Fixed-Dose Combinations of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in the Treatment of Hypertension: A Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors

Abstract

Fixed-dose combinations (FDCs) of different regimens are recommended in guidelines for the treatment of hypertension. However, clinical studies comparing FDCs of angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) and angiotensin-converting enzyme inhibitor (ACE inhibitor)/CCB in hypertensive patients are lacking.Using a propensity score matching of 4:1 ratio, this retrospective claims database study compared 2 FDC regimens, ARB/CCB and ACE inhibitor/CCB, in treating hypertensive patients with no known atherosclerotic cardiovascular disease. All patients were followed for at least 3 years or until the development of major adverse cardiovascular events (MACEs) during the study period. In addition, the effect of medication adherence on clinical outcomes was evaluated in subgroup analysis based on different portions of days covered.There was no significant difference in MACE-free survival (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.98-1.50; P = 0.08) and survival free from hospitalization for heart failure (HR: 1.15; 95% CI: 082-1.61; P = 0.431), new diagnosis of chronic kidney disease (HR: 0.98; 95% CI: 071-1.36; P = 0.906), and initiation of dialysis (HR: 0.99; 95% CI: 050-1.92; P = 0.965) between the 2 study groups. The results remained the same within each subgroup of patients with different adherence statuses.ARBs in FDC regimens with CCBs in the present study were shown to be as effective as ACE inhibitors at reducing the risks of MACEs, hospitalization for heart failure, new diagnosis of chronic kidney disease, and new initiation of dialysis in hypertensive patients, regardless of the medication adherence status.

FIGURE 1

Patient enrollment.

FIGURE 2

Comparison of the primary endpoints of FDCs of ARB/CCB versus ACE inhibitor/CCB: (A) all patient; (B) PDC < 50; (C) PDC = 50–80; (D) PDC ≥80. ACE = angiotensin-converting enzyme, ARB = angiotensin receptor blockers, CCB = calcium channel blockers, FDC = fixed-dose combination, PDC = proportion of days covered.

FIGURE 3

Comparison of the secondary endpoints of FDCs of ARB/CCB versus ACE inhibitor/CCB: hospitalization for heart failure—(A) all patients; (B) PDC < 50%; (C) PDC 50% to 80%; (D) PDC ≥80. ACE = angiotensin-converting enzyme, ARB = angiotensin receptor blockers, CCB = calcium channel blockers, FDC = fixed-dose combination, PDC = proportion of days covered.

FIGURE 4

Comparison of the secondary endpoints of FDCs of ARB/CCB versus ACE inhibitor/CCB: new diagnosis of chronic kidney disease—(A) all patients; (B) PDC < 50%; (C) PDC 50% to 80%; (D) PDC ≥80. ACE = angiotensin-converting enzyme, ARB = angiotensin receptor blockers, CCB = calcium channel blockers, FDC = fixed-dose combination, PDC = proportion of days covered.

FIGURE 5

Comparison of the secondary endpoints of FDCs of ARB/CCB versus ACE inhibitor/CCB: initiation of dialysis—(A) all patients; (B) PDC < 50%; (C) PDC 50% to 80%; (D) PDC ≥80. ACE = angiotensin-converting enzyme, ARB = angiotensin receptor blockers, CCB = calcium channel blockers, FDC = fixed-dose combination, PDC = proportion of days covered.