Moderate-dose Statin Research Articles

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Effect of preoperative moderate-dose statin and duration on acute kidney injury after cardiac surgery: a retrospective cohort study

Background The impact of preoperative statin use on postoperative acute kidney injury (AKI) is uncertain. We aimed to examine the association of statin therapy before cardiac surgery with postoperative AKI. Methods The retrospective cohort study consisted of 1581 patients undergoing cardiac surgery. Postoperative AKI were identified by the modified KDIGO definition. Propensity-score matching was employed to control for selection bias, and logistic regression was used to control for confounders. Subgroup and interaction analyses were performed to evaluate the robustness of the findings. Results The overall incidence of postoperative AKI and severe AKI were 42.19% and 12.27%, respectively. Preoperative moderate-dose statin was significantly associated with a reduced incidence of postoperative AKI (28.9% vs 43.0%, OR (95%CI): 0.54 (0.38, 0.77), p < 0.001) and severe AKI (6.9% vs 13.7%, OR (95%CI): 0.46 (0.26, 0.83), p = 0.009). The beneficial effect on postoperative AKI persisted after adjusting for major confounding factors (OR (95%CI): 0.47 (0.34, 0.66)). Decreased risk of postoperative AKI was observed in patients with preoperative statin duration of 7 ∼ 14 days (OR (95%CI): 0.41 (0.25, 0.65)) and over 14 days (OR (95%CI): 0.43 (0.28, 0.65)), but not in those with preoperative statin duration of <7 days. Similar favorable effects were noted in most subgroup patients, except for those with high-risk factors such as diabetes mellitus, previous congestive cardiac failure, arrhythmia, preoperative ACEI/ARB, aortic cross-clamping or IABP. Conclusion Preoperative moderate-dose statin was significantly related to a decreased risk of postoperative AKI, especially in patients who received statins for a longer duration. Further large-scale multicenter randomized controlled trials are needed to ascertain the impact of statin dose, duration, and timing on postoperative AKI in cardiac surgery patients.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus β-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.

Initial statin dose after myocardial infarction and long-term cardiovascular outcomes.

Effective statin therapy is a cornerstone of secondary prevention after myocardial infarction (MI). Real-life statin dosing is nevertheless suboptimal and largely determined early after MI. We studied long-term outcome impact of initial statin dose after MI. Consecutive MI patients treated in Finland who used statins early after index event were retrospectively studied (N=72401; 67% men; mean age 68 years) using national registries. High-dose statin therapy was used by 26.3%, moderate dose by 69.2%, and low dose by 4.5%. Differences in baseline features, comorbidities, revascularisation, and usage of other evidence-based medications were adjusted for with multivariable regression. The primary outcome was major adverse cardiovascular or cerebrovascular event (MACCE) within 10 years. Median follow-up was 4.9 years. MACCE was less frequent in high-dose group compared with moderate dose [adjusted hazard ratio (HR) 0.92; P<0.0001; number needed to treat (NNT) 34.1] and to low dose [adj.HR 0.81; P<0.001; NNT 13.4] as well as in moderate-dose group compared with low dose (adj.HR 0.88; P<0.0001; NNT 23.4). Death (adj.HR 0.87; P<0.0001; NNT 23.6), recurrent MI (adj.sHR 0.91; P=0.0001), and stroke (adj.sHR 0.86; P<0.0001) were less frequent with a high- vs. moderate-dose statin. Higher initial statin dose after MI was associated with better long-term outcomes in subgroups by age, sex, atrial fibrillation, dementia, diabetes, heart failure, revascularisation, prior statin usage, or usage of other evidence-based medications. Higher initial statin dose after MI is dose-dependently associated with better long-term cardiovascular outcomes. These results underline the importance of using a high statin dose early after MI.

Hepatocyte Rap1a contributes to obesity- and statin-associated hyperglycemia.

