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OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Dr. Peter S Sever ,
After many years when research in hypertension was in the doldrums, several new and exciting therapeutic approaches are currently under critical evaluation, the first two of which have lead to a rekindling of interest in the role of the sympathetic nervous system in the pathogenesis of certain types of hypertension.
Renal denervation, following years of painstaking research led by Murray Esler, has become established as a recognised treatment for resistant hypertension. Michael Bohm summarised the series of Simplicity trials, which have consistently shown dramatic (circa 30 mmHg) reductions in systolic pressure in patients with drug resistant hypertension. Falls in blood pressure were maintained for more than 2 years post procedure.
The procedure is well tolerated and new devices have made the intervention simpler and quicker. Uptake of this technique into clinical practice has however, in general, produced blood pressure reductions that are less impressive. Critical evaluation of “resistant “hypertensive patients is necessary to eliminate undiagnosed secondary hypertension and, in the author’s experience, more than one third of these patients are poorly compliant with drug treatment. Nevertheless, new insights into pathophysiological mechanisms, particularly the role of the renal efferent nerves, provide new targets for future therapy.
Another innovative treatment was presented by Peter De Leeuw. Baroreceptor activation therapy leads to reductions in sympathetic outflow, heart rate, and vasodilatation. In uncontrolled studies, blood pressure falls were impressive and similar to those seen with renal denervation. However, in randomised controlled studies results were less impressive. Some interesting data were presented on the differential responses to right and left carotid stimulation and we look forward to further developments in this promising approach to treatment of resistant hypertension.
After many years of research on alternatives to mineralocorticoid receptor antagonists (a very real need because of the unwanted side effects, particularly of spironolactone), aldosterone synthase inhibitors are now under investigation. Stefano Taddei presented results from proof of concept studies showing 70-80% inhibition of the enzyme, but associated, surprisingly, with relatively modest reductions in blood pressure. He outlined further studies with a non-steroidal mineralocorticoid antagonist developed from the dihydropyridine family of compounds, which shows promise in early heart failure trials, but further data on blood pressure responses are needed.
Finally, more than a decade after the demise of omapatrilat due to excessive angioedema, the concept of combined RAAS blockade and inhibition of breakdown of natriuretic peptides has been revisited with a dual action angiotensin receptor blocker (valsartan) and neprilysin inhibitor. Bryan Williams presented the results of early clinical studies, the results of which look promising, with blood pressure reductions about twice as large as those seen with valsartan alone. His presentation contained interesting speculations that this compound may preferentially affect cardiac remodelling, myocardial ischaemia, small vessel disease and microvascular injury. If this is found to be the case in future evaluations, then real progress will have been made in the treatment of hypertension.
So, good news for now in the field of hypertension with more progress than we have seen for many years.
Novel therapeutic interventions for hypertension
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