Long-term benefits and limitations of combined antianginal drug therapy in elderly patients with symptomatic chronic coronary artery disease.

BACKGROUND: Chronic angina is a common and disabling disorder in the elderly. Combined antianginal drug treatment represents the mainstay of therapy in this population. However, there is a paucity of data regarding the effect of this strategy on long-term outcome in the elderly. METHODS: To assess the long-term effect of combined antianginal drug therapy in elderly individuals, we performed a long-term follow-up analysis of all 148 patients of the Trial of Invasive versus Medical therapy in Elderly (TIME) patients with chronic symptomatic coronary-artery disease assigned to an optimized medical therapy strategy. Angina severity, measures of quality of life (QOL), and survival were assessed after a median of 3.7 (0.1-6.9) years. RESULTS: At baseline, patients were 79.8 +/- 3.5 years old with Canadian Cardiovascular Society (CCS) class angina 3.0 +/- 0.7 despite the use of 2.4 +/- 0.6 antianginal drugs. Although antianginal drugs were increased to 2.8 +/- 0.9 (P < .01), 63 (43%) patients needed revascularization for refractory symptoms during the first year of observation (REVASC). At baseline, REVASC patients had more frequently CCS class 4 angina (37% vs 20%, P < 0.05) but reported less prior heart failure (5% vs 20%, P < 0.01), fewer prior cerebral events (3% vs 13%, P < .05) and a lower rate of two or more comorbidities (10% vs 33%, P < .01) than patients on continued drug therapy (DRUG). At long-term follow-up, angina severity was still higher in DRUG compared to REVASC patients (CCS class, 1.8 +/- 1.6 vs 1.0 +/- 1.4, P < .05) despite more antianginal drugs (2.1 +/- 1.1 vs 1.5 +/- 1.0, P < .01), whereas measures of QOL had improved similarly in both groups. In addition, long-term mortality was significantly higher in DRUG than in REVASC patients (38% vs 13%, P < .01). CONCLUSION: Combined antianginal drug therapy successfully relieved symptoms in most elderly patients with chronic angina but failed to do so in 43%. Patients who needed revascularization for refractory symptoms reported less angina, despite lower drug use during long-term follow-up and had a better long-term survival. Thus, the widely used strategy to increase antianginal drug therapy in elderly patients instead of evaluating them for revascularization should be reconsidered.

Rhabdomyolysis in association with simvastatin and amiodarone.

OBJECTIVE: To report a case of severe myopathy associated with concomitant simvastatin and amiodarone therapy. CASE SUMMARY: A 63-year-old white man with underlying insulin-dependent diabetes, recent coronary artery bypass surgery, and postoperative hemiplegia was treated with aspirin, metoprolol, furosemide, nitroglycerin, and simvastatin. Due to recurrent atrial fibrillation, oral anticoagulation with phenprocoumon and antiarrhythmic treatment with amiodarone were initiated. Four weeks after starting simvastatin 40 mg/day and 2 weeks after initiating amiodarone 1 g/day for 10 days, then 200 mg/day, he developed diffuse muscle pain with generalized muscular weakness. Laboratory investigations revealed a significant increase of creatine kinase (CK) peaking at 40 392 U/L. Due to a suspected drug interaction of simvastatin with amiodarone, both drugs were stopped. CK normalized over the following 8 days, and the patient made an uneventful recovery. An objective causality assessment revealed that the myopathy was probably related to simvastatin. DISCUSSION: Myopathy is a rare but potentially severe adverse reaction associated with statins. Besides high statin doses, concomitant use of fibrates, defined comorbidities, and concurrent use of inhibitors of cytochrome P450 are important additional risk factors. This is especially relevant if statins predominantly metabolized by CYP3A4 are combined with inhibitors of this isoenzyme. Amiodarone is a potent inhibitor of several different CYP isoenzymes, including CYP3A4. CONCLUSIONS: Avoiding the concomitant use of drugs with the potential to inhibit CYP-dependent metabolism (eg, amiodarone) or elimination of statins may decrease the risk of statin-associated myopathy. Alternatively, if drug therapy with a potent CYP inhibitor is inevitable, choosing a statin without relevant CYP metabolism (eg, pravastatin) should be considered.

Initial clinical evaluation of cardiac systolic murmurs in the ED by noncardiologists.

It is not exactly known how ED physicians perform in evaluating cardiac systolic murmurs. In 203 consecutive medical ED patients with systolic murmur, we compared the initial clinical evaluation, including auscultation, with transthoracic echocardiography. Of the 203 patients, 132 (65%) had innocent murmurs and 71 patients (35%) had valvular heart disease. Sensitivity and specificity of the initial clinical routine evaluation in diagnosing echocardiographic valvular heart disease were 82% (70%-86%) and 69% (60%-76%), respectively. Independent significant positive predictors of valvular heart disease were grade >2/6 systolic murmur (odds ratio [OR], 8.3; confidence interval [CI], 3.5-19.7, P<.001) and pathologic electrocardiogram (ECG) (OR, 8.4; CI, 3.2-22, P<.001. Patients younger than 50 years with a systolic murmur graded < or =2/6 had innocent murmurs in 98%. The initial clinical evaluation, including auscultation, by experienced ED physicians in internal medicine distinguishes well between innocent murmurs and valvular heart disease in medical patients with cardiac systolic murmurs.

