Comparison of angiotensin-converting enzyme inhibitor alone and in combination with irbesartan for the treatment of heart failure

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Abstract

Objective

Angiotensin-converting enzyme inhibitor (ACEI) is beneficial in patients with congestive heart failure (CHF). Some, but not all, angiotensin receptor blocker (ARB) was demonstrated to be effective as “add-on” therapy. We investigated whether irbesartan is useful as an add-on therapy in CHF.

Setting

Single center.

Patients

50 CHF patients on stable doses of ACEI.

Interventions

Add-on therapy with irbesartan (300 mg/day) or continuation of conventional therapy (control group) for 1 year.

Main outcome measures

Serial clinical and echocardiographic assessment were performed as baseline, 3 months and 1 year after therapy.

Results

There was no difference in clinical characteristics between 2 groups. Patients in the add-on therapy group had significant increase in 6-Minute Hall-Walk distance (351 ± 89 to 392 ± 84 m, P < 0.01), achieved higher METs exercise time on treadmill test (3.9 ± 1.1 to 4.6 ±1.3 METs, P = 0.01), reduction of NYHA Class (2.4 ± 0.5 to 2.0 ± 0.8, P < 0.005) and improvement of QOL score (28 ± 19 to 17 ± 18, P < 0.05). These parameters were not improved in the control group and a worsening of exercise capacity was observed (P < 0.05). A reduction of left ventricular end-systolic diameter (4.94 ± 0.85 vs 4.30 ± 1.17 cm, P < 0.05) was observed in the add-on group. At the end of 1 year, more patients have normal or abnormal relaxation pattern in the add-on group than the control group (82% vs 53% χ2 = 7.1, P = 0.02). Blood pressure and renal function were unchanged in both groups.

Conclusion

The addition of irbesartan to conventional ACEI therapy in CHF further improves symptoms, exercise capacity and quality of life without adverse effects on hemodynamics and renal function.

Introduction

Angiotensin II plays an important role in the pathogenesis of chronic heart failure. Many clinical trials have demonstrated benefits of angiotensin-converting enzyme inhibitors (ACEI) on morbidity and mortality of chronic heart failure [1], [2], [3]. However, despite the use of ACEI, β-blockers and spironolactone, hospitalization related to heart failure is still common and the mortality is still high [4]. Given the fact that ACEI cannot achieve complete blockade of the effect of Angiotensin II in the heart and blood vessels [5], [6], addition of angiotensin receptor blockers (ARB) may supplement the inhibition of Angiotensin II and hence provides further clinical benefits. Several trials had been conducted to test this hypothesis utilizing different ARB. In the Valsartan Heart Failure Trial (VAL-HeFT), valsartan was shown to reduce the combined end-point of mortality and morbidity and improved clinical signs and symptoms in patients with heart failure [7]. However, the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan, ACEI and β-blocker raises concern about the potential safety of this specific combination. In the CHARM-Added trial [8], the addition of candesartan to ACEI and other standard treatment leads to further clinically important reduction in relevant cardiovascular events in patients with chronic heart failure and reduced left-ventricular ejection fraction. Our study aimed to determine whether the addition of irbesartan, another ARB, to conventional treatment for chronic heart failure with reduced left ventricular ejection fraction can provide extra benefits in terms of clinical outcome and echocardiographic parameters.

Section snippets

Patients

Fifty consecutive patients with chronic stable heart failure being followed up in the heart failure clinic of a university teaching hospital were recruited. They were suffering from left ventricular systolic dysfunction with an ejection fraction < 50% and already put on regular ACEI therapy for at least 3 months. These patients had moderate heart failure with New York Heart Association class II or III. Previous heart failure symptoms were adjudicated by typical signs and symptoms, and

Results

There was no difference in age, gender, clinical characteristics as well as baseline clinical and echocardiographic parameters between the add-on and control groups (Table 1). The medications were similar in the two groups, including the prescription pattern of ACEI. Systolic and diastolic blood pressures were similar in both groups at baseline (Table 1). All the patients tolerated the drug without any withdrawal due to major side effect and there was no attrition.

Discussion

This study investigated the effect of the addition of irbesartan to conventional therapy in terms of symptomatic improvement, change of echocardiographic parameters and cardiovascular morbidity and mortality in patients with moderate heart failure. All of the patients recruited into this study had been adequately treated with ACEI for at least 3 months while 64% of our patients had been treated with beta-blockers. No patients were taking spironolactone during the study period because

Conclusion

In conclusion, irbesartan add-on therapy on top of ACEI and beta-blockers in the treatment of systolic heart failure could further improve symptoms, exercise capacity and quality of life. It may have extra benefits in the regression of left ventricular remodeling and deterioration of cardiac systolic and diastolic function. Addition of irbesartan 300 mg daily also appears to have no significant adverse effects on blood pressure and renal function.

References (14)

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