Reader Reaction and Timely Answers From Experts (June 2005)

High LDL and HDL: Implications in a Perimenopausal Woman I would like to offer a few comments on the reply by Dr Michael Prisant to a reader’s question about whether statin therapy is appropriate for a 52-year-old woman with a high low-density lipoprotein (LDL) cholesterol level and a high high-density lipoprotein (HDL) cholesterol level (CONSULTANT, April 1, 2005). My comments are based on a poster presentation I made on atherothrombotic risk factors in women at a recent American Heart Association conference.1 LDL cholesterol rises dramatically in the perimenopausal period. Indeed, this patient’s LDL has risen despite a low-fat diet—and, as in many women her age, it can be expected to rise even further. A high HDL can compensate for an elevated LDL, but only up to a point. In our regional laboratory, a break point of 170 mg/dL is used. As LDL increases above 170 mg/dL, the HDL is progressively less able to compensate for the LDL elevation; in fact, once LDL levels reach 250 mg/dL, the HDL level is unable to compensate at all. In addition, the average LDL cholesterol value associated with atherothrombotic events in women is 152 mg/dL (in men, it is 145 mg/dL). However, if the range of LDL values seen in women is divided into sextiles (the highest being 200 mg/dL or more and the lowest, 99 mg/dL or less), the sextile associated with the most atherothrombotic events in women is 125 to 149 mg/dL. Because the patient’s LDL cholesterol most likely began to rise in the perimenopausal period, she probably does not have any clinical atherothrombotic disease at present. However, because women’s coronary arteries are smaller than men’s, her arteries will “clog up” more quickly than would those of a man with a similar history. Thus, I would advise treatment with a statin. Cyclic-sequential hormone replacement therapy could also lower her lipid levels, although the dosage of conjugated equine estrogen might need to be 1.25 mg/d (days 1 to 25) and the medroxyprogesterone dosage might need to be 10 mg/d (days 13 to 25). However, I would never recommend a continuous combined hormone regimen; such therapy has failed miserably to protect women’s hearts in clinical trials. — William E. Feeman, Jr, MD Bowling Green, Ohio REFERENCE: 1. Feeman WE Jr. Atherothrombotic risk factors in women. Presented at: American Heart Association Second International Conference on Heart Attacks and Strokes in Women; February 2005; Orlando, Fla. ___________________________________________________________________________________________________ Balancing Clot Prevention and Bleeding Risk in TIA Therapy I prescribed clopidogrel, 75 mg/d, for an 81-year-old man who had had a suspected transient ischemic attack (TIA); he was already taking aspirin (81 mg/d). Shortly after clopidogrel therapy was started, the patient began to bruise easily. Should I reduce the dosage of clopidogrel by having him cut the tablets in half or by initiating every-other-day dosing? — R. E. Nordling, MD Hendersonville, NC The situation you describe is typical and illustrates the difficulties in balancing the benefits of anticoagulant and antiplatelet therapies with their adverse effects. The most recent American College of Chest Physicians (ACCP) symposium on therapy for ischemic stroke offers helpful treatment paradigms for patients who have had either a noncardioembolic stroke or TIA.1  An antiplatelet agent is strongly recommended (grade 1 evidence) as initial therapy. Possible regimens include: • Aspirin, 50 to 325 mg/d. • A combination of aspirin and extended-release dipyridamole, 25 mg/200 mg bid. • Clopidogrel, 75 mg/d. Slightly less strong (grade 2) evidence supports the superiority of both the aspirin/extended- release dipyridamole combination (25 mg/200 mg bid) and clopidogrel (75 mg/d) to aspirin alone. However, in patients who are at moderate to high risk for bleeding, use low-dosage aspirin (50 to 100 mg/d). This patient’s initial regimen (aspirin, 81 mg/d) was appropriate. When a TIA occurs after aspirin has been initiated, one can infer from the ACCP recommendations that the next therapy to try is either the combination of aspirin and dipyridamole, 25 mg/200 mg bid, or clopidogrel, 75 mg/d. Clopidogrel alone, for example, is about 10% more effective than aspirin in reducing the risk of ischemic stroke, TIA, and vascular death.2 One can also infer from the ACCP recommendations that one of these alternative regimens should be tried alone before adding it to aspirin—to provide increased efficacy with less risk of bleeding. Clopidogrel in combination with aspirin probably confers still greater efficacy; such regimens are being used with increasing frequency in patients with coronary artery disease (eg, after stent placement).3  However, the increase in efficacy is accompanied by an increased risk of bleeding, as shown by your patient’s experience. Thus, I would suggest changing the patient’s regimen to aspirin/dipyridamole combination therapy or clopidogrel alone and monitoring him to determine whether this prevents TIA recurrence. If it does not, then a trial of clopidogrel, 75 mg/d, plus aspirin, 100 mg/d, is not unreasonable but can be expected to result in an increased risk of hemorrhage. No data have been published on the safety or efficacy of half doses or alternate-day dosing of clopidogrel. — Ronald N. Rubin, MD Professor of Medicine Temple University Medical School Chief of Clinical Hematology, Department of Medicine Temple University Hospital Philadelphia REFERENCES: 1. Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(suppl 3):483S-512S. 2. CAPRIE Steering Committee. A randomized, blinded trial of clopidogrel versus aspirin in patients at risk of ischemic events. Lancet. 1996;348:1329-1339. 3. Popma JJ, Berger P, Ohman EM, et al. Antithrombotic therapy during percutaneous coronary intervention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(suppl 3):576S-599S. __________________________________________________________________________________________________________ Pneumonia Risk in Patients With Achalasia In their Photoclinic case of a man with achalasia (CONSULTANT,  February 2005), Drs Sonia Arunabh and Manjula Thopcherla did not mention the extensive abnormalities evident in the left lung on both radiograph and CT (Figure). Did the patient also have aspiration pneumonia? — Dan Fairman, MD Sun Valley, Idaho Yes, the patient did have aspiration pneumonia, which was successfully treated with antibiotics. Poor esophageal motility and subsequent aspiration make patients with achalasia prone to aspiration pneumonia. — Sonia Arunabh, MD Forest Hills, NY