SUMMARYExcessive hepatic glucose production contributes to the development of hyperglycemia and is a key feature of type 2 diabetes. Here, we report that activation of hepatocyte Rap1a suppresses gluconeogenic gene expression and glucose production, whereas Rap1a silencing stimulates them. Rap1a activation is suppressed in obese mouse liver, and restoring its activity improves glucose intolerance. As Rap1a′s membrane localization and activation depends on its geranylgeranylation, which is inhibited by statins, we show that statin-treated hepatocytes and the human liver have lower active-Rap1a levels. Similar to Rap1a inhibition, statins stimulate hepatic gluconeogenesis and increase fasting blood glucose in obese mice. Geranylgeraniol treatment, which acts as the precursor for geranylgeranyl isoprenoids, restores Rap1a activity and improves statin-mediated glucose intolerance. Mechanistically, Rap1a activation induces actin polymerization, which suppresses gluconeogenesis by Akt-mediated FoxO1 inhibition. Thus, Rap1a regulates hepatic glucose homeostasis, and blocking its activity, via lowering geranylgeranyl isoprenoids, contributes to statin-induced glucose intolerance.

Efficacy of high- versus moderate-dose statin therapy on lower extremity artery disease after revascularization

Aim: Statins are one of the most important agents in the treatment of atherosclerotic peripheral arterial disease. We aim to compare high- and moderate-dose statin therapy in patients with lower extremity artery disease (LEAD) who have undergone percutaneous transluminal angioplasty (PTA). Patients and Methods: Ninety-four patients treated with PTA were selected consecutively and retrospectively and were divided into two groups according to the high- or moderate-dose statin treatments they were given. Groups were compared for the absence of restenosis and occlusion as primary patency and the need for reintervention in the treated arterial segment as secondary patency. All patients underwent computed tomography (CT) angiography or duplex scan one year after receiving PTA. Results: Coronary revascularization (p&amp;lt;0.001) and prior statin usage (p:0.02) were more common in the high-dose statin group when compared to the moderate-dose statin group. Lesion characteristics did not differ between the two groups. Primary patency rate was significantly higher (36.1% vs. 27.6%, p 0.01) in the high-dose statin group. Major amputation (4.2% vs. 10.6%, p:0.03) and minor amputation (12.7% vs. 19.1%, p:0.03) rates were significantly lower in the high-dose statin group. Regression analysis revealed that the usage of high-dose statin therapy was an independent predictor of higher primary patency in patients who were treated with prior PTA(Odds ratio:2.208, p&amp;lt;0.001) Conclusion: High-dose long-term statin treatment might have better outcomes on primary patency in patients who underwent prior PTA for infrapopliteal lesions as a subgroup of peripheral artery disease. The administration of the high-dose long-term statin therapy might be important in the prognosis of peripheral arterial disease, especially for those with infrapopliteal lesions.

Impact of China's Low Centralized Medicine Procurement Prices on the Cost-Effectiveness of Statins for the Primary Prevention of Atherosclerotic Cardiovascular Disease.

Background:Statin medications reduce the risk of atherosclerotic cardiovascular disease (ASCVD). China’s new central government medicine procurement policy lowered statin prices by five-fold or more, which may impact the cost-effectiveness of statin therapy.Objective:To explore the impact of China’s 2019 centralized medicine procurement policy on the cost-effectiveness of statins treatment for primary ASCVD prevention.Methods:A microsimulation decision tree analytic model was built using individual participant data from ASCVD-free adults aged 35–64 years (n = 21,265) in the China Multi-provincial Cohort Study. ASCVD incidence, costs (2019 Int$), and quality-adjusted life years (QALYs) over a 10-year period from health-care sector and societal perspectives were estimated. Effect and cost-effectiveness of low-dose statins (equivalent potency regimens of simvastatin 20 mg/day, atorvastatin 10 mg/day, or rosuvastatin 5 mg/day) and moderate-dose (double low dose) statins therapy were simulated. The incremental cost-effectiveness ratio (ICER) of statin treatment was compared with no treatment by category of 10-year ASCVD risk. New lower prices of statins were from the centralized procurement policy bid-winning announcement file. One-way and probabilistic sensitivity analyses quantified model uncertainty.Results:Low-dose statins interventions reduced 10-year ASCVD incidence by 4.1%, 9.7%, and 15.5% among people with low, moderate, and high risk comparing to no treatment. Lowering statin prices to the 2019 central government procurement policy level could lower the ICER of low-dose statins treatment for high-risk people from Int$ 141,000 to Int$ 51,300 per QALY gained from health-care sector perspective. Moderate-dose statin treatment lowered the ICER compared with the low-dose statins treatment in each ASCVD risk category (Int$ 43,100 vs. Int$ 51,300 per QALY gained from the health-care sector perspective for high risk people). Cost-effectiveness improved progressively with increased baseline ASCVD risk.Conclusion:Implementing low central government prices will substantially improve the cost-effectiveness of statins for primary ASCVD prevention in 35–64-year-old Chinese adults.

