Clinical Briefs

By Louis Kuritzky, MD

Exemestane after Tamoxifen Therapy in Breast Cancer

Tamoxifen (TAM) is well established to reduce, over 5 years, both risk of breast cancer (BCA) recurrence (47%) and mortality (26%) among women who have undergone surgery for BCA and who have estrogen-receptor positive tumors. Exemestane (EXE) is classified as an irreversible steroidal inactivator, and works by blocking the enzyme (aromatase) which is responsible for converting androgens to estrogens, ultimately inhibiting aromatization by about 98%. Although TAM is of remarkable positive benefit, it is not without risks, including increased likelihood of endometrial cancer attributed to endometrial stimulation. EXE is not known to induce endometrial proliferation, or increase proclivity for endometrial cancer.

The Intergroup Exemestane Study (IES) investigated whether substituting EXE for TAM after 2-3 years would provide better outcomes than simply treating with TAM continuously for 5 years. Study subjects were postmenopausal women (n = 4742) who remained free of recurrence during sustained TAM treatment. EXE (25 mg p.o. q.d.) was substituted for TAM in one half of the subjects.

After a median followup of 30.6 months, the risk of recurrence, contralateral BCA, or death was reduced by 32% in the EXE group compared with TAM. The adverse effects seen more frequently with EXE than TAM included diarrhea and arthralgia, but thromboembolisms was almost twice as common in the TAM group.

Coombes and colleagues suggest that switching women from TAM to EXE at the 2-3 year point in treatment may provide more favorable outcomes.

Coombes RC, et al. N Engl J Med. 2004;350(11):1081-1092.

An Analysis of How Long Patients Remain on Various BP Therapies

The term "drug efficacy" is technically intended to reflect impact of an agent on a designated end point in a study population participating in a clinical trial. "Drug effectiveness," on the other hand, refers to the "real life" effects drug treatment produces as seen separately from a clinical trial; ie, what impact might be seen when typical patients’ use a medication in, for instance, the community setting.

As many as half of patients who begin antihypertensive drug therapy (HTN-Rx) discontinue treatment within a few months of initiation. Study subjects from the area in and around Ravenna, Italy comprised this hypertensive patient population (n = 14,062). All were first-time recipients of a new HTN-Rx. "Persistent patients" were defined as either maintaining, combining with, or switching from their initial HTN-Rx to another HTN-Rx, for a duration of > 273 days from the day of enrollment.

Discouragingly, 48% of patients discontinued treatment after a single prescription! Medication choices were similar to those commonly used in the United States (ACE/ARB/HCTZ/CCB/Beta Blocker). Angiotensin receptor blockers demonstrated the highest continuation rate, followed by ACE inhibitors, CCBs, and diuretics.

Cost of treatment decreased as age increased, and increased for persons who switched or combined agents. Angiotensin receptor blockers were the most expensive single agents. Overall, specific individual drug cost and pattern of drug persistence correlated best with total cost of hypertension treatment. These data suggest that although drug cost is important, aspects of the drug treatment which affect persistence patterns ultimately have a substantial effect on overall cost.

Esposti LD, et al. J Clin Hypertens. 2004;6:76-84.

Endothelial Dysfunction with Insulin Resistance and CWT in Hypertension

Endothelial dysfunction (END) is a fundamental defect in essential hypertension (HTN) and is closely associated with carotid wall thickening (CWT), a consistent marker for early atherosclerotic change. Insulin resistance (IR) is also associated with both HTN and CWT, suggesting a potential relationship between IR and END.

HTN subjects (n = 41) were studied if they met inclusion criteria including HTN, no diabetes, no suggestion of secondary HTN, no major cardiovascular, renal, hepatic, or other endocrine disease, no smoking, and no medications which modulate carbohydrate or lipid metabolism (eg, statin, steroids) for at least 12 months. All subjects underwent measurement of endothelial function, carotid interomedial thickness by ultrasound, and insulin sensitivity as defined by insulin/glucose infusion.

END was found to be associated both with IR and CWT. The changes in CWT and END were strongly associated, suggesting a close correlation between functional (END) and structural (CWT) atherosclerotic changes. The confirmed association between END, CWT, and IR may prompt consideration of investigation to seek causality between, eg, IR and CWT.

Suzuki M, et al. Am J Hypertens. 2004;17:228-232.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.