Delapril plus Indapamide: A Review of the Combination in the Treatment of Hypertension

Luca Cavalieri; Giovanni Cremonesi


Clin Drug Invest. 2007;27(6):367-380. 

In This Article

Abstract and Introduction

Although many data indicate that the management of hypertension has improved over the last two decades, there is still a large proportion of hypertensive individuals who do not receive adequate management of their blood pressure (BP). Combination therapy with two or more antihypertensive agents from different drug classes is increasingly being recognised as the most effective means of achieving target BP values by pharmacological means, particularly in the large number of patients in whom monotherapy proves to be ineffective.

Use of an angiotensin-converting enzyme (ACE) inhibitor combined with a diuretic is a well established antihypertensive combination that is very effective because of the different, yet synergistic, mechanisms of actions of agents from these two drug classes. Delapril is a potent antihypertensive ACE inhibitor, and indapamide is a thiazide-like diuretic with additional antihypertensive properties. The combination of delapril and indapamide provides renoprotective effects, and indapamide is also cardioprotective. Use of these two drugs together is therefore a rational selection for combination therapy, and one that has consistently demonstrated lowering of BP to target values with a level of efficacy that is at least as good as other combinations of ACE inhibitors and diuretics. This combination has also been found to provide favourable effects on haemodynamic parameters, including left ventricular mass index and ejection fraction. Furthermore, combining an ACE inhibitor and a thiazide-type diuretic has been associated with a decreased risk of stroke and is recommended for patients with cerebrovascular disease, a setting in which the combination of delapril and indapamide has therapeutic potential.

Because of the additive mechanisms of delapril and indapamide, the dose required for an effective antihypertensive effect is relatively low, and the combination is well tolerated at such doses. In particular, metabolic effects normally associated with diuretics are rare at the therapeutic dose of indapamide used in combination with delapril, making the combination suitable for patients with metabolic disorders in whom diuretic therapy would otherwise not be recommended. Delapril 30mg and indapamide 2.5mg have been combined in a fixed combination, offering the convenience of a one-tablet-per-day antihypertensive drug regimen for most patients, which, along with good tolerability, helps to address the issue of noncompliance.

In spite of convincing data that the awareness and management of hypertension have improved, hypertension remains a leading cause of cardiovascular morbidity and mortality, accounting for approximately 4.4% of the global disease burden and for an estimated 7.1 million hypertension-associated deaths annually.[1,2] Suboptimal blood pressure (BP) [systolic BP >115mm Hg] is the single most common attributable risk factor for death, and is responsible for an estimated 49% and 62% of cases of ischaemic heart disease and cerebrovascular disease, respectively.[2]

While the number of hypertensive patients receiving therapy has improved, there are still a significant number of individuals with hypertension worldwide who are not being managed adequately, or even managed at all.[1,3,4] Experience in recent years has shown that monotherapy does not adequately control BP in up to one-half of patients,[4] and combination therapy with two or more drugs from different classes is increasingly being recognised as important. It has also become apparent that lower BP targets than those previously recommended are needed to decrease morbidity and mortality. Previous recommendations of a systolic BP goal of <160mm Hg for many patients were based primarily on observational data. Recent studies have indicated that for low- to medium-risk hypertensive patients, systolic BP <140mm Hg and diastolic BP <90mm Hg are beneficial.[4] The respective systolic and diastolic pressure targets for patients with hypertension complicated by established cardiovascular disease, diabetes mellitus or renal insufficiency are <130 and <80mm Hg.[4] Focus should also be on achieving systolic BP goals, as in most patients aged >55 years, diastolic BP goal will also be achieved concurrently.[4] In general, antihypertensive therapies that achieve these goals at the lowest possible doses are preferred.

There are many fixed-combination products available now for the treatment of hypertension. Fixed-combination products offer the advantage of convenience for the patient[1] and they improve patient compliance[3,5] and persistence with therapy[6] by reducing the number of tablets that need to be taken. This is important, as many hypertensive patients have co-morbid conditions and require polypharmacy. Furthermore, low doses of both drugs can be administered, reducing the likelihood of adverse effects.[3] The majority of available fixed combinations contain a diuretic combined with another diuretic or drug from another antihypertensive class, with the exception of a few that combine an angiotensin-converting enzyme (ACE) inhibitor with a calcium channel antagonist. The combination of an ACE inhibitor and a diuretic is particularly effective,[7,8] as these two drug classes offer different mechanisms of action that produce an additive antihypertensive effect.[9] The fixed combination of delapril and indapamide (Delapride®, Promedica, Italy)1 has been extensively researched in Italy and appears to offer a well tolerated and effective option for managing hypertension. This article reviews the pharmacology, clinical efficacy and safety of the combination of delapril and indapamide for the management of hypertension.


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