Here's What You Need To Know About The New Blood Pressure Medication Guidelines

If you have high blood pressure, your treatment may soon change.

New medication guidelines published Dec. 18 in the Journal of the American Medical Association (JAMA) suggest that not everyone with high blood pressure needs to be on drugs for it.

Here's the bottom line: If you are 60 or older and the first number of your blood pressure is less than 150, you don't necessarily need to be on medication for it.

Keep in mind that this choice is up to your doctor — blood pressure is just one risk factor for heart disease, and people using medication to maintain a number in the 140s without serious side effects should not suddenly stop and let that number drift up.

The new guideline will decrease the number of people medicated for their high blood pressure, but not everyone's happy about it.
Blood pressure and heart disease

People with naturally low blood pressure (BP) have a lower risk of cardiovascular problems and live longer. High blood pressure, when left uncontrolled, can lead to heart attack, stroke, and aneurysm. Smoking, obesity, and inactivity are all risk factors for high blood pressure, which also has a genetic component that's passed down in families.

Lifestyle changes like exercise and healthy eating are our first line of defense against heart disease and are especially encouraged if BP creeps above the "normal" level of 120/80.
But not everyone gets their blood pressure low enough with just lifestyle changes, and if that first number climbs above 140 — a condition affecting about two-thirds of people 60 and older — you officially have high blood pressure, or hypertension.
Until now, that's when doctors suggest medication to help lower BP. About 50 million Americans are on blood pressure drugs of all different kinds, including diuretics ("water pills"), beta blockers (which slow your heartbeat), and ACE inhibitors (which help stop blood vessels from narrowing).
Why change the guidelines?

"Over the last ten years, doctors have had the notion that the lower blood pressure is, the better," study researcher Paul A. James, of the University of Iowa, told Business Insider.

The problem? While there's no question that medication is crucial for people at high risk of heart attack and stroke, the researchers concluded that there's not enough evidence that driving that number all the way to 140 — rather than simply to 150 — provides much additional benefit.
The panel arrived at the new guidelines after reviewing previous studies that looked at how patients fared on a variety of approaches to lowering BP — different drugs and exercise regimens, for example.
Blood pressure drugs, like any medications, have some side effects (such as dizziness), which can be especially serious in older adults. So, the new guidelines may come as a relief for some.
Still, says James, "I'm absolutely sure there will be controversy."

Not everyone's happy

James is right. Some people are wary that the new guidelines aren't officially endorsed by the National Heart, Lung, and Blood Institute (NHLBI).
The NHLBI initially assembled the panel but has since stopped being involved in making guidelines, so in the end they weren't certified by any official organization. Eric D. Peterson of the Duke Clinical Research Institute told Business Insider that this lack of official endorsement may leave some practicing doctors scratching their heads about how to proceed.
Most experts point out that more research needs to be done. "We have very limited data to tell us what the right thresholds are," said Peterson.
While he agrees that no study says 140 is the magic BP number for beginning treatment in older adults, he notes that one major study showed a notable benefit when older patients brought their number from the mid-150s to the mid-140s — so 150 isn't necessarily right either.
Though Peterson agrees that too-aggressive treatment to lower a patient's blood pressure down to a specific number can harm overall health, he compared the target numbers to speed limits: If you tell people the maximum speed is 65, they may drive at 75. Similarly, leaving the target at 140 may mean more Americans actually bring their number below 150.

"There is always some slippage between targets set for clinicians and [those] actually achieved in routine practice," he writes in an editorial in the same issue of JAMA.

CARBOPLATIN USEFUL ADDITION IN NEOADJUVANT TREATMENT OF TRIPLE NEGATIVE BREAST CANCER

The addition of carboplatin to a neoadjuvant regimen significantly increased the rate of pathologic complete response in patients with triple-negative breast cancer. The results from the CALGB/Alliance 40603 study were reported at the 2013 San Antonio Breast Cancer Symposium (Abstract S5-01).

Bevacizumab (Avastin) was also evaluated in the study and had some effect when added to chemotherapy, but, due to its toxicity, was felt to be a less promising candidate for this approach.

