Lessons from antihypertensive drug trials that employed "stepped care": the case for rationalized individualized...

In clinical trials it has been common practice to use a diuretic as the first drug and then add antiadrenergic agents, vasodilators ad seriatim. This monolithic recipe, called "stepped care," has produced useful information on compliance and long-term effectiveness in various population studies. However, major clinical trials using this approach in the United States, Australia, and Oslo have failed to demonstrate significant protection from coronary artery disease--the major sequela of hypertension. In fact, in the MRFIT trial all patients receiving stepped care with diastolic blood pressures less than 95 did significantly worse than those receiving usual care, and those with control diastolic blood pressures of 90-105 and abnormal EKGs also did significantly worse than controls. Even in the HDFP trial--the only one that even claims cardioprotection from stepped care--the death rate for white women with control diastolic blood pressures greater than 105 was actually threefold higher than those receiving usual care. Such results indicate that a single recipe for all, based on a single process hypothesis, may be hazardous. A critical current issue is the question of whether it matters how the blood pressure is reduced. Thus, diuretics reduce pressure by lowering volume and flow, whereas the modern agents, CEI inhibitors and calcium influx inhibitors, reduce pressure while actually improving flow to the target organs.(ABSTRACT TRUNCATED AT 250 WORDS)