Lipid-lowering Statin Therapy Research Articles

Impact of CYP2C19 Gene Variants on Long-Term Treatment with Atorvastatin in Patients with Acute Coronary Syndromes.

The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of CYP2C19 on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the CYP2C19 gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of CYP2C19*2, CYP2C19*4, and CYP2C19*8 alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.

A281 CASE REPORT: STEATOTIC LIVER DISEASE DIAGNOSED IN A 24-YEAR-OLD FEMALE WITH RETT SYNDROME

Abstract Background Rett syndrome (RTT) is a rare, severe neurodevelopmental disorder seen almost exclusively in females that is caused by spontaneous loss-of-function mutations in the methyl CpG binding protein 2 (MECP2) gene. Girls with RTT typically demonstrate normal development for the first 6-18 months of life before displaying evidence of variable levels of developmental milestone regression and physical disability. Although perturbed lipid metabolism in the nervous system is the main contributor to the pathophysiology of RTT, mutations to the MECP2 gene also contribute to disease burden by causing perturbations to peripheral systems, leading to consequences such as dyslipidemia (DLD) and steatotic liver disease (SLD). Although DLD has been described in human cell lines and girls with RTT, SLD has only been described in RTT mouse models. Aims This report aims to present a case of a patient with RTT who was diagnosed with SLD on liver biopsy in the context of DLD but without insulin resistance or other comorbidities associated with metabolic syndrome. Methods Retrospective review of one patient. Results A 24-year-old woman with genetically proven RTT (T158M point mutation to MECP2) complicated by several physical disabilities was seen at a tertiary care center clinic for evaluation of abnormal liver enzymes (ALT 163, AST 51, ALP 258, total bilirubin 6). Abdominal ultrasound demonstrated moderately echogenic liver parenchyma consistent with hepatic steatosis. Additional investigations for an etiology were unremarkable and the patient had no history of alcohol misuse or the use of new medications or supplements. Regarding risk factors for SLD, her homeostatic model assessment for insulin resistance (HOMA-IR) score was 1.8, hemoglobin A1c was 4.8%, and her lipid profile demonstrated elevated triglycerides and LDL, in keeping with DLD. The decision was made to proceed with a liver biopsy. This demonstrated moderate steatosis and no ballooning, categorized as grade A1 and stage F1. Conclusions This case demonstrates that RTT patients have similar lipid metabolism perturbations to those seen in MECP2-null mouse models, resulting in similar metabolic abnormalities such as DLD and SLD. The absence of insulin resistance and other comorbidities associated with metabolic syndrome further support these perturbations are caused by a pathophysiologic mechanism specific to RTT. This demonstrates the importance of screening RTT patients for DLD and SLD despite their young age to detect these conditions before complications arise. It also demonstrates that MECP2-null mice can be used as reliable models to identify future therapies for RTT, such as ketogenic diet, ω-3 PUFAs supplementation, and lipid-lowering statin therapy. Funding Agencies None

S-17-4: EFFECTIVENESS OF STATIN INTENSIVE THERAPY IN TYPE 2 DIABETES WITH HIGH VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY

Objective: Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. Thus, we hypothesized that the benefit of intensive lipid-lowering therapy is larger in T2DM patients with high visit-to-visit SBP variability who are considered at higher risk. This study aimed to investigate the effectiveness of intensive versus standard statin therapy in primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability. Design and method: The EMPATHY study was the first randomized trial comparing statin intensive therapy targeting low- density lipoprotein cholesterol (LDL-C) &lt; 70 mg/dL and standard therapy targeting LDLC ®100 to &lt; 120 mg/dL in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within initial 6 months. The outcome was the composite incidence of cardiovascular events, including cardiac, cerebral, renal, and vascular events or death associated with cardiovascular events. Results: In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. The number of blood pressure measurements was 6.6 ± 1.6. The median value of SD and ARV of SBP was 9.78 mmHg and 10.29 mmHg, respectively. These median values were used as cutoffs. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95% CI 0.45–0.90, p = 0.012) and 1.21 (95% CI 0.82–1.80, p = 0.34) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (p = 0.018). The analysis using ARV of SBP showed similar results (high ARV: hazard ratio 0.62, 95% CI 0.44–0.88, p = 0.008; low ARV: hazard ratio 1.15, 95% CI 0.78–1.70, p = 0.48; p for interaction = 0.022.). Conclusion: Statin intensive therapy targeting LDL-C &lt; 70 mg/dL had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit to visit SBP variability. Stratification based on visit-to-visit SBP variability might be a novel and useful strategy to determine the target LDL-C levels in statin lipid-lowering therapy among T2DM patients with microvascular complications.