“Based on these results, and those of theGeparSixto trial, if you decide that a patient with triple-negative breast cancer should receive neoadjuvant chemotherapy, then it makes sense to add carboplatin to your neoadjuvant regimen. You can comfortably do so with acceptable additional toxicities,” saidWilliam M. Sikov, MD, FACP, of Brown University, Providence, Rhode Island, who presented the findings.

The rationale for the study was the achievement of pathologic complete responses in about one-third of patients with triple-negative disease after taxane-based neoadjuvant chemotherapy, the likelihood that patients with pathologic complete responses will have improved recurrence-free and overall survival, the activity of platinum analogues in advanced triple-negative disease, and the finding that bevacizumab can increase response rates and time to progression, he said.

Study Details

The phase II CALGB 40603 study enrolled 454 patients with stage II/III triple-negative breast cancer, randomly assigning participants to standard neoadjuvant chemotherapy or chemotherapy plus either carboplatin, bevacizumab, or the combination of carboplatin/bevacizumab. 

Patients were randomly assigned in a 2×2 schema to receive weekly paclitaxel for 12 courses plus dose-dense anthracycline/cyclophosphamide with or without either the addition of bevacizumab every 2 weeks for nine cycles or the addition of carboplatin AUC 6 every 3 weeks for four cycles. The primary endpoint was pathologic complete response in the breast, and a secondary endpoint was pathologic complete response in the breast and the axillae.

Highest Rate Achieved With Combination

The investigators evaluated the effect of carboplatin on all patients receiving it (alone or in combination) and the same for bevacizumab.

“The addition of carboplatin to standard neoadjuvant chemotherapy significantly increased the pathologic complete response in the breast and also in the breast plus axillae,” Dr. Sikov reported.

For patients receiving carboplatin, 60% achieved a pathologic complete response, compared to 46% of those not receiving carboplatin, an increase of 76% (P = .0018). Defined by no disease in the breast or axillae, rates were 54% with carboplatin vs 41% without carboplatin, a 71% increase (P = .0029), Dr. Sikov reported.

Bevacizumab was active as well, yielding a statistically significant difference in the breast but not the axillae. Among patients receiving bevacizumab, 59% achieved a pathologic complete response in the breast, while 48% achieved this without bevacizumab, a 58% increase (P = .0089). Absence of residual disease in both breast and axilla was observed in 52% of patients receiving bevacizumab, and in 44% of those not receiving this drug, a 36% nonsignificant increase (P = .0570). 

When carboplatin and bevacizumab were used in combination in addition to chemotherapy, 67% of patients achieved a pathologic complete response, however, a significant treatment interaction between the two drugs was not shown.

Bevacizumab More Toxic

Bevacizumab was considered more toxic, as was the combination. The total number of patients with a serious adverse event was 15 in the chemotherapy-alone arm, 39 with chemotherapy plus bevacizumab, 39 with chemotherapy plus carboplatin, and 46 with chemotherapy plus carboplatin/bevacizumab. Bevacizumab was associated with more grade 3 hypertension, infections, and postsurgical complications, with a slight increase in thrombosis and bleeding problems. Patients receiving carboplatin were more likely to experience neutropenia and thrombocytopenia, Dr. Sikov said.

Bevacizumab was discontinued in 23% of assigned patients, vs 6% to 13% for other agents.

“Bevacizumab did increase pathologic complete responses but at the cost of significant toxicities, and we don’t think it should be routinely added,” Dr. Sikov said at a press briefing.

Other Studies Support Carboplatin Use

Dr. Sikov noted that several studies now show that the addition of carboplatin increases pathological complete responses in patients with triple-negative disease, although recurrence-free and overall survival benefits have not yet been observed, largely due to short follow-up and lack of statistical power. He said that the general assumption is that achievement of pathologic complete response will, indeed, improve long-term outcomes, and he said that he incorporates carboplatin in the neoadjuvant setting in his patients. 