Cost-Effectiveness Analysis of Ezetimibe as the Add-on Treatment to Moderate-Dose Rosuvastatin versus High-Dose Rosuvastatin in the Secondary Prevention of Cardiovascular Diseases in China: A Markov Model Analysis.

BackgroundFor patients with inadequate control of cholesterol using moderate-dose statins in the secondary prevention of cardiovascular diseases (CVD), either doubling the dose of statins or adding ezetimibe should be considered. The cost-effectiveness of them is unknown in the Chinese context. The aim of this study is to compare the cost and effectiveness of the two regimens, and estimate the incremental cost-effectiveness ratio (ICER).MethodsA Markov model of five health statuses were used to estimate long-term costs and quality-adjusted life-years (QALYs) of the two treatment regimens from the healthcare perspective. The effectiveness data used to calculate the transition probability was based on a previously published randomized trial. The utility data was gathered from literature and the costs were gathered from the electronic medical record system of West China Hospital in Chinese Yuan (CNY) in 2017 price. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted.ResultsThe ICER for ezetimibe plus moderate-dose rosuvastatin was 47,102.99 CNY per QALY for 20 years simulation, which did not reach the threshold of per capita gross domestic product (GDP) of 59,660 CNY per QALY in 2017 in China. Non-CVD-related mortality and CVD-related mortality contributed most to the ICER.ConclusionAdding ezetimibe to the moderate-dose statin in secondary prevention for CVD is cost-effective, compared with the high-dose statin in the Chinese context whose low-density lipoprotein cholesterol (LDL-c) was not inadequately controlled by moderate-dose statin alone.

EZETYMIB JAKO LECZENIE DYSLIPIDEMII W PRZEWLEKŁEJ CHOROBIE NEREK

Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Primary and secondary prevention of cardiovascular events is one of the major CKD patients' treatment targets. Dyslipidaemia is the important modifiable risk factor in general population. Each 1.0 mmol reduction in LDL cholesterol with statins reduces annual rate of heart attack, coronary revascularization or ischemic stroke by 20% leading to 10% reduction of all-cause mortality. Adding ezetimibe, an inhibitor of intestinal lipids absorption, further reduces LDL cholesterol by 20%. Optimal lipid lowering treatment for CKD patients remains unclear. Cardiovascular risk reduction observed with statins therapy decreases together with a progression of the disease, moreover patients with advanced CKD treated with high doses of statins have an increased risk of adverse events. These patients might benefit from adding ezetimibe to moderate dose statin therapy for prevention of cardiovascular events.

PDG20 COST-EFFECTIVENESS ANALYSIS OF EZETIMIBE AS THE ADD-ON TREATMENT TO MODERATE-DOSE ROSUVASTATIN VERSUS HIGH-DOSE ROSUVASTATIN IN THE SECONDARY PREVENTION OF CARDIOVASCULAR DISEASES IN CHINA: A MARKOV MODEL ANALYSIS BASED ON NSTE-ACS

For patients with inadequate control of cholesterol using moderate-dose statins in the secondary prevention of cardiovascular diseases (CVD), either doubling the dose of statins or adding ezetimibe should be considered. However, the burden for each treatment is under due to difference of safety events and costs. The aim of this study is to assess the cost-effectiveness of the two treatment strategies. A Markov model of five health states was used to estimate long-term costs and quality-adjusted life years (QALYs) of two treatments in secondary prevention from healthcare perspective. The effectiveness data used to calculate the transition probability was based on a previously published randomized trial (NSTE-ACS). The utility data was gathered from literatures and the costs were gathered from electronic medical record system of West China Hospital. One-way sensitivity analysis and probability sensitivity analysis were conducted. The ezetimibe-add-on treatment was with higher costs and better effects, while the costs and effectiveness of the high-dose statins were low. The incremental cost effectiveness ratio (ICER) was 11,800 CNY（1782.5$） per QALY for 20 years simulation, which did not reach the threshold of 59,660 CNY(9012.1$) per QALY. Coronary heart diseases utility value, stroke utility value, CVD mortality rate of the ezetimibe-add-on treatment and other five parameters were related to the results. Adding ezetimibe to moderate-dose statin in secondary prevention for CVD is cost-effective, comparing with high-dose statin. With the patent on due, a decrease of price would make the result more cost-effective.