Cost-effectiveness of Ezetimibe plus statin lipid-lowering therapy: A systematic review and meta-analysis of cost-utility studies.

In addition to statin therapy, Ezetimibe, a non-statin lipid-modifying agent, is increasingly used to reduce low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease risk. Literature suggests the clinical effectiveness of Ezetimibe plus statin (EPS) therapy; however, primary evidence on its economic effectiveness is inconsistent. Hence, we pooled incremental net benefit to synthesise the cost-effectiveness of EPS therapy. We identified economic evaluation studies reporting outcomes of EPS therapy compared with other lipid-lowering therapeutic agents or placebo by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled Incremental Net Benefit (INB) in the US $ with a 95% confidence interval (CI). We used the modified economic evaluations bias checklist and GRADE quality assessment for quality appraisal. The pooled INB from twenty-one eligible studies showed that EPS therapy was significantly cost-effective compared to other lipid-lowering therapeutic agents or placebo. The pooled INB (95% CI) was $4,274 (621 to 7,927), but there was considerable heterogeneity (I2 = 84.21). On subgroup analysis EPS therapy is significantly cost-effective in high-income countries [$4,356 (621 to 8,092)], for primary prevention [$4,814 (2,523 to 7,106)], and for payers’ perspective [$3,255 (571 to 5,939)], and from lifetime horizon [$4,571 (746 to 8,395)]. EPS therapy is cost-effective compared to other lipid-lowering therapeutic agents or placebo in high-income countries and for primary prevention. However, there is a dearth of evidence from lower-middle-income countries and the societal perspective.

Vulnerable plaque derived from aspirated thrombi in recurrent acute coronary syndrome with familial hypercholesterolemia despite intensive lipid-lowering statin therapy.

Vulnerable plaque derived from aspirated thrombi in recurrent acute coronary syndrome with familial hypercholesterolemia despite intensive lipid-lowering statin therapy.

Abstract P199: Effectiveness Of Intensive Lipid-lowering Therapy With Statins In Type 2 Diabetes Mellitus Patients With Poorly Controlled Blood Pressure

Introduction: Control of blood pressure (BP) is associated with decreased risk of cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM). Lowering the level of low-density lipoprotein cholesterol (LDL-C) by statins is also effective to reduce CV events in T2DM patients with hyperlipidemia. In this study, we examined whether the effectiveness of statin lipid-lowering therapy was affected by baseline BP level in T2DM patients in a primary prevention setting. Methods: The EMPATHY study was a randomized controlled trial investigating the effects of statin intensive therapy targeting LDL-C &lt;70 mg/dL compared to standard therapy targeting LDL-C ≥100 to &lt;120 mg/dL in T2DM patients with diabetic retinopathy and hyperlipidemia without known CV diseases. In this post-hoc subgroup analysis, a total of 4980 patients were divided into two groups based on baseline BP: high BP (systolic BP ≥130 mmHg and/or diastolic BP ≥80 mmHg) and non-high BP (systolic BP &lt;130 mmHg and diastolic BP &lt;80 mmHg) groups. CV events were defined as composite of cardiac, cerebral, renal, and vascular events. Results: At baseline, mean systolic and diastolic BP values were 141.7 and 78.3 mmHg in high BP group (n=3335) and 120.2 and 67.9 mmHg in non-high BP group (n=1645). Compared to non-high BP group, the proportion of patients with diabetic nephropathy (55.5 % vs 46.6 %), body mass index (26.1 kg/m 2 vs 24.8 kg/m 2 ), HbA1c (7.82 % vs 7.67 %), and LDL-C (131.3 mg/dL vs 129.6 mg/dL) were significantly higher in high BP group. During a median follow-up of 36.8 months, 281 CV events were observed. In high BP group, statin intensive therapy was associated with low risk of CV events (HR 0.70, 95% CI 0.54-0.92, p=0.011) compared to standard therapy after adjustment. In non-high BP group, no such association was observed. Interaction between BP group and statin therapy was significant in CV events (p=0.036). Conclusion: Compared to statin standard therapy, statin intensive therapy targeting LDL-C &lt;70 mg/dL significantly reduced CV events in the primary prevention setting among T2DM patients with BP ≥130/80 mmHg, but not among those with BP &lt;130/80 mmHg.

