Major findings

Benazepril is a new angiotensin-converting enzyme inhibitor (ACE inhibitor) that has been shown to be effective in the treatment of mild to moderate essential hypertension. 7 In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide 25 mg, or placebo once daily for 4 weeks. 7 The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. 7 Hydrochlorothiazide was more effective in black subjects. 7 At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. 7 In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. 7

The ACCOMPLISH trial 2 showed that the combination of benazepril and amlodipine is superior to benazepril and hydrochlorothiazide in reducing cardiovascular events in high-risk hypertensive patients. 2 This effect was independent of baseline pulse pressure levels. 2 Benazepril has been shown to have renoprotective effects. 3 The ACCOMPLISH trial 3 showed that the combination of benazepril and amlodipine resulted in greater cardiovascular outcomes and renoprotective effects compared to the combination of benazepril and hydrochlorothiazide. 3 The GUARD trial 3 demonstrated that the combination of benazepril and hydrochlorothiazide was more effective than amlodipine and benazepril in reducing baseline urinary albumin/creatinine ratio and normalizing urinary albumin/creatinine ratio in patients with baseline microalbuminuria. 3 However, this effect was accompanied by a greater decrease in glomerular filtration rate compared to benazepril/amlodipine. 3

Benazepril 20 mg has been shown to lower blood pressure significantly compared to placebo. 1 Doses as low as 10 mg once daily may be effective in individual patients. 1 Adverse effects are uncommon and generally not dose related. 1 Thiazide diuretics add to the antihypertensive action of benazepril, which has little effect on blood chemistry, apart from a slight rise in serum potassium. 1

Treatment with the combination of an ACE inhibitor and a dihydropyridine calcium-channel blocker may be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic. 4

A combination of benazepril 10 mg plus hydrochlorothiazide 12.5 mg once daily was investigated in the treatment of patients with mild-to-moderate essential hypertension who had not responded to monotherapy with benazepril 10 mg. 6 Patients failing to respond to 4 weeks of benazepril 10 mg/d were randomized to continue with the monotherapy (n = 47) or receive the combination therapy (n = 46). 6 After 4 weeks of double-blind treatment, reductions in blood pressure were significantly greater among patients given the combination than among those receiving benazepril alone: a 4.7 +/- 1.5 mm Hg difference in mean sitting diastolic blood pressure was noted in favor of the combination therapy (P = 0.0037). 6 The incidence of adverse events, particularly cough, was lower with benazepril + hydrochlorothiazide than with benazepril alone; no notable changes in body weight or heart rate were seen in either group. 6

Benazepril and hydrochlorothiazide, given alone and in low- and high-dose combinations, were shown to significantly lower blood pressure in patients with essential hypertension compared to placebo. 5

Benefits and risks

Benefits summary

Benazepril is an effective ACE inhibitor for the treatment of mild to moderate hypertension. 7 Benazepril may lower blood pressure and reduce the risk of cardiovascular events. 2 Benazepril may also offer renoprotective effects. 3 The combination of benazepril and amlodipine resulted in greater cardiovascular outcomes and renoprotective effects compared to the combination of benazepril and hydrochlorothiazide. 3

Risks summary

Benazepril may cause side effects such as cough, dizziness, and headache. 7 The combination of benazepril and hydrochlorothiazide may cause fatal subfulminant hepatitis. Benazepril may slightly increase serum potassium levels. 1

Comparison between studies

Similarities between studies

Multiple studies have shown that benazepril is effective for the treatment of hypertension. 7 2 3 1 4 6 5 Additionally, benazepril has been shown to potentially reduce the risk of cardiovascular events. 2 3 Benazepril has also been shown to potentially have renoprotective effects. 3

Differences between studies

Some studies have indicated that the combination of benazepril and amlodipine resulted in greater cardiovascular outcomes and renoprotective effects compared to the combination of benazepril and hydrochlorothiazide. 3 Furthermore, a study has indicated that the combination of benazepril and hydrochlorothiazide may cause fatal subfulminant hepatitis.

Consistency and contradictions in the results

Multiple studies have demonstrated that benazepril is effective in treating hypertension. 7 2 3 1 4 6 5 It has also been shown that benazepril has the potential to reduce the risk of cardiovascular events. 2 3 However, there is a contradictory finding that the combination of benazepril and hydrochlorothiazide may cause fatal subfulminant hepatitis. Further research is needed regarding the risk of such side effects.

Considerations for real-world application

Benazepril is an effective medication for the treatment of hypertension. 7 When using benazepril, follow your doctor's instructions. 7 Benazepril may cause side effects. 7 Consult with your doctor if you have concerns about side effects. 7 Also, if you are taking benazepril and hydrochlorothiazide together, liver function monitoring is necessary.

Limitations of current research

There are not many studies regarding the effects of benazepril. 7 Further research is needed on the long-term effects and safety of benazepril. 7 Also, research on the combination of benazepril and hydrochlorothiazide is limited.

Future research directions

Further research on the long-term effects and safety of benazepril is needed. 7 Research on the combination of benazepril and hydrochlorothiazide is also necessary. In particular, it is necessary to investigate the effects on liver function.

Conclusion

Benazepril is an effective medication for the treatment of mild to moderate hypertension. 7 Benazepril may lower blood pressure and reduce the risk of cardiovascular events. 2 Benazepril may also offer renoprotective effects. 3 However, benazepril may cause side effects such as cough, dizziness, and headache. 7 The combination of benazepril and hydrochlorothiazide may cause fatal subfulminant hepatitis. When using benazepril, follow your doctor's instructions. 7