PDB4 - Risk of Diabetes Among Intensive and Moderate Dose Statin Users with Potential Modifying Effects of Treatment Duration

PDB4 - Risk of Diabetes Among Intensive and Moderate Dose Statin Users with Potential Modifying Effects of Treatment Duration

Dyslipidemia.

Dyslipidemia.

Effect of Pioglitazone in Combination with Moderate Dose Statin on Atherosclerotic Inflammation: Randomized Controlled Clinical Trial Using Serial FDG-PET/CT.

Background and ObjectivesNon-statin therapy plus lower intensity statin might be an alternative in patients with coronary artery disease (CAD). A recent data suggested an anti-inflammatory therapy can reduce recurrent cardiovascular events and pioglitazone is also an intriguing inflammatory-modulating agent. However, limited data exist on whether pioglitazone on top of statins further attenuates plaque inflammation.MethodsStatin-naïve patients with stable CAD and carotid plaques of ≥3 mm were randomly prescribed moderate dose atorvastatin (20 mg/day), or moderate dose atorvastatin plus pioglitazone (30 mg/day) for 3 months. The primary endpoint was the change in the arterial inflammation of the carotid artery measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during 3 months.ResultsOf the 41 randomized patients, 33 underwent an evaluation by fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT; 17 atorvastatin plus pioglitazone and 16 atorvastatin patients). The addition of pioglitazone significantly improved the insulin sensitivity and increased the high-density lipoprotein cholesterol after 3 months. Although a reduction in the (FDG) uptake by pioglitazone on top of atorvastatin in carotid arteries with plaque showed marginally statistical significance in the entire patient group (atorvastatin plus pioglitazone; −0.10±0.07 and atorvastatin −0.06±0.04, p=0.058), pioglitazone showed a further reduction of the fluorodeoxyglucose (FDG) uptake among patients who had a baseline FDG uptake above the median (atorvastatin plus pioglitazone; −0.14±0.04 and atorvastatin −0.03±0.03, p<0.001).ConclusionsPioglitazone demonstrated marginally significant anti-inflammatory effects in addition to moderate dose atorvastatin. This may have been due to the lack of power of the study. However, pioglitazone may have an anti-inflammatory effect in those patients with high plaque inflammation (Trial registry at ClinicalTrials.gov, NCT01341730).

Intensive versus moderate atorvastatin therapy and one-year graft patency after CABG: Rationale and design of the ACTIVE (Aggressive Cholesterol Therapy to Inhibit Vein Graft Events) randomized controlled trial (NCT01528709)

RationaleSaphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery (CABG). Statin therapy inhibits the development of vein graft disease and improves outcomes after CABG. However, it is unclear whether treatment with high-dose statins will further slow the process of vein graft disease and improve graft patency, as compared to conventional moderate doses. Therefore, the goal of this study will be to evaluate the efficacy of high-dose statin therapy versus moderate-dose statin therapy for the prevention of saphenous vein graft occlusion following CABG. Study designThe Aggressive Cholesterol Therapy to Inhibit Vein Graft Events (ACTIVE) trial is a multi-center double-blind randomized controlled trial enrolling patients who have undergone multi-vessel CABG with at least one saphenous vein graft. Patients will be randomized to receive either atorvastatin 80mg daily or atorvastatin 10mg daily for one year starting within 5days after surgery. The target enrollment is 100 patients in each arm (200 patients total). Lipid levels will be assessed every 3months. After one year, patients will undergo computed tomography (CT) coronary angiography to assess the incidence of vein graft occlusion and stenosis. ConclusionThis trial is the first prospective study to evaluate the impact of early postoperative high-dose statin therapy on graft patency after CABG. Should high-dose statin therapy reduce the incidence of postoperative graft occlusion, the results will add to the growing evidence supporting the role of high-intensity statins for modern lipid management after coronary surgical revascularization (ClinicalTrials.govNCT01528709).

