Difficult-to-Treat or Resistant Hypertension: Etiology, Pathophysiology, and Innovative Therapies

Despite the many therapeutic options available today for the treatment of hypertension, a sizable number of patients still remain resistant to treatment. The prevalence of resistant hypertension in the general population under optimal conditions is about 3–5%. Although several factors and conditions can be identified and corrected a percentage of hypertensive patients remain with unacceptably high blood pressure levels. The high prevalence of hypertension in the general population renders this small percentage significant, in terms of actual patient numbers. This special issue of the journal expoars a whole spectrum of topics related to resistant hypertension: several articles address pathophysiolog and secondary causes of resistant hypertension and modern approaches to therapy. Of interest is the referance to the newer interventional approaches, that is, Baroreceptor stimulation therapy and catheter based sympathetic renal denervation

P-624: Changes in plasma renin match the antihypertensive effects of aliskiren in patients with hypertension: Placebo/irbesartan-controlled trial with the orally active renin inhibitor aliskiren

For several decades, the lack of oral availability and poor antihypertensive effects of renin inhibitors (RI), despite seemingly powerful inhibition of conventionally measured plasma renin activity (PRA), have discredited RI as cardiovascular drugs. Aliskiren is a novel orally effective RI with antihypertensive potency comparable to losartan or irbesartan. The present study investigated the effects of aliskiren and irbesartan on PRA, measured by the reliable antibody trapping technique, as well as on plasma active renin concentration (ARC) and sitting systolic blood pressure (SBP). In 569 patients with mild to moderate hypertension (baseline sphygmomanometric sitting blood pressure 152±12/99±4 mmHg, mean±SD), PRA and ARC, as well as SBP were measured before and after 8 weeks of treatment with once daily oral doses of aliskiren (150, 300 or 600mg), irbesartan 150mg or placebo. The effects of study treatments on PRA, ARC and SBP are summarized in the Table. Treatment N PRA (ng/mL/h) ARC (pg/mL) SBP (mmHg) Baseline Week 8 Baseline Week 8 Baseline Week 8 Placebo 111 0.72 0.64 6.2 5.6 152 ± 12 147 ± 18 Aliskiren 150mg 112 0.66 0.20 6.0 15.3 151 ± 11 140 ± 14 Aliskiren 300mg 115 0.59 0.17 6.1 21.0 152 ± 10 137 ± 14 Aliskiren 600mg 113 0.64 0.16 5.8 34.9 153 ± 12 137 ± 16 Irbesartan 150mg 118 0.64 1.33 5.5 11.3 153 ± 11 140 ± 16 PRA and ARC values are geometric means; SBP values are mean ± SD Aliskiren reduced PRA by 69%, 71% and 75% at 150, 300 and 600mg respectively, while irbesartan doubled PRA. Most of the antihypertensive effect of aliskiren was obtained with the lowest dose, but higher doses slightly further decreased SBP. Aliskiren 150mg and irbesartan 150mg provided similar increases in ARC and hence comparably blocked the renin-angiotensin system (RAS), and the achieved SBP was also the same. Aliskiren 300mg and 600mg caused greater increases in ARC compared with irbesartan 150mg (p<0.05), and further decreases in SBP. The dose-dependent increases in ARC observed with aliskiren document increasing blockade of the RAS. In conclusion, aliskiren provides a parallel reduction in PRA and SBP, a dose-dependent blockade of the RAS and is at least as effective as irbesartan at comparable dosages (150mg

Mecanismos y tratamiento de la cardiopat\ueda hipertensiva: desde hipertrofia del ventriculo izquierdo hasta insuficiencia cardiaca

La cardiopat\ueda hipertensiva (HHD) es una gama de anormalidades que representa la acumulaci\uf3n de adaptaciones funcionales y estructurales durante mucho tiempo a aumento de la carga de presi\uf3n arterial. La hipertrofia del ventr\uedculo izquierdo (LVH), el aumento de la rigidez vascular y ventricular, y la disfunci\uf3n diast\uf3lica son caracter\uedsticas intermedias notorias de este s\uedndrome, que operan en paralelo con la cardiopat\ueda isqu\ue9mica, y que a la postre causan insuficiencia cardiaca (HF) si se tratan de manera inadecuada. Los resultados de la HHD y de la HF mejoran con los antihipertensivos a cualquier etapa del padecimiento. En esta revisi\uf3n se describe un modelo integrado de la evoluci\uf3n natural, la patogenia y la farmacoterapia de la cardiopat\ueda hipertensiva, que concuerda con las recomendaciones del Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, incluso una modificaci\uf3n importante de la pauta respecto a HF publicada por el American College of Cardiology y la American Heart Association, que incluye a la LUH y a la disfunci\uf3n diast\uf3lica como padecimientos susceptibles de tratamiento dentro del continuo de HHD-H

Aliskiren monotherapy does not cause paradoxical blood pressure rises: meta-analysis of data from 8 clinical trials.

Angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics all cause reactive rises in plasma renin concentration, but particularly high levels have been reported with aliskiren. This prompted speculation that blockade of plasma renin activity with aliskiren could be overwhelmed, leading to paradoxical increases in blood pressure. This meta-analysis of data from 4877 patients from 8 randomized, double-blind, placebo- and/or active-controlled trials examined this hypothesis. The analysis focused on the incidence of paradoxical blood pressure increases above predefined thresholds, after &gt; or =4 weeks of treatment with 300 mg of aliskiren, angiotensin receptor blockers (300 mg of irbesartan, 100 mg of losartan, or 320 mg of valsartan), 10 mg of ramipril, 25 mg of hydrochlorothiazide, or placebo. There were no significant differences in the frequency of increases in systolic (&gt;10 mm Hg; P=0.30) or diastolic (&gt;5 mm Hg; P=0.65) pressure among those treated with aliskiren (3.9% and 3.1%, respectively), angiotensin receptor blockers (4.0% and 3.7%), ramipril (5.7% and 2.6%), or hydrochlorothiazide (4.4% and 2.7%). Increases in blood pressure were considerably more frequent in the placebo group (12.6% and 11.4%; P&lt;0.001). None of the 536 patients with plasma renin activity data who received 300 mg of aliskiren exhibited an increase in systolic pressure &gt;10 mm Hg that was associated with an increase in plasma renin activity &gt;0.1 ng/mL per hour. In conclusion, the incidence of blood pressure increases with aliskiren was similar to that during treatment with other antihypertensive drugs. Blood pressure rises on aliskiren treatment were not associated with increases in plasma renin activity. This meta-analysis found no evidence that aliskiren uniquely causes paradoxical rises in blood pressure