Complementary mechanisms of action and rationale for the fixed combination of perindopril and indapamide in treating hypertension – update on clinical utility

Integrated Blood Pressure Control Dovepress open access to scientific and medical research R e v ie w Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 218.237.82.236 on 07-Jun-2020 For personal use only. Open Access Full Text Article Complementary mechanisms of action and rationale for the fixed combination of perindopril and indapamide in treating hypertension – update on clinical utility This article was published in the following Dove Press journal: Integrated Blood Pressure Control 10 May 2010 Number of times this article has been viewed Vivencio Barrios 1 Carlos Escobar 2 1 Department of Cardiology, Hospital Ramon y Cajal, Madrid, Spain; 2 Department of Cardiology, Hospital Infanta Sofia, Madrid, Spain Introduction Correspondence:Vivencio Barrios Department of Cardiology, Hospital Ramon y Cajal Madrid 28034, Spain Tel +34 91 336 8259 Fax +34 91 336 8665 Email ; submit your manuscript | www.dovepress.com Dovepress 6636 Powered by TCPDF (www.tcpdf.org) Abstract: Although reducing blood pressure is the most important approach to reduce cardiovascular outcomes in the hypertensive population, the majority of patients fail to attain the targets. Most patients with hypertension need at least 2 antihypertensive agents to achieve blood pressure goals. The 2007 European hypertension guidelines state that combined therapy is needed when monotherapy does not attain blood pressure objectives and as a first-line treatment in high-risk patients. This point has been reinforced in the 2009 update of the European guidelines. The advantages of combination therapy are well documented with the potential for increased antihypertensive efficacy as a result of different mechanisms of action, and a lower incidence of adverse effects because of the lower doses used and the possible compensatory responses. Moreover, the use of fixed dose combinations are specially recommended as they facilitate treatment compliance. The inhibition of the renin-angiotensin system appears to be very beneficial in the treatment of patients with hypertension along the cardiovascular continuum and the combination of a renin-angiotensin system inhibitor and a diuretic is particularly recommended. Many clinical trials have demonstrated the benefits of the fixed combination perindopril/indapamide in the treatment of hypertension. The aim of this manuscript is to update the p ublished data on the efficacy and safety of this fixed combination. Keywords: fixed dose, combination therapy, angiotensin-converting enzyme, diuretic Arterial hypertension, a major risk factor for the establishment and development of cerebrovascular, cardiovascular and renal diseases, is very prevalent worldwide. It has been estimated that about a quarter of the general population is hypertensive, a proportion that increases with age.1–3 In Spain, 44% of the middle-aged population and 68% of patients aged 60 years or older exhibit hypertension.1 In United States about 65 million people are hypertensive.2,3 It has been calculated that hypertension is responsible for 1 of every 14 deaths for any reason and for 1 of every 2.5 cardiovascular deaths.4 Even small elevations above optimal systolic or diastolic blood pressure (BP) values increase the probability of cardiovascular outcomes.5 Thus, in 18,876 healthy subjects, an increased risk of new onset heart failure in individuals with systolic BP 130–139 mmHg compared with those with optimal BP (,120 mmHg) has recently been reported, with a linear trend in heart failure risk across the normal range of systolic BP.6 Similar findings have been reported in patients with ischemic heart disease.7 A post hoc analysis of INVEST (International Verapamil SR-Trandolapril Study) trial, performed Integrated Blood Pressure Control 2010:3 11–19 11 © 2010 Barrios and Escobar, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Dovepress Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 218.237.82.236 on 07-Jun-2020 For personal use only. Barrios and Escobar in 22,576 patients with hypertension and coronary artery disease, showed there was a steep reduction in cardiovascular risk in parallel to the proportion of visits with controlled BP, independent of baseline characteristics and mean ontreatment BP.7 In the classical systematic review of Collins et al8 a 42% stroke risk reduction (P , 0.0001) and a 14% coronary heart disease risk reduction in those hypertensives who attained BP goals, when compared to those treated but not adequately controlled, was reported. As a result, it is crucial not only to reduce BP values but to achieve BP goals in order to improve cardiovascular prognosis.5 Although in the last decades BP control rates have progressively improved (ie, in Spain, BP control has increased from ,20% in 1990s to the current 40%),9 they are far from optimal and this occurs everywhere (Italy about 31%, United Kingdom 36%, Germany 40% and France 46%).2 However, after the results of EUROASPIRE III, it seems that this improvement has stopped or at least slowed.10 EUROASPIRE surveys analyzed rates of m odif iable c ardiovascular risk f actors in patients with coronary heart disease. EUROASPIRE I, II, and III were designed as cross-sectional studies and included the same selected geographical areas and hospitals in the Czech Republic, Finland, France, Germany, Hungary, Italy, the Netherlands, and Slovenia. These studies showed that although the proportion with raised total cholesterol has markedly decreased, from 94.5% in EUROASPIRE I to 76.7% in II, and 46.2% in III (P , 0.0001), the proportion of patients with raised BP ($140/90 mmHg in patients without diabetes or $130/80 mmHg in patients with diabetes) remained unchanged (58.1% in EUROASPIRE I, 58.3% in II, and 60.9% in III; P = 0.49).10 These data suggest that, although in the general hypertensive population BP control rates are rising, this does not occur in those hypertensive patients at higher risk such as those with coronary heart disease. In fact, as cardiovascular risk increases, a lesser proportion of patients attain BP goals.10,11 This is very relevant, since nowadays the majority of patients attended by specialists or general practitioners, belong to high- or very high-risk groups.12,13 Furthermore, since the prevalence of diabetes, obesity and sedentary life style is growing, it is likely that the number of high risk hypertensive patients will rise in the future.14 Although it is well known that the majority of hypertensive patients will need more than 1 antihypertensive drug to attain BP objectives (particularly those at higher risk),15,16 several surveys have reported that combined therapy is actually underused.9–12 The 2007 European guidelines for the management of arterial hypertension, indicate that 12 Powered by TCPDF (www.tcpdf.org) submit you (...truncated)