Effect Of Intensive Statin Therapy Research Articles

The effect of intensive statin therapy in non-symptomatic intracranial arteries: The STAMINA-MRI sub-study.

Pleiotropic effects of statins result in the stabilization of symptomatic intracranial arterial plaque. However, little is known about the effect of statins in non-symptomatic cerebral arteries. We hypothesized that intensive statin therapy could produce a change in the non-symptomatic cerebral arteries. This is a sub-study of a prospective observational study under the title of "Intensive Statin Treatment in Acute Ischemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging (HR-MRI) study." Patients with statin-naive acute ischemic stroke who had symptomatic intracranial artery stenosis (above 50%) were recruited for this study. HR-MRI was performed to assess the patients' cerebral arterial status before and 6 months after the statin therapy. To demonstrate the effect of statins in the non-symptomatic segment of intracranial cerebral arteries, we excluded symptomatic segments from the data to be analyzed. We compared the morphological changes using cerebrovascular morphometry. A total of 54 patients (mean age: 62.9 ± 14.4 years, 59.3% women) were included in this study. Intensive statin therapy produced significant morphological changes of overall cerebral arteries. Among the morphological features, the arterial luminal area showed the highest number of significant changes with a range from 5.7 and 6.7%. Systolic blood pressure (SBP) was an independent factor associated with relative changes in posterior circulation bed maximal diameter percentage change (beta -0.21, 95% confidence interval -0.36 to -0.07, p = 0.005). Intensive statin therapy produced a favorable morphological change in cerebral arteries of not only the target arterial segment but also non-symptomatic arterial segments. The change in cerebral arterial luminal diameter was influenced by the baseline SBP and was dependent on the topographic distribution of the cerebral arteries.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02458755.

Effect of intensive statin therapy on carotid plaque echogenicity in patients with nonobstructive asymptomatic carotid stenosis

Aim: Carotid plaque echogenicity quantified by the Gray-Scale Median (GSM) score has been associated with plaque vulnerability. Aim of the study was to assess whether intensive lipid-lowering treatment with atorvastatin in patients with nonobstructive asymptomatic carotid artery stenosis is more effective in increasing carotid plaque echogenicity than moderate lipid-lowering treatment.

Effects of Intensive Statin Therapy on Left Ventricular Function in Patients with Myocardial Infarction and Abnormal Glucose Tolerance

Objectives: Abnormal glucose tolerance in patients with acute myocardial infarction (AMI) is associated with greater mortality and adverse cardiovascular effects. As statins possess a range of beneficial pleiotropic effects on the cardiovascular system, we sought to assess the cardioprotective effects of statins on left ventricular function in patients with AMI in relation to glycometabolic state. Methods: In a prospective, randomized trial, 140 patients with AMI were randomized to intensive statin therapy receiving statin loading with 80 mg of rosuvastatin followed by 40 mg daily or standard statin therapy. Patients were assessed with an oral glucose tolerance test and their left ventricular (LV) function was assessed with speckle-tracking echocardiography measuring regional longitudinal systolic strain (RLSS) in the infarct area. Results: Overall RLSS in the infarct area improved by a mean (±SD) of -4.22% (±5.19) in the intensive-care group and -2.48% (±4.01) in the usual-care group after 1 month (p = 0.047). In patients with abnormal glucose tolerance, RLSS improved by -5.01% (±5.28) in the intensive-care group and -2.15% (±4.22) in the usual-care group (p = 0.01). Conclusions: Early high-dose statin treatment improved RLSS in the infarct area in patients with AMI, and a trend of greater improvement was seen in patients with abnormal glucose tolerance.