Lipid-lowering statin therapy is beneficial in elderly female patients with hypercholesterolaemia and diabetic retinopathy.

Lipid-lowering statin therapy is beneficial in elderly female patients with hypercholesterolaemia and diabetic retinopathy.

Effectiveness of Lipid-Lowering Statin Therapy in Patients With and Without Psoriasis.

Psoriasis is associated with dyslipidemia and metabolic syndrome, and has been linked to an increased cardiovascular risk. The aim of this study was to compare baseline characteristics and effects of statin therapy on lipid levels and cardiovascular outcomes in patients with and without psoriasis. This post-hoc analysis assessed patients from one primary cardiovascular prevention statin trial (Collaborative AtoRvastatin Diabetes Study [CARDS]) and two secondary cardiovascular prevention statin trials (Treating to New Targets [TNT] and Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL]). Baseline characteristics, lipid changes from baseline, and cardiovascular event rates were analyzed. TNT and IDEAL data were pooled. Baseline characteristics and lipid profiles differed minimally in patients with and without psoriasis. In CARDS and TNT/IDEAL, similar apolipoprotein B, total cholesterol, and low-density lipoprotein cholesterol reductions occurred with statin therapy in patients with or without psoriasis. High-dose atorvastatin significantly reduced cardiovascular events vs. standard/low-dose statins in patients without psoriasis in TNT/IDEAL; similar numeric differences in event rates were observed in patients with psoriasis. In this post-hoc analysis, statins improved lipid levels and cardiovascular outcomes in patients with and without psoriasis, supporting statin use in patients with psoriasis. Trial registration (ClinicalTrials.gov) NCT00327418, registered 16 May, 2006; NCT00327691, registered 16 May, 2006; NCT00159835, registered 8 September, 2005.

Statin-ezetimibe versus statin lipid-lowering therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

Studies comparing the clinical efficacy and safety of intensive statin therapy with ezetimibe-statin combination therapy are still rare at present, especially in Asian population. We enrolled 202 patients who suffered acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) between May and July in 2016. Patients were allocated into three groups based on the lipid lowering strategy: moderate-intensity statin group (n=118), ezetimibe combined with moderate-intensity statin group (ezetimibe-statin combination, n=55) and intensive statin group (n=29). The lipid profiles and side effects were analyzed and compared among the patients in three groups at admission, 1 month and 3 months after PCI. The clinical outcomes of the patients were observed through 6-month follow-up. One month after PCI, the level of non-high density lipoprotein-cholesterol (non-HDL-C) was decreased by 41.9%, 21.6% and 29.8% by ezetimibe-statin combination therapy, moderate-intensity statin therapy and intensive statin therapy, respectively (P<0.05). The reduction percentages of TC and LDL-C were significantly higher in ezetimibe-statin combination group than in moderate-intensity statin group (P<0.001). The proportion of patients reaching LDL-C goal was higher in ezetimibe-statin combination group (69.1%, P=0.007) and intensive statin group (67.9%, P=0.047) compared with moderate-intensity statin group (46.9%) at 1 month after PCI. There was no significant difference among the three groups with respect to hepatic enzymes level, creatine kinase (CK) level and incidence of muscle symptoms. The reduction percentage of non-HDL-C was larger in ezetimibe-statin combination group than intensive statin group. This finding suggested that statin/ezetimibe combination therapy could be an alternative to intensive statin therapy in Chinese patients with atherosclerotic cardiovascular disease.

