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Fulltext The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient

Ong HT

QJM, 2005 Aug;98(8):599-614.
PMID: 16006501

The landmark HMG-CoA reductase inhibitor (statin) studies have practical lessons for clinicans. The 4S trial established the importance of treating the hypercholesterolaemic patient with cardiovascular heart disease. Next, WOSCOPS showed the benefit of treating healthy, high-risk hypercholesterolaemic men. CARE, a secondary prevention trial, showed the benefit of treating patients with cholesterol levels within normal limits. This was confirmed by the LIPID trial, another secondary prevention study, which enrolled patients with cholesterol levels 155-271 mg/dl (4-7 mmol/l). The importance of treating patients with established ischaemic heart disease, and those at high risk of developing heart disease, regardless of cholesterol level, was being realized. In the MIRACL trial, hypocholesterolaemic therapy was useful in the setting of an acute coronary syndrome, while the AVERT study showed that aggressive statin therapy is as good as angioplasty in reducing ischaemic events in patients with stable angina. By showing the value of fluvastatin after percutaneous intervention, LIPS confirmed that benefit is a class action of the statins. The HPS randomized over 20 000 patients, and showed beyond doubt the value of statins in reducing cardiovascular events in the high-risk patient. Although PROSPER showed benefit in treating the elderly patients above 70 years, statin therapy in this trial was associated with an increase in cancer incidence. The comparative statin trials, PROVE-IT, REVERSAL, Phase Z of the A to Z, ALLIANCE and TNT, all showed that high-dose statins will better reduce cardiovascular events in the high-risk patient, although the adverse effects of therapy will also be increased. ALLHAT-LLT, ASCOT-LLA and CARDS showed that for statin therapy to demonstrate a significant benefit, hypertensive or diabetic patients must be at sufficiently high risk of cardiovascular events. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not the lipid level of the patient. No therapy is free of adverse effect. Treatment of those most at risk will bring the most benefit; treatment of those not at high risk of cardiovascular disease may expose patients who would not benefit much from therapy to its adverse effects.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
The A-SACT (Achievement in Singapore of Cholesterol Targets) study in patients with coronary heart disease

Ho KT, Chin KW, Ng KS, Alemao E, Rajagopalan S, Yin D

Am J Cardiovasc Drugs, 2006;6(6):383-91.
PMID: 17192128

BACKGROUND: Cardiovascular disease remains a leading cause of death worldwide, with hypercholesterolemia being a major risk factor. Evidence-based consensus guidelines have recommended consideration of increasingly stringent cholesterol-lowering goals, yet most patients do not meet these targets. Coronary heart disease (CHD) event and mortality rates and mean serum cholesterol levels have declined in Singapore in recent years; however, certain groups remain at elevated risk.
OBJECTIVE: To determine (i) proportions of patients with CHD in Singapore who achieved goals for serum low-density lipoprotein-cholesterol (LDL-C); and (ii) factors influencing goal attainment.
METHODS: A historical cohort study was conducted using records from the Singapore Cardiac Databank, a national registry of CHD patients. Serum LDL-C goal attainment was assessed in 5174 survivors of acute myocardial infarction or coronary revascularization (i.e. coronary artery bypass graft surgery or percutaneous coronary interventions), of whom 3811 (73.7%) were at very high risk.
RESULTS: At baseline, the mean patient age was 60.3 years, mean serum value of total cholesterol was 228 mg/dL, and mean LDL-C was 163 mg/dL. Of all CHD patients, approximately 70% did not achieve a serum LDL-C target of <100 mg/dL. Most patients receiving HMG-CoA reductase inhibitor (statin) regimens were treated initially with low- to medium-equipotency regimens and were never titrated to stronger regimens. The vast majority (approximately 94%) of patients at very high risk did not achieve the stringent serum LDL-C target of <70 mg/dL. Patients receiving higher potency statins were significantly more likely to achieve LDL-C goals, whereas those with higher baseline LDL-C levels or Malaysian ethnicity were less likely to achieve LDL-C goals.
CONCLUSIONS: Most CHD patients in the large group of Singapore residents with CHD in the present study did not achieve recommended LDL-C targets. A more effective disease-management approach, including patient education concerning lifestyle modification (e.g. diet, physical activity), efforts to enhance medication adherence, and more effective, well tolerated therapies such as high-equipotency or high-dose statins and statin combination regimens, may be needed to improve achievement of consensus cholesterol targets. This is the first study of cholesterol goal attainment in a large group of Southeast Asians and serves as a baseline for future evaluations in Asian populations.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Statin alternatives or just placebo: an objective review of omega-3, red yeast rice and garlic in cardiovascular therapeutics

