本帖最後由 lsc0019 於 2009-4-5 20:47 編輯
作者：Janis Kelly
出處：WebMD醫學新聞
March 19, 2009 — 將癲癇病患的抗癲癇藥物從較舊的，會誘發細胞色素P450的，轉換為較新的，不會影響這個酵素的藥物，可能戲劇化地降低心臟血管疾病風險。
賓州費城Thomas Jefferson大學的研究者們，將研究結果於3月18日線上發表於美國神經學期刊，內容包括34位癲癇病患，從phenytoin或是carbamazepine轉換為lamotrigine（Lamictal，格蘭素史克藥廠）或是levetiracetam（Keppra，UCB藥廠）。
在六星期內轉換期，病患的總膽固醇、非高密度脂蛋白（造成動脈粥狀硬化）、三酸甘油酯與C反應蛋白（CRP）濃度顯著地下降。這四個標記都與粥狀動脈硬化、心臟血管疾病及中風風險有關。
臨床醫師們應該從這項研究獲得的最重要發現是，carbamazepine及phenytoin與被認為顯著增加心肌梗塞和中風風險的血清學標記變化有關。
主要研究者Scott Mintzer醫師向Medscape精神學表示，在癲癇的領域裡，這代表這些藥物是否應該作為第一線治療是高度存疑的；在精神醫學上，這必須在替代治療的潛在風險與好處上取得平衡。
【脂蛋白（a）濃度意外地下降】
這項重複檢驗、病患間的研究也因為這是少數以癲癇成人病患進行的血管風險研究；大部分過去的研究都是針對兒童進行，或是斷面性研究。
在轉換為lamotrigine或levetiracetam後，受試者總膽固醇濃度平均下降24.8 mg/dl、造成粥狀動脈硬化膽固醇下降19.9 mg/dl、三酸甘油酯下降47.1 mg/dl（所有P值都<0.0001），CRP濃度平均下降31.4%（P=0.027）。
停止使用carbamazepine病患另一個意外的發現是脂蛋白（a）（Lp[a]）濃度下降31.2%（P=0.0004），而停止使用phenytoin病患的半胱胺酸（homocysteine）濃度下降1.7 mmol/L（P=0.005）。
許多發現是意料中的，但有兩個發現令我感到意外，首先，carbamazepine與phenytoin對於Lp（a）的影響顯然較大；其次，CRP受到這些藥物影響的程度顯然較大。Mintzer醫師表示，就我所知，並沒有研究針對癲癇病患或是正在使用這些藥物病患的CRP濃度進行研究。
需要更多的研究數據，來確認使用這些舊型藥物對癲癇未發作病患換為較新型的藥物仍然可以免於癲癇發作；然而，Mintzer醫師表示，以我來看，所有癲癇病患都可以考慮這樣的轉換療法。
【能降低健康相關費用嗎？】
當臨床醫師開始從較舊型藥物(通常是較便宜的藥物)，轉換到較新的藥物時(通常是比較昂貴的)，就會有費用相關的問題。Mintzer醫師的數據被期望對於與第三方付款公司、國家健康主管機關、或是處方委員會爭論這個問題的臨床醫師會有助益。
他預測，將病患的藥物轉換為較新的藥物時，將可以透過下降這些病患目前心血管問題的風險，而省下健康照護費用。他附帶表示，在這些情況下，大部分新的藥物才剛剛過專利期，因此他們的價錢將會在不久的將來顯著下降。
Newer Antiepileptic Drugs Reduce Cardiovascular Risk in Epileptic Patients
By Janis Kelly
Medscape Medical News
March 19, 2009 — Switching patients with epilepsy from older antiepileptic drugs that induce cytochrome P450 to 1 of the newer drugs that do not affect this enzyme system can dramatically reduce cardiovascular risk.
Investigators at Thomas Jefferson University, in Philadelphia, Pennsylvania, report these findings online March 18 in the Annals of Neurology in 34 epilepsy patients switched from phenytoin or carbamazepine to either lamotrigine (Lamictal, GlaxoSmithKline) or levetiracetam (Keppra, UCB).
Within 6 weeks of the switch, patients had significant decreases in total cholesterol, non–high-density-lipoprotein (atherogenic) cholesterol, triglycerides, and C-reactive protein (CRP). All 4 markers are associated with elevated risk for atherosclerosis, cardiovascular disease, and stroke.
"The most important point that clinicians should take from this study is that carbamazepine and phenytoin cause a panoply of serologic changes that would be expected to increase myocardial infarction and stroke risk significantly.
"In the epilepsy field, that means that it is highly questionable whether or not these drugs should be first-line agents. In psychiatry, this has to be balanced against the potential risks and benefits of alternative treatments," principal investigator Scott Mintzer, MD, told Medscape Psychiatry.
Unexpected Reduction in Lipoprotein(a)
This repeated-measures, within-patient study is also notable because it is 1 of the few vascular risk studies done in adults with epilepsy. Most previous studies are either conducted in children or are cross-sectional.
After changing to lamotrigine or levetiracetam, subjects had average declines of 24.8 mg/dL in total cholesterol, 19.9 mg/dL in atherogenic cholesterol, and 47.1 mg/dL in triglycerides (all P < .0001). Average CRP levels fell by 31.4% (P = .027).
One unexpected finding was that patients who stopped taking carbamazepine also had a 31.2% decline in lipoprotein(a) (Lp[a]) levels (P = .0004), while those who stopped phenytoin had a 1.7 mmol/L decrease in homocysteine (P = .005).
"Many of the findings were expected, but 2 findings surprised me — first, that carbamazepine and phenytoin appear to have suchsharply different effects on Lp(a); and second, that CRP appears to be markedly affected by these drugs. No one has ever examined CRP in epilepsy patients or in any patients who take these drugs, to my knowledge," said Dr. Mintzer.
More data are needed to establish that patients who were seizure-free on the older drugs will remain seizure-free on the newer drugs. However, said Dr. Mintzer, in his opinion, all epilepsy patients are potential candidates for this switch.
Reduction in Health Costs?
Cost questions typically arise when clinicians begin pressing for switching from older, usually cheaper agents, to newer, usually more expensive, drugs. Dr. Mintzer's data are expected to be helpful to clinicians arguing this point with third-party payers, national health agencies, or formulary committees.
He predicts that changing patients to the newer drugs will actually save healthcare dollars by reducing the current high rate of cardiovascular problems in these patients. “In any case, most of the newer drugs have just come off patent, so their prices will drop substantially in the not-too-distant future,” he added.
Ann Neurol. Published online March 18, 2009 |
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