Effect of intensive statin therapy on coronary intervention outcomes, cardiac markers, vaspin, and adiponectin levels in elderly patients with coronary heart disease

Aim: To explore the effect of intensive statin therapy (different doses) on percutaneous coronary intervention (PCI) outcomes in elderly patients with coronary heart disease (CHD). Methods: In this Institutional Ethics Committee-approved study, 105 elderly patients (> 80-year-old) with CHD admitted into the First Affiliated Hospital of Jinan University from June 2012 to June 2014 were randomly divided into three groups and received 20 mg/day, 40 mg/day, or 60 mg/day atorvastatin, respectively, before PCI surgery. Postsurgical (1 month after surgery) changes in major adverse cardiovascular events (MACEs), cardiac markers, vaspin, and adiponectin levels were compared among the groups. Results: Among the study groups, the incidence of MACE and PCI-related myocardial infarction rate was the lowest in 60 mg group (2.9%) reaching significance ( P P P P P > 0.05). No study subjects showed statin-related myopathy. Conclusion: The application of 60 mg/d intensive statin therapy in short term could improve outcomes of PCI in patients with elderly CHD, maintain stable levels of cardiac markers, Vaspin and adiponectin, with exact effect and good safety.

The effect of statin therapy on thyroid autoimmunity in patients with Hashimoto's thyroiditis: A pilot study.

Statins have been found to exert antiinflammatory and immunomodulatory properties. The aim of this study was to compare the effects of intensive and less aggressive statin treatment on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in patients with Hashimoto's thyroiditis. The study included 38 adult women with Hashimoto's thyroiditis, who required statin therapy and were allocated into one of two groups. Patients at very high cardiovascular risk (n=16) received intensive statin treatment (rosuvastatin 20-40mg daily), while patients at moderate or moderately high cardiovascular risk (n=22) were treated with simvastatin (20-40mg daily) for the following 6 months. Serum levels of thyrotropin, total and free thyroid hormones, and high-sensitivity C-reactive protein (hsCRP), as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning and at the end of the study. Thirty-six individuals completed the study and were included in the final analyses. Apart from improving plasma lipids and reducing circulating levels of hsCRP, intensive, but not less aggressive, statin therapy reduced thyroid peroxidase and thyroglobulin antibody titers, as well as tended to reduce circulating levels of thyrotropin. The effect of intensive statin therapy on thyroid antibody titers was lipid-independent but correlated with treatment-induced changes in thyrotropin and hsCRP. Although 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are able to reduce thyroid autoimmunity in women with Hashimoto's thyroiditis, intensive statin therapy is required to produce this effect.

Effect of Intensive Statin Therapy on Coronary High-Intensity Plaques Detected by Noncontrast T1-Weighted Imaging: The AQUAMARINE Pilot Study

BackgroundCoronary high-intensity plaques detected by noncontrast T1-weighted imaging may represent plaque instability. High-intensity plaques can be quantitatively assessed by a plaque-to-myocardium signal-intensity ratio (PMR). ObjectivesThis pilot, hypothesis-generating study sought to investigate whether intensive statin therapy would lower PMR. MethodsProspective serial noncontrast T1-weighted magnetic resonance imaging and computed tomography angiography were performed in 48 patients with coronary artery disease at baseline and after 12 months of intensive pitavastatin treatment with a target low-density lipoprotein cholesterol level <80 mg/dl. The control group consisted of coronary artery disease patients not treated with statins that were matched by propensity scoring (n = 48). The primary endpoint was the 12-month change in PMR. Changes in computed tomography angiography parameters and high-sensitivity C-reactive protein levels were analyzed. ResultsIn the statin group, 12 months of statin therapy significantly improved low-density lipoprotein cholesterol levels (125 to 70 mg/dl; p < 0.001), PMR (1.38 to 1.11, an 18.9% reduction; p < 0.001), low-attenuation plaque volume, and the percentage of total atheroma volume on computed tomography. In the control group, the PMR increased significantly (from 1.22 to 1.49, a 19.2% increase; p < 0.001). Changes in PMR were correlated with changes in low-density lipoprotein cholesterol (r = 0.533; p < 0.001), high-sensitivity C-reactive protein (r = 0.347; p < 0.001), percentage of atheroma volume (r = 0.477; p < 0.001), and percentage of low-attenuation plaque volume (r = 0.416; p < 0.001). ConclusionsStatin treatment significantly reduced the PMR of high-intensity plaques. Noncontrast T1-weighted magnetic resonance imaging could become a useful technique for repeated quantitative assessment of plaque composition. (Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technique [AQUAMARINE]; UMIN000003567)