Lajos Pusztai, MD, DPhil, of Yale University, New Haven, Connecticut, the formal discussant of the paper, said there is mounting evidence for using carboplatin, but less support for bevacizumab. He and his own research team have estimated that carboplatin plus chemotherapy will result in a 15% reduction in the risk for recurrence, “but this will most likely not reach statistical significance,” largely attributed to small sample size and limited statistical power.

“This provides a valuable new treatment option for patients with high-risk triple-negative disease,” Dr. Pusztai concluded. “The impact on survival may be modest, but real, I believe. Patient-level benefits, other than survival, exist that can be derived from more effective neoadjuvant chemotherapies.”

The study was funded by the National Institutes of Health, Genentech, and the Breast Cancer Research Foundation. Dr. Sikov reported no potential conflicts of interest.

AGE NOT A BARRIER TO HSCT

Age is no longer a barrier to hemopoietic stem cell transplantation (HSCT), but ageism still exists, and many older patients are not being referred for a transplant, even though transplantation offers the only chance of a cure for hematologic malignancies.

Advances in transplant technology have greatly improved success rates, so that the outcomes in older patients are now similar to those seen in younger patients, as shown here in several presentations at the American Society of Hematology (ASH) 55th Annual Meeting.

"However, these advances have not penetrated through to the general oncology community and are not widely appreciated, so the idea persists that transplants are only feasible for younger patients (under 55 years of age)," commented Mary Horowitz, MD, scientific director of the Center for International Blood and Marrow Transplant Resercah (CIBMTR) and chief of the Division of Hematology and Oncology at the Medical College of Wisconsin, in Milwaukee.

"There are many 55- to 65-year-olds who could benefit from a transplant, but these patients are not being referred by their primary oncologist," she commented in an interview with Medscape Medical News. "A 60-year-old now would be expected to live to 85 or so, and if they suddenly develop a life-threatening disease that is curable, well it is worth trying to cure it," she said.

Age Not a Barrier

That chronologic age need no longer be a barrier was illustrated in a study reported at the meeting by Yvette Kasamon, MD, of the Johns Hopkins Kimmel Center in Baltimore, Maryland, and highlighted today in a conference press briefing.

Dr. Kasamon discussed data on 273 patients who underwent a haploidentical, or "half-matched," bone marrow transplant (BMT) without prior myeloablative therapy but with high-dose post- trasplantation cyclophosphamide. These patients had poor-risk hematologic malignancies (56% lymphoma, 35% acute leukemia or myelodysplastic syndrome, 9% other disorders), and 15% of patients had undergone autologous bone marrow transplantation.

"The similarly positive outcomes we observed among patients in their 50s, 60s, and 70s clearly illustrate that advanced age need no longer be a significant barrier to successful outcomes after half-matched BMT," Dr. Kasamon said.

All 3 age groups showed similar 2-year probability of progression-free survival (PFS) and overall survival (OS), and there was also no statistically significant difference in the risk for nonrelapse death or severe graft-vs-host disease.

Patients' Age (years)	Est 2-Year PFS	Est 2-Year OS
50 - 59	39%	51%
60 - 69	36%	56%
70 - 75	39%	44%

"These results underscore that a reduced-intensity, related haploidentical transplant should be considered a very reasonable treatment option for suitable patients up to at least age 75 who require a transplant," Dr. Kasamon said. In fact, she added, her clinic has recently raised the age limit to 75 years for a transplant.

However, she also noted that there are not many treatment centers that carry out haploidentical transplantations on a regular basis, and that, age aside, the successful outcomes in this study using this approach represent an advance in their own right.

Until recently, haploidentical transplants carried excessive risk, she pointed out. The use of post-transplant cyclophosphamide for prophylaxis of graft-vs-host disease has been a major advance, she said, and with the use of this treatment, haploidentical transplantation has become a safe and effective treatment in the outpatient setting.

The outcomes with haploidentical transplants with post-transplant cyclophosphamide are now similar to those seen with matched BMT, Dr. Kasamon added.

