CANVAS: 下肢切断リスク増加

カナグリフロジン（商品名：カナグル）存亡の危機？

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心血管高リスク・2型糖尿病患者対象の２つのトライアル

総数10,142名の高心血管リスク2型糖尿病


ランダムにカナグリフロジン vs プラシーボ
平均188.2週間フォローアップ


Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
Bruce Neal, et al. , for the CANVAS Program Collaborative Group
June 12, 2017DOI: 10.1056/NEJMoa1611925
http://www.nejm.org/doi/full/10.1056/NEJMoa1611925



下肢切断リスクと心血管イベント減少効果ベネフィット

プライマリアウトカム＜心血管死亡・非致死性MI、非致死性卒中＞
1000人年 26.9 vs 31.5 ;ハザード比 0.86 ; 95% 信頼区間 [CI], 0.75 to 0.97

下肢切断リスク
1000人年 6.3 vs 3.4   ;ハザード比 1.97 ; 95% 信頼区間 [CI], 1.41 to 2.75

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Table 2. Adverse Events.*
Event	Canagliflozin	Placebo	P Value}-
	event rate per 1000 patient-yr
All serious adverse events	104.	120.0	0.04
Adverse events leading to discontinuation	36.	33.	0.07
Serious and nonserious adverse events of interest recorded in the CANVAS Program
Acute pancreatitis (adjudicated)	0.5	0.4	0.63
Cancer
Renal cell	0.6	0.2	0.17
Bladder	1.0	1.	0.74
Breast	3.	3.	0.65
Photosensitivity	1.0	0.3	0.07
Diabetic ketoacidosis (adjudicated)	0.6	0.3	0.14
Amputation	6.	3.	<0 .001="" font="">
Fracture (adjudicated)*
All	15.	12.	0.02
Low-trauma	12.	9.	0.06
Venous thromboembolic events	2.	2.	0.63
Infection of male genitaliaS	35.	11.	<0 .001="" font="">
Serious and nonserious adverse events of interest collected in CANVAS alone
Osmotic diuresis	35.	13.	<0 .001="" font="">
Volume depletion	26.0	19.	0.009
Hypoglycemia	50.0	46.	0.20
Acute kidney injury	3.0	4.	0.33
Hyperkalemia	7.	4.	0.10
Urinary tract infection	40.0	37.0	0.38
Mycotic genital infection in women	69.	18.	<0 .001="" font="">
Severe hypersensitivity or cutaneous reaction	9.	6.	0.17
Hepatic injury	7.	9.	0.35
Renal-related (including acute kidney injury)	20.	17.	0.32

* Analyses were performed on data from the on-treatment data set (patients who had a safety outcome while they were  receiving canagliflozin or placebo or within 30 days after discontinuation of the drug or placebo), except for fracture,  amputation, cancer, and diabetic ketoacidosis outcomes, which included all events at any time point in all patients who  underwent randomization and received at least one dose of canagliflozin or placebo. P values were estimated from Cox regression models.

記事：
http://www.medpagetoday.com/mastery-of-medicine/mastery-in-diabetes-management/65973