Ong HT, Cheah JS

Chin Med J (Engl), 2008 Aug 20;121(16):1588-94.
PMID: 18982874

The aim of this review is to objectively access the trial evidence on the role of omega-3, red yeast rice and garlic in preventing clinical cardiovascular events. Given the large number of clinical trials favoring statin use in cardiovascular disease, it is important to see if evidence is available for these supplements and whether they could replace statin therapy.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Short-term effect of atorvastatin on endothelial function in healthy offspring of parents with type 2 diabetes mellitus

Amudha K, Choy AM, Mustafa MR, Lang CC

Cardiovasc Ther, 2008;26(4):253-61.
PMID: 19035876 DOI: 10.1111/j.1755-5922.2008.00064.x

Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow-mediated dilation (FMD) was measured in 56 first-degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age-, sex-, and BMI-matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA(IR)), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4-week double-blind, placebo-controlled trial. The FDRs had significantly impaired FMD (4.4 +/- 8.1% vs. 13.0 +/- 4.2%; P < 0.001), higher HOMA(IR) (1.72 +/- 1.45 vs. 1.25 +/- 0.43; P = 0.002), and elevated levels of plasma markers of inflammation-highly sensitive C-reactive protein (hsCRP) (2.6 +/- 3.8 mg/L vs. 0.7 +/- 1.0 mg/L; P = 0.06), interleukin (IL)-6 (0.07 +/- 0.13 ng/mL vs. 0.03 +/- 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 +/- 30.7 ng/mL vs. 238.2 +/- 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin-treated subjects when compared with the placebo-treated subjects (atorvastatin, from 3.7 +/- 8.5% to 9.8 +/- 7.3%; placebo, from 3.9 +/- 5.6% to 4.7 +/- 4.2%; P = 0.001). There were also reductions in the levels of IL-6 (0.08 +/- 0.02 ng/mL vs. 0.04 +/- 0.01 ng/mL; P < 0.001) and hsCRP (3.0 +/- 3.9 mg/L vs. 1.0 +/- 1.3 mg/L; P = 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Fulltext A multicenter study in Malaysia to determine the efficacy and safety of a generic atorvastatin

Punithavathi N, Ong LM, Lena YL, Leekha S, Storvas Clinical Trial Study Group

Med J Malaysia, 2009 Jun;64(2):150-4.
PMID: 20058576 MyJurnal

A multicenter study was conducted to assess the efficacy of a generic form of Atorvastatin (Ranbaxy's Storvas) in the treatment of Primary Hypercholesterolemia. One hundred and nineteen patients were given 10 mg of Storvas for four weeks and increased to 20 mg if target LDL-Cholesterol was not achieved. LDL-Cholesterol was reduced by 36.6% at four weeks and 37.5% at eight weeks from baseline. Total cholesterol and triglycerides were significantly reduced. There were no drug-related serious adverse events. We conclude that the generic atorvastatin is safe and effective in the treatment of primary hypercholesterolaemia and the results are comparable to published data on innovator atorvastatin.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Statin use prior to ischemic stroke onset is associated with decreased in-hospital mortality

Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH

Fundam Clin Pharmacol, 2011 Jun;25(3):388-94.
PMID: 20608996 DOI: 10.1111/j.1472-8206.2010.00846.x

