Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metformin is contraindicated in patients with renal failure because of the risk of lactic acidosis. This study assessed the complications of metformin treatment in patients with non-insulin-dependent diabetes mellitis with normal and raised serum creatinine. Subjects using metformin with serum creatinine above the upper reference range (120 mu mol/l) were identified (n = 17) from a hospital diabetes register; those with abnormal liver function, cardiac failure, peripheral vascular disease or recent severe illness were excluded. Reference plasma lactate levels were established, mean 1.742 mu mol/l (SD 0.819) using age-matched non-diabetic subjects. Age-matched patients treated with metformin with normal serum creatinine levels formed the control group (n = 24). Details of gastrointestinal disturbance were recorded, and plasma lactic acid and vitamin B12 levels measured. The median total daily dose of metformin in both groups was 1700 mg. The mean plasma lactate in subjects with serum creatinine 80-120 mu mol/l (2.640 mmol/l (SD 1.434) p < 0.02) was higher than non-diabetic control levels while diabetic subjects with serum creatinine 120-160 mumol/l had a mean of 2.272 mmol/l (SD 0.763) p < 0.05. There was no significant difference between the two groups taking metformin, nor any significant difference in the reporting of gastrointestinal symptoms between the groups on metformin (11.76% vs 12.5%). Plasma lactic acid levels are higher in diabetic subjects taking metformin compared with healthy volunteers but, within the diabetic groups, the small elevation of serum creatinine was not associated with higher plasma lactate levels.
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PMID:Metformin treatment in NIDDM patients with mild renal impairment. 875 14

Metformin is an effective anti-hyperglycaemic and cardioprotective agent, but a long list of contraindications precludes millions of patients with type 2 diabetes from using it. This is largely due to the historical experience of lactic acidosis with phenformin, despite the fact that metformin does not predispose to this when compared with other therapies. Contraindications such as old age, renal impairment and cardiac insufficiency are increasingly disregarded in clinical practice, yet there is no evidence that the incidence of lactic acidosis has changed. Metformin has been shown to improve metabolic control without causing lactic acidosis in elderly patients with multiple comorbidities, including explicit contraindications, and its use in patients with type 2 diabetes over the age of 70 with mild renal impairment did not produce a clinically relevant increase in plasma lactate. There is no correlation between levels of metformin and lactate in patients with lactic acidosis, and its prognosis is mainly related to the causal hypoxic underlying disease and comorbidities. These findings raise doubts about the pathogenetic significance of metformin in lactic acidosis. We propose that advanced age per se, mild renal impairment and compensated heart failure can no longer be upheld as contraindications for metformin. A clear re-definition of contraindications to metformin will enable more physicians to prescribe within guidelines.
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PMID:Contraindications can damage your health--is metformin a case in point? 1656 48

For fear of lactic acidosis the currently listed contraindications to the use of metformin exclude a large number of people with type 2 diabetes from efficacious anti-hyperglycemic and cardioprotective treatment. Yet recent data call the traditional contraindications to metformin into question. As the incidence of lactic acidosis in patients with type 2 diabetes is the same with or without metformin therapy (about 9 per 100,000 patient years) there is no evidence that metformin therapy is associated with an increased risk of lactic acidosis. Similarly, despite disregard internationally of major metformin contraindications, there has been no corresponding increase in the incidence of lactic acidosis. Metformin treatment of elderly diabetics with multiple comorbidities and explicit contraindications has led to significantly better clinical parameters in them than in the control group without metformin; and there were no cases of lactic acidosis. The two groups did not differ with regard to progression of renal failure, patient-oriented endpoints or overall mortality. Compared with its predecessors phenformin and buformin, metformin is considerably less lipophilic and has a shorter plasma half-life; it is eliminated renally in unchanged form. In type 2 diabetics treated with metformin -- even those over 70 years of age and those in mild renal failure -- no relevant increases in lactate levels were found. In patients with lactic acidosis there was no correlation between the levels of metformin and lactate. The prognosis of lactic acidosis is determined less by the serum concentrations of metformin and lactate than by the hypoxia caused by the underlying disease and comorbidities. These findings raise doubts about the significance of metformin in the pathogenesis of lactic acidosis. On the basis of the current data, advanced age per se, mild renal impairment and stable heart failure can no longer be upheld as contraindications to the use of metformin. It should be safe to withdraw metformin the evening before radiological examinations with intravenous contrast media or surgical procedures under general anaesthesia in diabetics with normal renal function.
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PMID:[Traditional contraindications to the use of metformin -- more harmful than beneficial?]. 1641 51

