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高用量スタチンで新規糖尿病リスク上昇の可... >
日循の機関誌「Circ J」の記事で勉強しました。
心筋梗塞の二次予防にカルシウム拮抗剤がβ遮断剤と同様に有効（非劣性）だったという内容です。
VSA(CSA)の既往の症例は除外してあるということがこの論文のポイントのようです。
しかし、完全に除外することは、VSA(CSA)の診断と同様に困難なことです。
これは日本人でのデータで、"Study Limitations"でも言及しているように、症例数自体も十分ではありません。
今回除外された顕性のVSA(CSA)でなくとも、スパスムスが起きやすい日本人でのデータのため、このまま欧米人に当てはまることなのかどうかが興味深いことです。
もし、欧米で同じようなスタディが行われ、CCA（CCB）の非劣性が証明出来なければ、日本人の特殊性ということが、あぶり出されるかも知れないと思いました。
Secondary preventive Effects of a Calcium Antagonist for Ischemic Heart AttackRandomized Parallel Comparison With β-Blockers Akihiro Nakagomi et al. Circ J 2011; 75: 1696 – 1705Background: Beta-blockers (BB) have been widely used in the management of hypertension and acute myocardial infarction (AMI), and both national and international guidelines have recommended them as first-line agents. Calcium channel antagonists (CCA) are also effective in the treatment of hypertension and angina pectoris. However, the efficacy of CCA in the prevention of cardiovascular events in post-myocardial infarction (MI) patients in comparison to that of BB remains unclear. Methods and Results: A total of 120 post-MI patients (71 patients who were at least 1 month after the onset AMI and 49 stable coronary artery disease patients with a history of MI) were randomly assigned to receive a BB (atenolol, 25-50mg/day, n=60) or a CCA (benidipine, 4-8mg/day, n=60). All patients with AMI within the previous 1 month or with vasospastic angina were excluded from the present study. The baseline clinical characteristics were generally similar in the BB and CCA groups. The rate of primary composite outcome was 26.3% in the BB group in comparison to 13.3% in the CCA group, with no significant between-group differences (hazard ratio with the CCA group 0.640, P=0.276). Both treatments were well tolerated with few severe adverse events. Conclusions: CCA treatment was found to be as effective as BB in reducing cardiovascular events in post-MI patients. ■ The use of CCA in post-MI patients is limited in the guidelines (ACC/AHA), and is recommended only in patients with ongoing or recurring ischemia-related symptoms, those unable to tolerate BB, or patients with VSA. ■ There are currently no data available regarding the efficacy of CCA in comparison to BB on cardiac events in post-MI patients without VSA. ■ Propranolol was first reported to reduce mortality after AMI in 1965.Several subsequent studies, including the β-Blocker Heart Attack (BHAT) trial (propranolol reduced all-cause mortality by 26%) and the Norwegian Multicenter Study Group trial (timolol reduced all-cause mortality by 39%), have confirmed this observation. Therefore, BB are widely used in the treatment of hypertension and post-MI patients, and national and international guidelines recommended BB as first-line agents. ■ Freemantle et al showed that the number of treatments necessary to reduce mortality for 2 years was much fewer for BB (42 for BB) in comparison to the use of anti-platelet agents (153 for anti-platelet agents) or statins (94 for statins) in post-MI patients. ■ The Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN) trial showed that carvedilol, a non-selective BB with α-blocking capabilities, significantly reduced all-cause mortality by 23% in patients with AMI with eft systolic dysfunction (ejection fraction ≤40%). ■ Several clinical trials of ACEIs have shown a substantial improvement in both mortality and morbidity in post-MI patients with left ventricular dysfunction.Almost all patients (98%) in the CAPRICORN trial were given ACEIs and 86% were on aspirin. These data indicated that BB therapy using carvedilol had an additional beneficial effect in reducing mortality in post-MI patients with left ventricular dysfunction who were also treated 
with 