Search for occult malignancy in patients with deep venous thrombosis. Results of a retrospective cohort study.

QUESTIONS UNDER STUDY: The association of deep vein thrombosis (DVT) and cancer is well established. It is controversial how large the association is and how extensive the evaluation for an underlying cancer should be. PRINCIPLES AND METHODS: 485 patients without a known cancer and a proven DVT formed the cohort of a retrospective study. Newly diagnosed (prevalent) cancers in patients with idiopathic (IDVT) and secondary (SDVT) during the index hospitalisation were compared and the contribution of the steps in an institutional tumour search program was analysed. The incidence of cancer in 204 patients with IDVT and 230 patients with SDVT during follow-up was determined. RESULTS: During the index hospitalisation routine evaluation revealed eleven cancers in 236 patients (4.7% [95%-CI: 2.0-7.3]) with IDVT and five cancers in 249 patients (2.0% [95%-CI: 0.3-3.7]) with SDVT. Combining patient history, clinical examination, routine laboratory tests and chest x-ray showed a sensitivity of 88% and a specificity of 79% for the diagnosis of cancer. Abdominal ultrasound did not significantly increase the yield. 93% of the patients were followed for up to 5 years (mean 32 months). Sixteen cancers occurred in 204 patients (7.8% [95%-CI: 4.0-11.5]) with IDVT and ten in 230 patients (4.35% [95%-CI: 1.7-7.0]) with SVDT (p<0.001). CONCLUSION: Prevalence and incidence of cancer were higher in IDVT patients compared to those with SDVT. Combining patient history, clinical examination, simple laboratory tests, and a routine chest x-ray is an appropriate strategy to detect underlying cancer in patients with IDVT. Routine abdominal ultrasound can safely be omitted.

A computer-based intervention for improving the appropriateness of antiepileptic drug level monitoring.

We designed and implemented 2 automated, computerized screens for use at the time of antiepileptic drug (AED) test order entry to improve appropriateness by reminding physicians when a potentially redundant test was ordered and providing common indications for monitoring and pharmacokinetics of the specific AED. All computerized orders for inpatient serum AED levels during two 3-month periods were included in the study. During the 3-month period after implementation of the automated intervention, 13% of all AED tests ordered were canceled following computerized reminders. For orders appearing redundant, the cancellation rate was 27%. For nonredundant orders, 4% were canceled when information on specific AED monitoring and pharmacokinetics was provided. The cancellation rate was sustained after 4 years. There has been a 19.5% decrease in total AED testing volume since implementation of this intervention, despite a 19.3% increase in overall chemistry test volume. Inappropriateness owing to repeated testing before pharmacologic steady state was reached decreased from 54% of all AED orders to 14.6%. A simple, automated, activity-based intervention targeting a specific test-ordering behavior effectively reduced inappropriate laboratory testing. The sustained benefit supports the idea that computerized interventions may durably affect physician behavior. Computerized delivery of such evidence-based boundary guidelines can help narrow the gap between evidence and practice.

Septic deep venous thrombosis in intravenous drug users.

OBJECTIVE: To review diagnostic and therapeutic experience in seven patients with septic deep vein thrombosis (DVT) after intravenous use of illicit drugs. METHODS: Retrospective review of medical records and prospective data collection in intravenous drug users (IVDU) who presented with a confirmed diagnosis of DVT and sepsis during a period of 18 months in a single institution. RESULTS: Of seven long-term IVDU (age 24-40 years), who had repeatedly attempted venous access to proximal veins, five had femoral DVT and one each jugular and brachial DVT. All DVT were confirmed by contrast-enhanced helical CT or ultrasonography. Median C-reactive protein (CRP) was 215 mg/l (range 76-386). Multiple blood cultures grew Gram-positive bacteria in 7 of 8 patients, chiefly Staphylococcus aureus, confirming an intravascular infection with continuous bacteraemia. Therapy consisted of intravenous b-lactamase-resistant penicillin until normalisation of CRP (3-4 weeks), initially combined with an aminoglycoside for a few days. The mean defervescence time was 7.4 days (range 3-12). All patients were given intravenous heparin overlapping with oral anticoagulation without major side effects. Surgical exploration of the venous vasculature was never necessary. Mean hospital stay was 25.7 days (range 10-47). CONCLUSION: Septic DVT in IVDU is a potentially life-threatening disorder that may become more frequent as the number of long-term IVDU increases. Helical CT or colour-coded Doppler ultrasound is the confirmatory imaging procedure of choice. Empirical antibiotic therapy should include a ss-lactamase-resistant penicillin since S. aureus is the most common pathogen isolated. Anticoagulation can be safely initiated once the diagnosis of DVT is confirmed. Surgery is necessary only in rare instances of septic DVT.