Legacy effects of statins on cardiovascular and all-cause mortality: a meta-analysis

Nayak, Agnish; Hayen, Andrew; Zhu, Lin; McGeechan, Kevin; Glasziou, Paul; Irwig, Les; Doust, Jenny; Gregory, Gabriel A; Bell, Katy J.L.

doi:10.1136/bmjopen-2017-020584

Cited by 32 publications

(18 citation statements)

References 51 publications

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“…In addition, IFG combined with DLP alone significantly increased the risk for CVDdeath. The reason why IFG in the absence of HTN, but not in the absence of both HTN and DLP did increase the risk for CVD-death might be explained by the confounding effect of medications such as statin that has been previously shown to be independently associated with a decrease in the risk for CVD mortality [39].…”

Section: Discussionmentioning

confidence: 97%

Impaired fasting glucose and major adverse cardiovascular events by hypertension and dyslipidemia status: the Golestan cohort study

Madani

Ismail‐Beigi

Nalini

et al. 2020

BMC Cardiovasc Disord

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Background: Whether pre-diabetes in the absence of hypertension (HTN) or dyslipidemia (DLP) is a risk factor for occurrence of major adverse cardiovascular events (MACE) is not fully established. We investigated the effect of impaired fasting glucose (IFG) alone and in combination with HTN, DLP or both on subsequent occurrence of MACE as well as individual MACE components. Methods: This longitudinal population-based study included 11,374 inhabitants of Northeastern Iran. The participants were free of any cardiovascular disease at baseline and were followed yearly from 2010 to 2017. Cox proportional hazard models were fitted to measure the hazard of IFG alone or in combination with HTN and DLP on occurrence of MACE as the primary endpoint. Results: Four hundred thirty-seven MACE were recorded during 6.2 ± 0.1 years follow up. IFG alone compared to normal fasting glucose (NFG) was not associated with an increase in occurrence of MACE (HR, 0.87; 95% CI, 0.19-4.02; p, 0.854). However, combination of IFG and HTN (HR, 2.88; 95% CI, 2.04-4.07; p, 0.000) or HTN + DLP (HR, 2.98; 95% CI, 1.89-4.71; p, 0.000) significantly increased the risk for MACE. Moreover, IFG + DM with or without HTN, DLP, or both was also associated with an increase in the incidence of MACE. Conclusion: IFG, per se, does not appear to increase hazard of MACE. However, IFG with HTN or HTN + DLP conferred a significant hazard for MACE in an incremental manner. Moreover, IFG without HTN, adjusted for DLP, can be associated with an increase in the risk for CVD-death.

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Section: Discussionmentioning

confidence: 97%

Impaired fasting glucose and major adverse cardiovascular events by hypertension and dyslipidemia status: the Golestan cohort study

Madani

Ismail‐Beigi

Nalini

et al. 2020

BMC Cardiovasc Disord

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“…The legacy effect was observed in relation to lower all-cause mortality but, appeared to have no effect on CVD mortality. Additionally, in a subgroup analysis, there appeared to be a greater legacy effect when statins were used for primary prevention compared to secondary prevention in CVD and all-cause mortality (HR 0.87 and 0.90, respectively), suggesting the importance of long-term prevention in these patients [58].…”

Section: Legacy Effect After Lipid Controlmentioning

confidence: 97%

The Legacy Effect in the Prevention of Cardiovascular Disease

2020

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The “legacy effect” describes the long-term benefits that may persist for many years after the end of an intervention period, involving different biological processes. The legacy effect in cardiovascular disease (CVD) prevention has been evaluated by a limited number of studies, mostly based on pharmacological interventions, while few manuscripts on dietary interventions have been published. Most of these studies are focused on intensive treatment regimens, whose main goal is to achieve tight control of one or more cardiovascular risk factors. This review aims to summarise the legacy effect-related results obtained in those studies and to determine the existence of this effect in CVD prevention. There is sufficient data to suggest the existence of a legacy effect after intensive intervention on cardiovascular risk factors; however, this effect is not equivalent for all risk factors and could be influenced by patient characteristics, disease duration, and the type of intervention performed. Currently, available evidence suggests that the legacy effect is greater in subjects with moderately-high cardiovascular risk but without CVD, especially in those patients with recent-onset diabetes. However, preventive treatment for CVD should not be discontinued in high-risk subjects, as the level of existing evidence on the legacy effect is low to moderate.

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“…The finding of a legacy effect would have important clinical implications, including the potential benefits of early initiation of fibrate treatment in the setting of diabetic dyslipidemia. Although potential legacy effects for statin treatment have been investigated in a number of posttrial follow up studies [23], those for combined statinfibrate treatment remain unexplored [24,25]. Post-trial data after a statin-fibrate RCT provide the opportunity to investigate potential legacy effects in people with T2DM and dyslipidemia.…”

Section: Introductionmentioning

confidence: 99%

Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study

Zhu

Hayen

Bell

2020

Cardiovasc Diabetol

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Background: The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid study found no evidence of a beneficial effect of statin-fibrate combined treatment, compared to statins alone, on cardiovascular outcomes and mortality in type 2 diabetes mellitus after 5 years of active treatment. However, a beneficial reduction in major CVD events was shown in a pre-specified subgroup of participants with dyslipidemia. The extended follow-up of this trial provides the opportunity to further investigate possible beneficial effects of fibrates in this group of patients. We aimed to evaluate possible "legacy effects" of fibrate add-on therapy on mortality and major cardiovascular outcomes in patients with dyslipidemia. Methods: The ACCORD-lipid study was a randomized controlled trial of 5518 participants assigned to receive simvastatin plus fenofibrate vs simvastatin plus placebo. After randomized treatment allocation had finished at the end of the trial, all surviving participants were invited to attend an extended follow-up study (ACCORDION) to continue prospective collection of clinical outcomes. We undertook a secondary analysis of trial and post-trial data in patients who had dyslipidemia. The primary outcome was all-cause and cardiovascular mortality, and secondary outcomes were nonfatal myocardial infarction, stroke, congestive heart failure and major coronary heart disease. We used an intention-to-treat approach to analysis to make comparisons between the original randomized treatment groups. Results: 853 participants with dyslipidemia had survived at the end of the trial. Most participants continued to use statins, but few used fibrates in either group during the post-trial period. The incidence rates in the fenofibrate group were lower with respect to all-cause mortality, CVD mortality, nonfatal myocardial infarction, congestive heart failure and major coronary heart disease than those in the placebo group over a post-trial follow-up. Allocation to the combined fibrate-statin treatment arm during the trial period had a beneficial legacy effect on all-cause mortality (adjusted HR = 0.65, 95% CI 0.45-0.94; P = 0.02). Conclusions: Fibrate treatment during the initial trial period was associated with a legacy benefit of improved survival over a post-trial follow-up. These findings support re-evaluation of fibrates as an add-on strategy to statins in order to reduce cardiovascular risk in diabetic patients with dyslipidemia.

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Legacy effects of statins on cardiovascular and all-cause mortality: a meta-analysis

Cited by 32 publications

References 51 publications

Impaired fasting glucose and major adverse cardiovascular events by hypertension and dyslipidemia status: the Golestan cohort study

Impaired fasting glucose and major adverse cardiovascular events by hypertension and dyslipidemia status: the Golestan cohort study

The Legacy Effect in the Prevention of Cardiovascular Disease

Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study

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