專題討論4:高血壓之診斷與治療

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S4-5
Novel Antihypertensive Therapies: Pharmacological and Instrumental
王宗道
臺大醫院內科部心臟內科

  Despite the numerous available drugs and resources for lifestyle modification, approximately half of all hypertensive patients do not achieve their blood pressure targets. Whether a result of physiological resistance to the pharmacological agents or to patients’ reluctance to adhere to lifelong pharmacological treatments, the prevalence of drug-resistant hypertension is clearly a problem. Hence, novel therapies to reduce elevated blood pressure, improve blood pressure control, treat resistant hypertension, and reduce the associated cardiovascular risk factors are still needed.

  A number of drugs are in development or being tested in clinical trials. Several of these agents have innovative mechanisms of action (an aldosterone synthase inhibitor, a natriuretic peptide agonist, a soluble epoxide hydrolase inhibitor, and an angiotensin II type 2 receptor agonist) or dual activity (a combined angiotensin-receptor blocker [ARB] and neutral endopeptidase inhibitor, an ARB and endothelin receptor A blocker, and an endothelin-converting enzyme and neutral endopeptidase inhibitor). Among them, the angiotensin-receptor/neprilysin inhibitor (ARNI) LCZ696 seems quite promising and effective against heart failure with preserved ejection fraction in the phase II trial. In addition, several novel fixed-dose combinations, including triple combinations, with the aim to facilitate proper blood pressure control were approved.

  Sympathetic overactivity is one of the essential mechanisms of hypertension. Several studies show that renal sympathetic nerves contribute to the development and perpetuation of hypertension. Recently developed endovascular catheter technology enables selective denervation of the human kidney, with radiofrequency energy delivered in the renal artery lumen, accessing the renal nerves located in the adventitia of the renal arteries. The Symplicity HTN-2 trial assessed 106 patients with treatment-resistant hypertension (baseline blood pressure of 178/96 mmHg) and showed that renal sympathetic denervation resulted in impressive reductions in mean office, home, and ambulatory blood pressure (28/10 mmHg, 20/12 mmHg, 11/7 mmHg, respectively) in 12 months, without substantial procedure-related complications. Moreover, the experience from longer-term follow-up shows that its effect remains evident up to 3 years.

  Although this procedure holds considerable promise, there are still many questions remained. Unlike angioplasty or catheter ablation for supraventricular arrhythmias, there is no way to assess whether renal denervation is successful or not and to predict who will respond favorably after the procedure. It is not certain whether renal denervation will be more effective than established drug therapy for resistant hypertension such as aldosterone antagonist. It is not certain whether the initial success of Symplicity trials could be replicated in the real world, particularly Asia.