Abhimanyu Beri

Non-atheroprotective effects of statins: a systematic review.

Since the introduction of HMG-CoA reductase inhibitors (statins) for lowering lipids, a large amount of data has been published demonstrating their potential benefits in conditions as varied as cancer, osteoporosis, and Alzheimer’s dementia. We reviewed the published literature on MEDLINE from articles between 1950 and 2008 on the non-atheroprotective effects of statins and noted consistent benefits of statin use in improving outcomes of ventricular arrhythmias, sudden cardiac death, cardiac transplant rejection, chronic obstructive pulmonary disease, and sepsis. However, for these conditions, the level of evidence was inadequate to recommend statin use. The evidence for improving outcomes in atrial fibrillation, mortality in heart failure, contrast-induced nephropathy, cataract, age-related macular degeneration, sub-arachnoid hemorrhage, osteoporosis, dementia, and cancer incidence was conflicting and inconclusive. Furthermore, we found that most of the literature consists of small observational studies and their conclusions are often not corroborated by results from larger or randomized studies. Pending large, well designed, randomized trials, we conclude that there is no definite evidence for the use of statins in any condition besides hyperlipidemia and atherosclerosis.

Association between statin therapy and tendon rupture: A case-control study

Although case reports of a possible association between statin therapy and tendon rupture have been published, no analytical studies exploring this relationship have been reported. We conducted a case-control study using the electronic medical records at Michigan State University from 2002 to 2007 to assess whether statin use is a risk factor for tendon rupture. We compared exposure to statins in 93 cases of tendon rupture with similar exposure in 279 sex- and age-matched controls. Exposure to statins was defined as documentation in the electronic medical record of statin use in the 12 months preceding tendon rupture. For controls, the exposure period was defined as 1 year preceding the last office visit. We used a multivariate logistic regression model, controlling for diabetes, renal disease, rheumatologic disease, and steroid use, to calculate the adjusted odds ratios (ORs). There was no significant difference between cases and controls in the rates of statin use, with either univariate [OR = 1.0, 95% confidence interval (CI) 0.54-1.84] or multivariate analyses (OR = 1.10, 95% CI 0.57-2.13). Based on predetermined subgroup analyses, statin exposure was found to be a significant risk factor for tendon rupture in women (adjusted OR = 3.76, 95% CI 1.11-12.75) but not in men (adjusted OR = 0.66, 95% CI 0.29-1.51). In conclusion, we found no overall association between statin use and tendon rupture, but subgroup analysis suggested that women with tendon rupture were more likely to be on statins.

Statins and the reduction of sudden cardiac death: antiarrhythmic or anti-ischemic effect?

Sudden cardiac death is an important cause of cardiovascular mortality with the majority of cases occurring in low-risk groups. HMG-CoA reductase inhibitors (statins) have recently been shown to reduce the incidence of ventricular tachycardia (VT)/fibrillation (VF) and sudden cardiac death, and this has been attributed to their pleiotropic effects. However, it is unclear whether this occurs through an ‘indirect’ anti-ischemic or ‘direct’ antiarrhythmic effect. We systematically reviewed articles published on MEDLINE between January 1996 and December 2009 focusing on the reduction of VT/VF and sudden cardiac death by statins and the potential mechanisms. Studies reporting sudden cardiac death or VT/VF outcomes with statin use (n = 23) or the pathophysiology of sudden cardiac death reduction by statins (n = 19) were included. We found that statins have been shown to reduce VT/VF and sudden cardiac death only in subjects with underlying coronary artery disease or ischemic cardiomyopathy. No definite benefits were seen with statins in sudden cardiac death and VT/VF in patients with non-ischemic cardiomyopathy. There is insufficient evidence to point toward a benefit in populations at low risk for VT/VF. In conclusion, an anti-ischemic rather than a primary antiarrhythmic effect emerges as the likely mechanism of sudden cardiac death reduction with statins.

Is Statin Use Associated With Tendon Rupture? A Population-Based Retrospective Cohort Analysis.

Previous case reports and small studies have suggested that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA-Is) may increase the risk of tendon rupture. We conducted a population-based retrospective cohort evaluation to better assess this relationship. From approximately 800,000 enrollees of a private insurance database, those who were aged ⩽64 years with at least 1 year of continuous enrollment were selected. Exposure was defined as initiation of HMG-CoA-I after the beginning of the study period. Each exposed person was matched with 2 controls of similar age and gender. Baseline characteristics, including known risk factors for tendon rupture, were compared between exposed and control cohorts with fidelity to the studys matched design. After adjusting for differences in follow-up and baseline characteristics, incidence rate ratios for tendon rupture was assessed in HMG-CoA-I users and nonusers. A total of 34,749 exposed patients were matched with 69,498 controls. There was no difference in the occurrence of tendon ruptures in HMG-CoA-I users versus nonusers. The results remained unchanged after adjustment for age and gender. In conclusion, this population-based retrospective cohort evaluation suggests that use of HMG-CoA-Is as a group are not associated with tendon rupture.

Anticoagulation in patients with acute ischemic stroke and atrial fibrillation--a balance of risks and benefits.

ObjectivesWe reviewed the current literature regarding anticoagulation in patients presenting with acute ischemic stroke and atrial fibrillation.MethodsA systematic literature search was performed using PUBMED. All relevant articles including meta-analysis, original case studies and cross-references from relevant articles were included in this review.ResultsAtrial fibrillation is a thrombogenic state and predisposes to acute embolic strokes. Most studies do not show any mortality or morbidity benefit of anticoagulation with unfractionated or low-molecular weight heparins in patients with acute stroke. The relative risk of hemorrhagic transformation of the ischemic stroke is higher than the lowering of stroke due to recurrent embolism. Large infarcts, greater patient age, extensive small vessel disease and uncontrolled hypertension should prompt a further delay in anti-coagulation.ConclusionAvoid anticoagulation with heparins in patients with acute ischemic stroke with atrial fibrillation for 7–10 days. Further studies are needed to delineate when to start oral anticoagulation.

