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Diabetics Face Increased Treatment-resistant Hypertension Risk

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Major finding: Diabetes patients with treatment-resistant hypertension had a 6.2% combined rate of death, myocardial infarction, and stroke over a 2-year period, compared with a 3.8% rate in nondiabetics.

Data source: The 3A registry, which enrolled nearly 15,000 patients with diabetes from 899 physician practices in Germany.

Disclosures: The German 3A registry is sponsored by Novartis. Dr. Friedrich said she had no relevant financial disclosures. Dr. Schmieder has been a consultant to, and a speaker on behalf of, Medtronic, which markets a renal denervation device.

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Options exist for managing treatment-resistant hypertension

The relatively high rate of major adverse cardiac and cerebrovascular events seen in patients with diabetes and treatment-resistant hypertension in this study is worrying, but several different approaches could potentially improve outcomes in these patients.


Dr. Per-Henrik Groop

The clearest message is that physicians need to do a better job getting their hypertensive patients to take all their prescribed medications. Patients who need four drugs to control their blood pressure will often take only a fraction of the pills they are supposed to take. A lot of treatment-resistant hypertension results from poor patient compliance or physician negligence.

Another option that my colleagues and I have recently explored is slow breathing, at a rate of about 15 breaths per minute, as is often done in yoga. My associates and I published results 2 years ago showing that deep breathing can improve the blunted baroreflex sensitivity often seen in patients with diabetes (Diabetologia 2011;54:1862-70). This approach may also be effective for reducing blood pressure in patients who are not ideally responsive to antihypertensive drugs. With deep breathing, patients can exert some control over their autonomic nervous system.

Another nondrug option is renal denervation, but for the time being I see this as a last resort. I have reservations about widely using renal denervation right now because I believe it remains investigational. There is no way to assess the effect of denervation treatment at the time it is delivered, the long-term consequences of the treatment are not yet fully known, and in many patients the effect is modest, especially when measured with ambulatory blood pressure monitoring. For some patients with treatment-resistant hypertension, renal denervation may be the only option for getting their blood pressure to their target level, but for the time being, I would use it very cautiously.

Dr. Per-Henrik Groop is professor and head of nephrology at the University of Helsinki (Finland). He made these comments in an interview. He has been a consultant to, or a speaker on behalf of, Boehringer Ingelheim, Novartis, Cebeix, Novo Nordisk, Merck, Abbott, Genzyme, and Eli Lilly.


 

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BARCELONA – Patients with treatment-resistant hypertension and diabetes face a significantly increased risk for major cardiovascular adverse events, compared with those without diabetes, a study has shown.

The combined rate of death, myocardial infarction, and stroke was 6.2% among patients with treatment-resistant hypertension (TRH) and diabetes, and 3.8% in patients with TRH but no diabetes during 2 years of follow-up of more than 8,000 patients enrolled in a German registry, Dr. Stefanie Friedrich reported at the annual meeting of the European Association for the Study of Diabetes.

"Patients with treatment-resistant hypertension, and in particular patients with diabetes, need to have their blood pressure reduced to less than 140/90 mm Hg, combined with other organ-protective therapies, to improve their outcomes," said Dr. Friedrich of the division of nephrology and hypertension at Alexander-Friedrich University in Erlangen-Nürnberg (Germany).

"If you don’t succeed with blood pressure control with drugs, you should move along to another alternative like renal denervation with no inertia," said Dr. Roland E. Schmieder, professor and chief of nephrology and hypertension at the university and a collaborator with Dr. Friedrich on this study. "In this registry nothing happened for many of these resistant patients during 2 years. I would recommend waiting no more than about 6 months if patients remain hypertensive despite maximum medical therapy. If drugs do not succeed after 6 months, you need to go to the next step, which for some patients could be renal denervation," he said in an interview. "This should be the approach for all patients with treatment-resistant hypertension, but especially when patients have diabetes."

Data on renal denervation show that it is as effective in patients with diabetes as in those without diabetes, Dr. Schmieder said. Renal denervation devices first became available for routine European use in 2010, but remain investigational in the United States.

Their study used data collected from the nearly 15,000 patients enrolled in the Registry for Ambulant Therapy With RAS-Inhibitors in Hypertensive-Patients in Germany (3A registry). The registry enrolled patients with either newly diagnosed hypertension or established hypertension that required treatment intensification at 899 physician practices in Germany during October 2008 through April 2009. The study assigned patients to receive aliskiren (Tekturna), an ACE inhibitor, or an angiotensin receptor blocker in a 4:1:1 ratio, but otherwise participating physicians were allowed to manage these patients by whichever regimen they preferred. The current analysis focused on the 8,698 patients from the 3A registry who had 2-year follow-up, and the 2,772 patients from this group with TRH, defined as an office-measured blood pressure of 140/90 mm Hg or higher despite treatment with at least three antihypertensive medications.

The TRH subgroup included 1,170 with either type 1 or type 2 diabetes, 47% of all patients with diabetes followed in the registry for 2 years, and 1,602 patients without diabetes, 26% of the enrolled patients without diabetes followed for 2 years. These TRH prevalence rates show that "resistant hypertension is common in outpatients, especially patients with diabetes," Dr. Friedrich said. At the time they entered the registry, the TRH patients had an average blood pressure of 162/91 mm Hg, with similar averages in both the diabetic and nondiabetic subgroups. At entry, the patients with diabetes averaged 71 years of age, while those without diabetes were an average of 68 years old. The median duration of hypertension was 11 years in the diabetes patients and 8 years in those without diabetes.

After 2 years, 55% of the TRH patients with diabetes and 48% of those without diabetes remained at blood pressures above the goal of less than 140/90 mm Hg. The average level of hemoglobin A1c among the diabetes patients was 6.8% at baseline, and 6.9% after 2 years.

In addition to having a significantly greater rate of combined adverse cardiac and cerebrovascular events at 2 years, the patients with diabetes also had significantly more events for each of the three outcomes included in this composite: The rate of all-cause death was 4.4% in the patients with diabetes and 2.9% in those without; the incidence of myocardial infarction was 1.3% in the diabetes patients and 0.6% in the others; and stroke incidence was 1.4% in the patients with diabetes and 0.8% in those without, Dr. Friedrich reported.

The German 3A registry is sponsored by Novartis. Dr. Friedrich said she had no relevant financial disclosures. Dr. Schmieder has been a consultant to, and a speaker on behalf of, Medtronic, a company that markets a renal denervation device.

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