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Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: A Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials.
J Cardiovasc Pharmacol Ther. 2018 09; 23(5):433-445.JC

Abstract

BACKGROUND

Dihydropyridine calcium channel blockers are a heterogeneous group of antihypertensive drugs. Long-acting dihydropyridine agent amlodipine is widely used for monotherapy and combination therapy for hypertension in clinical practice, while intermediate-acting dihydropyridine agents have shown inconsistent results in randomized clinical trials (RCTs).

METHODS AND RESULTS

A meta-analysis of 18 RCTs enrolling a total of 80,483 patients with hypertension followed for a mean of 51.4 months was performed. Amlodipine therapy was associated with 25% higher risk of heart failure (relative risk [RR]: 1.25, 95% confidence interval [CI], 1.05-1.49, P = .019) but 17% lower risk of stroke (RR: 0.83, [95% CI, 0.72-0.97], P = .009) without statistically significant effect on acute myocardial infarction (AMI) compared to major alternative antihypertensive therapy (MAAT), including β-blocker, diuretic, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. Intermediate-acting dihydropyridine calcium channel blocker therapy was associated with 25% higher risk of heart failure (RR: 1.25, [95% CI, 1.06-1.47], 0.005, P = .005) and 26% higher risk of AMI (RR: 1.26, [95% CI, 1.05-1.51], 0.019, P = .019) compared to MAAT. Results of the subgroup analysis suggested that the intermediate-acting dihydropyridine calcium channel blocker was associated with higher risk of heart failure (RR: 1.30, [95% CI, 1.08-1.56], P = .005) and AMI (RR: 1.50, [95% CI, 1.01-2.22], P = .043) compared to renin-angiotensin system blockers and a trend toward higher risk of AMI (RR: 1.17, [95% CI, 0.99-1.38], P = .064) compared to conventional therapy, including β-blockers and diuretics. Meta-regression analyses suggested that long-acting dihydropyridine calcium channel blocker is associated with lower risk of AMI (B: -0.327, [95% CI, -0.530 to -0.123], P = .002) with a trend toward lower risk of stroke (B: -0.203, [95% CI, -0.410 to 0.003] P = .054).

CONCLUSIONS

This study suggests that Amlodipine offers greater protection against major complications of hypertension compared to intermediate-acting dihydropyridine calcium channel blockers.

Authors+Show Affiliations

1 Division of Clinical Pharmacology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.2 Section for Preventive Medicine and Epidemiology, Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway.3 Faculty of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.1 Division of Clinical Pharmacology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.4 Faculty of Medicine, Department of Preventive Medicine and Public Health, Fukuoka University, Fukuoka, Japan. 5 The George Institute for Global Health, University of Sydney, Sydney, Australia.

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

29739234

Citation

Chaugai, Sandip, et al. "Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: a Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials." Journal of Cardiovascular Pharmacology and Therapeutics, vol. 23, no. 5, 2018, pp. 433-445.
Chaugai S, Sherpa LY, Sepehry AA, et al. Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: A Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials. J Cardiovasc Pharmacol Ther. 2018;23(5):433-445.
Chaugai, S., Sherpa, L. Y., Sepehry, A. A., Kerman, S. R. J., & Arima, H. (2018). Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: A Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials. Journal of Cardiovascular Pharmacology and Therapeutics, 23(5), 433-445. https://doi.org/10.1177/1074248418771341
Chaugai S, et al. Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: a Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials. J Cardiovasc Pharmacol Ther. 2018;23(5):433-445. PubMed PMID: 29739234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Long- and Intermediate-Acting Dihydropyridine Calcium Channel Blockers in Hypertension: A Systematic Review and Meta-Analysis of 18 Prospective, Randomized, Actively Controlled Trials. AU - Chaugai,Sandip, AU - Sherpa,Lhamo Yangchen, AU - Sepehry,Amir Ali, AU - Kerman,Scott Reza Jafarian, AU - Arima,Hisatomi, Y1 - 2018/05/08/ PY - 2018/5/10/pubmed PY - 2019/6/25/medline PY - 2018/5/10/entrez KW - acute myocardial infarction KW - calcium channel blockers KW - dihydropyridine KW - heart failure KW - hypertension KW - stroke SP - 433 EP - 445 JF - Journal of cardiovascular pharmacology and therapeutics JO - J Cardiovasc Pharmacol Ther VL - 23 IS - 5 N2 - BACKGROUND: Dihydropyridine calcium channel blockers are a heterogeneous group of antihypertensive drugs. Long-acting dihydropyridine agent amlodipine is widely used for monotherapy and combination therapy for hypertension in clinical practice, while intermediate-acting dihydropyridine agents have shown inconsistent results in randomized clinical trials (RCTs). METHODS AND RESULTS: A meta-analysis of 18 RCTs enrolling a total of 80,483 patients with hypertension followed for a mean of 51.4 months was performed. Amlodipine therapy was associated with 25% higher risk of heart failure (relative risk [RR]: 1.25, 95% confidence interval [CI], 1.05-1.49, P = .019) but 17% lower risk of stroke (RR: 0.83, [95% CI, 0.72-0.97], P = .009) without statistically significant effect on acute myocardial infarction (AMI) compared to major alternative antihypertensive therapy (MAAT), including β-blocker, diuretic, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. Intermediate-acting dihydropyridine calcium channel blocker therapy was associated with 25% higher risk of heart failure (RR: 1.25, [95% CI, 1.06-1.47], 0.005, P = .005) and 26% higher risk of AMI (RR: 1.26, [95% CI, 1.05-1.51], 0.019, P = .019) compared to MAAT. Results of the subgroup analysis suggested that the intermediate-acting dihydropyridine calcium channel blocker was associated with higher risk of heart failure (RR: 1.30, [95% CI, 1.08-1.56], P = .005) and AMI (RR: 1.50, [95% CI, 1.01-2.22], P = .043) compared to renin-angiotensin system blockers and a trend toward higher risk of AMI (RR: 1.17, [95% CI, 0.99-1.38], P = .064) compared to conventional therapy, including β-blockers and diuretics. Meta-regression analyses suggested that long-acting dihydropyridine calcium channel blocker is associated with lower risk of AMI (B: -0.327, [95% CI, -0.530 to -0.123], P = .002) with a trend toward lower risk of stroke (B: -0.203, [95% CI, -0.410 to 0.003] P = .054). CONCLUSIONS: This study suggests that Amlodipine offers greater protection against major complications of hypertension compared to intermediate-acting dihydropyridine calcium channel blockers. SN - 1940-4034 UR - https://www.unboundmedicine.com/medline/citation/29739234/Effects_of_Long__and_Intermediate_Acting_Dihydropyridine_Calcium_Channel_Blockers_in_Hypertension:_A_Systematic_Review_and_Meta_Analysis_of_18_Prospective_Randomized_Actively_Controlled_Trials_ L2 - https://journals.sagepub.com/doi/10.1177/1074248418771341?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -