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


Therapeutics

Nifedipine had a more negative effect on quality of life than cilazapril or atenolol

ACP J Club. 1992 Nov-Dec;117:81. doi:10.7326/ACPJC-1992-117-3-081


Source Citation

Fletcher AE, Bulpitt CJ, Chase DM, et al. Quality of life with three antihypertensive treatments: cilazapril, atenolol, nifedipine. Hypertension. 1992 Jun;19:499-507.


Abstract

Objective

To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (cilazapril), a β-blocker (atenolol), and a calcium channel blocker (nifedipine retard) on the quality of life of patients with mild-to-moderate hypertension.

Design

6-month, randomized, double-blind trial.

Setting

31 centers, primarily general practices, in 10 European countries.

Patients

636 patients aged 35 to 65 years entered a 4-week, medication-free, placebo run-in period. Sitting diastolic blood pressure (DBP) was required to be 95 to 115 mm Hg at the clinic visits during weeks 3 and 4. Exclusion criteria included serious cardiovascular or other clinically significant illness or childbearing potential. 32 of 572 randomized patients were excluded before breaking the code, and 540 (57% men) were included in the analysis (94%).

Interventions

Patients were assigned to cilazapril, 2.5 mg/d; atenolol, 50 mg/d; or nifedipine, 20 mg twice daily. If DBP was > 90 mm Hg at monthly clinic visits, the dose was doubled once until after week 12 when hydrochlorothiazide (HCTZ), 12.5 mg increasing to 25 mg, was added.

Main outcome measures

Quality of life (including scales for complaints, psychologic and physical health, and life and work satisfaction) was assessed by self-report and by blinded interview at baseline, randomization, and after weeks 12 and 24 of active therapy.

Main results

The groups did not differ in mean change from baseline in DBP (cilazapril -14.7, atenolol -15.5, nifedipine -14.7 mm Hg), but more patients in the cilazapril group (36%) than in the atenolol group (25%) or the nifedipine group (24%) required HCTZ (P = 0.01). {For nifedipine compared with cilazapril, the 12% absolute risk reduction (ARR) in need for HCTZ means that 8 patients would need to be treated (NNT) with nifedipine (rather than cilazapril) to prevent 1 additional patient from requiring HCTZ (95% CI 5 to 30); the relative risk reduction was 35%, CI 11% to 54%; for atenolol compared with cilazapril, the ARR was 11%, NNT 9, CI 5 to 48; and RRR 32%, CI 7% to 51%.}* The nifedipine group had a greater increase in complaints score (most commonly edema, flushing, and headache) than the atenolol group (P = 0.02) or the cilazapril group (P = 0.05). Fatigue score was improved (less fatigue) on nifedipine compared with the 2 other drugs (P = 0.04). The cumulative drop-out rate was higher for the nifedipine group (21%) than for the atenolol group (13%) or the cilazapril group (14%) (P = 0.04). Side effects were the most common reason for withdrawal with nifedipine recipeints having a greater withdrawal rate than atenolol or cilazapril recipients (17%, 8%, and 5% of patients, respectively, P = 0.001). The groups did not differ in other quality-of-life variables.

Conclusion

Cilazapril, atenolol, and nifedipine were equally effective in controlling blood pressure but nifedipine was associated with more frequent adverse-effect-related drug discontinuation than was atenolol or cilazapril.

Source of funding: F. Hoffmann-LaRoche.

For article reprint: Dr. A.E. Fletcher, Epidemiology Research Unit, Division of Geriatric Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 ONN, England, UK.

*Numbers calculated from data in article.


Commentary

Few large trials have evaluated the relative efficacy of different antihypertensive agents in decreasing cardiovascular events, and it is generally accepted that most agents have roughly equivalent efficacy in their blood pressure-lowering effects. Many experts recommend, therefore, that drug selection be based on comorbid profiles of patients, metabolic neutrality, ability to retard left ventricular hypertrophy, and costs and side effects of individual medications. A burgeoning literature, including the article by Fletcher and colleagues, addresses the latter important issue of potential differences in quality of life and side effects among various agents. The principal findings of little to no differences in measurements of quality of life, but increased symptom reporting leading to more frequent discontinuation of nifedipine, are consonant with earlier findings. They are not, however, necessarily generalizable to other calcium channel-blocking agents.

Other than documenting more side effects with nifedipine, how do results such as these help us? Given at least 7 classes of antihypertensive medications and several agents within each class, how can the bedazzled clinician successfully evaluate the many antihypertensive therapeutic options? Because it is unlikely that comprehensive comparative studies of all agents will ever be done, several points are worth repeating. Quality of life and side effects are not the only factors to consider when selecting a drug; studies evaluating relative cardiovascular efficacy with the newer ACE-inhibitor and calcium channel-blocking agents are needed. Costs should be considered because many patients might opt to have some side effects in exchange for relatively inexpensive therapy. Finally, group results from randomized trials are not necessarily applicable to individual patients; clinicians and their patients should continue to try different agents before selecting the one that best controls the individual's blood pressure with the lowest costs and least untoward side effects.

Cynthia Mulrow, MD
Audie L. Murphy Memorial Veterans HospitalSan Antonio, Texas, USA