Hypertension Treatment News: Device Promising for Resistant Hypertension
Device Promising for Resistant Hypertension
Although a baroreflex activation therapy device designed to treat resistant hypertension lowered blood pressure, it failed to meet two of five coprimary endpoints in a pivotal trial, researchers found.
The trial did not meet endpoints regarding short-term systolic blood pressure response and safety of the procedure to implant the device, according to John Bisognano, MD, PhD, of the University of Rochester in New York, and colleagues.
It did, however, show a benefit on sustained response, safety of baroreflex activation therapy, and safety of the device, the researchers reported online in the Journal of the American College of Cardiology.
The findings were originally reported at the American College of Cardiology meeting in April.
The authors noted that all five of the coprimary endpoints needed to be met to establish the overall efficacy and safety of the Rheos device.
However, they wrote, “the weight of the overall evidence suggests that over the long-term, baroreflex activation therapy can safely reduce systolic blood pressure in patients with resistant hypertension. Future clinical trials will address the limitations of this study and further define the therapeutic benefit of [the therapy].”
They added that “new technology for delivering baroreflex activation therapy that involves a less invasive implant procedure has been developed by [Rheos manufacturer] CVRx and is currently undergoing confirmatory study in Europe.”
The Rheos system is targeted to the 20% to 30% of patients with hypertension who are resistant to treatment, defined as a failure to achieve a blood pressure less than 140/90 mm Hg with maximally tolerated doses of at least three antihypertensives, including a diuretic.
The system involves leads strung from a pulse generator implanted in a patient’s chest to each carotid sinus. The electrical impulses stimulate the baroreceptors there, reducing sympathetic activity and increasing parasympathetic activity, which causes the blood vessels to open and heart rate and blood pressure to drop.
In the current phase III trial, 265 patients with resistant hypertension — who were taking an average of 5.2 antihypertensives at baseline — were implanted with the device, which was turned off.
After one month, they were randomized 2:1 to have the device turned on for 12 months (181 patients) or to have the device turned off for the first six months and then turned on for the last six months (84 patients).
At six months, the mean decrease in systolic blood pressure was greater in the group with the device turned on, although the difference did not reach statistical significance (16 versus 9 mm Hg, P=0.08).
By 12 months, when both groups had had the device turned on for at least six months, the mean reduction in systolic blood pressure from baseline was 25 mm Hg in both groups.
The trial failed to meet two of the five coprimary endpoints:
The percentage of patients who achieved at least a 10 mm Hg drop in systolic pressure from baseline at six months was not significantly greater in the group with the device on (54% versus 46%, P=0.97).
The percentage of patients in both groups who remained free of serious procedure- or system-related adverse events 30 days after implantation (74.8%) did not exceed the goal of 82%. Most events were related to lead placement and involved transient or permanent nerve injury in 4.4 to 4.8% of patients.
The trial did meet the other three endpoints:
The percentage of patients who had the device turned on for the entire 12-month study who had a significant blood pressure response at six months and who maintained that response at one year (88%) exceeded the goal of 65%.
The percentage of patients who remained free of adverse events related to baroreflex activation therapy from 30 days to six months post implantation did not differ between the groups by more than 15% (91.7% with the device on for 12 months versus 89.3% in the other group). That met criteria for noninferiority (P<0.001).
The percentage of patients in both groups who remained free of hypertension-related and serious device-related adverse events from 30 days to 12 months post implantation (87.2%) exceeded the goal of 72%.
A prespecified ancillary analysis showed that a greater percentage of patients who had the device turned on achieved a systolic blood pressure of 140 mm Hg or less at six months (42% versus 24%, P=0.005), although the proportion was about 50% in both groups by one year.
Researchers admitted that certain assumptions had to be made that could not be verified beforehand because of the novelty of the device.
Also, variability in blood pressure measurements could have been reduced if the trial design had allowed for several qualifying measurements.
Pluristem stem-cell out-license comes into effect
The license that Pluristem Therapeutics Ltd. (Nasdaq:PSTI; DAX: PJT: PLTR) awarded to United Therapeutics Corporation (Nasdaq: UTHR) to use of its PLacental eXpanded (PLX) cells to develop and commercialize a cell-based product for the treatment of pulmonary hypertension came into effect yesterday. Pluristem awarded the license on June 19, after obtaining permission from the Office of the Chief Scientist.
United Therapeutics paid Pluristem a down payment of $4 million when the agreement was signed, and it will make up to $55 million in milestone payments, and cover the costs of development and clinical trials for this indication. If the product is commercialized, United Therapeutics will also pay royalties.
Pluristem’s share price fell 5.7% on Nasdaq yesterday to $3.15, giving a market cap of $131 million, but rose 1.3% premarket trading today, but fell 2.8% by mid-afternoon on the TASE today to NIS 10.89.
JIPMER to test genes for personalised treatment
PUDUCHERRY: At a time when the world is looking towards personalised medicine, the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) has taken the lead among government hospitals in the country by introducing pharmacogenomics testing of genes to provide personalised treatment.
