Emerging drug combinations to optimize renovascular protection and blood pressure goals

Abstract

Hypertension and renal disease are closely related. In fact, there is an inverse linear relationship between renal function and prevalence of hypertension. Hypertensive patients with renal dysfunction exhibit a poor clinical profile, which markedly increases their risk for cardiovascular outcomes. This review considers the available evidence on the best therapeutic approach for optimizing renovascular protection in the hypertensive population. To effectively reduce or at least slow the establishment and progression of renal disease in the hypertensive population it is critical to reach blood pressure targets. Many studies have shown that angiotensinconverting enzyme inhibitors and angiotensin receptor blockers prevent or at least delay the development of microalbuminuria in patients with hypertension and type 2 diabetes, reduce the incidence of overt diabetic nephropathy, and are also beneficial in patients with nondiabetic renal disease. Therefore, renin-angiotensin system (RAS) inhibition plays a key role in the prevention of renal outcomes. As the majority of patients with hypertension will need at least two antihypertensive agents to achieve blood pressure goals, the use of RAS inhibitors is a mandatory part of antihypertensive therapy. The question of which antihypertensive agent is the best choice for combining with RAS blockers should be considered. Many studies have shown that diuretics and calcium channel blockers are the best choice. However, more studies are needed to clarify the subgroups of patients who will benefit more from a combination with a diuretic or from a combination with a calcium channel blocker. To date, RAS inhibitors recommended in this context are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Aliskiren, the first oral direct renin inhibitor available, has shown promising results. Keywords: antihypertensive drugs, renin-angiotensin system, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, combined therapy Hypertension and renal diseaseHypertension is the most important modifiable risk factor for cardiovascular disease. It has been estimated that about 30% of the general population is hypertensive, a proportion that increases to two-thirds in the elderly.1 Remarkably, this prevalence is increased in patients with renal insufficiency. Thus, in a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stage 3 (n = 434) and 4 (n = 695) chronic kidney disease, hypertension was almost universal (91.2% and 94.1%, respectively). Moreover, proteinuria (.300 mg/day) was present in more than 60% of patients, without significant differences between stages 3 and 4 (1.2 ± 1.8 and 1.3 ± 1.8 g/day, respectively).2 In fact, there is an inverse linear relationship between renal function and prevalence of hypertension (from 66% at a glomerular filtration rate of 83 mL/minute per 1.73 m 2 of body surface area to 95% at

Which thiazide to choose as add-on therapy for hypertension?

“…It has been reported that most patients with hypertension need at least two antihypertensive agents to achieve BP goals, particularly patients at higher risk 14,15. Combining antihypertensive drugs with different mechanisms of action is a logical approach, because hypertension is caused by multifactorial interacting mechanisms 15.…”

“…However, in clinical practice, the majority of fixed combinations containing a renin angiotensin system inhibitor and a diuretic have included HCTZ 12,14. Are there differences between these diuretics?…”

“…It has been reported that most patients with hypertension need at least two antihypertensive agents to achieve BP goals, particularly patients at higher risk. 14 , 15 Combining antihypertensive drugs with different mechanisms of action is a logical approach, because hypertension is caused by multifactorial interacting mechanisms. 15 As a result, the combination of drugs with different mechanisms of action can enhance the antihypertensive efficacy of each agent in monotherapy when combined, and may block counter-regulatory mechanisms, thereby reducing the incidence of side effects.…”

“…However, in clinical practice, the majority of fixed combinations containing a renin angiotensin system inhibitor and a diuretic have included HCTZ. 12 , 14 Are there differences between these diuretics? The aim of this review was to analyze the available evidence regarding the efficacy and safety of these drugs alone and as add-on therapy in patients already taking agents that block the renin angiotensin system.…”