Comparison of hydrocholorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment
Title: Comparison of hydrocholorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the Hane study
Authors: Philipp T, Anlauf M, Distler A, et al.
Reference: British Medical Journal. 1997;315:154-159
Reviewer: Max A Luna
Problem addressed: Despite the fact that beta adrenergic blockers and thiazides have been shown to reduce clinical end points in controlled studies, international committees have recommended the use of angiotensin converting enzyme inhibitors and calcium channel blockers for initial single drug antihypertensive therapy.
Purpose of study: To evaluate the effectiveness and the tolerability of four different classes of drugs.
Methods: Approximately 870 hypertensive patients were randomized to atenolol, hydrocholorothiazide, nitrendipine or enalapril on similar escalating doses. After an initial eight week titration period, patients who had blood pressure within normal limits where followed for 40 more weeks to assess longer term blood pressure control and tolerability.
After the 8-week titration period atenolol had a significantly better response rate of 63.7% compared to enalapril (50%), HCTZ 44.7% and Nitrendipine (44.5%). After 48 weeks, atenolol continued to have the best response and tolerability rate of 48% compared to enalapril (42.7%), HCTZ (35.4%), and Nitrendipine (32.9%).
Results: Response rate in the titration phase was of 50.7% in the entire population. This was more often achieved with atenolol in 63.7% than with the other of the drugs. The superiority of atenolol persisted up to the 48 week follow- up compared to HCTZ and nitrendipine but was not significant when compared to Enalapril.
Women responded better to antihypertensive therapy than men (55 vs. 47.7%). In older patients (>45 years) no difference could be found within the therapeutic regimens. Nitrendipine and HCTZ were significantly more effective in older than in younger patients. Nitrendipine turned out to be equally effective in patients with higher blood pressure (Diastolic BP > 102 mm Hg) compared to lower blood pressure people in that group. The other three regimens were better in the people with lower diastolic BP (<102 mm Hg). Incidence of withdrawals because of adverse events was significantly higher in the nitrendipine group than in the other three.
Discussion: In the absence of evidence that shows superiority on morbidity and mortality among antihypertensive drugs, minimum requirement for recommending agents should be based on their effectiveness. This study suggests that among the four drugs representing each of their classes, there appears to be no superiority by the newer more expensive agents. (ACE Inhibitors and Calcium channel blockers).
Comparison of drugs should include not only their effectiveness but also their tolerability. The comparison becomes more difficult, however if superior antihypertensive potency of one drug is associated with poorer tolerability or vice versa. According to this, atenolol was superior to the other three reference drugs after eight weeks of treatment because it showed the highest responder rate and a treatment related rate of dropout that was similar to the other drugs. After 48 weeks, the responder rate of atenolol was no longer different from enalapril, but remained superior to HCTZ and nitrendipine. On the other hand, the assessment of nitrendipine would be more negative as its clearly higher dropout rate and was not associated with higher effectiveness.
Comments: This study is very appropriate to the needs of health systems were cost is a critical aspect in the treatment of hypertension. Atenolol and HCTZ represent the least expensive antihypertensive classes. Here they show to be at least equivalent to ACE inhibitors and calcium channel blockers to achieve blood pressure response in eight and 48-week follow-up. It is important to consider that this data is of greatest benefit when starting antihypertensive therapy to patients that would not have any other benefit from a specific drug class. For example, the use of ACE inhibitors in diabetic patients may still be a better fist choice for antihypertensive and the prevention of diabetic nephropathy.
Hypertension frequently is an asymptomatic condition leading to high rates of noncompliance. This issue requires the clinician to choose a medication that will not add any unfavorable side effect that would justifiably become a reason for non-compliance. The slow titration of beta-blockers and the close surveillance for side effects is suggested.
It is possible that the absence of statistically significant difference in the response rate between some drugs could have been due to the small number of patients in each group, a source of limited statistical power.