Statins can reduce the risk of stroke in at-risk populations and improve survival after acute ischemic stroke (AIS) among patients with previous statin use. This study aimed to investigate the impact of statin use before AIS onset on in-hospital mortality and identify the factors related to in-hospital mortality among patients with and without previous statin use. A retrospective cohort study of all patients with AIS attending hospital from June 1, 2008 to December 31, 2008. Data were collected from medical records including demographic information, diagnostic information, risk factors, previous statin use, and vital discharge status. Chi-square, Fisher's exact tests, student's t-test, and Mann-Whitney U test, whatever appropriate, were used to test the significance between the variables, and multiple logistic regression was used to identify factors associated with in-hospital mortality. Altogether, 386 patients with AIS were studied, of which 113 (29.3%) had a documented previous statin use. A total of 62 (16.1%) patients with AIS died in hospital. In-hospital mortality was significantly lower among previous statin users (P = 0.013). The presence of atrial fibrillation (AF) increased in-hospital mortality among patients with or without previous statin use. The independent predictors for in-hospital mortality among AIS patients without previous statin use were the presence of diabetes mellitus (P = 0.047), AF (P = 0.045), and renal impairment (P < 0.001). The prophylactic administration of statins significantly reduces post-AIS in-hospital mortality. Furthermore, the identification of predictors of in-hospital mortality might reduce death rates and enhance the application of specific therapeutic and management strategies to patients at a high risk of dying.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Fulltext Long-term efficacy and safety of a generic atorvastatin in usual clinical care setting

Ong LM, Punithavathi N, Lena YLL, Mahanim O, Leekha S, Storvas Clinical Trial Study Group

Med J Malaysia, 2011 Aug;66(3):214-9.
PMID: 22111443

A multicentre study was conducted to assess the long term efficacy and safety of a generic atorvastatin in the treatment of primary hypercholesterolaemia. Eighty five patients who received 10mg or 20 mg of atorvastatin for 8 weeks depending on target cholesterol goal were followed up by their own physicians and had final evaluation at 52 weeks. Reduction in mean low density Lipoprotein (LDL-C) was 36.5%, 37.9% and 32.2% at weeks 4, 8 and 52 respectively. LDL-C target was maintained in 81% and 69% of patients at week 8 and 52 respectively without drug related serious adverse events. Generic atorvastatin is safe and effective in usual clinical care setting.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Medication prescribing patterns among chronic kidney disease patients in a hospital in Malaysia

Al-Ramahi R

Saudi J Kidney Dis Transpl, 2012 Mar;23(2):403-8.
PMID: 22382249

To determine the medication prescribing patterns in hospitalized patients with chronic kidney disease (CKD) in a Malaysian hospital, we prospectively studied a cohort of 600 patients in two phases with 300 patients in each phase. The first phase was carried out from the beginning of February to the end of May 2007, and the second phase was from the beginning of March to the end of June 2008. Patients with CKD who had an estimated creatinine clearance ≤ 50 mL/min and were older than 18 years were included. A data collection form was used to collect data from the patients' medical records and chart review. All systemic medications prescribed during hospitalization were included. The patients were prescribed 5795 medications. During the first phase, the patients were prescribed 2814 medication orders of 176 different medications. The prescriptions were 2981 of 158 medications during the second phase. The mean number of medications in the first and second phases was 9.38 ± 3.63 and 9.94 ± 3.78 respectively (P-value = 0.066). The top five used medications were calcium carbonate, folic acid/vitamin B complex, metoprolol, lovastatin, and ferrous sulfate. The most commonly used medication classes were mineral supplements, vitamins, antianemic preparations, antibacterials, and beta-blocking agents. This study provides an overview of prescription practice in a cohort of hospitalized CKD patients and indicates possible areas of improvement in prescription practice.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Fulltext Impact of the additive effect of angiotensin-converting enzyme inhibitors and /or statins with antiplatelet medication on mortality after acute ischaemic stroke

Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH

Basic Clin Pharmacol Toxicol, 2012 Apr;110(4):370-7.
PMID: 22023326 DOI: 10.1111/j.1742-7843.2011.00825.x