Moderate statin treatment reduces prebeta-1 high-density lipoprotein levels in dyslipidemic patients

Elevated plasma levels of prebeta-1 high-density lipoprotein (HDL), the principal acceptor of cholesterol effluxed from macrophages, are associated with increased risk of atherosclerotic coronary heart disease and myocardial infarction. The objective of the study was to assess the effects on prebeta-1 HDL levels of 6-week moderate-dose statin treatment. We studied 101 patients (mean age 52.7years; 53.5% female; 63 with primary hypercholesterolemia; 38 with combined hyperlipidemia) before and after treatment with statins. Mean atorvastatin potency equivalence was 23.6mg/d. Prebeta-1 HDL plasma levels were measured by immunofixation of agarose gels using anti-apolipoprotein A-1 antibody. We observed a 42.0% reduction of low-density lipoprotein cholesterol (181±56 vs 105mg/dL, P<.001). Triglyceride (TG) levels decreased by 22.3% (157 vs 122mg/dL, P<.001), HDL cholesterol levels remained similar (56.0 vs 57.1, P= NS). Levels of prebeta-1 HDL were significantly reduced by 17.9% after statin treatment (mean 11.4 vs 9.4mg apoA-1/dL, P<.001). The magnitude of this decrease was similar with each of 3 statins (atorvastatin, simvastatin, and rosuvastatin). The decrease in prebeta-1 HDL was strongly associated with the decline in TG, but not with the decline in low-density lipoprotein cholesterol. The association of high prebeta-1 HDL with coronary heart disease identifies it as an inferential measure of the rate of cholesterol efflux from the artery wall. Our observations demonstrate a reduction of prebeta-1 HDL with statin therapy, partially reflecting the reduced TGs, and probably reflecting a direct beneficial impact on cholesterol efflux.

Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase 3 clinical trials

Low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by background statin dose due to increased PCSK9 levels with higher statin doses. Data from 8 Phase 3 trials conducted with background statin (n = 4629) were pooled by alirocumab dose (75 or 150 mg every 2 weeks) and control (placebo/ezetimibe), and analyzed by background statin type/dose. Overall, 58.4% received high-dose statins (atorvastatin 40–80 mg, rosuvastatin 20–40 mg, simvastatin 80 mg), 28.6% moderate-dose statins (atorvastatin 20–<40 mg, rosuvastatin 10–<20 mg, simvastatin 40–<80 mg), and 12.9% low-dose statins (atorvastatin <20 mg, rosuvastatin <10 mg, simvastatin <40 mg). Mean baseline PCSK9 levels were higher with high versus moderate and low statin doses (318.5 vs 280.6 ng/mL). Baseline LDL-C levels were similar across pools, regardless of statin intensity. No associations were observed between statin type/dose and LDL-C % change from baseline or % of patients achieving LDL-C goals at Week 24 for alirocumab versus control (interaction P-values non-significant). Incidence of adverse events was similar for alirocumab versus control, except for a higher rate of injection-site reactions with alirocumab. In summary, alirocumab provided consistent LDL-C reductions and was generally well tolerated independent of background statin type/dose.

Guideline: The USPSTF recommends low- to moderate-dose statins to prevent CVD in selected adults 40 to 75 years of age.

Source Citation US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:1997-2007. 27838723

Addition of Ezetimibe to statins for patients at high cardiovascular risk: Systematic review of patient-important outcomes.

Ezetimibe is widely used in combination with statins to reduce low-density lipoprotein. We sought to examine the impact of ezetimibe when added to statins on patient-important outcomes. Medline, EMBASE, CINAHL, and CENTRAL were searched through July, 2016. Randomized controlled trials (RCTs) of ezetimibe combined with statins versus statins alone that followed patients for at least 6months and reported on at least one of all-cause mortality, cardiovascular deaths, non-fatal myocardial infarctions (MI), and non-fatal strokes were included. Pairs of reviewers extracted study data and assessed risk of bias independently and in duplicate. Quality of evidence was assessed using the GRADE approach. We conducted a narrative review with complementary subgroup and sensitivity analyses. IMPROVE-IT study enrolled 93% of all patients enrolled in the 8 included trials. Our analysis of the IMPROVE-IT study results showed that in patients at high risk of cardiovascular events, ezetimibe added to statins was associated with i) a likely reduction in non-fatal MI (17 fewer/1000 treated over 6years, moderate certainty in evidence); ii) a possible reduction in non-fatal stroke (6 fewer/1000 treated over 6years, low certainty); iii) no impact on myopathy (moderate certainty); iv) potentially no impact on all-cause mortality and cardiovascular death (both moderate certainty); and v) possibly no impact on cancer (low certainty). Addition of ezetimibe to moderate-dose statins is likely to result in 17 fewer MIs and possibly 6 fewer strokes/1000 treated over 6years but is unlikely to reduce all-cause mortality or cardiovascular death. Patients who place a high value on a small absolute reduction in MI and are not adverse to use of an additional medication over a long duration may opt for ezetimibe in addition to statin therapy. Our analysis revealed no increased specific harms associated with addition of ezetimibe to statins.

