Fourth-generation ARB offers cardioprotection
MOSES trial shows what sets eprosartan apart from other antihypertensives
Hypertension is the foremost cause of cerebrovascular disease worldwide. It also induces coronary-artery disease and is a risk factor for ventricular hypertrophy and the development of congestive heart failure. Next to diabetes, hypertension is the leading cause of renal failure. Hypertension also promotes peripheral vascular disease, a major risk factor for stroke.
In managing hypertension, the challenge for physicians, according to Dr. Venkata Ram, is to control the risk factors and stop the progression of vascular disease, so that patients do not a stroke, myocardial infarction, or renal disease.
"The greatest benefit of the treatment of hypertension is stroke [prevention]," said Ram, who chairs the board of governors of the American Society of Hypertension. "It reduces the risk of stroke by a large percentage. Fortunately, when we treat hypertension, we reduce the risk of many of [its] complications."
MOSES sets eprosartan apart
But Ram said reduction in systolic pressure appears to bring more benefits than reduction in diastolic pressure. This has been shown in several studies like the Multiple Risk Factor Intervention Trial, the Systolic Hypertension-Europe trial, and lately the Morbidity and mortality after Stroke-Eprosartan v. nitrendipine in Secondary prevention (MOSES) trial, results of which were presented by Ram in a local symposium organized by Solvay Pharma in December.
MOSES assessed how well eprosartan (Teveten), an angiotensin- receptor blocker (ARB), held up against the calcium-channel-blocker nitrendipine in reducing cerebro- and cardiovascular events in hypertensive stroke patients. Almost 700 patients in each treatment group were followed up for an average of two-and-a-half years.
Patients in both groups showed similar BP reduction. Most of them achieved the targeted systolic BP of 140 mm Hg within three months, lower at the end of the study.
But there ended the similarities. The nitrendipine group had a significantly higher number of combined cerebrovascular and cardiovascular events. Eprosartan offered a 21-percent reduction in the risk for the primary end points compared with nitrendipine (p = 0.014). Similarly, eprosartan registered fewer cardiovascular events--with a 25-percent reduction in risk (p = 0.06).
"With the same level of BP reduction, there appears to be greater protection bestowed in the group receiving the ARB, [which] cannot be attributed solely to blood pressure," Ram explained.
Ram suggested that the difference lies in the ARBs' effect on the renin-angiotensin-aldosterone system (RAAS). The RAAS, he said, is "an important mechanism that causes hemodynamic and structural abnormalities." Alone or together with the sympathetic nervous system (SNS), the RAAS, if inappropriately activated, causes vasoconstriction, cardiac and vascular hypertrophy, inflammation, atherosclerosis, and hypertension. Ram explained that unlike ACE inhibitors, ARBs block the RAAS where it matters most and without involving the ACE pathway, making it unlikely to cause edema.
Ram also distinguished fourth-generation eprosartan from other ARBs. It has the longest half-life and blocks the SNS to some extent. It also gently suppresses norepinephrine release from the neurons and decreases its activity in the blood vessel. "Therefore it is considered [to have] a dual mode of action," he said.
More benefits
Ram also noted a synergistic action when eprosartan is combined with a diuretic. It reduces arterial blood pressure greater than monotherapy. "This is a very good combination to achieve the goal levels of blood pressure in many patients with uncomplicated hypertension," he said. Metabolically, the combination also works toward maintaining euvolemia and eukalemia, since diuretic-induced hypokalemia and secondary hyperaldosteronism are blunted by ARB-related potassium retention and its associated pharmacologic hypoaldosteronism. Eprosartan is also known to reduce markers of inflammation such as monocyte chemotactic protein, an action not shared by diuretics. There is also significant reduction in superoxide generation associated with eprosartan use.
Like ACE inhibitors, ARBs also induce greater regression of left ventricular hypertrophy (LVH) than calcium-channel blockers at the same level of blood pressure, presumably by blocking the response of the cardiac myocyte to angiotensin. Ram said this is important because LVH is a strong predictor of cardiovascular complications. It increases the risk for myocardial ischemia, ventricular fibrillation and tachycardia, congestive heart failure, and sudden cardiac death.
Summing up, Ram stressed that lifestyle modification is not enough for most hypertensive patients. "We have to choose an effective drug or a combination that is well tolerated. We must always protect the blood vessels against endothelial dysfunction, and prevent cardiac hypertrophy and coronary disease, prevent nephrosclerosis, and most importantly, reduce the risk of stroke."
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