Reduction in the Intensity Rate of Appropriate Shocks for Ventricular Arrhythmias With Statin Therapy

Higher rate of implantable cardioverter-defibrillator (ICD) shocks has been associated with increased mortality and morbidity. The aim of our study was to determine whether statins reduced the intensity rate of appropriate shock therapy for ventricular tachycardia/fibrillation in patients with an ICD placed for left ventricular systolic dysfunction. In this retrospective single center analysis, patients with an ejection fraction ≤35% who underwent ICD implantation were divided into treatment and control groups based on statin use. A zero-inflated negative binomial model was used to compare the intensity rate of appropriate ICD shocks between the 2 groups. Characteristics associated with shock-free follow-up were assessed using a stepwise logistic regression model. We found 699 patients eligible for inclusion, with 412 (59%) in the statin treatment group. The adjusted mean intensity rate of shocks was lower in patients on statin therapy (intensity rate ratio = 0.22; 95% confidence interval, 0.12-0.41; P < 0.001). Statin use was associated with a significantly higher probability of shock-free follow-up (odds ratio = 1.64; 95% confidence interval, 1.09-2.48; P = 0.019). In conclusion, statins reduced the intensity rate of appropriate shock therapy for ventricular tachycardia/fibrillation and increased probability of shock-free follow-up in patients with cardiomyopathy. Larger randomized trials are needed to confirm this relationship.

Statins reduce appropriate implantable cardioverter-defibrillator shocks in ischemic cardiomyopathy with no benefit in nonischemic cardiomyopathy

Statins have been hypothesized to decrease ventricular arrhythmias through a direct antiarrhythmic effect. Clinical studies have demonstrated a clear reduction only in populations with underlying ischemic heart disease. This study was designed to compare the effect of statins on appropriate shocks between ischemic and nonischemic cardiomyopathy. Patients with an ejection fraction 35% or less who received an implantable cardioverter–defibrillator and had follow-up for at least 1 month were included. The ischemic and nonischemic groups were divided into statin treatment and control subgroups and the occurrence of appropriate shocks was compared. The frequency of shocks was analyzed using negative binomial models to account for overdispersion of the “count” data (number of appropriate shocks) and an adjusted intensity rate ratio was calculated for statin use. A total of 676 patients were included, of which statins were used by 65% (329 of 506) of the ischemic and 42% (72 of 170) of the nonischemic groups. Occurrence of appropriate shocks was significantly reduced with statins in ischemic (13.4% vs 20.9%; relative risk 0.64, P = 0.028), but not in the patients with nonischemic cardiomyopathy. Similarly, although use of statins lowered the intensity rate of appropriate shocks in ischemic patients (intensity rate ratio, 0.23; 95% confidence interval, 0.12–0.47), no such benefit was noted in the nonischemic group (intensity rate ratio, 1.27; 95% confidence interval, 0.37–4.40). In conclusion, statins reduced the occurrence and frequency of appropriate shocks for ventricular arrhythmias in ischemic but not in nonischemic cardiomyopathy. Larger, randomized controlled trials are needed to confirm these findings.

Fibrinolysis versus primary percutaneous intervention in ST-elevation myocardial infarction with long interhospital transfer distances.

Current guidelines recommend rapid initiation of reperfusion therapy for ST‐elevation myocardial infarction (STEMI), with short‐distance transfer for primary percutaneous coronary intervention (pPCI) preferred over fibrinolysis in non–pPCI‐capable hospitals. Comparative outcomes in patients with longer transfer times are unclear.

Hormone Replacement Therapy–Induced Giant Aortic Thrombus

CLINICAL PRESENTATION A 54-year-old white woman presented with a 4-day history of postprandial, periumbilical abdominal pain. She was hypertensive and a 20 pack-year smoker. Her medications included nebivolol and combined estrogen/progesterone hormone replacement therapy (HRT) for hot flashes and mood swings for 8 years. On examination, bowel sounds were normal, and her abdomen was diffusely tender without guarding or rigidity. A contrast-enhanced computerized tomographic scan of the chest and abdomen revealed an extensive intraluminal filling defect in the aorta consistent with a nonobstructive aortic mural thrombus (Figure 1A). It was 16.5 cm in length and extended proximally from the initial part of the descending thoracic aorta (Figure 1B) to the origin of celiac axis distally (Figure 1C). There was no evidence of embolic disease in the abdominal viscera. She was started on aspirin and clopidogrel, and the hypercoagulable workup was negative. After an uneventful hospital course, she was discharged with strict instructions to stop smoking and discontinue HRT. Despite a significant decrease in the use of HRT, it is occasionally the only effective treatment for women with refractory postmenopausal symptoms.1 It has been known to predispose to both arterial and venous thrombosis, by increasing the levels of procoagulant factors (VII, X, XII, and XIII) and decreasing the levels of anticoagulant factors (protein S and antithrombin).2 Aortic thrombi usually occur in the setting of atherosclerosis, aortitis, aneurysm, dissection, or trauma.3 This is a rare case of a giant aortic thrombus resulting from HRT. Smoking and hypertension were other contributing factors. This serves to remind physicians about the potentially serious consequences of long-term HRT.

In hypertensive people treated with an antihypertensive, concomitant statin administration has no additional effect on blood pressure

Commentary on: ManciaGParatiGReveraM. Statins, antihypertensive treatment, and blood pressure control in clinic and over 24 hours: evidence from PHYLLIS randomised double blind trial. BMJ 2010;340:c1197.