1A.11

Objective: Cardiovascular disease (CVD) represents the most common and lethal chronic disease worldwide. Lipids levels are the strongest risk factors for CVD and this is demonstrated by the fact that lipid-lowering statin therapy is largely used to prevent CVD. The role of the KIF6 gene in response to the statin therapy is controversial, and the biological mechanism through which it may act is still unknown. We investigated the role of KIF6 locus variants alone and their interaction with the well-established lipid locus at HMGCR in the variability of metabolic traits and in response to statin therapy in an Italian sample. Design and method: We genotyped two intronic rs20455, rs9462535 and a coding rs9471077 within the KIF6 gene, as well as two non-coding rs3761740 and rs3846662 at HMGCR. We tested the association of these SNPs with 19 cardiometabolic phenotypes and lipid-lowering therapy response in a sample of 1645 individuals from the Brisighella cohort (BC). Results: Established rs3846662 (Willer et al, Nat Gen 2013) at HMGCR is associated (P = 8.5x10-4) with LDL cholesterol (LDL-C) in BC. We did not find any significant association of KIF6 variants with response to statin therapy. We observe a locus-wide significant association at KIF6 between rs9471077 and APOB levels and rs20455 and HDL-C (P less than 0.001). rs3761740 at HMGCR showed an effect on systolic and diastolic blood pressure (SBP/DBP, P less than 0.007), which however wasn’t significant after multiple testing correction. Conclusions: This is the first genetic study reported for Brisighella cohort, which confirms association with LDL-C at HMGCR locus. We noticed an effect of KIF6 variants on APOB and HDL-C, while we don’t observe any effect on statin therapy. The study sample is relatively small to discover a common variant effect and might still be due to chance; therefore, we are seeking for replication in additional cohorts. These findings, if confirmed, might contribute to development of approaches for stratified patient care.

Coronary atherosclerosis is already ongoing in pre-diabetic status: Insight from intravascular imaging modalities.

Diabetes mellitus is a powerful risk factor of coronary artery disease (CAD), leading to death and disability. In recent years, given the accumulating evidence that prediabetes is also related to increasing risk of CAD including cardiovascular events, a new guideline has been proposed for the treatment of blood cholesterol for primary prevention of cardiovascular events. This guideline recommends aggressive lipid-lowering statin therapy for primary prevention in diabetes and other patients. The ultimate goal of patient management is to inhibit progression of systemic atherosclerosis and prevent fatal cardiovascular events such as acute coronary syndrome (ACS). Because disruption of atherosclerotic coronary plaques is a trigger of ACS, the high-risk atheroma is called a vulnerable plaque. Several types of novel diagnostic imaging technologies have been developed for identifying the characteristics of coronary atherosclerosis before the onset of ACS, especially vulnerable plaques. According to coronary angioscopic evaluation, atherosclerosis severity and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable to that in diabetic patients. In addition, pharmacological intervention by statin therapy changed plaque color and complexity, and the dynamic changes in plaque features are considered plaque stabilization. In this article, we review the findings of atherosclerosis in prediabetes, detected by intravascular imaging modalities, and the therapeutic implications.