ACEIs. ■ Questions surfaced about the safety of CCA in the early 1990s, particularly that of short-acting (dihydropridines) agents, and their use in patients with coronary artery disease, including post-MI was abandoned. The safety concerns about the short-acting CCA were subsequently extrapolated to the long-acting formulations as well. ■ Long-acting CCA, including benidipine, significantly reduce myocardial oxygen demand by decreasing afterload, heart rate and contractility. ■ Intracelular calcium overload induces ischemic cell death in both the heart and brain. ■ Therefore, CCA reduced ischemia -induced myocardial and brain injury. ■ The Japanese β-blockers and Calcium Antagonists Myocardial Infarction (JBCMI) Study was a multicenter, openlabel, controlled, randomized clinical trial, which demonstrated no significant differences in the incidence of cardiac events, including cardiac death, non-fatal MI, uncontrolled unstable angina, and non-fatal stroke between groups of patients receiving CCA and BB. ■ However, the incidence of HF and coronary spasm were significantly higher in the BB group than in the CCA group. ■ Lipophilic BB might be preferable to atenolol to prevent the development of HF in post-MI patients. http://www.jstage.jst.go.jp/article/circj/75/7/75_1696/_article/-char/ja/出典 Circulation Journal Nol.75, July 2011 EDITORIAL■ A landmark study of coronary artery spasm by a Japanese and Italian joint research group was published in 2000. In that study, both Japanese and Italian patients underwent a coronary spasm provocation test after acute myocardial infarction (AMI) to examine racial differences in coronary spasm.The authors reported that Japanese patients exhibited a 3-fold greater incidence of spasm and more vasoconstriction of nonspastic segments after acetylcholine than Caucasians . ■ It is well known that endothelial function is impaired in patients with coronary artery spasm. Nitric oxide (NO) production from the endothelium is decreased in these patients,and several genetic mechanisms have been proposed: one is a mutation in the gene coding for endothelial NO synthase(eNOS). Nakayama et al reported that the incidence of the T-786→C mutation in the eNOS gene was significantly greater in patients with than in those without coronary spasm.Furthermore, they reported that the mutation resulted in a significant reduction in eNOS gene promoter activity.This type of gene mutation could lead to racial differences in the incidence of coronary spasm.Nakayama M, et al. T-786→C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 1999; 99: 2864 – 2870. ■ Clinical trials have never shown that BB are truly harmful in AMI patients who also have coronary artery spasm. ■ To clarify the role of BB and CCA for secondary prevention in Japanese patients after AMI, Ogawa et al conducted a large-scale randomized trial, the JBCMI (Japanese Beta Blockers and Calcium Antagonists Myocardial Infarction) study in which CCA were as beneficial as BB, and CCA inhibited heart failure and unstable angina attacks caused by coronary artery spasm.The results of that study suggest that CCA are potentially better than BB in reducing cardiovascular events in Japanese patients with AMI. Japanese beta-Blockers and Calcium Antagonists Myocardial Infarction (JBCMI) Investigators. Comparison of the effects of beta blockers and calcium antagonists on cardiovascular events after acute myocardial infarction in Japanese subjects. Am J Cardiol 2004; 93: 969 – 973. ■ The main lesson is that it is not necessary to use BB in AMI patients for the secondary prevention of cardiovascular events, in particular in those patients with heart failure and coronary artery spasm, and most importantly, in those without diabetes. http://www.jstage.jst.go.jp/browse/circj/75/7/_contents/-char/ja/ ＜私的コメント＞この論文を読破して、ふと思ったことがあります。それは心筋梗塞の二次予防について CCAとBBは二者択一的なものではない、ということです。もちろん、気管支喘息や糖尿病合併例ではBBは使用が難しくなりますが、併用は少なからず可能なはずです。両者の併用例の検討もあれば、と思った次第です。 
中西 繁 カダケスの家並（スペイン）F8 ＜きょうの一曲＞ プッチーニ "ラ・ボエーム"より 「私の名前はミミ」Angela GHEORGHIU - Si mi chiamano Mimi - La Bohème - Puccinihttp://www.youtube.com/watch?v=eiyT5_UipMs&feature=related "Si mi chiamano Mimi" from Puccini's La Bohemehttp://www.youtube.com/watch?v=OjvC8J0_AkM&feature=related Maria Callas Bohème: Si, mi chiamano Mimì...http://www.youtube.com/watch?v=UgaN3vIqJUY&feature=related Anna Netrebko-Si mi chiamano Mimìhttp://www.youtube.com/watch?v=IcPEfocVb9M&feature=related
おぺきちの日月抄 : 『ラ・ボエーム(La Boheme)』
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