Also included in the HOPE301 or EUROPA296 trials were participants who did not have one of these conditions but did have multiple cardiac risk factors, and it seems that they also benefited from use of ACE ARBs also play an important role in vascular protection. They bind in a competitive or insurmountable manner to the type 1 angiotensin II receptor, increasing plasma renin activity, plasma renin, and angiotensin I and II concentra- tions. In patients with hypertension or cardiovascular disease, ARBs produce reductions in BP equivalent to those achieved with ACE inhibitors.804 These agents significantly reduce LV mass and stroke incidences compared with beta blockers and improve outcomes in diabetic nephropathy and heart fail- ure.563,565,792,805 A meta-regression analysis of 26 trials com- pared the effects of ACE inhibitors and ARBs on major vascular events by BP effects.804 Treatment with ACE inhib- itor based regimens was associated with a reduction in the risk for stroke (by 19%), IHD (by 16%), and heart failure (by 27%) for each 5 mm Hg reduction in BP; corresponding figures for the reduction in risk for ARBs were 26%, 17%, and 12%, respectively. There were no significant differences between ARB- and ACE inhibitor based regimens in the risk of stroke, IHD, and heart failure for each 5 mm Hg reduction in BP. When these outcomes were assessed at zero BP reduction, the risk reduction for IHD was significantly greater for ACE inhibitors than for ARBs (P0.002). Furthermore, unlike ARBs, ACE inhibitors were associated with a signif- icant additional risk reduction for IHD of 9% (P0.004), without differences seen for stroke or heart failure versus ARBs. It is therefore recommended that ARBs be substituted for ACE inhibitors in patients with SIHD and hypertension who are intolerant of ACE inhibitors.563,565,792,804,805 4.4.2.4. Influenza Vaccination Class I 1. 