Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Low-dose aspirin reduced the risk for cardiovascular events in treated hypertension

ACP J Club. 1998 Nov-Dec; 129:59. doi:10.7326/ACPJC-1998-129-3-059


Source Citation

Hansson L, Zanchetti A, Carruthers SG, et al., for the HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998 Jun 13;351:1755-62.


Abstract

Questions

In adults with hypertension, what is the optimal target for diastolic blood pressure (BP) to prevent major cardiovascular (CV) events? Does the addition of low-dose aspirin reduce the rate of CV events and CV mortality?

Design

Randomized, placebo-controlled, factorial trial with mean follow-up of 3.8 years (Hypertension Optimal Treatment [HOT] trial).

Setting

Clinical centers in 26 countries in Europe, North and South America, and Asia.

Patients

19 193 patients 50 to 80 years old (mean age 61.5 y, 53% men) who had hypertension (diastolic BP 100 to 115 mm Hg). Follow-up was 97%.

Intervention

6264 patients were allocated to a diastolic BP goal of ≤ 90 mm Hg, 6264 to ≤ 85 mm Hg, and 6262 to ≤ 80 mm Hg. A 5-step treatment was used to reach this goal: felodipine, 5 mg/d; adding an angiotensin-converting enzyme (ACE) inhibitor or β-blocker; increasing felodipine to 10 mg/d; doubling the dose of the ACE inhibitor or β-blocker; and adding a diuretic. Patients were also allocated to aspirin, 75 mg/d (n = 9399) or placebo (n = 9391).

Main outcome measures

Major CV events (nonfatal myocardial infarction, nonfatal stroke, and CV death).

Main results

Treatment reduced diastolic BP to 85.2, 83.2, and 81.1 mm Hg in the 90, 85, and 80 mm Hg target groups, respectively. Overall CV event rates were low and did not differ among the 3 target groups. Regression analysis showed that most of the reduction in CV events occurred with reduction of diastolic BP from the baseline of 105 to 90 mm Hg. In the subgroup of patients with diabetes mellitus, reduction of diastolic BP to 81.1 mm Hg (vs 85.2 mm Hg) was associated with fewer major CV events and CV deaths. Aspirin reduced the rate of major CV events (P = 0.03) and myocardial infarction (P = 0.002) (Table) but was not associated with increased risk for stroke or fatal hemorrhage.

Conclusion

Low-dose aspirin was associated with decreased cardiovascular events in adults with treated hypertension.

Sources of funding: Astra AB, Sweden; Astra Merck Inc., USA; TEVA, Israel; Hoechst, Argentina.

For correspondence: Professor L. Hansson, University of Uppsala, Department of Public Health and Social Sciences, Clinical Hypertension Research, PO Box 609, S-751 25 Uppsala, Sweden. FAX 46-18-17-7973.


Table. Low-dose aspirin vs placebo for treated hypertension*

Outcomes at 3.8 y Aspirin Placebo RRR (95% CI) NNT (CI)
Major cardiovascular events 3.4% 3.9% 14.5% (0.9 to 26.2) 176 (90 to 3115)
Myocardial infarction 0.9% 1.4% 35.5% (15.0 to 51.0) 208 (127 to 551)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

The major finding of the HOT trial is that aspirin, 75 mg/d, significantly reduced CV events in persons with hypertension. The HOT trial also provides insight into the extent to which diastolic BP should be reduced to prevent CV events. Reducing diastolic BP below 85 mm Hg did not reduce CV events. In the subgroup of patients with diabetes, reducing diastolic BP from 85 to 81 mm Hg decreased CV events. These data suggest that the goal diastolic BP should be 85 to 90 mm Hg for patients with hypertension but not diabetes and approximately 80 mm Hg in patients with diabetes.

Does the HOT trial tell us which antihypertensive agents are best? It does not. The authors found that the CV event rates in the HOT trial were lower than those seen in previous trials, and no control group was included.

3 randomized trials suggest that dihydropyridine-type calcium channel blockers, such as felodipine, are inferior to other antihypertensive agents. In patients with hypertension, 1 trial (1) showed that hydrochlorothiazide was superior to isradipine in the prevention of angina with a 3-year number needed to treat (NNT) of 55 (CI 44 to 1289). In patients with diabetes and hypertension, another trial (2) showed that enalapril was superior to nisoldipine in the prevention of myocardial infarction with a 5-year NNT of 12 (CI 10 to 19). A third trial (3) showed that fosinopril was superior to amlopidine in the prevention of CV events with a 3-year NNT of 15 (CI 10 to 185).

Until further trials are published, we should treat hypertension with proven and less expensive medications, such as low-dose thiazides and ACE inhibitors.

Christopher M. Rembold, MD
University of VirginiaCharlottesville, Virginia, USA


References

1. Borhani NO, Mercuri M, Borhani PA, et al. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial. JAMA. 1996;276:785-91.

2. Estacio RO, Jeffers BW, Hiatt WR, et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes inpatients with non-insulin-dependent diabetes and hypertension. N Engl J Med. 1998;338:664-52.

3. Tatti P, Pahor M, Byington RP, et al. Outcome results of the Fosinopril versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998;21:597-603.