Statin Discontinuation and Cardiovascular Events Among Older People in Denmark

Thompson, Wade; Morin, Lucas; Jarbøl, Dorte Ejg; Andersen, Jacob Harbo; Ernst, Martin; Nielsen, Jesper Bo; Haastrup, Peter; Schmidt, Morten; Pottegård, Anton

doi:10.1001/jamanetworkopen.2021.36802

Cited by 53 publications

(30 citation statements)

References 55 publications

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“…Rodriguez et al 29 examined 347 104 CVD patients from the US Veterans Affairs Health System and observed that patients with the lowest statin adherence levels (MPR <50%) had a hazard ratio for all-cause mortality of 1.30 (95% CI, 1.27-1.34) as compared with the most adherent patients (MPR ≥90%). Using data from the Danish Health Data Authority, Thompson et al 41 found that 30% of older people (n = 8311) in Denmark discontinued statin use in the primary prevention cohort. In our study, about one-fifth and two-thirds of statin users had either discontinued use or had low-adherent use, respectively.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk

Zhou

Wang

et al. 2022

JAMA Netw Open

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Section: Discussionmentioning

confidence: 99%

“…Fourth, statin discontinuation was defined as the absence of statin prescriptions for 3 or 6 consecutive months within the first 2 years of outcome measurements. 40 , 41 Fifth, we included those who had CVD during follow-up (n = 49) in the analysis of progression of arterial stiffness.…”

Section: Methodsmentioning

confidence: 99%

Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk

Zhou

Wang

et al. 2022

JAMA Netw Open

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“…In addition to their anti-inflammatory action, the anti-oxidative and antithrombotic effects of statins, including those also on endothelial function [ 165 , 166 ], have been reported in numerous studies, thus contributing to explain the beneficial effects of statins in reducing CVD [ 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 ]. On the other hand, in comparison with statin continuation, especially in older people taking long-term statin treatment both in primary and secondary prevention, statin discontinuation has been associated with a significant increase in the risk of major adverse CV events [ 177 ].…”

Section: Current Hypolipidemic Drugs With Effects On the Redox Balanc...mentioning

confidence: 99%

“…Taking into account the concept that statins influence platelet function, it is not surprising that a condition of platelet hyperactivation may occur after statin discontinuation [ 178 ]. This finding together with the loss of beneficial effects of statins on endothelial function can contribute to account for an increased hypercoagulable state, thrombus formation, and cardiovascular events rate after statin discontinuation [ 177 ]. Some of the antiplatelet effects of statins could be explained by mechanisms summarized in Figure 3 .…”

Section: Current Hypolipidemic Drugs With Effects On the Redox Balanc...mentioning

confidence: 99%

Platelet Redox Imbalance in Hypercholesterolemia: A Big Problem for a Small Cell

Morotti

Barale

Melchionda

et al. 2022

IJMS

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The imbalance between reactive oxygen species (ROS) synthesis and their scavenging by anti-oxidant defences is the common soil of many disorders, including hypercholesterolemia. Platelets, the smallest blood cells, are deeply involved in the pathophysiology of occlusive arterial thrombi associated with myocardial infarction and stroke. A great deal of evidence shows that both increased intraplatelet ROS synthesis and impaired ROS neutralization are implicated in the thrombotic process. Hypercholesterolemia is recognized as cause of atherosclerosis, cerebro- and cardiovascular disease, and, closely related to this, is the widespread acceptance that it strongly contributes to platelet hyperreactivity via direct oxidized LDL (oxLDL)-platelet membrane interaction via scavenger receptors such as CD36 and signaling pathways including Src family kinases (SFK), mitogen-activated protein kinases (MAPK), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In turn, activated platelets contribute to oxLDL generation, which ends up propagating platelet activation and thrombus formation through a mechanism mediated by oxidative stress. When evaluating the effect of lipid-lowering therapies on thrombogenesis, a large body of evidence shows that the effects of statins and proprotein convertase subtilisin/kexin type 9 inhibitors are not limited to the reduction of LDL-C but also to the down-regulation of platelet reactivity mainly by mechanisms sensitive to intracellular redox balance. In this review, we will focus on the role of oxidative stress-related mechanisms as a cause of platelet hyperreactivity and the pathophysiological link of the pleiotropism of lipid-lowering agents to the beneficial effects on platelet function.

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“…A very recent cohort study evaluated the association between statin discontinuation and the rate of major adverse cardiovascular events among elderly patients aged 75 years or older who had been on long-term statin treatment [ 25 ]. The study showed that the patients who discontinued statin use had a significantly higher rate of such major adverse events.…”

Section: Statins Paxlovid and Heterozygous Familial Hypercholesterolemiamentioning

confidence: 99%

Cholesterol-lowering Drugs for High-Risk Hypercholesterolemia Patients with COVID-19 While on Paxlovid™ Therapy

2022

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Paxlovid™ is a promising antiviral oral medication for patients at a high risk of a severe form of COVID-19. Regarding COVID-19 patients who have hypercholesterolemia and are at high or very high risk for an acute atherothrombotic cardiovascular event, we are highlighting patients with heterozygous familial hypercholesterolemia as an example of severe hypercholesterolemia. Unfortunately, the concomitant use of Paxlovid and a statin, which is highly dependent on cytochrome P4507A (CYP3A) for clearance, may result in significant drug interactions. Since an abrupt withdrawal of statin use may cause serious negative rebound effects on the cardiovascular system, it is essential to continue statin treatment also during the 5-day Paxlovid treatment period. During Paxlovid treatment, simvastatin and lovastatin need to be substituted with another statin, such as pravastatin or fluvastatin, while a reduction of the dose of atorvastatin and rosuvastatin is recommended.

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Statin Discontinuation and Cardiovascular Events Among Older People in Denmark

Abstract: This cohort study uses registry data from Denmark to evaluate the association between discontinuation of long-term statin treatment and major adverse cardiovascular events among individuals aged 75 years or older.

Cited by 53 publications

References 55 publications

Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk

Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk

Platelet Redox Imbalance in Hypercholesterolemia: A Big Problem for a Small Cell

Cholesterol-lowering Drugs for High-Risk Hypercholesterolemia Patients with COVID-19 While on Paxlovid™ Therapy

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