The case for combining angiotensinconverting enzyme inhibitors and calcium-channel blockers

Abstract

Tight blood pressure control among diabetic and nondiabetic patients with hypertension is perhaps the single most effective intervention used to delay progression to end-stage renal disease (ESRD). The renoprotective actions of angiotensin-converting enzyme (ACE) inhibitors in patients with diabetic and hypertensive nephropathy is well established. Drugs of this class fairly uniformly reduce glomerulosclerosis, delay the deterioration in renal function, and improve proteinuria, a predictive surrogate marker for renal injury. Calcium- channel blockers (CCBs) in the phenylalkylamine (verapamil) and benzothiazepine (diltiazem) classes also improve proteinuria and delay the progression of renal disease in diabetic and nondiabetic hypertensive nephropathy beyond that attributable to blood pressure control. The short-acting dihydropyridine CCBs worsen proteinuria and accelerate renal injury in both animal models and humans with hypertension or diabetes. A very limited number of studies in animals or humans with hypertension or diabetes have demonstrated at least an additive renoprotective effect when the combination of ACE inhibitors and nondihydropyridine CCBs has been compared with each agent administered as monotherapy. Because patients with impaired renal function and either hypertension or diabetes appear to benefit from aggressive blood pressure reduction, many of these patients will require two or more drugs to achieve the currently recommended blood pressure goals. Combinations of ACE inhibitor and CCB are attractive because they may provide better blood pressure control, appear to be better tolerated with fewer side effects than either drug alone, and may exert a greater renoprotective effect in patients at risk for renal failure than either an ACE inhibitor or a CCB.

Evaluation of the effects of inhibition of angiotensin converting enzyme with enalapril in dogs with induced chronic renal insufficiency

“…There is evidence in humans that reduction of BP within reference range may be beneficial for the preservation of renal function. 31,32 Consequently, we cannot determine the relative contribution of a reduction in systemic versus intraglomerular blood pressure to effects on renal structure observed in our study. Although structural protection of the kidneys by ACEIs has generally been attributed to hemodynamic effects of these agents, there are a variety of nonhemodynamic effects that might alter progression of renal injury.…”

Treatment of Hypertension in African Americans and Latinos: The Effect of JNC VI on Urban Prescribing Practices

“…ACE inhibitors appear to be an effective adjunct to diuretic therapy in African Americans due to both the enhanced blood pressure lowering of that combination, and to the decreased production of angiotensin II 15 . It appears that the ACE inhibitors may also have beneficial effects on the progression of hypertensive renal disease, especially when compared to some of the shorter‐acting CCBs 16 . Given the disproportionately high incidence of renal failure among African Americans, and the importance of hypertension in the etiology of this renal disease, the regimen of an ACE inhibitor and diuretic in combination seems appropriate 17 …”

Rationale for Combination Therapy as Initial Treatment for Hypertension

“…Combination antihypertensive therapy, consisting of agents from two or more antihypertensive drug classes, increases the likelihood of achieving the blood pressure goal by targeting more than a single pathologic mechanism and achieving additive or even synergistic blood pressure‐lowering effects 25 . Compared with monotherapy, combination therapy also offers the potential for greater protection against target‐organ damage.…”