Effectiveness of the direct renin inhibitor, aliskiren, in patients with resistant hypertension.

Currently there is no consensus regarding which add-on therapy to use in resistant hypertension. We have conducted an open observational study of the use of aliskiren in resistant hypertensive patients. Forty-three patients with resistant hypertension were included in the study. The inclusion criteria were as follows: 1) office blood pressure (BP) > 140/90 mmHg despite treatment with at least three or more antihypertensive drugs; 2) no prior therapy with aliskiren; and 3) no renal insufficiency. Follow-up BP was determined at 1 and 3 months. Baseline BP was 153 ± 12/79 ± 12 mmHg. After 3 months, systolic BP (SBP) and diastolic BP (DBP) dropped significantly: 140 ± 19/73 ± 13 mmHg (P < 0.0001). Twenty-one patients (49%) had an office BP < 140/90 mmHg, and these patients were assigned to the good BP control group. Another 22 were placed into the poor BP control group. BP reductions from baseline in the good BP control group (SBP/ DBP: 19 ± 11/8 ± 7 mmHg) were larger than those in the poor BP control group (5 ± 15/3 ± 9 mmHg, P < 0.05). Mean BP (MBP) values at baseline, 1, and 3 months were higher in the poor BP control group. There was no significant difference in pulse pressure at baseline between the 2 groups. In multivariate analysis, only MBP at baseline correlated with lack of BP control. Aliskiren administration to resistant hypertensive patients was effective in reducing BP. The present findings suggest aliskiren may be useful as a fourth-line or fifth-line treatment added to other drugs in the treatment of resistant hypertension.

Angiotensin-converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients.

OBJECTIVES: We compared the effects of perindopril and losartan on endothelium-dependent coronary vasomotor and fibrinolytic function. BACKGROUND: The renin-angiotensin system regulates the vascular fibrinolytic balance. However, the effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on coronary fibrinolytic function have not been compared in hypertensive patients. METHODS: Forty-five patients with hypertension were randomly assigned to three groups: 16 patients were treated with perindopril (4 mg/day) for four weeks; 15 were treated with losartan (50 mg/day) for four weeks; and 14 were not treated with either perindopril or losartan (control group). Graded doses of bradykinin (BK) (0.2, 0.6, and 2.0 microg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. RESULTS: Bradykinin induced dose-dependent increases in CBF in all groups. The increases in CBF induced by BK in the perindopril and losartan groups were significantly greater than those in the control group. Net coronary tissue-type plasminogen activator (t-PA) release was enhanced by BK in all groups, and the increase in the perindopril group was greater than that in the losartan and control groups. Bradykinin did not alter plasminogen activator inhibitor type 1 levels in any of the groups. CONCLUSIONS: Perindopril and losartan similarly augment BK-induced coronary vasodilation. Perindopril may have a greater potential to enhance the BK-induced coronary release of t-PA than losartan.

Long-term outcome of primary percutaneous transluminal coronary angioplasty for low-risk acute myocardial infarction in patients older than 80 years: a single-center, open, randomized trial.

BACKGROUND: Although coronary reperfusion therapy with thrombolytic agents or percutaneous transluminal coronary angioplasty (PTCA) immediately after acute myocardial infarction (AMI) has survival benefits for younger patients, the effect of coronary reperfusion therapy for very elderly (aged 80 years and older) patients with AMI remains controversial. METHODS AND RESULTS: We studied 120 patients aged 80 years and older at relatively low risk with AMI. The patients were randomized into a primary PTCA group (n = 61) or a "conservative" no-PTCA group (n = 59). Long-term follow-up examination was conducted with regard to endpoints, which included all causes of death, cardiac death, nonfatal re-MI, the development of congestive heart failure, and cerebral vascular accident. End-diastolic volume index and end-systolic volume index were significantly increased in both groups at follow-up examination 6 months after AMI. However, left ventricular ejection fraction, end-diastolic volume index, and end-systolic volume index were similar between both groups. With endpoints of all causes of death, cardiac death, reinfarction, congestive heart failure, and cerebral vascular accident, a 3-year Kaplan-Meier event-free survival rate analysis revealed no significant benefits in the PTCA group. Anteroseptal MI, multivessel disease, and left ventricular ejection fraction were significantly associated with the combined events with multivariate Cox proportional hazards analysis results. CONCLUSION: First, primary PTCA for very elderly patients with AMI appears to have few beneficial effects on combined events during a 3-year period. Second, early PTCA did not prevent left ventricle remodeling after AMI in patients with AMI at relatively low risk.

Coronary endothelium-dependent and independent vasomotor responses in patients with hypertrophic cardiomyopathy.

It is well known that coronary flow reserve (CFR) is decreased in patients with hypertrophic cardiomyopathy (HCM), but it is unclear whether coronary endothelial function is impaired. Coronary endothelial function and CFR in the coronary macro- and microcirculation was evaluated in 14 patients with HCM and 11 control subjects. Acetylcholine (ACh), bradykinin (BK) and papaverine were infused into the left coronary artery. Coronary cross-sectional area was determined by quantitative coronary angiography and coronary blood flow (CBF) was determined by the product of the coronary cross-sectional area and CBF velocity measured by an intracoronary Doppler guidewire. Acetylcholine at 100 microg induced diffuse coronary spasms of the left anterior descending coronary arteries in 3 of the patients with HCM. The changes in the diameter of the left anterior descending coronary artery and the increases in CBF induced by BK (0.2, 0.6, and 2.0 microg/min) did not differ between the 2 groups. CFR was lower in the HCM group than in the control group (p<0.01). Moreover, the ratio of BK-induced CBF increase to papaverine-induced CBF increase was comparable between the 2 groups. Endothelium-dependent vasodilation of the epicardial and resistance coronary arteries induced by BK was preserved despite the decreased CFR in patients with HCM.