The ANDI study demonstrated that in hypertensive patients with diabetes whose BP was not controlled with 20 mg quinapril alone, initiation of combination therapy by adding 5 mg amlodipine besylate to quinapril 20 mg was more effective in reducing BP than increasing the dose of quinapril to 40 mg.
Worldwide hypertension treatment guidelines recommend an ACEI in the treatment of people with diabetes and hypertension.4,5,15 The goal of this recommendation includes BP lowering in addition to target organ protection.16 Long-term blockade of the renin-angiotensin-aldosterone system (RAAS) has been shown to delay progression to end-stage renal disease.17,18 Renal protection is particularly critical in patients with diabetes because of their accelerated risk of renal dysfunction.4,5,19 Furthermore, activation of the RAAS is associated with increased expression of inflammatory mediators; and blockade of the RAAS may provide CV protection in part through reduction of these inflammatory factors.20 The inflammatory marker CRP has been suggested by some investigators to be associated with an increased risk of developing diabetes21 and hypertension.22 Yasunari and coworkers23 recently reported that inhibition of the RAAS with valsartan in hypertensive patients significantly reduced CRP concentrations and reactive oxygen species formation. In a recent study, quinapril, but not enalapril, was shown to be effective in reducing the increased concentration of CRP in patients following an acute myocardial infarction.24
In the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) study,10 which compared the efficacy of amlodipine besylate with or without perindopril and atenolol with or without thiazide diuretic, 53% of all patients had reached goal BP (<140/90 mm Hg without diabetes; <130/80 mm Hg with diabetes), whereas only 32% of patients with diabetes achieved goal BP. Additional therapy with doxazosin was allowed if hypertension was not controlled by the 2 primary agents studied. For patients receiving an amlodipine-based regimen, the average number of antihypertensive agents was 2.2, and the average for patients receiving an atenolol-based regimen was 2.3. As expected, many patients required 3 or more antihypertensive drugs in an effort to achieve significant and sustained reductions to goal BP.
Although BP was reduced from baseline in both treatment groups, fewer than 11% in either group achieved the recommended target BP for patients with diabetes mellitus. The low fraction of patients who achieved target BP in ANDI is consistent with what has been reported previously.6 In clinical practice, patients might have received additional antihypertensive medications in an effort to bring BP to goal, as various clinical trials have demonstrated the benefits of combination therapy to help reach the rigorous target of <130/80 mm Hg in hypertensive diabetic patients.2,3,11,25,26 Future studies with quinapril and amlodipine besylate that include an additional agent or agents, such as a diuretic, are needed in this patient population to increase the proportion of patients reaching goal BP.
The tolerability profile of the combination of quinapril and amlodipine besylate in the ANDI study compared favorably with that of quinapril alone. During the double-blind treatment phase, the incidence of AEs considered by the investigator to be treatment-related was similar between the 2 treatment groups (6.6% and 10.5%, respectively, for the high-dose quinapril and combination-therapy groups). In addition, 6 patients (3.6%) in the high-dose quinapril group and 2 patients (1.2%) in the combination quinapril/amlodipine group were withdrawn from the study because of an AE. In other studies, quinapril has been demonstrated to be similarly safe and well tolerated in patients with hypertension,27,28 and additionally has been shown to preserve renal function in patients with diabetes.29
A secondary outcome of the ANDI study was to evaluate the effect of quinapril alone compared with quinapril and amlodipine besylate in lowering hsCRP. High hsCRP values (>3 mg/L) have been shown to be associated with increased CV risk.30 In this study, similar and small changes in hsCRP were observed that were not clinically relevant. Other studies, however, have shown quinapril to be associated with a clear anti-inflammatory effect.24,31–33 Because drugs such as statins, fibrates, niacin, thiazolidinediones, and antiplatelet agents are also associated with lowering CRP,34 the neutral effect on CRP observed with quinapril in this study may be a result of the concomitant drugs used in this high-risk patient population.