unit if the hemoglobin level dropped below 7.5 g/dL and another unit if the level remained or dropped below 7.5 g/dL again.

The primary outcome was a composite of a serious infection (sepsis or a wound infection) or an ischemic event such as a permanent stroke, myocardial infarction, infarction of the gut, or acute kidney injury within 3 months. Health care costs, excluding the index surgery, were estimated from the day of surgery to 3 months afterward. Results appeared in the March 12 New England Journal of Medicine. 

Transfusion rates after randomization were 53.4% in the restrictive strategy group and 92.2% in the liberal strategy group. Primary outcomes occurred in 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group (odds ratio, 1.11; 95% CI, 0.91 to 1.34; P=0.30). There were more deaths in the restrictive-threshold group than in the liberal-threshold group (4.2% vs. 2.6%; hazard ratio=1.64; 95% CI, 1.00 to 2.67; P=0.045). The researchers noted that serious postoperative complications, excluding primary-outcome events, occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of participants in the liberal-threshold group. Total costs did not differ significantly between the groups.

The study creates new uncertainty about using a restrictive threshold for transfusion after cardiac surgery, the researchers wrote. The TITRe2 trial differs from previous observational studies of transfusion thresholds in that all the participants had cardiovascular disease and a substantial proportion of participants were likely to have been dependent on oxygen supplementation immediately after surgery. This group may have been at the limits of their cardiovascular reserve and may benefit from higher hemoglobin levels, the authors speculated. "Patients with cardiovascular disease may represent a specific high-risk group for which more liberal transfusion thresholds are to be recommended," they wrote.

The results are surprising, said an accompanying editorial. "Cardiac surgery departments should review the findings of the TITRe2 trial and decide which threshold they deem to be most appropriate for transfusion. Protocols should be developed to minimize deviation from the agreed-upon approach, and feedback should be provided to hold operators accountable to the institution's standard of care," the editorialist wrote.

Lighter Jogging May Be Better Than Strenuous Jogging.

TIME (2/3, Park) reports that research published in the Journal of the American College of Cardiology suggests that individuals “who push their bodies too hard may essentially undo the benefit of exercise.”

Bloomberg News (2/3, Ostrow) reports that investigators “looked at 5,048 people in the Copenhagen City Heart Study, a long-term examination of thousands of people that has been the basis for many reports on cardiovascular health.” The investigators “sifted 12 years’ worth of data on 1,098 healthy joggers and 413 healthy but sedentary non-joggers.” The investigators “found those who jogged one to 2.4 hours a week at a slow or average pace with no more than three running days in a week had the best survival rates.”

The Los Angeles Times (2/3, Morin) “Science Now” blog reports that “strenuous joggers – people who ran faster than 7 mph for more than four hours a week; or who ran faster than 7 mph for more than 2.5 hours a week with a frequency of more than three times a week – had a mortality rate that ‘is not statistically different from that of the sedentary group,’ the authors wrote.”