There has been recent interest in combining antiplatelets, angiotensin-converting enzyme inhibitors (ACEIs) and statins in primary and secondary ischaemic stroke prevention. This observational study was performed to evaluate the impact of adding ACEIs and/or statins to antiplatelets on post-stroke in-hospital mortality. Ischaemic stroke patients attending a hospital in Malaysia over an 18-month period were evaluated. Patients were categorized according to their vital status at discharge. Data included demographic information, risk factors, clinical characteristics and previous medications with particular attention on antiplatelets, ACEIs and statins. In-hospital mortality was compared among patients who were not taking antiplatelets, ACEIs or statins before stroke onset versus those who were taking antiplatelets alone or in combination with either ACEIs, statins or both. Data analysis was performed using SPSS version 15. Overall, 637 patients met the study inclusion criteria. After controlling for the effects of confounders, adding ACEIs or statins to antiplatelets significantly decreased the incidence of death after stroke attack by 68% (p = 0.036) and 81% (p = 0.010), respectively, compared to patients on antiplatelets alone or none of these medications. Additionally, the addition of both ACEIs and statins to antiplatelet medication resulted in the highest reduction (by 94%) of the occurrence of death after stroke attack (p < 0.001). Our results suggest that adding ACEIs and/or statins to antiplatelets for patients at risk of developing stroke, either as a primary or as a secondary preventive regimen, was associated with a significant reduction in the incidence of mortality after ischaemic stroke than antiplatelets alone. These results might help reduce the rate of ischaemic stroke morbidity and mortality by enhancing the application of specific therapeutic and management strategies for patients at a high risk of acute stroke.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
The impact of pharmacist-initiated interventions in improving acute coronary syndrome secondary prevention pharmacotherapy prescribing upon discharge

Hassan Y, Kassab Y, Abd Aziz N, Akram H, Ismail O

J Clin Pharm Ther, 2013 Apr;38(2):97-100.
PMID: 23441979 DOI: 10.1111/jcpt.12027

Pharmacists have the knowledge regarding optimal use of medications and the ability to influence physician prescribing. Successful interventions by a pharmacist to implement cardioprotective medications to a coronary artery disease patient's regimen would not only improve the patient's quality of care but may also increase his or her likelihood of survival. Therefore, the aim of this study was to (i) evaluate the effectiveness of pharmacist initiated interventions in increasing the prescription rates of acute coronary syndrome (ACS) secondary prevention pharmacotherapy at discharge, and to (ii) evaluate the acceptance rate of these interventions by prescribers.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Update on statins: hope for osteoporotic fracture healing treatment

Ibrahim N', Mohamed N, Shuid AN

Curr Drug Targets, 2013 Dec;14(13):1524-32.
PMID: 23876090

Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
A review on the use of statins and tocotrienols, individually or in combination for the treatment of osteoporosis

Abdul-Majeed S, Mohamed N, Soelaiman IN

Curr Drug Targets, 2013 Dec;14(13):1579-90.
PMID: 23848479

Skeletal tissue undergoes continuous remodeling which makes it unique among other body tissues. Osteoporosis is a common bone metabolic disorder affecting both men and women. Osteoporosis and its complications mainly osteoporotic fractures, have a high impact on health and economy. Current approved medications are associated with numerous side effects, which limit their use. Identification of a new and safe therapy is mandatory. Statins, also known as HMGCoA reductase inhibitors, are frequently used for the treatment of hypercholesterolemia and for the prevention of morbidity and mortality associated with cardiovascular disease. Statins improved bone health status in intact and ovariectomised rodents following high clinically intolerable oral doses. However, this beneficial effect of statins could not be significantly demonstrated in humans. The reason behind this discrepancy might be due to the safety and bioavailability of the currently used oral statins. Vitamin E, especially the tocotrienols at the dose 60 mg/kg/day provided significant antiosteoporotic effects in different animal models of osteoporosis. The use of the aforementioned dose of tocotrienols was shown to be safe in both humans and animals. Enhancement of bone formation and reduction of bone resorption were achieved more effectively by a combination of tocotrienols and statins than by either treatment when supplemented separately at clinically tolerable doses. Therefore, the adverse effects associated with high statin doses might be avoided with the coadministration of tocotrienols. Moreover, the combination therapy strategy might be useful for patients who are at high risk of osteoporosis, cardiovascular events and hypercholesterolaemia.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Fulltext Statins in heart failure: do we need another trial?

