Objective

Statin therapy is indicated in patients with peripheral arterial disease (PAD). National Institute for Health and Care Excellence guidelines suggest the use of “high intensity” statins, although evidence with PAD specific data are lacking. The effect of statin therapy and dose on outcomes in PAD is investigated.

Data Sources

Studies measuring statin use in PAD patients and outcomes were identified based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The EMBASE and MEDLINE databases were interrogated from January 1957 until February 2020. Twenty-two observational cohort studies and two randomised control trials were included (n = 268 611).

Review Methods

Pooled estimates of dichotomous outcome data were calculated using the odds/hazard ratios (OR/HR) and 95% confidence interval (CI). Meta-analysis was conducted using the inverse variance or Mantel–Haenszel method. Outcomes included all cause mortality (ACM), cardiovascular mortality (CVM), major adverse cardiac events (MACE), and amputation. Subgroup analysis was performed on studies comparing patients taking high dose vs. combined low and moderate doses of statins. The GRADE criteria assessed the quality of evidence for outcomes.

Results

Statin therapy (vs. no statins) was significantly protective for ACM: OR 0.68 (95% CI 0.60 – 0.76) (number needed to treat [NNT] = 48), HR 0.74 (95% CI 0.70 – 0.78) (NNT = 10 – 91); MACE: OR 0.84 (95% CI 0.78 – 0.92) (NNT = 53), HR 0.78 (95% CI 0.65 – 0.93) (NNT = 167); and amputations: OR 0.59 (95% CI 0.33 – 1.07) (NNT = 333), HR 0.74 (95% CI 0.62 – 0.89) (NNT = 50). High doses of statins (vs. combined low and moderate doses) were significantly better protective against ACM OR 0.69 (95% CI 0.43 – 1.09) (NNT = 17), HR 0.74 (95% CI 0.62 – 0.89) (NNT = 16 – 200) but work less significantly for MACE OR 0.77 (95% CI 0.49 – 1.21) (NNT = 25). Amputations were less frequent in patients on high doses HR 0.78 (95% CI 0.69 – 0.90) (NNT = 53 – 1 000).

Conclusion

Higher dosing of statins confers a significant improvement in patient outcomes, especially ACM and amputations, although the quality of the evidence was variable. Such findings require confirmation in larger, PAD specific trials.

中文翻译：

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他汀类药物治疗和剂量对外周动脉疾病心血管和肢体结局的影响：系统评价和荟萃分析

客观的

他汀类药物治疗适用于外周动脉疾病 (PAD) 患者。国家健康与护理卓越研究所指南建议使用“高强度”他汀类药物，尽管缺乏 PAD 特定数据的证据。研究了他汀类药物治疗和剂量对 PAD 结果的影响。

数据源

根据系统评价和荟萃分析的首选报告项目 (PRISMA) 标准确定了测量 PAD 患者中他汀类药物使用和结果的研究。从 1957 年 1 月到 2020 年 2 月，对 EMBASE 和 MEDLINE 数据库进行了查询。纳入了 22 项观察性队列研究和两项随机对照试验（n  = 268 611）。

审查方法

使用优势/风险比 (OR/HR) 和 95% 置信区间 (CI) 计算二分类结果数据的汇总估计值。使用逆方差或 Mantel-Haenszel 方法进行 Meta 分析。结果包括全因死亡率（ACM）、心血管死亡率（CVM）、主要不良心脏事件（MACE）和截肢。对比较服用高剂量他汀类药物与低剂量和中剂量他汀类药物的患者的研究进行亚组分析。GRADE 标准评估了结果的证据质量。

结果

他汀类药物治疗（与无他汀类药物相比）对 ACM 有显着保护作用：OR 0.68（95% CI 0.60 – 0.76）（需要治疗的人数 [NNT] = 48），HR 0.74（95% CI 0.70 – 0.78）（NNT = 10 – 91); MACE：OR 0.84 (95% CI 0.78 – 0.92) (NNT = 53)，HR 0.78 (95% CI 0.65 – 0.93) (NNT = 167)；和截肢：OR 0.59 (95% CI 0.33 – 1.07) (NNT = 333)，HR 0.74 (95% CI 0.62 – 0.89) (NNT = 50)。高剂量他汀类药物（与低剂量和中剂量组合）对 ACM 的保护效果显着更好 OR 0.69 (95% CI 0.43 – 1.09) (NNT = 17), HR 0.74 (95% CI 0.62 – 0.89) (NNT = 16 – 200），但对 MACE OR 0.77（95% CI 0.49 – 1.21）（NNT = 25）的影响较小。高剂量 HR 0.78 (95% CI 0.69 – 0.90) (NNT = 53 – 1 000) 的患者截肢频率较低。

结论

尽管证据质量参差不齐，但更高剂量的他汀类药物可显着改善患者预后，尤其是 ACM 和截肢。这些发现需要在更大的 PAD 特定试验中得到证实。