Abstract 11107: Efficacy and Safety of Intensive Statin Therapy for Hypercholesterolemic Patients With Bioprosthetic Aortic Valve Replacement for Aortic Valve Stenosis

Objectives: Intensive rather than standard statin therapy has been proven to be superior in improving cardiovascular outcome, whereas the effects of intensive statin therapy on inflammation and lipoprotein biomarkers are not well defined. The purpose of this study was to validate the efficacy of intensive statin therapy for hypercholesterolemic patients with bioprosthetic aortic valve replacement for aortic valve stenosis. Methods: In this study, we performed a single-center, randomized, single-blind clinical trial. A total of 30 hypercholesterolemic patients with bioprosthetic aortic valve replacement were enrolled and randomly divided into two groups [intensive-dose rosuvastatin therapy (target LDL-C level: 70 mg/dl) and standard-dose rosuvastatin therapy (target LDL-C level: 120 mg/dl). Evaluation variables, including changes in serum lipid profile, aortic valve area, and E/e’ representing left ventricular diastolic function, from baseline to years 1 and 2, were used to compare the benefits of these two statin therapies. Results: At baseline, there were no differences between the two groups, including in LDL-C level (intensive 121+/-27 vs. standard 118+/-31, n.s.), aortic valve area (intensive 1.58+/-0.47 vs. standard 1.54+/-0.42, n.s.), and E/e’ (intensive 19+/-20 vs. standard 20+/-10, n.s.). After 2 years of treatment, improvements of LDL-C level (intensive 75+/-11 vs. standard 95+/-10, p&lt;0.001), aortic valve area (intensive 1.63+/-0.24 vs. standard 1.43+/-0.32, n.s.), and E/e’ (intensive 16+/-6 vs. standard 23+/-8, p&lt;0.05) were all better in the intensive group. Conclusions: Compared with standard statin therapy, long-term intensive-dose statin appears to be safe and lowered the LDL-C level significantly, further improved left ventricular diastolic function, and preserved bioprosthetic aortic valve.

Comparison of Efficacy of Intensive versus Mild Pitavastatin Therapy on Lipid and Inflammation Biomarkers in Hypertensive Patients with Dyslipidemia

ObjectiveIntensive as compared to mild statin therapy has been proven to be superior in improving cardiovascular outcome, whereas the effects of intensive statin therapy on inflammation and lipoprotein biomarkers are not well defined.MethodsThis study assigned essential hypertensive patients with dyslipidemia to 6 months administration of mild (1 mg/day, n = 34) or intensive pitavastatin therapy (4 mg/day, n = 29), and various lipid and inflammation biomarkers were measured at baseline, and 3 and 6 months after the start of treatment.ResultsBoth pitavastatin doses were well tolerated, and there were no serious treatment-related adverse events. After 6 months, significant improvements in total cholesterol, triglycerides, low-density lipoprotein (LDL-) cholesterol, LDL/high-density lipoprotein cholesterol (LDL/HDL), apolipoproteins B, C-II, and E, apolipoprotein-B/apolipoprotein-A-I (Apo B/Apo A-I), and malondialdehyde (MDA-) LDL were observed in both groups. Compared with the mild pitavastatin group, the intensive pitavastatin therapy showed significantly greater decreases in C reactive protein (F = 3.76, p<0.05), total cholesterol (F = 10.65), LDL-cholesterol (F = 23.37), LDL/HDL (F = 12.34), apolipoproteins B (F = 19.07) and E (F = 6.49), Apo B/Apo A-I (F = 13.26), and MDA-LDL (F = 5.76) (p<0.01, respectively).ConclusionIntensive pitavastatin therapy may have a more favorable effect not only in decreasing LDL-cholesterol but also in pleiotropic benefits in terms of improvement of apolipoproteins, inflammation, or oxidation.