Bonsu KO, Kadirvelu A, Reidpath DD

Vasc Health Risk Manag, 2013;9:303-19.
PMID: 23807852 DOI: 10.2147/VHRM.S44499

Statins lower serum cholesterol and are employed for primary and secondary prevention of cardiovascular events. Clinical evidence from observational studies, retrospective data, and post hoc analyses of data from large statin trials in various cardiovascular conditions, as well as small scale randomized trials, suggest survival and other outcome benefits for heart failure. Two recent large randomized controlled trials, however, appear to suggest statins do not have beneficial effects in heart failure. In addition to lowering cholesterol, statins are believed to have many pleotropic effects which could possibly influence the pathophysiology of heart failure. Following the two large trials, evidence from recent studies appears to support the use of statins in heart failure. This review discusses the role of statins in the pathophysiology of heart failure, current evidence for statin use in heart failure, and suggests directions for future research.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Fulltext Lipophilic versus hydrophilic statin therapy for heart failure: a protocol for an adjusted indirect comparison meta-analysis

Bonsu KO, Kadirvelu A, Reidpath DD

Syst Rev, 2013;2:22.
PMID: 23618535 DOI: 10.1186/2046-4053-2-22

Statins are known to reduce cardiovascular morbidity and mortality in primary and secondary prevention studies. Subsequently, a number of nonrandomised studies have shown statins improve clinical outcomes in patients with heart failure (HF). Small randomised controlled trials (RCT) also show improved cardiac function, reduced inflammation and mortality with statins in HF. However, the findings of two large RCTs do not support the evidence provided by previous studies and suggest statins lack beneficial effects in HF. Two meta-analyses have shown statins do not improve survival, whereas two others showed improved cardiac function and reduced inflammation in HF. It appears lipophilic statins produce better survival and other outcome benefits compared to hydrophilic statins. But the two types have not been compared in direct comparison trials in HF.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Fulltext Does use of pooled cohort risk score overestimate the use of statin?: a retrospective cohort study in a primary care setting

Chia YC, Lim HM, Ching SM

BMC Fam Pract, 2014;15:172.
PMID: 25388219 DOI: 10.1186/s12875-014-0172-y

BACKGROUND: Initiation of statin therapy as primary prevention particularly in those with mildly elevated cardiovascular disease risk factors is still being debated. The 2013 ACC/AHA blood cholesterol guideline recommends initiation of statin by estimating the 10-year atherosclerotic cardiovascular disease (ASCVD) risk using the new pooled cohort risk score. This paper examines the use of the pooled cohort risk score and compares it to actual use of statins in daily clinical practice in a primary care setting.
METHODS: We examined the use of statins in a randomly selected sample of patients in a primary care clinic. The demographic data and cardiovascular risk parameters were captured from patient records in 1998. The pooled cohort risk score was calculated based on the parameters in 1998. The use of statins in 1998 and 2007, a 10-year interval, was recorded.
RESULTS: A total of 847 patients were entered into the analysis. Mean age of the patients was 57.2 ± 8.4 years and 33.1% were male. The use of statins in 1998 was only 10.2% (n = 86) as compared to 67.5% (n = 572) in 2007. For patients with LDL 70-189 mg/dl and estimated 10-year ASCVD risk ≥7.5% (n = 190), 60% (n = 114) of patients were on statin therapy by 2007. There were 124 patients in whom statin therapy was not recommended according to ACC/AHA guideline but were actually receiving statin therapy.
CONCLUSIONS: An extra 40% of patients need to be treated with statin if the 2013 ACC/AHA blood cholesterol guideline is used. However the absolute number of patients who needed to be treated based on the ACC/AHA guideline is lower than the number of patients actually receiving it in a daily clinical practice. The pooled cohort risk score does not increase the absolute number of patients who are actually treated with statins. However these findings and the use of the pooled cohort risk score need to be validated further.
Study site: Primary care clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Fulltext Mechanisms of action and efficacy of statins against influenza

