Effect of ramipril on renal function in patients with intermittent claudication

Abstract

Background: The Heart Outcomes Prevention Study (HOPE) demonstrated that ramipril resulted in a blood-pressure-independent 25% reduction in cardiovascular events in patients with peripheral arterial disease (PAD). Despite this, general practitioners and vascular surgeons remain reluctant to prescribe ACE inhibitors in this group of patients because of concerns about renal artery stenosis (RAS). We aimed to define the effect of ramipril on renal function in patients with intermittent claudication (IC).

Methods and results: Of 132 unselected patients with IC entering the study 78 (59%) were excluded due to: current ACE inhibitor use (38%), renal impairment (serum creatinine above normal range) (15%), known severe RAS (1%) or unwillingness to participate (5%). The remaining 54 patients were titrated to 10 mg ramipril and renal function was monitored at 1, 5, and 12 weeks. Treatment was discontinued during titration in 5 patients due to symptoms (3) or lack of compliance (2). In the remainder, median [IQR] serum creatinine increased (94 [85.8-103.3] to 98 [88.0-106.5] micromol/L, p < or = 0.001) and median [IQR] GFR decreased (71.5 [64.6-82.3] to 68.7 [59.8-74.7] mL/min per 1.73 m2, p < or = 0.001) between baseline and 5 weeks. These changes were not considered clinically significant. By 12 weeks these values had returned almost to baseline (Cr 95.5 [88.0-103.25] micromol/L, GFR 71.8 [65.3-77.4] mL/min). No patient had a serum creatinine rise > 30%.

Conclusion: Most of patients with IC and a normal serum creatinine can be safely commenced on ramipril provided they are screened, titrated and monitored as described above. Studies in patients with borderline renal impairment (serum creatinine up to 30% above baseline) are on-going.

Figure 1

Boxplots of change in serum creatinine in response to initiation of ramipril. Patients are commenced on ramipril 2.5 mg for 1 week, increased to 5 mg for 3 weeks, and then maintained on 10 mg. Compared with baseline, 1 week p = 0.015, 5 weeks p ≤ 0.001, 12 weeks p = 0.003, Wilcoxon signed ranks).

Figure 2

Boxplots of change in glomerular filtration rate in response to initiation of ramipril. Patients are commenced on ramipril 2.5 mg for 1 week, increased to 5 mg for 3 weeks, and then maintained on 10 mg. Compared with baseline, 1 week p = 0.009, 5 weeks p ≤ 0.001, 12 weeks p = 0.015, Wilcoxon signed ranks).