Angiotensin receptor blockers and endpoint protection

These drugs prevent endpoints – and patients may need to be told

Angiotensin receptor blockers (ARBs) are selective and specific antagonists of the type‐1 angiotensin receptor. They are exceptionally well tolerated, i.e. the side‐effects are at the placebo level or even lower, since fewer patients report headache when compared to placebo. The main indication for ARBs is the treatment of hypertension. The blood pressure lowering abilities have been extensively investigated and appear to be of the same magnitude as other commonly prescribed antihypertensive drugs. Though the ideal combination seems be with low doses of hydrochlorothiazide, ARBs may in principle be combined with any other class of antihypertensive drugs. Since these drugs block at a different site from the renin–angiotensin system compared with angiotensin‐converting enzyme inhibitors (ACEIs), even combination with an ACEI may be meaningful in selected patients in order to provide additive blood pressure lowering effects and additional cardiovascular protection. When combining an ARB with potassium‐sparing diuretics, control of electrolytes is recommended. The drug should not be used in suspected or expected pregnancy, and effects on serum creatinine may be untoward in patients with renal artery stenosis, particularly if the condition is bilateral [1].

ARBs lower blood pressure by reducing peripheral vascular resistance while cardiac output is mainly unchanged. The effect sets in gradually and further decrease in blood pressure may be observed over several weeks after initiating treatment. Over months and years of treatment, there is regression of pathological structural changes in the smooth musculature in blood vessels and improved arterial or arteriolar compliance. Thus, ARBs work towards normalizing the typical pathological vascular structure and function in hypertensive patients and normalizing the hemodynamic abnormalities. There is also regression of left ventricular hypertrophy (LVH) and improvements in cardiac function. Experimental studies indicate that the cardiac effects may be explained, at least in part, by favorable effects on counteracting cardiac fibrosis. ARBs induce a modest improvement in insulin sensitivity, possibly through the beneficial effects on small arteries, thus improving nutritional blood supply to skeletal muscle and fat tissue, and ARBs have other potential beneficial effects on glucose metabolism. Lipids are mostly unchanged and renal function preserved [1].

Never before has a class of drugs become so quickly tested in large outcome studies in hypertension, diabetes, nephropathy, post‐myocardial infarction, heart failure and post stroke. Approximately 100,000 patients have presently been investigated in prospective randomized clinical trials with hard endpoints, and more large trials are ongoing. The current issue of Blood Pressure contains a thorough review of the therapeutic targets and cardiovascular protection by ARBs [2]. Some of the trials suggest superior protection against stroke, or protection in stroke patients; several show prevention of new onset diabetes, and heart failure seems to be very well prevented; besides that, ARBs are effective drugs in patients with overt heart failure. The review [2] summarizes the numerous potential beneficial effects of treating patients with these disorders with ARBs. Recently, some confusion was created regarding prevention of myocardial infarction by ARBs by a review of selected studies [3]. However, a later and updated overview including all the ARB trials [4] indicates that this class of drugs is neutral compared to other drug classes in this aspect.

In conclusion, therefore, ARBs are safe, exceptionally well tolerated, have target organ protective abilities and they prevent endpoints – a message that patients need to be told.