Mehrbod P, Omar AR, Hair-Bejo M, Haghani A, Ideris A

Biomed Res Int, 2014;2014:872370.
PMID: 25478576 DOI: 10.1155/2014/872370

The influenza virus (IV) is known to be a resistant virus with frequent mutations, causing severe respiratory diseases in the upper respiratory system. Public health concerns about clinical efficacy of all conventional drugs are ambiguous; therefore, finding additional therapeutic agents is critical to prevent and control influenza outbreaks. Influenza is associated with the induction of proinflammatory cytokines. Scientists have reported that anti-inflammatory drugs, with pleiotropic effects, reduce the burden of severe influenza diseases. Therefore, statins, which are cardioprotective drugs with anti-inflammatory and immunomodulatory effects, may help patients suffering from influenza virus (IV). This review delineates the potential use of statins as an alternative therapy in treating influenza related illness.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
The use of delta-tocotrienol and lovastatin for anti-osteoporotic therapy

Abdul-Majeed S, Mohamed N, Soelaiman IN

Life Sci, 2015 Mar 15;125:42-8.
PMID: 25534439 DOI: 10.1016/j.lfs.2014.12.012

Statins are competitive inhibitors of HMGCoA reductase and are commonly used as antihypercholesterolemic agents. Experimental studies clearly demonstrate the beneficial effects of statins on bone. Tocotrienols have also been shown to have anti-osteoporotic effects on the skeletal system. This study was conducted to observe the effect of a combination of delta-tocotrienol and lovastatin on structural bone histomorphometry and bone biomechanical strength in a postmenopausal rat model at clinically tolerable doses, and to compare it with the effect of delta-tocotrienol or lovastatin.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials

Bonsu KO, Reidpath DD, Kadirvelu A

Cardiovasc Ther, 2015 Dec;33(6):338-46.
PMID: 26280110 DOI: 10.1111/1755-5922.12150

Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data

Khatib R, McKee M, Shannon H, Chow C, Rangarajan S, Teo K, et al.

Lancet, 2016 Jan 2;387(10013):61-9.
PMID: 26498706 DOI: 10.1016/S0140-6736(15)00469-9

BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability.
METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, β blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry.
FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55).
INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025.
FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Lipophilic Statin Versus Rosuvastatin (Hydrophilic) Treatment for Heart Failure: a Meta-Analysis and Adjusted Indirect Comparison of Randomised Trials

Bonsu KO, Reidpath DD, Kadirvelu A

Cardiovasc Drugs Ther, 2016 Apr;30(2):177-88.
PMID: 26780905 DOI: 10.1007/s10557-015-6636-z

OBJECTIVES: This study aims to compare lipophilic and hydrophilic statin therapy on clinical outcomes of heart failure (HF) using a systematic review and an adjusted indirect comparison meta-analysis. Outcomes were all-cause mortality, cardiovascular mortality, cardiovascular hospitalization and hospitalization for worsening HF.
METHODS: We conducted a search of PubMed, EMBASE and Cochrane databases until 31st December 2014 for randomized control trials (RCTs) in HF evaluating statins versus placebo. Identified RCTs and their respective abstracted information were grouped according to statin type evaluated and analyzed separately. Outcomes were initially pooled with the Peto's one-step method, producing odd ratios (OR) and 95 % confidence intervals (CI) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons of lipophilic versus hydrophilic statin for each outcome.
RESULTS: Thirteen studies involving 10,966 patients were identified and analyzed. Lipophilic statins were superior to hydrophilic rosuvastatin regarding all-cause mortality (OR 0 · 50; 95 % CI, 0 · 11-0 · 89; p = 0 · 01), cardiovascular mortality (OR 0 · 61; 0 · 25-0 · 97; p = 0 · 009), and hospitalization for worsening HF (OR 0 · 52; 0 · 21-0 · 83; p = 0 · 0005). However, both statins were comparable with regards to cardiovascular hospitalization [OR 0 · 80 (0 · 31, 1 · 28); p = 0 · 36].
CONCLUSIONS: Lipophilic statin treatment shows significant decreases in all-cause mortality, cardiovascular mortality and hospitalization for worsening HF compared with rosuvastatin treatment. This meta-analysis provides preliminary evidence that lipophilic statins offer better clinical outcomes in HF till data from head to head comparisons are available.

Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*

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