Metformin is associated with decreased mortality and morbidity in stable heart failure patients with diabetes mellitus type II. Diabetic heart failure patients with elevated systolic blood pressure are at increased risk for developing acute decompensated heart failure, which is often associated with decreased kidney function. Metformin-associated lactic acidosis is a rare but fatal side effect that may occur when kidney function is decreased. During acute decompensated heart failure, timely treatment may prevent the decrease in kidney function to the threshold associated with an increased risk of metformin-associated lactic acidosis. Metformin should not be withheld in diabetic patients with stable heart failure who do not have other risk factors for acute decompensated heart failure or lactic acidosis.
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PMID:Metformin use in decompensated heart failure. 1870 28

Clinical studies have reported that the widely used antihyperglycemic drug metformin significantly reduces cardiac risk factors and improves clinical outcomes in patients with heart failure. The mechanisms by which metformin exerts these cardioprotective effects remain unclear and may be independent of antihyperglycemic effects. We tested the hypothesis that chronic activation of AMP-activated protein kinase (AMPK) with low-dose metformin exerts beneficial effects on cardiac function and survival in in vivo murine models of heart failure. Mice were subjected to permanent left coronary artery occlusion or to 60 minutes left coronary artery occlusion followed by reperfusion for 4 weeks. High-resolution, 2D echocardiography was performed at baseline and 4 weeks after myocardial infarction to assess left ventricular dimensions and function. Metformin (125 microg/kg) administered to mice at ischemia and then daily improved survival by 47% (P<0.05 versus vehicle) at 4 weeks following permanent left coronary artery occlusion. Additionally, metformin given at reperfusion and then daily preserved left ventricular dimensions and left ventricular ejection fraction (P<0.01 versus vehicle) at 4 weeks. The improvement in cardiac structure and function was associated with increases in AMPK and endothelial nitric oxide synthase (eNOS) phosphorylation, as well as increased peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha expression in cardiac myocytes. Furthermore, metformin significantly improved myocardial cell mitochondrial respiration and ATP synthesis compared to vehicle. The cardioprotective effects of metformin were ablated in mice lacking functional AMPK or eNOS. This study demonstrates that metformin significantly improves left ventricular function and survival via activation of AMPK and its downstream mediators, eNOS and PGC-1alpha, in a murine model of heart failure.
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PMID:Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. 1921 62

Clinicians are faced with an expansive array of treatment choices when caring for patients with type 2 diabetes. Because patient compliance may be affected when media sensationalism about controversial findings is misunderstood, we sought to clarify the recent controversy surrounding the cardiovascular and bone-health risks of thiazolidinediones, the risk of lactic acidosis with metformin, and the risk of hypoglycemia with oral therapies. The side effect profile of thiazolidinediones includes fluid retention, heart failure; and an increased risk of fracture. A recent controversial meta-analysis suggested that rosiglitazone increases the risk of myocardial infarction, which is possibly related to thiazolidinedione-induced lipid changes, weight gain, congestive heart failure, and anemia. Metformin is restricted to patients with normal renal function because of concerns that metformin may cause lactic acidosis. However, few cases of metformin-associated lactic acidosis have been reported, and most have occurred in patients with other reasons for developing lactic acidosis, such as sepsis or renal failure. Although the use of metformin continues to increase, observational studies have not been able to demonstrate an increased incidence of lactic acidosis in metformin-treated patients, even when it is used in populations with relative contraindications. Some oral hypoglycemic medications can cause hypoglycemia. Hypoglycemia is especially common in older patients, alcoholics, and patients with liver or renal disease. Patients on sulfonylureas and meglitinides have the highest incidence of hypoglycemia because of their pharmacological action of increasing insulin secretion. Of the sulfonylureas, glyburide presents the highest risk of hypoglycemia. Combination therapies, especially those regimens containing a sulfonylurea, increase the risk of hypoglycemia.
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PMID:Balancing risk and benefit with oral hypoglycemic drugs. 1942 67

Metformin is a biguanide, insulin sensitiser that reduces blood sugar levels. There are concerns about the risk of lactic acidosis in patients receiving metformin who have procedures requiring iodinated contrast, and in those with renal impairment or heart failure. The data on which these concerns are based are reviewed, with the conclusion that metformin treatment is rarely to blame for lactic acidosis. A generic policy of stopping metformin 48 h before and 48 h after the procedure in all patients is counterintuitive, lacks any evidence base and does not conform to the principles of best practice. In patients with heart failure, although the underlying condition can predispose to lactic acidosis, existing evidence suggests that metformin use is associated with improved outcome rather than increased risk.
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PMID:Metformin: safety in cardiac patients. 1956 48

