Ishikawa Toshitsugu, Ito Hideki, Ouchi Yasuyoshi, Ohashi Yasuo, Saito Yasushi, Nakamura Haruo, Orimo Hajime
Wellness Center, Sony Corporation, Tokyo, Japan.
Tokyo Metropolitan TamaGeriatric Hospital, Tokyo, Japan.
Curr Ther Res Clin Exp. 2005 Jan;66(1):48-65. doi: 10.1016/j.curtheres.2005.03.004.
The Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE) was the first large-scale, prospective clinical trial to show that cholesterol-lowering therapy with pravastatin is effective in reducing the risk for cardiovascular events (CVEs) in elderly (aged ≥60 years) patients with hypercholesterolemia. PATE also included a subgroup of patients with diabetes mellitus (DM).
The aim of this post hoc analysis was to assess the effects of lon-gtermpravastatin therapy on cardiovascular outcomes in the subgroup of patients with DM compared with a subgroup without it.
PATE was conducted at 50 hospitals, universities, and clinics acrossJapan. Patients were randomly allocated to 1 of 2 treatment groups: low-dose pravastatin (5 mg PO QD; L group) or standard-lose pravastatin (in Japan, 10 mg PO QD; S group). Treatment was given for 3 to 5 years. Serum cholesterol levels were measured and the prevalence of CVEs was determined. The primary end point of the study was the S:L risk ratio for fatal or nonfatal CVEs. The secondary end point was the effect of diabetic patients' glycemic control on CVEs.
A total of 665 patients (527 women, 138 men; mean [SD] age, 72.8[5.7] years) were followed up for a mean of 3.9 years (range, 3-5 years). Among these, 199 patients had DM; 104 patients with DM were allocated to the L group and 95 to the S group. Four hundred sixty-six patients did not have DM (L group, 230 patients; S group, 236 patients). Overall, between 3 months and 3 years after the initiation of treatment, patients in the L group (mean dose, 4.5 mg/d) experienced reductions from baseline total cholesterol level of 11% to 13%. Those in the S group (mean dose, 8.3 mg/d) experienced reductions from baseline of 15% to 17%. Decreases in low-density lipoprotein cholesterol (LDL-C) levels were 17% to 20% and 23% to 26% in the L and S groups, respectively. Statistically similar reductions were noted between patients with DM and those without it in response to either dose. The DM subgroup experienced 32 CVEs (L group, 17; S group, 15) compared with 39 CVEs (L group, 25; S group, 14) in the subgroup without DM. The S:L CVE risk ratio (primary end point) was 0.94 (95% Cl, 0.46-1.92) in patients with DM and 0.54 (95% Cl, 0.28-1.05) in those without DM; the differences between the treatment groups were not statistically significant. The risk for CVEs in patients with DM whose glycosylated hemoglobin concentrations were <8.0% and ≥8.0% were, respectively, 1.87-fold (95% Cl, 1.09-3.20; P = 0.02) and 3.79-fold (95% Cl, 1.92-7.48; P < 0.01) higher than that in patients without DM.
In this post hoc analysis of the effects of long-term cholesterol-loweringtherapy (low- and standard-dose pravastatin) on cardiovascular outcomes in elderly patients with DM, dose had no effect on the risk for CVEs in these patients as it did in those without DM. Poorer glycemic control in patients with DM was related to a higher risk for CVEs. The lack of pravastatin efficacy found in the subgroup with DM may have been attributable to the small differences in LDL-C levels found between the 2 treatment groups and/or the small sample size of the study.
老年普伐他汀抗动脉粥样硬化试验（PATE）是首个大规模前瞻性临床试验，表明普伐他汀降胆固醇治疗可有效降低老年（≥60岁）高胆固醇血症患者发生心血管事件（CVE）的风险。PATE还纳入了糖尿病（DM）患者亚组。
本事后分析旨在评估长期普伐他汀治疗对DM患者亚组心血管结局的影响，并与无DM的亚组进行比较。
PATE在日本50家医院、大学和诊所开展。患者被随机分配至2个治疗组之一：低剂量普伐他汀（5mg口服，每日一次；L组）或标准剂量普伐他汀（在日本为10mg口服，每日一次；S组）。治疗持续3至5年。测量血清胆固醇水平并确定CVE的发生率。研究的主要终点是致命或非致命CVE的S:L风险比。次要终点是糖尿病患者血糖控制对CVE的影响。
共665例患者（527例女性，138例男性；平均[标准差]年龄72.8[5.7]岁）接受了平均3.9年（范围3 - 5年）的随访。其中，199例患者患有DM；104例DM患者被分配至L组，95例被分配至S组。466例患者无DM（L组230例患者；S组236例患者）。总体而言，在开始治疗后3个月至3年期间，L组患者（平均剂量4.5mg/d）的总胆固醇水平较基线降低了11%至13%。S组患者（平均剂量8.3mg/d）较基线降低了15%至17%。L组和S组的低密度脂蛋白胆固醇（LDL-C）水平分别降低了17%至20%和23%至26%。DM患者和无DM患者对任一剂量的反应在统计学上有相似的降低。DM亚组发生32例CVE（L组17例；S组15例），而无DM亚组发生39例CVE（L组25例；S组14例）。DM患者的S:L CVE风险比（主要终点）为0.94（95%可信区间，0.46 - 1.92），无DM患者为0.54（95%可信区间，0.28 - 1.05）；治疗组之间的差异无统计学意义。糖化血红蛋白浓度<8.0%和≥8.0%的DM患者发生CVE的风险分别比无DM患者高1.87倍（95%可信区间，1.09 - 3.20；P = 0.02）和3.79倍（95%可信区间，1.92 - 7.48；P < 0.01）。
在这项关于长期降胆固醇治疗（低剂量和标准剂量普伐他汀）对老年DM患者心血管结局影响的事后分析中，剂量对这些患者发生CVE的风险没有影响，而在无DM患者中剂量有影响。DM患者较差的血糖控制与较高的CVE风险相关。在DM亚组中发现的普伐他汀疗效缺乏可能归因于两个治疗组之间LDL-C水平的微小差异和/或研究的小样本量。
