The relentless crumbling of the renin-angiotensin system (RAS)-blockade halo

In 1999 a thorough review article in the New England Journal of Medicine stated that “Patients with diabetes mellitus may represent a special sub-group for whom calcium antagonist therapy increases the risks of cardiovascular complications (1).” This dictum was met with unanimous approval by the medical community since at that time it was clear beyond any doubt that diabetes was the sole domain of angiotensin converting enzyme (ACE) inhibitors. In fact, in what they called a “consensus approach,” a rather distinguished group of nephrologists and endocrinologists concluded that “in patients with diabetes… the preferred initial therapy is an ACE-inhibitor, with the dose titrated upward to the moderate or high dose range, as tolerated (2).” So powerful was the marketing machine of Big Pharma at that time that rather solid evidence of benefits of calcium channel blockers (CCB) in diabetes (3), showing that CCB based therapy reduced cardiovascular morbidity and mortality about twice as much in diabetic than in non-diabetic hypertensive patients (Table 1) was completely ignored. The statement of Mancia et al. (4) pertaining to the diabetic subpopulation of the INSIGHT study “that nifedipine could be considered as first-line therapy for hypertensive diabetics,” was met with disbelief in the US and considered an aberration.