Classical non-insulin antihyperglycemic drugs currently approved for the treatment of type 2 diabetes mellitus (T2DM) comprise five groups: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. Novel compounds are represented by the incretin mimetic drugs like glucagon like peptide-1 (GLP-1), the dipeptidyl peptidase 4 (DPP-4) inhibitors, dual peroxisome proliferator-activated receptors (PPAR) agonists (glitazars) and amylin mimetic drugs. We review the cardiovascular effects of these drugs in an attempt to improve knowledge regarding their potential risks when treating T2DM in cardiac patients. Metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as recent myocardial infarction, heart or renal failure. Sulfonylureas exert their effect by closing the ATP-dependent potassium channels. This prevents the opening of these channels during myocardial ischemia, impeding the necessary hyperpolarization that protects the cell. The combined sulfonylurea/metformin therapy reveals additive effects on mortality in patients with coronary artery disease (CAD). Meglitinides effects are similar to those of sulfonylureas, due to their almost analogous mechanism of action. Glitazones lower leptin levels, leading to weight gain and are unsafe in NYHA class III or IV. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates is yet unknown. The incretin GLP-1 is associated with reductions in body weight and appears to present positive inotropic effects. DPP-4 inhibitors influences on the cardiovascular system seem to be neutral and patients do not gain weight. The future of glitazars is presently uncertain following concerns about their safety. The amylin mimetic drug paramlintide, while a satisfactory adjuvant medication in insulin-dependent diabetes, is unlikely to play a major role in the management of T2DM. Summarizing the present information it can be stated that 1. Four out the five classical oral antidiabetic drug groups present proven or potential cardiac hazards; 2. These hazards are not mere 'side effects', but biochemical phenomena which are deeply rooted in the drugs' mechanism of action; 3. Current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of T2DM with proven CAD; 4. Glitazones should be avoided in patients with overt heart failure; 5, The novel incretin mimetic drugs and DPP-4 inhibitors--while usually inadequate as monotherapy--appear to be satisfactory adjuvant drugs due to the lack of known undesirable cardiovascular effects; 6. Customized antihyperglycemic pharmacological approaches should be implemented for the achievement of optimal treatment of T2DM patients with heart disease. In this context, it should be carefully taken into consideration whether the leading clinical status is CAD or heart failure.
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PMID:A cardiologic approach to non-insulin antidiabetic pharmacotherapy in patients with heart disease. 1961 27

Evidence indicates that hospitalized patients with hyperglycemia do not benefit from tight blood glucose control. Maintaining a blood glucose level of less than 180 mg per dL (9.99 mmol per L) will minimize symptoms of hyperglycemia and hypoglycemia without adversely affecting patient-oriented health outcomes. In the absence of modifying factors, physicians should continue patients' at-home diabetes mellitus medications and randomly check glucose levels once daily. Sulfonylureas should be withheld to avoid hypoglycemia in patients with limited caloric intake. Patients with cardiovascular conditions may benefit from temporarily stopping treatment with thiazolidinediones to avoid precipitating heart failure. Metformin should be temporarily withheld in patients who have worsening renal function or who will undergo an imaging study that uses contrast. When patients need to be treated with insulin in the short term, using a long-acting basal insulin combined with a short-acting insulin before meals (with the goal of keeping blood glucose less than 180 mg per dL) better approximates normal physiology and uses fewer nursing resources than sliding-scale insulin approaches. Most studies have found that infusion with glucose, insulin, and potassium does not improve mortality in patients with acute myocardial infarction. Patients admitted with acute myocardial infarction should have moderate control of blood glucose using home regimens or basal insulin with correctional doses.
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PMID:Glucose control in hospitalized patients. 2043 21

Metformin is a biguanide, insulin sensitiser that reduces blood sugar levels. There are concerns about the risk of lactic acidosis in patients receiving metformin who have procedures requiring iodinated contrast, and in those with renal impairment or heart failure. The data on which these concerns are based are reviewed, with the conclusion that metformin treatment is rarely to blame for lactic acidosis. A generic policy of stopping metformin 48 h before and 48 h after the procedure in all patients is counterintuitive, lacks any evidence base and does not conform to the principles of best practice. In patients with heart failure, although the underlying condition can predispose to lactic acidosis, existing evidence suggests that metformin use is associated with improved outcome rather than increased risk.
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PMID:Metformin: safety in cardiac patients. 2054 5


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