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


Therapeutics

Antihypertensive drugs had either a neutral or beneficial effect on lipids

ACP J Club. 1996 Sept-Oct;125:38. doi:10.7326/ACPJC-1996-125-2-038


Source Citation

Grimm RH Jr, Flack JM, Grandits GA, et al for the Treatment of Mild Hypertension Study (TOMHS) Research Group. Long-term effects on plasma lipids of diet and drugs to treat hypertension. JAMA. 1996 May 22/29;275:1549-56.


Abstract

Objective

To evaluate the effect on blood lipids of adding various classes of hypertension medication to lifestyle counseling.

Design

4-year randomized, double-blind, placebo-controlled trial (Treatment of Mild Hypertension Study [TOMHS]).

Setting

4 clinical research units in the United States.

Patients

902 patients who were 45 to 69 years of age (mean age 55 y, 62% men) and had mild hypertension with no clinical evidence of coronary heart disease. 97% of patients had ≥ 1 follow-up cholesterol reading.

Intervention

In addition to counseling to achieve weight loss, alcohol and sodium reduction, and increased physical activity, patients were allocated to placebo (n = 234) or to 1 of 5 classes of antihypertensive medication: diuretic (chlorthalidone, 15 mg/d) (n = 136); β-blocker (acebutolol, 400 mg/d) (n = 132); α1-antagonist (doxazosin, 2 mg/d) (n = 134); calcium antagonist (amlopidine, 5 mg/d) (n = 131); angiotensin-converting-enzyme inhibitor (enalapril, 5 mg/d) (n = 135). If diastolic blood pressure was ≥ 95 mm Hg on 3 successive visits or ≥ 105 mm Hg on 1 visit, initial doses were doubled; if hypertension persisted, enalapril, 2.5 to 5 mg/d (chlorthalidone group), or chlorthalidone, 15 to 30 mg/d (all other groups), was added.

Main outcome measures

Change from baseline in plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.

Main results

During follow-up, all plasma lipids were favorably affected in all groups (P ≤ 0.01 for average change over follow-up). Patients who received doxazosin had a greater decrease in total cholesterol than did patients who received placebo (mean change -0.36 vs -0.13 mmol/L, P < 0.01; {95% CI for the 0.23 mmol/L difference 0.12 to 0.34}*. Patients who received either doxazosin or acebutolol had greater decreases in LDL cholesterol than did patients who received placebo (mean change -0.29 vs -0.09 mmol/L, P < 0.01; {CI for the 0.2 mmol/L difference 0.09 to 0.3}* and mean change -0.27 vs -0.09 mmol/L, P < 0.01; {CI for the 0.18 mmol/L difference 0.07 to 0.29}*, respectively. The mean increase in HDL cholesterol in patients who received acebutolol, 0.01 mmol/L, was less than increases with enalapril, 0.07 mmol/L, chlorthalidone, 0.06 mmol/L, or doxazosin, 0.06 mmol/L (P < 0.01). Weight loss was associated with improvement in lipids in all groups.

Conclusion

The addition of various antihypertensive medications to lifestyle management had either a neutral or beneficial effect on lipids.

Sources of funding: National Institutes of Health; Pfizer Inc; Merck, Sharp & Dohme Research Laboratories. For drugs: Boehringer Ingelheim Pharmaceuticals Inc; Merck, Sharp & Dohme Research Laboratories; Pfizer Inc; Wyeth-Ayerst Laboratories.

For article reprint: Dr. R.H. Grimm, Jr, Shapiro Center for Evidence-Based Medicine, 914 South Eighth Street, D-5, Minneapolis, MN 55404, USA. FAX 612-347-7761.

*Numbers calculated from data in article.


Commentary

Coexistent hyperlipidemia and hypertension increase the risk for cardiovascular morbidity and mortality, and both risk factors cluster in persons with obesity and insulin resistance. These risks respond favorably to a program of weight loss and exercise, but clinicians generally feel frustrated because they perceive that recommendations for lifestyle modifications fail to satisfactorily accomplish weight loss. In the current report from the TOMHS and in the preceding main report (1), the participants were moderately successful in maintaining weight loss for 4 years and did more exercise during this period than before.

A decrease in weight was associated with an improvement in lipids, and changes seen in patients who lost ≥ 10 pounds were especially impressive. Patients who received certain types of blood pressure medications had additional beneficial effects on lipids. Overall, doxazosin treatment was the most beneficial. Low-dose chlorthalidone treatment (15 mg/d) for 4 years had no negative effects, which provides further evidence that low-dose diuretics do not adversely affect lipid levels.

What does this information offer the practitioner? First, it reinforces the practical value of recommending lifestyle modifications. In the main TOMHS trial paper (1), a trend toward reduction in frequency of cardiovascular events was observed in patients who received antihypertensive therapy beyond lifestyle alterations alone. In addition to lowering blood pressure, a benefit of these medications may be further improvement in lipid levels. Taken together, the practicing physician should be encouraged to follow the guidelines from the Joint National Committee (2) for lifestyle modification and to consider early implementation of antihypertensive medication.

Jon H. Levine, MD
Meharry Medical CollegeNashville, Tennessee, USA


References

1. Neaton JD, Grimm RH Jr, Prineas RP, et al. JAMA. 1993;270:713-24.

2. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1993;153:154-83.