Statin use in patients with peripheral arterial disease

BackgroundStatins are recommended for use in patients with peripheral arterial disease (PAD) to reduce cardiovascular events and mortality. However, much of the data regarding benefits of statins stem from the cardiovascular literature. Here, we review the literature regarding statin use specifically in patients with PAD regarding its effects on cardiovascular events and mortality, limb-related outcomes, statin use after endovascular interventions, statin dosing, and concerns about statins. MethodsWe performed a literature review using PubMed for literature after the year 2000. Search terms included “statins,” “peripheral arterial disease,” “peripheral vascular disease,” “lipid-lowering medication,” and “cardiovascular disease.” ResultsThere is good evidence of statins lowering cardiovascular events and cardiovascular-related mortality in patients with PAD. Though revascularization rates were reduced with statins, amputation rates and amputation-free survival did not improve. Small randomized controlled trials show that patients taking statins can slightly improve pain-free walking distance or pain-free walking time, although the extent of the effect on quality of life is unclear. Statin use for patients undergoing endovascular interventions is recommended because of the reduction of postoperative cardiovascular events. Not enough data exist to support local effects of systemic statin therapy, such as prevention of restenosis. For statin dosing, there is little increased benefit to intense therapy compared with the adverse effects, whereas moderate-dose therapy has significant benefits with very few adverse effects. Adverse effects of moderate-dose statin therapy are rare and mild and are greatly outweighed by the cardiovascular benefits. ConclusionsThere is strong evidence to support use of statins in patients with PAD to reduce cardiovascular events and mortality. Use in patients undergoing open and endovascular interventions is also recommended. Statin use may reduce the need for revascularization, but reductions in amputation have not been shown. Moderate-dose statin therapy is safe, and the minor risks are greatly outweighed by benefits.

Longitudinal treatment patterns among US patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia initiating lipid-lowering pharmacotherapy

The most recent American College of Cardiology-American Heart Association guidelines recommend high-dose statin therapy for most patients with confirmed atherosclerotic cardiovascular disease (ASCVD) and patients with high cardiovascular risk. There is limited information regarding long-term treatment patterns among these patients. To examine longitudinal treatment modifications in patients with ASCVD or familial hypercholesterolemia (FH). This retrospective analysis of administrative claims data identified patients initiating statin or ezetimibe therapy between January 1, 2007, and December 31, 2012, who had evidence of ASCVD or FH. Patients were followed for up to 3years and up to 4 treatment episodes. After initial treatment, subsequent treatment episodes began on the date of a treatment modification, which included discontinuation, statin dose change, switching, and augmentation. A total of 92,621 patients (mean age 64.7years, 57.3% male) were identified; 91,740 had ASCVD, 937 had FH (56 had both). Most ASCVD (89.6%) and FH (85.8%) patients initiated on statin monotherapy. The most common treatment modification in the first treatment episode was discontinuation (ASCVD: 42.0%; FH: 58.4%); among patients who discontinued, most reinitiated therapy (70.5% of ASCVD, 76.8% of FH). Most ASCVD (68.2%) and FH (71.1%) patients initiated on moderate-dose statins; statin dose increase occurred in 10.3% of ASCVD and 18.5% of FH patients in the first episode. Among patients with high cardiovascular risk, most initiated on moderate-dose statins with infrequent uptitration. In light of the recent American College of Cardiology-American Heart Association guidelines, statin initiation practices will need to change to ensure appropriate therapy for high-risk patients.