Protective effects of renin-angiotensin blockade beyond blood pressure control

Antihypertensive drugs exert a number of blood pressure-independent benefits. However, demonstrating the clinical significance of these effects may be difficult for a number of reasons. First, blood pressure can be measured in the clinic, at home and over the 24-h period by ambulatory monitoring. Second, differences between these measures mean that achieving equivalent blood pressure reductions in two treatment arms may be difficult, if not impossible. Furthermore, even small differences in blood pressure can translate into significant effects on cardiovascular risk, especially in the later stages of the cardiovascular continuum. In large clinical trials, other errors limiting the sensitivity to treatment differences include high patient dropouts and unplanned crossover. In addition, as so many patients fail to achieve blood pressure goals even in clinical trials where patient's and physician's motivation is high, the need for cardiovascular protection beyond blood pressure control is unequivocal. Clinical trials of angiotensin II receptor blockers have suggested significant effects beyond blood pressure control, which are observed throughout and with greater consistency in the early phases of the cardiovascular continuum. There may also be differences between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. Conclusive demonstration that these blood pressure-independent effects do exist will require, however, a much more accurate and extended assessment of the blood pressure effects of the drugs. Journal of Human Hypertension (2009) 23, 570-577; doi: 10.1038/jhh.2008.171; published online 29 January 2009