Effect of intensive statin therapy on regression of carotid intima-media thickness in patients with subclinical carotid atherosclerosis (a prospective, randomized trial: PEACE (Pitavastatin Evaluation of Atherosclerosis Regression by Intensive Cholesterol-lowering Therapy) study)

Atherosclerosis often advances before symptoms appear. It remains uncertain whether intensive cholesterol-lowering therapy with statin is beneficial when compared with moderate cholesterol-lowering therapy in patients with subclinical carotid atherosclerosis. The PEACE study was a prospective, randomized, open-labeled, blinded end points, two-arm parallel treatment group comparison study conducted at 15 centers in Japan. A total of 303 patients with carotid intima-media thickness (CIMT) thickening (>1.1 mm) whose low-density lipoprotein cholesterol (LDL-C) level was more than 100 mg/dl were enrolled, in which 223 patients completed the 12 months' follow-up study. Patients were randomly assigned to receive either moderate (target LDL-C; 100 mg/dl) or intensive (target LDL-C; 80 mg/dl) cholesterol-lowering therapy with pitavastatin. The primary end point was the change in mean far wall common CIMT. LDL-C level declined to 89.4 ± 20 mg/dl in the intensive group, while it declined to 95.1 ± 22.5 mg/dl in the moderate group at 12 months' follow-up (p < 0.05 between the groups). The change in mean CIMT was -0.024 (95% confidence interval -0.046 to -0.0014) mm/year (p < 0.05 vs. baseline) in the intensive group, and -0.0078 (95% confidence interval -0.028 to 0.012) mm/year (p = 0.4406 vs. baseline) in the moderate group. However, there was no significant difference in the change in mean far wall common CIMT between the groups (p = 0.29). Intensive cholesterol-lowering therapy did not show superior effects on the progression of CIMT to moderate cholesterol-lowering therapy, whereas only intensive cholesterol-lowering therapy regressed the carotid atherosclerosis over one year.

Effect of Intensive Statin Therapy on Regression of Coronary Atherosclerosis in Patients With Acute Coronary Syndrome: A Multicenter Randomized Trial Evaluated by Volumetric Intravascular Ultrasound Using Pitavastatin Versus Atorvastatin (JAPAN-ACS [Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome] Study)

The objective of this study was to evaluate whether the regressive effects of aggressive lipid-lowering therapy with atorvastatin on coronary plaque volume (PV) in patients with acute coronary syndrome (ACS) are generalized for other statins in multicenter setting. A previous single-center study reported beneficial regressive effects of atorvastatin in patients with ACS on PV of the nonculprit site by intravascular ultrasound (IVUS) evaluation. The effect of statins other than atorvastatin on PV has not been evaluated in the setting of ACS. The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) study was a prospective, randomized, open-label, parallel group study with blind end point evaluation conducted at 33 centers in Japan. A total of 307 patients with ACS undergoing IVUS-guided percutaneous coronary intervention were randomized, and 252 patients had evaluable IVUS examinations at baseline and 8 to 12 months' follow-up. Patients were randomly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin. The primary end point was the percentage change in nonculprit coronary PV. The mean percentage change in PV was -16.9 +/- 13.9% and -18.1 +/- 14.2% (p = 0.5) in the pitavastatin and atorvastatin groups, respectively, which was associated with negative vessel remodeling. The upper limit of 95% confidence interval of the mean difference in percentage change in PV between the 2 groups (1.11%, 95% confidence interval: -2.27 to 4.48) did not exceed the pre-defined noninferiority margin of 5%. The administration of pitavastatin or atorvastatin in patients with ACS equivalently resulted in significant regression of coronary PV (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome; NCT00242944).

