Effects of Statin Therapy and Dose on Cardiovascular and Limb Outcomes in Peripheral Arterial Disease: A Systematic Review and Meta-analysis

Eur J Vasc Endovasc Surg. 2021 Sep;62(3):450-461. doi: 10.1016/j.ejvs.2021.05.025. Epub 2021 Aug 10.

Abstract

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.

Keywords: Cardiovascular; Dose; Mortality; Peripheral Arterial Disease; Statin.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amputation, Surgical
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Cause of Death
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / mortality
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / drug therapy*
  • Peripheral Arterial Disease / mortality
  • Primary Prevention
  • Risk Assessment
  • Secondary Prevention
  • Treatment Outcome

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors