The use of amlodipine, but not of P-glycoprotein inhibiting calcium channel blockers is associated with clopidogrel poor-response

2010 ◽  
Vol 103 (05) ◽  
pp. 920-925 ◽  
Author(s):  
Ankie Harmsze ◽  
Karen Robijns ◽  
Jochem van Werkum ◽  
Nicoline Breet ◽  
Christian Hackeng ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Platelet Reactivity ◽  
Poor Response ◽  
Individual Variability ◽  
Light Transmittance ◽  
Channel Blockers ◽  
P Glycoprotein ◽  
Increased Risk

SummaryClopidogrel is a prodrug that has to be converted in vivo to its active metabolite by cytochrome (CYP)P450 iso-enzymes. As calcium channel blockers (CCBs) are inhibitors of CYP3A4, concomitant use of these drugs might play a role in the wide inter-individual variability in the response to clopidogrel. However, some CCBs also have strong inhibitory effects on the drug transporter P-glycoprotein (Pgp), which mediates clopidogrel‘s intestinal absorption. It was the aim of this study to evaluate the effect of co-administration of Pgp-inhibiting and non-Pgp-inhibiting CCBs on on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective percutaneous coronary intervention (PCI). In a total of 623 consecutive patients undergoing elective PCI treated with clopidogrel and aspirin, platelet reactivity to 5 and 20 μM adenosine diphospate (ADP) and clopidogrel poor-response (defined as > 70% platelet aggregation to 20 μM ADP) were evaluated by light transmittance aggregometry. A total of 222 patients (35.6%) were on CCB treatment, of which 98 used Pgp-inhibiting CCBs (verapamil, nifedipine, diltiazem, barnidipine) and 124 patients used the non-Pgp-inhibiting CCB amlodipine. Adjusted mean ADP-induced on-clopidogrel platelet reactivity was significantly higher in both users of Pgp-inhibiting CCBs and amlodipine as compared to CCB non-users (all p<0.05). However, only the use of amlodipine was significantly associated with a 2.3-fold increased risk of clopidogrel poor-response. This study demonstrates that concomitant use of Pgp-inhibiting CCBs and amlodipine increases on-clopidogrel platelet reactivity. Only amlodi-pine was associated with clopidogrel poor-response. The drug-drug interaction between clopidogrel and amlodipine might be more clinically relevant as compared to P-glycoprotein-inhibiting CCBs.

scholarly journals Impact of Calcium Channel Blockers on Aspirin Reactivity in Patients With Coronary Artery Disease

2021 ◽  
Author(s):  
Afek Kodesh ◽  
Eli Lev ◽  
Dorit Leshem-Lev ◽  
Alejandro Solodky ◽  
Ran Kornowski ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Platelet Reactivity ◽  
Aspirin Resistance ◽  
Control Group ◽  
Channel Blockers ◽  
Artery Disease ◽  
Stable Cad

Abstract Purpose: Calcium channel blockers (CCBs) do not reduce the risk of initial or recurrent myocardial infarction (MI) in patients diagnosed with stable coronary artery disease (CAD). The aim of this current study was to evaluate the association between CCBs and aspirin resistance in patients with CAD. Methods: Patients with stable CAD who were regularly taking aspirin (75-100 mg qd) for at least one month prior to enrollment in the study were included. The VerifyNow system was used for platelet function testing with high on-aspirin platelet reactivity (HAPR) defined as aspirin reaction units (ARU) >550. We compared patients treated with CCBs versus control group. Results: 503 patients with CAD were included in this study, 88 were treated with CCBs; Mean age (67.9±9.7 in the CCB group vs 66.5±11.4 in the control group, p=0.288), gender (77.3 male vs. 82.9%, p=0.214) and rates of diabetes mellitus (34.7 vs. 36.9%, p=.121) were similar. Rates of hypertension were higher in the CCB group (83.9 vs. 63.5%, p<0.01), but rates of past MI were lower (47.1 vs. 59.7%, p=0.039). The mean ARU was 465.4P70.0 for patients treated with CCBs versus 445.2u60.0 in controls (p=0.006). Similarly, 15.9% of CCB patients demonstrated HAPR compared to 7.0% (p=0.006). In a multivariate analysis, the administration of CCBs was independently associated with HAPR (OR- 1.72, 95% CI 1.04 – 8.91, p=0.047). Conclusions: Usage of CCBs is positively correlated with aspirin resistance. These findings may suggest an adverse pharmacologic effect of CCBs among patients with stable CAD treated with aspirin.

scholarly journals Investigation of Calcium Channel Blockers as Antiprotozoal Agents and Their Interference in the Metabolism ofLeishmania (L.) infantum