Endogenous tissue plasminogen activator and risk of recurrent cardiac events after an acute coronary syndrome in the MIRACL study

Objective To examine the relationship of baseline tissue plasminogen activator (t-PA) to early cardiovascular risk after an acute coronary syndrome, and the effect of intensive statin therapy. Methods We measured plasma t-PA in 2860 of the 3086 (93%) subjects in the MIRACL study, an international randomized trial of atorvastatin 80 mg daily versus placebo in patients with acute coronary syndromes. The relationship of t-PA to death, non-fatal acute myocardial infarction, cardiac arrest, or worsening angina over 16 weeks was assessed by Cox Proportional Hazards. D-dimer was measured in a random sample of 395 subjects. Results Higher baseline t-PA was significantly related to the risk of recurrent events (HR = 1.25, p = 0.0014). This relationship was unaffected by adjustment for age, sex, troponin, hsCRP, and lipids (HR = 1.17, p = 0.029), but was attenuated by adjustment including body mass index and smoking (HR = 1.14, p=0.08). D-dimer and t-PA concentrations were not related. Atorvastatin reduced the risk of recurrent events, but did not affect t-PA or D-dimer concentrations or the relationship of t-PA to outcomes. Conclusion In patients with acute coronary syndromes, increasing t-PA concentration was related to a higher early risk of recurrent events, paradoxically reflecting impaired endogenous fibrinolysis. This relationship is due in part to the association of t-PA with age, body mass index and smoking. Although statins lower the risk of recurrent events after acute coronary syndromes, it is unlikely that this benefit is achieved through thrombolytic and fibrinolytic pathways.

Effect of intensive statin therapy on arterial elasticity in patients with coronary artery disease

Objective — Reduced arterial compliance is an independent predictor of cardiovascular mortality and is commonly encountered in patients with coronary artery disease. Statins may produce cholesterol-independent effects which can result at least in part from direct improvement of the arterial function. In this study, we sought to determine the effect of intensive statin therapy according to the Adult Treatment Panel III guidelines on arterial compliance in dyslipidaemic patients with angiographically-proven CAD selected for medical treatment.Methods — Patients (n = 33) received atorvastatin 40 mg/day for 6 months. Large arterial compliance and small arterial compliance were measured at baseline and after 6 months of atorvastatin treatment.Results — After treatment, the large artery elasticity index (LAEI) increased from 11.85 ± 3.46 to 13.80 ± 3.95 ml/mm Hg x 100 (P < 0.001) and the small artery elasticity index (SAEI) increased from 3.84 ± 1.97 to 4.97 ± 1.98 ml/mm Hg (P= 0.03).There was no correlation between the change in either LAEI or SAEI and other baseline variables or changes in lipid levels.Conclusion — Our findings suggest that intensive statin therapy according to the Adult Treatment Panel III guidelines improves arterial elasticity in CAD patients selected for medical treatment.The beneficial vascular effect of atorvastatin on arterial elasticity was independent of lipid parameters.

Outcomes of Patients With Acute Coronary Syndrome and Previous Coronary Artery Bypass Grafting (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy [PROVE IT-TIMI 22] and the Aggrastat to Zocor [A to Z] Trials)

We examined the effects of intensive statin therapy in patients with acute coronary syndromes (ACSs) and previous coronary artery bypass graft surgery (CABG) participating in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) and the Aggrastat to Zocor (A to Z) trials. Of the 8,655 patients enrolled in PROVE IT-TIMI 22 or A to Z, 640 (7.4%) had undergone CABG before enrollment. After a median follow-up of 2 years, compared with patients without previous CABG, those with previous CABG had a higher risk of cardiovascular death (6.2% vs 2.8%), myocardial infarction (14.2% vs 6.6%), and readmission for ACS (7.9% vs 4.4%, p <0.001 for all comparisons) but a lower rate of repeat coronary revascularization (22.7% vs 26.9%, p = 0.01). Compared with moderate statin therapy, intensive statin therapy appeared to decrease the composite of cardiovascular death, myocardial infarction, stoke, and readmission for an ACS (A to Z primary end point) to a similar extent in patients with (26.1% vs 21.6%, hazard ratio 0.84, p = 0.27) and without (13.9% vs 12.0%, hazard ratio 0.86, p = 0.016) previous CABG, although the decrease was not statistically significant in the previous CABG group, likely due to the small number of patients with previous CABG. In conclusion, compared with patients with ACS without previous CABG, those with previous CABG have a higher risk for adverse cardiac events and may derive similar benefit from intensive statin therapy.