Initially, the testing would be done for CYP2C9, CYP2C19 and VKORC1 genes which would promote personalised treatment of patients with epilepsy, peptic ulcer, diabetes, hypertension, stroke, cardiac diseases, deep vein thrombosis and patients undergoing valve therapy, said Dr C Adithan, professor and head , department of pharmacology, JIPMER. He added that it was the first step towards personalised medicine.
The idea behind the pharmogenomic testing is to understand the genetic make up of an individual associated with drug metabolism and treatment response to drugs. Pharmocogenomics stems from the concept that one drug doesn’t fit all. Instead of the patient undergoing a ‘trial and error’ of various drugs, all it takes is one DNA test to analyse one’s genes which are the code for drug metabolising enzymes.
Knowing the patient’s genetic constitution would enable the physician to prescribe more confidently the appropriate drug. One could do away with the adverse drug reaction (ADR) or non-response. He added that there was no accounting for the cost effectiveness in the long run.
The testing would be done in the PCR laboratory of JIPMER. After the logistics are put in place, the testing would begin in the next three to six months and thereafter testing of other genes would be introduced in a phased manner, he said.
The department of pharmacology, JIPMER, also has a drug information centre, where on an average 70 area reports are received on ADR.
Symposium on Hepatitis B
A symposium on ‘hepatitis B-resolving the dilemma’ was held at JIPMER on Saturday.
Dr Sankaranarayanan from Chennai KK trust hospital who spoke on hepatitis in children emphasised on the importance of hepatitis B vaccination in high risk groups. The methods of testing used to diagnose acute and chronic hepatitis B were elaborated by Dr George Kurien.
Dr Piramanayagam from Apollo hospital, Chennai, spoke on hepatitis B and pregnancy and Dr Thomas Alexander from Pondicherry Institute of Medical Sciences on hepatitis B in adults.
Dr Biju Pottakkat from JIPMER who spoke on liver cancer detailed the various therapeutic options in liver cancer associated with Hepatitis B. Dr Lakshmi and Dr Amit Goel, gastroenterologists from JIPMER, outlined several aspects to prevent hepatitis B in adults and children.
The symposium urged the delegates to increase the awareness among health workers and public about hepatitis B and its complications.
Dangers of hypertension
Hypertension sharply increases the risk of heart attack, stroke, heart failure, and kidney failure
Hypertension is one of the most common medical problems in the US; at present, one of every American adults has high blood pressure. It’s a shame since many, if not most, cases could be prevented by simple lifestyle measures such as dietary salt restriction, weight control, and moderate exercise.
Hypertension is also one of the most important medical problems in America; it sharply increases the risk of heart attack, stroke, heart failure, and kidney failure. That’s also a shame, since excellent drugs are available to lower blood pressure and prevent these deadly complications.
You don’t have to bring your pressure down to normal (below 120/80 millimetres of mercury) to get the benefit of treatment. Simply lowering an elevated blood pressure to modest treatment targets (below 140/90 for people without certain complicating conditions; below 130/80 for those with diabetes, kidney disease, heart failure, or atherosclerosis) can cut the risk of heart attack and stroke by about 34 per cent and 21 per cent, respectively.
But the biggest shame of all is that only about 44 per cent of hypertensive patients reach these goals.
There are many explanations for these sorry results. A study highlights one of the most important reasons: poor adherence to medication regimes.
The study
Researchers in Italy obtained information from 400 primary care physicians to identify 18,806 patients ages 35 and older who were first diagnosed with hypertension during 2000 and 2001. None of the patients had been diagnosed with coronary artery disease, heart failure, or cerebrovascular disease when they entered the study; the scientists followed the patients for an average of 4.6 years to track the onset of these complications.
All patients in the study received prescriptions for one or more effective antihypertensive medications. Based on how often they filled their prescriptions, the patients were classified into three adherence levels: high (pills on at least 80 per cent of days), medium (40 per cent to 79 per cent), or low (below 40 per cent).
At the start of the study, only 8 per cent were in the high-adherence group; by the end of the study, 19 per cent achieved this level. Intermediate adherence fell from 41 per cent to 32 per cent, and low adherence was stubbornly high, declining only minimally from 51 per cent to 49 per cent.
Did adherence matter? It sure did. As compared with their low-adherence counterparts, the high-adherence patients enjoyed a 38 per cent lower risk of acute cardiovascular events during the study period.
Perspectives
Although previous research has demonstrated that good adherence to medication results in lower blood pressure readings, fewer hospitalisations, and lower medical costs, the study is one of the first to document reduced cardiovascular events. Curiously, though, the study did not provide information on blood pressure readings, nor did it rate the patients according to their adherence to the lifestyle changes that can also lower blood pressure. Despite these limitations, the research serves to emphasize the importance of compliance with medication.
In randomised clinical trials of anti-hypertensive therapy, only 5 per cent to 10 per cent of motivated, supervised volunteers discontinue their medications over the course of a year, but in real world clinical practice, discontinuation rates can be 50 percent or higher within just six months. But why?
Doctors often blame their patients, but physicians who fail to explain the importance of continually taking medication, long-term lifestyle changes, and careful blood pressure monitoring and follow-up surely deserve some of the blame. And patients are often discouraged by complex medication schedules, expensive drugs, or both.