Comparing Hypertensive Therapies and Outcomes
Abstracts & Commentary
Synopsis: In these studies, end points were similar, independent of therapy used.
Sources: Hansson L, et al. Lancet 2000;356:359-365;
Brown MJ, et al. Lancet 2000;356:366-372.
These two studies have the same goal; name-ly, to determine whether important cardiovascular (CV) end points are differently affected according to the choice of antihypertensive treatment when compared to traditional therapy with either a diuretic, b-blocker, or both. The Nordic Diltiazem (NORDIL) study compared treatment with diltiazem (initially short-acting but later long-acting) to thiazide diuretic or b-blocker—or both—and used as its primary combined end point fatal and nonfatal stroke, myocardial infarction (MI), or other CV death. In the diuretic and b-blocker group, step 1 was either a thiazide diuretic or b-blocker. Step 2 was their combination. Step 3 was an added ACE inhibitor or a-blocker. Step 4 was the addition of any other agent. In the cardiazem group, step 1 was 180-360 mg diltiazem. Step 2 was an added ACE inhibitor. Step 3 added a diuretic. Step 4 was any other antihypertensive drug. A total of 10,916 patients were randomized in this multicenter trial. The mean age was 60 years.
Over the course of the NORDIL study, mean blood pressure averaged 154.9/88.6 mm Hg in the diltiazem group and 151.7/88.7 mm Hg in the diuretic b-blocker group. The primary end point occurred in 403 patients in the diltiazem group and in 400 patients in the diuretic and b-blocker group. There were 159 fatal plus non-fatal strokes in the diltiazem group and 186 in the diuretic and b-blocker group. There were 183 fatal and nonfatal MIs in the diltiazem group and 157 in the diuretic and b-blocker group. Hansson and colleagues conclude that the two treatment approaches were almost indistinguishable for the primary combined end point (whether the patient had type 2 diabetes mellitus) and stated that the difference in MI/stroke outcome may have been due to chance.
The INSIGHT study compared treatment with 30 mg nifedipine in a long-acting gastrointestinal-transport system (GITS) formulation with co-amilozide (hydrochlorthiazide 25 mg + amiloride 2.5 mg). Dose titration was by dose doubling and addition of either atenolol 25-50 mg or enalapril 5-10 mg. The primary outcome was CV death, MI, heart failure, or stroke. A total of 6321 patients ranging in age from 55 to 80 years were randomized in this multicenter trial. Over the course of the study, a mean blood pressure of 138/82 mm Hg was achieved for both groups. There were 200 primary outcomes in the nifedipine group and 182 in the co-amilozide group. The difference is not statistically significant. Neither treatment selectively improved an individual risk factor.
Comment by Michael K. Rees, MD, mph
In 1997, the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure issued its sixth report, which—like all preceeding reports—emphasized selection of either a diuretic or a b-blocker as initial treatment of uncomplicated hypertension.1 These two major randomized, controlled trials provide further evidence of the validity of this long-term recommendation, reporting no difference in cardiovascular primary outcomes when hypertension is treated with either a diuretic, a b-blocker, nifedipine GITS, or cardizem long-acting, and this was true whether or not the patient had type 2 diabetes mellitus. Although neither of these studies demonstrated a selective difference in outcome (that is, one drug better for reduction in stroke vs another better for reduction of heart disease), Hansson et al and Brown and colleagues note that there were too few primary outcomes to detect a statistical difference. Thus far, the risk reduction achieved when treating patients with uncomplicated hypertension should be attributed to the degree of blood pressure control achieved, as predicted by the Framingham Risk Profile.2
References
1. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2413-2440.
2. Anderson KM, et al. Am Heart J 1990;121:293-298. (You can calculate your patients’ risk profile on line at http://www.hyp.ac.uk/bhs/risk.xls. Cholesterol and HDL can be entered in either mg/dl or mmol/l).
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