Chimeric Antigen Receptor-CAR LYMPHOCYTES A NEW PROMISING TREATMENT

There is palpable excitement here at American Society of Hematology (ASH) 55th Annual Meeting over results that are being reported with a new approach to treatment, engineered T cells. Although the results come from pilot clinical trials conducted in a small number of patients with leukemia and lymphoma, these are patients with very aggressive and refractory disease, and yet some of them have shown dramatic responses to the therapy, going into complete remission and no longer showing visible signs of tumor on computed tomography (CT) scans.

"It looks like the disease has disappeared after a single infusion of these engineered T cells," commented James Kochenderfer, MD, from the Experimental Transplantation and Immunology Branch of the National Cancer Institute (NCI) in Bethesda, Maryland.

However, he cautioned that there is a significant patient variation in both efficacy and toxicity with this approach.

Several groups in the United States are working on this approach to treatment, and some have teamed up with pharmaceutical companies. The T cells developed at NCI have been licensed to Kite Pharmaceuticals, and a similar approach developed at the University of Pennsylvania, which has the most clinical data so far, has been licensed to Novartis.

Some observers say that this pharmaceutical company involvement, as well as accelerated approval for an urgent medical need, could result in these therapies becoming available as early as 2016, but others forecast a longer development time and suggest the therapies will not be available for clinical use until 2020.

Like a Smart Bomb

The novel approach to therapy involves extracting T cells from the patient, subjecting the cells to chimeric antigen receptor (CAR) cell engineering, and then infusing the engineered T cells back into the patient.

The engineering, which takes about 10 days, changes the T cell in 2 ways. First, it adds a receptor that targets the CD19 antigen that is found on most leukemic cells; when the cells are inserted back into the patient’s body, they home in on this antigen, latch on and destroy the leukemic cell. Second, the process inserts a viral vector mechanism into the cells which – once the cells have latched on to the leukemia – triggers these T cells to expand and proliferate, so that they seek out and destroy all the remaining leukemic cells.

There is tremendous excitement over this approach, because it acts like a smart bomb, said Mary Horowitz, MD, scientific director at the Center for International Blood and Marrow Transplant Research and chief of the Division of Hematology and Oncology at the Medical College of Wisconsin, in Milwaukee. Whereas bone marrow transplantation is like carpet bombing of a city in order to destroy a specific building, these CAR cells are like smart bombs that seek out and destroy just the building, she commented to Medscape Medical News.

The clinical results have been dramatic and unprecedented in such advanced disease.

Results in Lymphoma

Dr. Kochenderfer presented results from 15 adult patients with advanced B cell lymphomas (abstract 168), including 9 patients with chemotherapy-refractory large cell lymphoma such as primary mediastinal B cell lymphoma and diffuse B cell lymphoma. They received reduced-intensity conditioning with cyclophosphamide and fludarabine and then an infusion of their own T cells that had been CAR engineered.

Thirteen of the 15 patients treated were evaluable for response, and 12 of those 13 responded: 7 patients had complete remissions, and 5 had partial remissions, Dr. Kochenderfer said. The remaining patients had stable disease.

Dr. Kochenderfer gave details of one of the patients who had a complete remission, showing CT scans with visible tumor in the liver and abdomen prior to the treatment, and none visible after treatment. This was a patient who had undergone 10 prior therapies, including many different combinations of rituximab plus chemotherapy regimens, and the disease progressed a month after chemotherapy finished, so she was "clearly refractory," he said.

"Our data provide the first true glimpse of the potential of this approach in patients with aggressive lymphomas that, until this point, were virtually untreatable," Dr. Kochenderfer told journalists at an ASH press briefing at which these novel therapies were highlighted.

"We are particularly encouraged by the partial and complete responses that we observed in a number of patients with diffuse large B cell lymphomas who had exhausted all other treatment options…and who are not generally thought to be good candidates for hematopoietic stem cell transplantation," he added.

However, he tempered his enthusiasm by adding that "this approach is still an early-stage experimental therapy."

