New class of agents for treatment of hypertension: focus on direct renin inhibition

Aliskiren, the first orally active direct renin inhibitor, is an effective antihypertensive drug with distinctive characteristics, including good blockade of the renin-angiotensin system, a prolonged duration of action, pharmacologic effects that persist after drug discontinuation, and favorable tolerability comparable with placebo. The blood pressure-lowering effect of aliskiren monotherapy is similar, if not superior, to that of other first-line antihypertensive agents, and is greatly enhanced when aliskiren is combined with various other antihypertensive medications, without any adverse drug interactions. Aliskiren is also an effective and well tolerated therapy in special populations, including diabetic, obese, and elderly hypertensives. Beyond its blood pressure-lowering efficacy, results from experimental and clinical trials suggest that aliskiren has positive effects on markers of cardiovascular and renal damage. The ASPIRE (Aliskiren Study in Post-MI patients to Reduce rEmodelling) HIGHER clinical trials program is further assessing whether the promising pharmacologic properties of aliskiren translate into reduced risk of adverse cardiovascular and renal outcomes

Effect of telmisartan and ramipril on atrial fibrillation recurrence and severity in hypertensive patients with metabolic syndrome and recurrent symptomatic paroxysmal and persistent atrial fibrillation

This study evaluated the effect of telmisartan, ramipril, and amlodipine on atrial fibrillation (AF) recurrence and severity in hypertensive patients with metabolic syndrome. A total of 391 hypertensive outpatients with metabolic syndrome, in sinus rhythm but with at least 2 episodes of AF in the previous 6 months were randomized to telmisartan, ramipril, or amlodipine for 1 year. At the first AF, ventricular rate (VR) and plasma cardiac troponin I (TnI) were evaluated. P-wave dispersion (PWD) and procollagen type I carboxy-terminal peptide (PIP) were evaluated before and after 12 months of treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were similarly and significantly reduced by all treatments (P < .001). In all, 49\% of patients treated with amlodipine had a recurrence of AF as did 25.5\% of patients with ramipril and 12.9\% of patients with telmisartan (P < .01 vs amlodipine and P < .05 vs ramipril). Ventricular rate and TnI at the first AF recurrence were significantly lower with telmisartan and ramipril than with amlodipine. P-wave dispersion was reduced by ramipril (-5.1 ms, P < .05) and even more by telmisartan (-11 ms, P < .01). Telmisartan and ramipril induced a similar PIP reduction (-52.8 and -49.8 µg/L, respectively, P < .01). These findings suggested that in these patients telmisartan was more effective than ramipril in reducing AF recurrence and severity as well as in improving PWD, despite a similar BP reduction and a similar improvement in cardiac fibrosis. This could be related to a specific effect of telmisartan on atrial electric remodeling

Effect of valsartan and ramipril on atrial fibrillation recurrence and P-wave dispersion in hypertensive patients with recurrent symptomatic lone atrial fibrillation

This study compared the effect of antihypertensive treatment with valsartan or ramipril on atrial fibrillation (AF) recurrence, on P-wave dispersion, (PWD) and on serum procollagen type I carboxy terminal peptide (PIP).A total of 369 mild hypertensive (systolic blood pressure (SBP) >140 and/or 90 < diastolic blood pressure (DBP) < 110 mm Hg) outpatients in sinus rhythm but with at least two episodes of AF in the previous 6 months were randomized to valsartan (n = 122), ramipril (n = 124), or amlodipine (n = 123) for 1 year. Clinic blood pressure (BP) and a 24-h electrocardiogram (ECG) were evaluated monthly. Patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. PWD and serum PIP levels were evaluated before and after each treatment period.SBP and DBP were significantly reduced by the three treatments (P < 0.001). A total of 46 (47.4\%) patients treated with amlodipine had a recurrence of AF as did 26 (27.9\%) patients treated with ramipril (P < 0.01 vs. amlodipine) and 16 (16.1\%) patients treated with valsartan (P < 0.01 vs. amlodipine and P < 0.05 vs. ramipril). The Kaplan-Meyer analysis showed a significant reduction of AF episodes in the valsartan group (P = 0.005 log-rank test) as well as in the ramipril group (P = 0.021), even if at a lesser degree. PWD values were significantly reduced by ramipril (-4.2 ms, P < 0.05) and even more by valsartan (-11.2 ms, P < 0.01), the difference being significant (P < 0.01). Serum PIP levels were reduced by ramipril (-49.7 microg, P < 0.001) and valsartan (-49.3 microg, P < 0.001).Despite similar BP lowering, valsartan and ramipril were more effective than amlodipine in preventing new episodes of AF, but the effect of valsartan was greater than that of ramipril. This could be related to the greater PWD reduction observed with valsartan

Matrix metalloprotease activity is enhanced in the compensated but not in the decompensated phase of pressure overload hypertrophy

BACKGROUND: During the transition of pressure overload hypertrophy (POH) to heart failure (HF) there is intense interstitial cardiac remodeling, characterized by a complex balance between collagen deposition and degradation by matrix metalloproteases (MMPs). This study was aimed at investigating the process of cardiac remodeling during the different phases of the transition of POH to HF. METHODS: Guinea pigs underwent thoracic descending aortic banding or sham operation. Twelve weeks after surgery, left-ventricular (LV) end-diastolic internal dimension and ventricular systolic pressure were measured by combined M-mode echocardiography and micromanometer cathetherization. The MMP activity, tissue-specific MMP inhibitors (TIMPs), and collagen fraction were evaluated in LV tissue samples by zymography, ELISA, and computer-aided analysis, respectively. RESULTS: Banded animals were divided by lung weight values into either compensated left-ventricular hypertrophy (LVH) or HF groups, as compared with sham-operated controls. All HF animals exhibited a restrictive pattern of Doppler transmitral inflow, indicative of diastolic dysfunction, and developed lung congestion. Compensated LVH was associated with increased MMP-2 activity, which was blunted after transition to HF, at a time when TIMP-2 levels and collagen deposition were increased. CONCLUSIONS: The cardiac remodeling process that accompanies the development of POH is a phase-dependent process associated with progressive deterioration of cardiac function

Beta-blockers in chronic treatment after acute myocardial infarction

Postinfarction treatment trials have demonstrated that beta-blockers are beneficial after myocardial infarction (MI), significantly reducing postinfarction cardiac mortality and nonfatal reinfarction, aside from bringing about an improved quality of life. Such cardioprotective action is probably mediated by both antiarrhythmic and anti-ischemic effects of these drugs. Beta-Blockers without ISA seem to be more effective in reducing cardiac mortality than those with ISA, which is probably due to their different effects on heart rate. Patients deriving major benefit from beta-blocker therapy after MI should be "high risk," elderly, and, perhaps, hypertensive patients. The suitable duration of postinfarction beta-blocker therapy is unknown: results from recent long-term trials speak in favor of continuous postinfarction beta-blocker therap