New vs. Old Drugs for Hypertension

Source: Hansson L, et al. Lancet 1999;354:1751-1756.

Concern has been raised about the efficacy of newer antihypertensive agents for the prevention of cardiovascular morbidity and mortality in elderly patients. Thus, the results of the Swedish Trial in Older Patients with Hypertension-2 (STOP-HTN-2) study are of interest. From 312 centers in Sweden, 6614 elderly patients with hypertension (HTN) were randomized to conventional drugs (diuretics, beta blockers) or angiotensin-converting enzyme inhibitors (ACE1) or calcium antagonists. All the patients were older than 70 years of age (average 76) and two-thirds were women. Criteria for HTN were systolic blood pressure greater than 180 or diastolic greater than 105 mmHg or both. End points included stroke, myocardial infarction (MI), and cardiovascular death on an intent-to-treat basis. Blood pressure lowering was similar for the three groups, with an average 35/17 mmHg difference. Compliance at the last visit (24 months) was about 60% for all three groups and 46% were receiving more than one drug. Total adverse events were similar on the three treatments, with about one-quarter of patients experiencing at least one event. The most common side effect of conventional treatment was dyspnea (12%); ACE1 was cough (30%) and calcium antagonist was edema (26%). Cardiovascular death rates were similar in the three groups, as was the combined end point of stroke, MI, or cardiac death. However, fatal or nonfatal MIs were significantly less on ACE1 as compared to the calcium blocker group, as was congestive heart failure. Also, the results in diabetics were similar in the three groups. Hansson and colleagues conclude that new and old antihypertensive agents were similarly effective in preventing cardiovascular events and death in elderly patients.

Comment by Michael H. Crawford, MD

After concerns were raised about the safety of calcium antagonists, this trial is reassuring that mortality was not higher in the calcium blocker group. That ACE1 would prevent heart failure more than calcium blockers is not surprising, given the action of the two drug classes. That ACE1 prevented MI more than calcium blockers is somewhat of a surprise, but consistent with the recently released HOPE study results. Interestingly, ACE1 did not perform better in diabetics despite theoretic advantages in such patients. Thus, ACE1 seems to hold a slight edge over calcium blockers, but only in the prevention of MI, not total mortality.

There has also been concern about the relative lack of efficacy of conventional therapy vs. newer agents in the prevention of cardiovascular events (both being effective for stroke prevention). However, this study shows equivalent efficacy. One reason for this may be that STOP-HTN-2 included patients with isolated systolic and diastolic HTN; newer drugs may be more effective for the former and conventional drugs for the latter, and cardiovascular events are more closely related to systolic HTN. Thus, on balance, the new and old drugs are equivalent, but a breakdown of the data along the lines indicated above would have been of interest. Also, combinations of drugs from the different classes were permitted to achieve blood pressure control, further complicating the analysis of drug classes and emphasizing the dominant role of adequate blood pressure control. The major message of this study is that blood pressure control is more important for preventing cardiovascular events in the elderly than how it is achieved.