ORAL ARSENIC AS GOOD AS IV FOR APL

An oral arsenic-based formula treats acute promyelocytic leukemia (APL) as effectively as an IV formulation, auguring the promise of out-patient treatment for this condition, Chinese researchers say.

In a multicenter phase III trial reported online October 14 in the Journal of Clinical Oncology, they compared the oral formula, Realgar-Indigo naturalis (RIF) containing tetra-arsenic tetra-sulfide (As4 S4), to intravenous arsenic trioxide (ATO), for induction and maintenance.

The components of RIF include Indigo naturalis and Radix salviae miltiorrhizae, which promote transport of arsenics intracellularly. Triggered by higher aquaglyceroporin 9 (AQP9) expression, they have clear synergistic effects with As4S4 on the differentiation and apoptosis of APL cells, according to senior author Dr. Xiao-Jun Huang of the Peking University People's Hospital in Beijing and colleagues.

In all, 242 patients with newly-diagnosed APL were randomly assigned to oral RIF (60 mg/kg) or ATO (0.16 mg/kg). All patients also received all-trans retinoic acid (ATRA; 25 mg/m2) during induction therapy.

Patients who achieved complete remission (CR) then received consolidation chemotherapy with homoharringtonine, cytarabine, daunorubicin, and mitoxantrone.

Maintenance treatment consisted of sequential ATRA plus either RIF or ATO for two years.

The primary end point was the rate of disease-free survival (DFS) at two years, which was assessed for noninferiority with a 10% noninferiority margin.

After a median follow-up time of 39 months the results show DFS at two years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6%, and the lower limit of the 95% CI of DFS difference was greater than the 10% noninferiority margin, confirming noninferiority (p<0 .001="" p="">

No significant differences were noted between the RIF and ATO groups in complete remission rate (99.1% vs 97.2%; p=0.62) or in overall survival at 3 years (99.1% vs 96.6%; p<0 .18="" p="">

Rates of adverse events were similar in the two groups.

The authors also note that the toxicity of arsenic-containing agents is a major concern. However, this study showed no severe adverse effects despite the two-year continuation period, with a cumulative dose of approximately 2,500 mg.

Analysis of arsenic levels in the plasma, urine, nails, and hair of patients indicated that there was no significant accumulation.

The authors note that previous studies have shown, as did theirs, that the frequency and extent of arsenic toxicity are much milder during maintenance therapy than during induction therapy.

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"Other contributing factors were sufficient support therapy, enrolling only patients with a white blood cell count less than 50x10 to the 9th per liter, favorable characteristics of the enrolled patients (good performance status and exclusion of patients older than age 60 years), and experience in treating APL22; the latter is recognized as a potentially important factor in the outcome," the authors write.

Acute promyelocytic leukemia (APL) is characterized by the translocation t(15;17) and the expression of a PML/RAR alpha fusion protein that is diagnostic of the disease. To closely observe the molecular kinetics, the study authors also analyzed serial bone marrow samples from 93 patients. Expression of PML-RAR alpha in the RIF and ATO groups was similar at diagnosis.

They found, at the end of consolidation therapy, that the PML-RAR transcript was undetectable in any patient in either group. The two relapsed patients had detectable PML-RAR transcript levels before hematologic relapse.

The authors conclude "oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients."

Dr. Francesco Lo-Coco, a hematologist at the University of Tor Vergata in Rome and an expert on the use of arsenic trioxide in PML, told Reuters Health by email that the study was well-conducted and represented "remarkable progress."

"This study hold promise that in the near future we will be able to cure APL not only sparing chemo but also on an outpatient basis (after the initial two to three weeks, when patients have to stay in hospital given the hemorrhagic risk)," Dr. Lo-Coco said.

He says toxicity profiles are similar and patients receiving the oral treatment will clearly have better quality of life.

"In fact, the IV infusion patients have to spend almost half a day in hospital each day. This affects negatively their normal life, work and other activities," he writes.

He says that just because the authors of the present study did not include patients older than 60 years, does not mean it doesn't work in the elderly.