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Juliana Quero Reimão ◽  
Juliana Tonini Mesquita ◽  
Daiane Dias Ferreira ◽  
Andre Gustavo Tempone
Keyword(s):  
Calcium Channel ◽  
Chagas Disease ◽  
Calcium Channel Blockers ◽  
Channel Blockers ◽  
Antiprotozoal Activity ◽  
Additive Interaction ◽  
Therapeutic Class ◽  
Species Production

Leishmaniasis and Chagas disease are neglected parasitic diseases endemic in developing countries; efforts to find new therapies remain a priority. Calcium channel blockers (CCBs) are drugs in clinical use for hypertension and other heart pathologies. Based on previous reports about the antileishmanial activity of dihydropyridine-CCBs, this work aimed to investigate whether thein vitroanti-Leishmania infantumand anti-Trypanosoma cruziactivities of this therapeutic class would be shared by other non-dihydropyridine-CCBs. Except for amrinone, our results demonstrated antiprotozoal activity for fendiline, mibefradil, and lidoflazine, with IC50values in a range between 2 and 16 μM and Selectivity Index between 4 and 10. Fendiline demonstrated depolarization of mitochondrial membrane potential, with increased reactive oxygen species production in amlodipine and fendiline treatedLeishmania, but without plasma membrane disruption. Finally,in vitrocombinations of amphotericin B, miltefosine, and pentamidine againstL. infantumshowed in isobolograms an additive interaction when these drugs were combined with fendiline, resulting in overall mean sum of fractional inhibitory concentrations between 0.99 and 1.10. These data demonstrated that non-dihydropyridine-CCBs present antiprotozoal activity and could be useful candidates for futurein vivoefficacy studies against Leishmaniasis and Chagas’ disease.

scholarly journals In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models

PLoS ONE ◽  
2009 ◽  
Vol 4 (10) ◽  
pp. e7320 ◽  
Author(s):  
Ying Sun ◽  
Benjamin Liou ◽  
Brian Quinn ◽  
Huimin Ran ◽  
You-Hai Xu ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Mouse Models ◽  
Calcium Channel Blockers ◽  
Gaucher Disease ◽  
Ex Vivo ◽  
Channel Blockers

Abstract 12688: Long Term Use of Calcium Channel Blockers and Risk of Breast Cancer Development

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Uyen T Lam ◽  
Stacey Knight ◽  
Tami L Bair ◽  
Viet T Le ◽  
Joseph B Muhlestein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Positive Family History ◽  
Channel Blockers ◽  
Increased Risk ◽  
History Of ◽  
Incident Breast Cancer

Introduction: Calcium channel blockers (CCBs) are a mainstay in treating hypertension (HTN). Recently, Li et-al published a population based case-control study (JAMA 2013; 289:2354) reporting CCB use to be associated with incident breast cancer (odds ratio 2.6). We prospectively analyzed 2 Intermountain Healthcare (IHC) databases (db) to confirm or refute this provocative report. Methods: Two separate analyses were conducted using general patients (GP) seen at IHC and patients undergoing coronary angiography (CV) at IHC facilities. Subjects were females aged 50-70 with no history of breast cancer. Those prescribed CCB were matched 1:1 to subjects not on CCB based on age, race, tobacco, alcohol, body mass index, HTN and follow up time. Multivariable Cox proportional hazards regression was used for the primary analysis of time to incident breast cancer by CCB use adjusting for history of other cancers and family history of breast cancer. Results: A total of 2612 GP subjects (cases/controls) and 1106 CV subjects (cases/controls) were studied. In the GP db, there was a statistically significant increased risk of breast cancer for subjects using CCB (HR=1.58; 95% CI: 1.10-2.26). Risk was also associated with a positive family history (HR=2.79; 1.96-3.97) and a personal history of cancer (HR=1.87; 1.07-3.26). Breast cancer predominantly developed in <5 y of follow up (64% of cases). However, a reverse relationship was found in the CV db, where the HR was 0.51 (95% CI: 0.27-0.97). This observation was found despite consistent associations with several secondary outcomes, including for incident diabetes, coronary and renal disease. Conclusion: A modest association between CCB use and incident breast cancer was observed in the GP db, but results were not reproducible in the CV db. Given lack of a credible mechanism and failure of previous randomized CCB studies to detect a signal, we interpret these modest and conflicting associations to likely represent uncorrected confounding, e.g. prescriber bias or drug interactions. Similarly, we believe the results of Li et-al may represent confounding. Given the important role of CCBs in clinical medicine, further studies are warranted, including randomized trials to assess CCB safety with respect to breast cancer risk.

scholarly journals Effects of calcium channel blockers on gastric emptying and acid secretion of the rat in vivo

1986 ◽  
Vol 89 (4) ◽  
pp. 627-633 ◽  
Author(s):  
R. Brage ◽  
J. Cortijo ◽  
J. Esplugues ◽  
J. V. Esplugues ◽  
E. Martí-Bonmatí ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Acid Secretion ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Channel Blockers
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