Primary Prevention of Major Cardiovascular and Cerebrovascular Events with Statins in Diabetic Patients

Patients with diabetes mellitus are at increased risk of developing cardiovascular disease. Controlling lipid levels has a preventive effect on the occurrence of major cardiovascular and cerebrovascular events. Individual trials have shown varying data on the efficacy of treatment with lipid-lowering statin therapy in the primary prevention of such events in diabetes. The objective of this study was to assess the efficacy of statins in the primary prevention of the first-time occurrence of a major cardiovascular or cerebrovascular event in diabetic patients. Secondary endpoints were fatal/non-fatal stroke, fatal/non-fatal myocardial infarction and all-cause mortality. A systematic search for trial reports was conducted in PubMed, EMBASE, The Cochrane library and clinicaltrials.gov for the years 1966-2011. Reference lists of reviews and meta-analyses of related subjects were searched. High-quality, randomized, double-blinded clinical trials comparing a statin with placebo for the primary prevention of major cardiovascular and cerebrovascular events in diabetic patients were selected. Only large studies with a minimum of 500 diabetic participants followed-up for at least 2 years were included. Endpoints were major cardiovascular and cerebrovascular events. Trial and patient characteristics were extracted by three researchers. The quality of the included studies was tested with the Jadad score. The combined effect on primary as well as secondary endpoints was measured with a fixed-effect model. Publication bias was examined with a funnel plot. Four trials were included, for a total of 10,187 participants. Treatment with statins in the primary prevention of major cardiovascular and cerebrovascular events in diabetic patients resulted in a significant relative risk (RR) reduction in the first-time occurrence of major cardiovascular or cerebrovascular events (RR 0.75, 95% CI 0.67-0.85), fatal/non-fatal stroke (RR 0.69, 95% CI 0.51-0.92) and fatal/non-fatal myocardial infarction (RR 0.70, 95% CI 0.54-0.90) and a non-significant RR reduction in all-cause mortality (RR 0.84, 95% CI 0.65-1.09). Among the studies there was non-significant heterogeneity in the individual effect estimates and no publication bias. Exclusion criteria and endpoints varied slightly between studies. The type and dosing of statin therapy differed between studies. Non-compliance in the statin treatment group and the use of statin treatment in the placebo group could have led to lower risk reductions. Treatment with statins in primary prevention among diabetic patients has a significant beneficial effect on event rates of the first-time occurrence of a major cardiovascular or cerebrovascular event, fatal/non-fatal stroke and fatal/non-fatal myocardial infarction. There was a non-significant RR reduction in all-cause mortality.

Lipemia retinalis – an unusual cause of visual acuity deterioration

SummaryBackgroundHyperlipidemia is an identified factor of premature vessel atherosclerosis. Lipemia retinalis is an unusual retinal manifestation of hyperlipidemia and is thought to be directly correlated with the serum triglyceride level.Case ReportThis paper discusses the case of a 55-year-old patient with lipemia retinalis, which deteriorated his visual acuity. The patient had an extremely high serum cholesterol level (1053 mg/dl) and a very high level of triglycerides (1513 mg/dl). The normalization of serum lipids, reversion of retinal vessels alterations and visual acuity improvement was achieved after an intensive statin lipid-lowering therapy. Pathological changes of the patient’s retina, connected with lipemia retinalis, disappeared completely.ConclusionsHyperlipidemia can cause lipemia retinalis, which is characterized by the hyperlipidemic vascular lesions-whitish color of vessels, lipid infiltration into the retina and decrease of visual acuity. The lipid-lowering therapy may lead to the normalization of the appearance of the fundus and restore the visual acuity.

