eprosartan and Ventricular-Dysfunction--Left

It is clear that the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) play key roles in sustaining elevated blood pressure, subsequently resulting in increased risks of cardiovascular (CV), cerebrovascular and kidney disease. Modifying these systems with antihypertensive agents has led to the discovery that their effects may indeed extend beyond controlling blood pressure. Within blood vessels, angiotensin II type 1 receptor blockers (ARBs) inhibit postsynaptic angiotensin II type 1 receptors (AT1). The ARB eprosartan, in contrast to other ARBs, also inhibits prejunctional AT1 receptors, which regulate noradrenaline release. The positive effects of eprosartan on blood pressure have been studied extensively, and are due to modulation of both the RAS and the SNS (through stimulation of the angiotensin II type 2 [AT2] receptor). Of importance to isolated systolic hypertension, trough sitting systolic blood pressure (SBP) is also significantly reduced with eprosartan. In addition, many studies have shown how the benefits of eprosartan go beyond that of blood pressure control alone. Eprosartan has shown positive effects on vascular inflammation and resistance to oxidation and/or modification of low-density lipoprotein. A wealth of other positive actions are associated with eprosartan treatment, including effects on platelet aggregation, kidney function and structure, progressive left ventricular dysfunction and central SBP. Clinical studies have clearly demonstrated the benefits of RAS blockade alongside the additional effects beyond blood pressure control with eprosartan treatment. These data place eprosartan as an effective agent to prevent CV, cerebrovascular and renal complications associated with high blood pressure.

Topics: Acrylates; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Atherosclerosis; Humans; Imidazoles; Kidney Diseases; Platelet Aggregation; Renin-Angiotensin System; Sympathetic Nervous System; Thiophenes; Ventricular Dysfunction, Left

Patients with left ventricular ejection fraction below 45% (mean 39+/-3.7%) were randomized either to captopril (n=33) or eprosartan after miocardial infarction (n=33) on days 3-7 of myocardial infarction. All patients were subjected to echocardiography and 40 to perfusion myocardial scintigraphy with (99m)TC-Technetril. Myocardial viability was defined as presence of perfusion reserve in dysfunctional segments during test with nitroglycerin. Dysfunctional myocardium was found to be viable in 62.5% of patients. Fifty six patients completed 3 months follow up and were restudied. By the time of the second study 28 patients continued captopril (37.5-150 mg, average dose 72+/-34.2 mg/day) and 28 - eprosartan (300-600 mg, average dose 471+/-151 mg/day). Captopril was stopped or its dose corrected in 28% of patients. In eprosartan group there were no side effects which required withdrawal of the drug. Similar increases of ejection fraction occurred on both groups (from 38+/-2.1 to 49+/-6.7%, p<0.001 and from 39+/-4 to 51+/-6.5%, p<0.001, in eprosartan and captopril groups, respectively). Magnitude of left ventricular ejection fraction change did not depend on the presence of viable myocardium. However in both treatment groups improvement of myocardial perfusion and decrease of left atrial dimensions were found only in patients with viable myocardium at initial study.

Topics: Acrylates; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Severity of Illness Index; Systole; Thiophenes; Ventricular Dysfunction, Left

1. We examined the effects of eprosartan, an AT(1) receptor antagonist, on the progression of left ventricular (LV) dysfunction and remodelling in dogs with heart failure (HF) produced by intracoronary microembolizations (LV ejection fraction, EF 30 to 40%). 2. Dogs were randomized to 3 months of oral therapy with low-dose eprosartan (600 mg once daily, n=8), high-dose eprosartan (1200 mg once daily, n=8), or placebo (n=8). 3. In the placebo group, LV end-diastolic (EDV) and end-systolic (ESV) volumes increased after 3 months (68+/-7 vs 82+/-9 ml, P<0.004, 43+/-1 vs 58+/-7 ml, P<0.003, respectively), and EF decreased (37+/-1 vs 29+/-1%, P<0.001). In dogs treated with low-dose eprosartan, EF, EDV, and ESV remained unchanged over the course of therapy, whereas in dogs treated with high-dose eprosartan, EF increased (38+/-1 vs 42+/-1%, P<0.004) and ESV decreased (41+/-1 vs 37+/-1 ml, P<0.006), Eprosartan also decreased interstitial fibrosis and cardiomyocyte hypertrophy. 4. We conclude that eprosartan prevents progressive LV dysfunction and attenuates progressive LV remodelling in dogs with moderate HF and may be useful in treating patients with chronic HF.

Topics: Acrylates; Angiotensin Receptor Antagonists; Animals; Disease Progression; Dogs; Heart Failure; Imidazoles; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Thiophenes; Ventricular Dysfunction, Left