Comparison of the effects of long-acting nifedipine CR and diltiazem R in patients with vasospastic angina: Aomori coronary spastic angina study

Higuma, Takumi; Oikawa, Koichi; Kato, Takeshi; Mori, Yasuhiro; Kudo, Takeshi; Yamamoto, Tohru; Hoshi, Yoshiki; Kameda, Kunihiko; Suto, Naoyuki; Fujita, Norio; Inokubo, Yoichi; Konta, Atsushi; Osanai, Tomohiro; Okumura, Ken

doi:10.1016/j.jjcc.2010.07.010

Cited by 15 publications

(17 citation statements)

References 20 publications

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“…DL inhibits coronary spasm via inhibition of PKC activation and Cav1.2 phosphorylation: VSMC contraction is primarily controlled by Ca 2+ influx from the extracellular space through the LTCC. [22][23][24] LTCC antagonists including dihydropyridines, phenylalkylamines, and benzothiazepines bind to Cav1.2 and inhibit Ca 2+ inflow, which consequently inhibits vasoconstriction. Cav1.2 consists of four domains (I-IV), and each domain has six transmem- brane segments (S1-S6).…”

Section: Discussionmentioning

confidence: 99%

Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina

et al. 2021

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Calcium antagonists are used for coronary spastic angina (CSA) treatment. We previously identified a phospholipase C (PLC)-δ1 gene variant that results in enhanced PLC activity in patients with CSA and developed a CSA animal model by generating vascular smooth muscle cell-specific human variant PLC-δ1 overexpression (PLC-TG) mice. In this study, we investigated the molecular mechanism of CSA using the PLC-TG mice and the inhibitory effect of a calcium antagonist, diltiazem hydrochloride (DL).We treated the PLC-TG and wild-type (WT) mice with oral DL or trichlormethiazide (TM) (control) for 2 weeks. Ergometrine injection-induced coronary spasm was observed on the electrocardiogram in all 5 PLC-TG mice treated with TM, but only in 1 of 5 PLC-TG mice treated with DL. Voltage-dependent calcium channel (Cav1.2) phosphorylation and protein kinase C (PKC) activity were enhanced in the aortas of PLC-TG mice treated with TM. DL treatment significantly inhibited Cav1.2 phosphorylation and PKC activity. Although total Cav1.2 expression was similar between WT and PLC-TG mice treated with TM, DL treatment significantly increased its expression in PLC-TG mice. Furthermore, its expression remained high after DL discontinuation. DL and PKC inhibitor suppressed intracellular calcium response to acetylcholine in cultured rat aortic smooth muscle cells transfected with variant PLC-δ1.These results indicate that enhanced PLC activity causes coronary spasm, presumably via enhanced Cav1.2 phosphorylation and PKC activity, both of which were inhibited by DL. Enhanced total Cav1.2 expression after DL discontinuation and high PKC activity may be an important mechanism underlying the calcium antagonist withdrawal syndrome.

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Section: Discussionmentioning

confidence: 99%

Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina

et al. 2021

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“…Nevertheless, the previous LDA users had higher incidence of CAS during ACh provocation test as compared with non aspirin users. According to these results, we assumed that in the real world, the previous LDA users have much more chances of severe endothelial dysfunction than expected and would require more aggressive medical treatment using antianginal drugs than until now [13,14].…”

Section: Discussionmentioning

confidence: 99%

Impact of low-dose aspirin on coronary artery spasm as assessed by intracoronary acetylcholine provocation test in Korean patients

Park

Rha

Poddar

et al. 2012

Journal of Cardiology

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High-dose aspirin has been reported to aggravate coronary artery spasm (CAS). However, it is unknown whether low-dose aspirin (LDA; 100 mg) has deleterious impact on CAS. We assessed the impact of LDA on CAS induced by intracoronary acetylcholine (ACh) provocation test. A total of 2789 consecutive patients without significant coronary artery disease who underwent ACh test between November 2004 and March 2010 were enrolled. The patients were divided into two groups: the aspirin group taking LDA before ACh test (n=221) and the no aspirin group not taking aspirin (n=2568). At baseline, the prevalence of old age, diabetes mellitus, hypertension, and hyperlipidemia were higher in the aspirin group. During the ACh test, the incidence of significant CAS, ischemic chest pain, as well as severe and multivessel spasm was higher in the aspirin group. The response rate to lower ACh dose was higher in the aspirin group. Multivariate analysis showed that the previous use of LDA was an independent predictor of CAS (adjusted odds ratio, 1.6, 95% confidence interval, 1.0-2.3; p=0.031). However, it is likely that the association of LDA and CAS that we have observed is not causal but may be hypothesis generating due to significant baseline differences. Further, male gender, old age, lipid-lowering drugs, baseline spasm, and myocardial bridge were independent predictors of CAS. LDA was more frequently associated with CAS and ischemic symptoms, as well as severe and multivessel spasm, suggesting the patients who have received LDA would require more intensive medical therapies and close follow up.

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“…The studies showed that Diltiazem decrease the frequency of chest pain in VSA patients, and increase the quality of life based on the Seattle Angina Questionnaire. 2 6 However, in a study which participants consumed Diltiazem for VSA, recurrent angina up till fourth week and asymptomatic AV block were found in a single separate patient. 2 …”

Section: Resultsmentioning

confidence: 97%

Comparison of various calcium antagonist on vasospastic angina: a systematic review

Singh

Elton²,

Kwa

2023

Open Heart

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BackgroundCoronary artery vasospasm is an abnormal spasm of coronary arteries that cause transient or complete occlusion without exertion. It causes stable angina to ACS. However, this can be prevented by calcium channel blockers (CCBs) which suppress Ca2+influx into the vascular muscle cells. Nevertheless, several CCBs adverse effects are harmful for these patients. Selecting the right CCBs would give the best clinical practice.MethodThe studies were obtained from four major medical databases by various keywords. Inclusion and exclusion criteria were implemented as adult >18 years, observational study, English language and drug of interest. Duplicates were eliminated, and the remaining studies were reviewed. Final full-texts assessment was conducted independently by Newcastle-Ottawa Scale and Revised Cochrane.ResultsThe search found 1378 articles. However, six studies were selected after implementing the study criteria. Diltiazem was found to decrease angina and increase quality of life until 12th week of treatment; however, some adverse effects include atrioventricular block and recurrent angina up till 4th week were found. Meanwhile, nifedipine was found to decrease vasospastic angina (VSA) by the fourth and eighth weeks of treatment. Nevertheless, it caused excessive drop in BP and increase heart rate by eighth week. In addition, slow-release preparation of both CCBs were found to increase efficacy and compliance. Lastly amlodipine was also found to decrease VSA by 17%±140% and 33% after 6 weeks, but further studies needed.ConclusionDiltiazem, nifedipine and amlodipine are potent in decreasing VSA, however, tailoring specific CCBs adverse reactions to patient condition and the drug preparation would be substantially beneficial for the outcome.

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Comparison of the effects of long-acting nifedipine CR and diltiazem R in patients with vasospastic angina: Aomori coronary spastic angina study

Abstract: Once-daily administration of nifedipine CR was as effective as twice-daily diltiazem R in the prevention of VSA attacks.

Cited by 15 publications

References 20 publications

Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina

Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina

Impact of low-dose aspirin on coronary artery spasm as assessed by intracoronary acetylcholine provocation test in Korean patients

Comparison of various calcium antagonist on vasospastic angina: a systematic review

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