Hyperlipidemia due to Biliary Stricture After Living-Donor Liver Transplantation

Hyperlipidemia due to Biliary Stricture After Living-Donor Liver Transplantation

Reduction in Recurrent Cardiovascular Events With Intensive Lipid-Lowering Statin Therapy Compared With Moderate Lipid-Lowering Statin Therapy After Acute Coronary Syndromes: From the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) Trial

In addition to reducing first events in patients after an acute coronary syndrome (ACS), we hypothesized that high-dose atorvastatin 80 mg would also reduce recurrent cardiovascular events, and therefore total events, compared with pravastatin 40 mg during the 2-year follow-up. In the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial, more intensive lipid lowering with high-dose atorvastatin reduced the first occurrence of the primary end point (death, myocardial infarction, unstable angina requiring rehospitalization, stroke, or revascularization > or = 30 days) compared with moderate lipid lowering with pravastatin. Poisson regression analysis was performed to compare the number of occurrences of the primary end point between high-dose atorvastatin and pravastatin in the PROVE IT-TIMI 22 trial. As previously reported, first primary end point events were reduced by 16% with atorvastatin 80 mg versus pravastatin 40 mg (n = 464 vs. n = 537, respectively; p = 0.005). Additional events were also reduced by 19% with atorvastatin 80 mg (n = 275 vs. n = 340, respectively; p = 0.009). Overall, there were 138 fewer primary efficacy events with atorvastatin 80 mg versus pravastatin 40 mg (n = 739 vs. n = 877, respectively; rate ratio: 0.85, 95% confidence interval: 0.77 to 0.94, p = 0.001). Although analytic techniques commonly used in clinical outcomes trials censor patients who experience a component of the primary composite end point, total cardiovascular events are important to patients, clinicians, and health care payers. Maintaining low levels of low-density lipoprotein cholesterol is central to preventing additional atherosclerotic development and subsequent cardiovascular events. Atorvastatin 80 mg, a more intensive low-density lipoprotein cholesterol lowering agent, reduced both first and subsequent primary end point events compared with pravastatin 40 mg after ACS.

Analysis of Efficacy and Safety in Patients Aged 65–75 Years at Randomization

Rates of cardiovascular disease are highest in the elderly. Lipid-lowering statin therapy reduces the proportional risk as effectively in older patients as in younger individuals; however, limited data are available for elderly patients with type 2 diabetes. We conducted a post hoc analysis to compare the efficacy and safety of atorvastatin among 1,129 patients aged 65-75 years at randomization with 1,709 younger patients in the Collaborative Atorvastatin Diabetes Study (CARDS). CARDS was a randomized placebo-controlled trial of 10 mg/day atorvastatin for primary prevention of cardiovascular disease in patients aged 40-75 years with LDL cholesterol concentrations </=4.14 mmol/l followed for a median of 3.9 years. The primary end point was time to first occurrence of acute coronary heart disease events, coronary revascularizations, or stroke. Atorvastatin treatment resulted in a 38% reduction in relative risk ([95% CI -58 to -8], P = 0.017) of first major cardiovascular events in older patients and a 37% reduction ([-57 to -7], P = 0.019) in younger patients. Corresponding absolute risk reductions were 3.9 and 2.7%, respectively (difference 1.2% [95% CI -2.8 to 5.3], P = 0.546); numbers needed to treat for 4 years to avoid one event were 21 and 33, respectively. All-cause mortality was reduced nonsignificantly by 22% ([-49 to 18], P = 0.245) and 37% ([-64 to 9], P = 0.98), respectively. The overall safety profile of atorvastatin was similar between age-groups. Absolute and relative benefits of statin therapy in older patients with type 2 diabetes are substantial, and all patients warrant treatment unless specifically contraindicated.