Abstract 1515: Outcomes of Patients With Acute Coronary Syndromes and Prior Coronary Artery Bypass Grafting. Results From the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT-TIMI 22) and the Aggrastat to Zocor (A to Z) trials.

Background: Patients with prior coronary artery bypass graft surgery (CABG) who develop acute coronary syndromes (ACS) are at high risk for major adverse cardiac events. The benefits of intensive statin therapy, targeting an LDL cholesterol of &lt; 70 mg/dL, in patients with ACS and prior CABG have not been well studied. Methods: The effect of intensive vs. moderate statin therapy was assessed in patients with and without prior CABG participating in the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT TIMI 22) or the Aggrastat to Zocor (A to Z) trials. Results: Six hundred and forty of the 8655 patients (7.4%) enrolled in PROVE IT-TIMI 22 or A to Z had undergone CABG prior to enrollment. Prior CABG patients were older, more likely to be men and had a higher TIMI risk score. After a median follow-up of 2 years, compared to patients without prior CABG, those with prior CABG had higher risk of cardiovascular death (6.2 vs. 2.8%), myocardial infarction (14.2% vs. 6.6%), and readmission for ACS (7.9% vs. 4.4%) (p&lt;0.001 for all comparisons), but a lower rate of repeat coronary revascularization (22.7% vs. 26.9%, p=0.01). Compared to moderate statin therapy, intensive statin therapy decreased the combined endpoint of cardiovascular death, myocardial infarction, stoke, and readmission for an acute coronary syndrome (A to Z primary endpoint) to a similar extent in patients with and without prior CABG (Table ). The benefit of intensive statin therapy in prior CABG patients appeared to be due to a reduction in unstable angina requiring hospitalization, with no significant difference in the incidence of death, myocardial infarction, or coronary revascularization. Conclusions: Compared to ACS patients without prior CABG, those with prior CABG have significantly higher risk for death and adverse cardiac events and appear to show similar benefit from intensive statin therapy. Effect of intensive statin therapy on outcomes of patients with and without prior CABG

Relation of Characteristics of Metabolic Syndrome to Short-Term Prognosis and Effects of Intensive Statin Therapy After Acute Coronary Syndrome

We examined relations between characteristics of the metabolic syndrome, early cardiovascular risk, and effect of early, intensive statin therapy after acute coronary syndrome. A total of 3,038 patients in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial were characterized by the presence or absence of a history of diabetes, a history of hypertension and/or blood pressure > or = 130/> or = 85, BMI >30 kg/m2, HDL cholesterol <40 mg/dl (men) or <50 mg/dl (women), and triglycerides > or = 150 mg/dl. Patients with three or more of these characteristics were categorized as having metabolic syndrome. A total of 38% of patients (n = 1,161) met criteria for metabolic syndrome as defined in this study and had a 19% incidence of a primary end point event (death, nonfatal myocardial infarction, cardiac arrest, or recurrent unstable myocardial ischemia) during the 16-week trial. Patients with two or fewer characteristics (n = 1,877) were classified as not having metabolic syndrome and had a 14% incidence of a primary end point event. In univariate analysis, the individual characteristics that bore a significant relation to risk were diabetes and low HDL cholesterol. In a multivariable model including age, sex, and randomized treatment assignment, presence of metabolic syndrome was associated with a hazard ratio of 1.49 (95% CI 1.24-1.79, P < 0.0001). Relative risk reduction with 80 mg atorvastatin daily compared with placebo was similar in patients with and without metabolic syndrome. Metabolic syndrome, as defined in the context of this clinical trial, is a strong predictor of early recurrent ischemic events after acute coronary syndrome.