The evolution of renin-angiotensin blockade: angiotensin-converting enzyme inhibitors as the starting point.

The renin-angiotensin system has been a target in the treatment of hypertension for close to three decades. Several medication classes that block specific aspects of this system have emerged as useful therapies, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and, most recently, direct renin inhibitors. There has been a natural history to the development of each of these three drug classes, starting with their use as antihypertensive agents; thereafter, in each case they have been employed as end-organ protective agents. To date, there has been scant evidence to favor angiotensin receptor blockers or direct renin inhibitors over angiotensin-converting enzyme inhibitors in treating hypertension or in affording end-organ protection; thus, angiotensin-converting enzyme inhibitors remain the standard of care when renin-angiotensin system blockade is warranted.

Use of the ACE inhibitor zofenopril in the treatment of ischemic heart disease.

Zofenopril, an inhibitor of the angiotensin-converting enzyme (ACE), has recently been widely introduced into the pharmaceutical market. Its clinical safety and efficacy has been demonstrated in patients with hypertension and in patients with acute myocardial infarction (AMI). The Survival of Myocardial Infarction Long-term Evaluation (SMILE) project provided valuable information regarding the safety of early onset ACE inhibition with zofenopril after AMI and a greater perception of the early and late benefits. The SMILE-I study demonstrated that most benefits of ACE inhibition may be obtained early after AMI and persist after discontinuation of treatment. The SMILE-II study demonstrated that early zofenopril treatment (initiated <12 h) is safe and associated with a low rate of severe hypotension in thrombolyzed patients with acute myocardial infarction when administered in accordance with an adequate dose-titration scheme. Many other studies of clinical ACE-inhibitors (ACEIs) over the last 30 years have provided us with information in order to understand the effects of ACEIs and have demonstrated that patients benefit from ACEI treatment at different stages of the pathophysiological continuum of cardiovascular diseases. The current guidelines recommend that ACEIs should be used for routine secondary prevention in all patients with coronary artery disease and should be considered for all other patients with coronary or other vascular disease unless contraindicated.

Sir John Robert Vane: 29 March 1927 - 19 November 2004.

Sir John Robert Vane, who died on 19 November 2004, will be remembered as one of the most influential British pharmacologists. During his distinguish career he published more than 700 scientific papers and wrote or editing 20 books. His many awards include the Nobel Prize in Physiology or Medicine (1982) and a knighthood in 1984.