October 4, 2016
View Full PaperInvestigational calcium channel blockers for the treatment of hypertension
Key Result
Dual L/N- and L/T-type CCBs decreased intraglomerular pressure and provided a greater decrease in proteinuria compared with L-type CCBs, despite similar blood pressure lowering effects.
Structured PICO
Do dual L/N- and L/T-type CCBs improve renoprotective effects compared to L-type CCBs in hypertensive patients?
P
Population
Hypertensive patients, including those with chronic kidney disease
I
Intervention
Dual L/N- and L/T-type calcium channel blockers (cilnidipine, benidipine, efonidipine)
C
Comparator
L-type calcium channel blockers (azelnidipine)
O
Outcome
Antihypertensive and renoprotective effects (blood pressure, intraglomerular pressure, renal hemodynamics, and proteinuria)surrogate
Dual L/N- and L/T-type CCBs may offer superior renoprotection compared to standard L-type CCBs in hypertensive patients, though large-scale trials are needed to confirm clinical outcome benefits.
Limitations
- Clinical trials supporting these advantages present important biases
Abstract
Introduction: Voltage-gated Ca2+ channels are the primary route of Ca2+ entry in vascular smooth muscle cells, playing a key role in the regulation of arterial tone and blood pressure. Since the 60´s, L-type Ca2+ channel blockers (CCBs) have been widely used for the treatment of hypertension.Areas covered: T-type Ca2+ channels regulate vascular tone in small-resistance vessels and aldosterone secretion, and N-type channels expressed in sympathetic nerve terminals regulate the release of neurotransmitters. We performed a literature search in MEDLINE, PubMed and ClinicalTrials.gov to identify eligible studies published between January 2001 and March 2016 and reviewed the antihypertensive and renoprotective effects of four CCBs with different pharmacological profiles: azelnidipine (L-type), cilnidipine (L-/N-type) and benidipine and efonidipine (L-/T-type CCBs). Despite similar blood pressure lowering effects, L/N- and L/T-type CCBs, compared with L-type CCBs, decreased intraglomerular pressure, improved renal hemodynamics and provided a greater decrease in proteinuria even in patients already treated with renin-angiotensin-aldosterone inhibitors.Expert opinion: Dual L/N- and L/T-type CCBs may exhibit therapeutic advantages over L-type blockers in hypertensive patients with chronic kidney disease. Because clinical trials supporting these advantages present important biases, further large-scale, long-term comparative trials are needed to confirm that these differences translate into improved clinical outcomes.