Profound regression of coronary atherosclerosis with statins

A 60-year-old man was admitted to hospital because of chest pain. His only risk factor for coronary artery disease was hypercholesterolemia (cholesterol 7.64 mmol/L). Quantitative coronary angiography showed a 52% lesion in the proximal left anterior descending artery (Figure 1A). The patient was placed on acetylsalicylic acid and atorvastatin, and was followed up on a yearly basis with an exercise sestamibi nuclear scan, which was normal. A repeat coronary angiogram performed five years later for follow-up showed marked regression in the severity of the lesion in the proximal left anterior descending (15% stenosis by quantitative angiography) (Figure 1B). The patient’s cholesterol concentration decreased to 4.45 mmol/L. Figure 1 A Coronary angiography at baseline showing a 52% lesion in the proximal left anterior descending artery (LAD) (arrow). B Repeat angiogram after five years, with intensive statin therapy, showing significant regression of the LAD lesion (arrow) to 15% ... Statins have been proven to stabilize coronary atherosclerotic plaques and prevent coronary events in primary and secondary prevention clinical trials (1–3). Furthermore, Nissen et al (4) recently showed that intensive lipid-lowering therapy with atorvastatin reduces the progression of coronary atherosclerosis as assessed by intravascular ultrasound. These findings were extrapolated into clinical end points by Cannon et al (5), who showed that in patients recently hospitalized with an acute coronary syndrome, intensive lipid-lowering statin therapy reduces the incidence of future cardiac events. Our case report suggests that lipid-lowering therapy with statins can sometimes be associated with profound regression of coronary atherosclerosis.

Effects of lipids and lipid‐lowering therapy on hemostatic factors in patients with myocardial infarction

The risk of cardiovascular disease (CVD) is associated with specific hemostatic markers and lipid profiles, and evidence indicates that there are associations between lipid profiles and the levels of certain hemostatic factors. The disturbances in hemostasis and the risk of CVD can be ameliorated by lipid-lowering therapy. We investigated the associations of lipid profiles with factor (F)VIIa, von Willebrand factor (VWF), D-dimer and plasminogen activator inhibitor-1 (PAI-1), and examined whether lipid-lowering statin therapy would affect the levels of these hemostatic markers. This cross-sectional study analyzed 1045 postmyocardial infarction patients. In multivariate regression analyses (without adjusting for clinical covariates) HDL-cholesterol (HDL-C) and HDL size were independent and significant predictors of FVIIa; HDL size was a predictor of VWF; HDL size, HDL-C and LDL size were predictors of D-dimer; and triglyceride and HDL size were predictors of PAI-1. After adjusting for clinical covariates, HDL-C, lipoprotein (Lp)(a), apolipoprotein B (apoB) and warfarin were independent and significant predictors of FVIIa; HDL size, age, diabetes mellitus, insulin, race and warfarin were predictors of VWF; HDL-C, HDL size, LDL size, age, warfarin, hypertension and gender were predictors of D-dimer; and triglyceride, HDL size, body mass index, insulin and hypertension were predictors of PAI-1. Patients on statin therapy had significantly lower levels of D-dimer than those who were not on this therapy. There are significant associations of lipid profiles with hemostatic factors, the directions of which suggest novel pathways by which dyslipidemia may contribute to coronary heart disease.

Statin Lipid-Lowering Therapy for Acute Myocardial Infarction and Unstable Angina: Efficacy and Mechanism of Benefit

The use of statin agents in patients with acute coronary syndromes (ACSs) remains an area of intense clinical interest. Statin therapy has an established secondary preventive benefit in patients with coronary artery disease, and its extension to ACS seems logical. A number of observational studies have shown an association between initiation of statin therapy early in ACS and improved clinical outcome. Additionally, 4 randomized controlled trials have examined the use of statin therapy for ACS: the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study, the Pravastatin Turkish Trial, the Fluvastatin on Risk Diminishing After Acute Myocardial Infarction (FLORIDA) study, and the Lipid-Coronary Artery Disease (L-CAD) study. Three of these trials showed a benefit with early initiation of statin therapy, whereas 1 trial demonstrated neither benefit nor harm. All the available trials lacked the power and design to sufficiently evaluate whether early initiation of statin therapy reduces mortality and reinfarction in patients with ACS. Four ongoing trials have been designed and sufficiently powered to determine whether statin therapy reduces the risk of death and reinfarction when initiated early in ACS treatment. A body of evidence suggests that the pleiotropic actions of statin agents might modulate benefit in ACS. This article summarizes the available data and provides a rationale for early initiation of statin therapy for patients with ACS.