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Calcium antagonists: effects on cardio-renal risk in hypertensive patients
Sandeep Nathan1, Carl J Pepine, George L Bakris
1Department of Preventive Medicine, Hypertension/Clinical Research Center, Rush University Medical Center, Chicago, IL 60612, USA.
Insights
Calcium antagonists are safe and effective for lowering blood pressure. Long-acting versions show no difference from other antihypertensives, but dihydropyridines require renin-angiotensin system blockers for proteinuric kidney disease.
Area of Science:
- Cardiovascular Medicine
- Nephrology
Background:
- Calcium antagonists, including dihydropyridines and nondihydropyridines, are widely used for hypertension.
- Early studies suggested increased mortality with short-acting calcium antagonists.
- Recent meta-analyses indicate long-acting calcium antagonists are comparable to other antihypertensives for cardiovascular outcomes in low-to-moderate risk patients.
Purpose of the Study:
- To evaluate the efficacy and safety of calcium antagonists in hypertensive patients, focusing on cardiovascular outcomes and kidney disease progression.
- To compare cardiovascular outcomes between long-acting calcium antagonists and other antihypertensive drug classes.
- To assess the role of calcium antagonists in different stages of kidney disease, particularly proteinuric kidney disease.
Main Methods:
- Review of meta-analyses and clinical trial data on calcium antagonists in hypertensive patients.
- Analysis of cardiovascular outcomes, including cardiovascular events, stroke, and heart failure.
- Evaluation of kidney disease progression, specifically in patients with nonproteinuric and proteinuric kidney diseases.
Main Results:
- Calcium antagonists decrease stroke incidence but do not prevent new-onset heart failure.
- Long-acting calcium antagonists show no significant difference in cardiovascular outcomes compared to other antihypertensives in low-to-moderate risk or nonproteinuric kidney disease.
- Dihydropyridine calcium antagonists, without renin-angiotensin aldosterone system blockers, do not optimally slow nephropathy progression in proteinuric kidney disease due to a lack of antiproteinuric effects.
Conclusions:
- Calcium antagonists are safe and efficacious for reducing cardiovascular risk, comparable to other antihypertensive agents.
- Avoid calcium antagonists in patients with systolic dysfunction; they are suitable for blood pressure lowering in preserved systolic function.
- In proteinuric kidney disease, dihydropyridine calcium antagonists must be co-administered with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for optimal kidney function preservation.
Abstract:
Calcium antagonists comprise 2 main subclasses, dihydropyridines and nondihydropyridines, and have been studied extensively in hypertensive patients. Early meta-analyses suggested that short-acting calcium antagonists were associated with higher mortality rates resulting from cardiovascular events and other etiologies. Recent meta-analyses failed to show any substantive difference between long acting calcium antagonists and other antihypertensive drug classes with regard to cardiovascular outcomes in those with low to moderate cardiovascular risk or kidney disease progression among those with stage 2 or 3 nonproteinuric kidney diseases. The data from calcium antagonist trials are consistent in that they decrease stroke incidence but fail to protect against new-onset heart failure. In people with proteinuric kidney disease, that is > 300 mg protein/gram creatinine, use of dihydropyridine calcium antagonists to lower blood pressure without the use of agents that block the renin angiotensin aldosterone system does not provide optimal slowing of nephropathy progression. This relates directly to lack of antiproteinuric effects with this subclass and not seen with nondihydropyridine agents that reduce proteinuria to a greater degree than dihydropyridines. Thus, calcium antagonists are safe and as efficacious as other antihypertensive agents to reduce cardiovascular risk. They should be avoided in people with systolic dysfunction but may be used for blood pressure lowering in people with preserved systolic function. Dihydropyridine calcium antagonists should only be used in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in proteinuric kidney disease because they will not optimally slow kidney function loss in their absence.
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