"We know from other studies it works equally well," he said.

NO EVIDENCE FOR ORAL CANCER SCREENING

The evidence is insufficient to assess the balance of benefits and harms of screening by primary care providers for oral cancer in asymptomatic adults, according to updated guidelines from Virginia A. Moyer, MD, MPH, on behalf of the US Preventive Services Task Force (USPSTF). The guidelines will be published online November 26 in the Annals of Internal Medicine.

"According to National Cancer Institute data, the estimated new cases and deaths from oral cancer (oral cavity and pharynx) in the United States in 2013 is 41,380 new cases and 7890 related deaths," Dipika Bumb, BDS, MDS, an oral oncologist and tobacco control officer at the Indian Cancer Society in New Delhi, India, told Medscape Medical News when asked for independent comment. "The burden of disease is not less."

Squamous cell carcinoma accounts for 90% of all cases of oral cavity and pharyngeal cancer. More than half of persons with oral and pharyngeal cancer have regional or distant metastases when they are first diagnosed. The USPSTF therefore stated that screening for oral cancer may be helpful if potentially malignant disorders can be identified earlier and treated successfully.

"In clinical practice, screening can help in detection of oral cancer at a very early stage, where the lesions are either reversible or can be treated efficiently," Dr. Bumb said. "The changes occur at a slower pace in oral mucosa, [but the need for] oral cancer screening lacks recognition all over the world. Awareness among the medical community and government is the need of the hour."

USPSTF Deems Evidence to Be Insufficient

The revised guidelines, which update the 2004 USPSTF recommendation on screening for oral cancer, apply to screening of the oral cavity performed by primary care providers, and not by dental providers or otolaryngologists. The USPSTF reviewed the evidence both on whether screening for oral cancer was associated with lower morbidity or mortality and on the accuracy of the oral screening examination to detect oral cancer or potentially malignant disorders that are highly likely to progress to oral cancer.

On the basis of this evidence review, the USPSTF concluded that the current evidence was insufficient to evaluate the balance of benefits and harms of screening for oral cancer in asymptomatic adults aged 18 years or older who are seen by primary care providers. This is an I-level statement.

However, the USPSTF recognizes that clinical decisions, as well as policy and coverage decisions, involve more considerations than evidence of clinical benefits and harms alone. Therefore, clinicians should individualize decision making to the specific patient or situation.

"Potentially malignant disorders can be detected by visual examination by trained clinicians," Dr. Bumb said."The agony of the situation is that clinicians don't realize this, leading to late diagnosis and referral. During screening, the habit of tobacco and alcohol use can be regulated by professional counseling, leading to reduction in risk for other noncommunicable diseases."

The USPSTF found inadequate evidence that the oral screening examination accurately detects oral cancer or that screening for oral cancer and treatment of screen-detected oral cancer reduces morbidity or mortality. Furthermore, they found inadequate evidence on the harms of screening, as no study reported on harms from the screening test, from false-negative results, or from false-positive results leading to unnecessary surgery, radiation, and chemotherapy.

Because the natural history of screen-detected oral cancer or potentially malignant disorders is unclear, the degree of overdiagnosis resulting from screening is unknown.

Potential Harms of Not Screening

If practitioners stop screening for oral cancer, Dr. Bumb is concerned about the following potential consequences:

• Abandoning screening could substantially increase the incidence of oral cancer and other tobacco/alcohol/HPV-related disorders in the young population.
• Tobacco and alcohol cessation could become difficult, with interrelated addiction leading to further deterioration of health.
• Treatment of oral cancer not detected until late in the course results in disfigurement and disability of the face and neck.
• Treatment of oral cancer not detected until late in the course hinders delivery of palliative care and harms the individual's psychological integrity.

"In developing countries like India, oral cancer accounts for 95% of all cancers, and screening serves as the best tool in reduction of mortality and morbidity," Dr. Bumb said. "Like breast lumps are helpful in detection of breast cancer at an early stage, similarly, oral potentially malignant disorders (OPMD) are a stepping stone towards development of oral cancer."