PREOPERATIVE PSA VELOCITY AND THE RISK OF DEATH FROM PROSTATE CANCER AFTER RADICAL PROSTATECTOMY

Investigators sought to determine if men who are at risk for death from prostate cancer after radical prostatectomy can be identified using information available at diagnosis. They studied 1095 men with localized prostate cancer to assess whether the rate of rise in the prostate-specific antigen (PSA) level—the PSA velocity—during the year before diagnosis, the PSA level at diagnosis, the Gleason score, and the clinical tumor stage could predict the time to death from prostate cancer and death from any cause after radical prostatectomy. Compared to an annual PSA velocity of < 2.0 ng/mL, an annual PSA velocity of > 2.0 ng/mL was associated with a significantly shorter time to death from prostate cancer and death from any cause. An increasing PSA level at diagnosis, a Gleason score of 8, 9, or 10, and a clinical tumor stage of T2 also predicted the time to death from prostate cancer. It was found that for men with an annual PSA velocity of > 2.0 ng/mL, estimates of the risk of death from prostate cancer and death from any cause 7 years after radical prostatectomy were also influenced by the PSA level, tumor stage, and Gleason score at diagnosis. Researchers concluded that men with a PSA level that increased by > 2.0 ng/mL during the year before diagnosis may have a relatively high risk of death from prostate cancer despite undergoing radical prostatectomy.

D’Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med 2004;351(2):125-135.

LIPID-LOWERING THERAPY WITH STATINS IN HIGH-RISK ELDERLY PATIENTS

There is adequate evidence of the benefits of cardiovascular therapies such as statins for secondary prevention, although they may not be optimal in those patients most likely to benefit from them. If physicians are aware of their patients’ risk profiles, one can assume that patients at highest baseline cardiovascular risk should be treated most aggressively, but that is often not the case with many cardiovascular therapies. In fact, patients with multiple chronic conditions are less likely to receive evidence-based therapies than healthier patients with lower illness severity. The authors performed a retrospective cohort study to determine the association between physicians’ treatment aggressiveness and baseline cardiovascular risk. The study incorporated multiple linked health care administrative databases covering more than 1.4 million elderly residents of Ontario, Canada. About 396,000 patients were included, aged 66 years or older with a history of cardiovascular disease or diabetes while undergoing medical treatment, and who were alive on April 1, 1998. Baseline cardiovascular risk was obtained from a risk-adjustment index, in which probability of death after 3 years of follow-up was determined. After adjusting for age, sex, socioeconomic status, and rural or urban residence, the likelihood of statin use, stratified by baseline cardiovascular risk, was measured. It was found that only 75,617 patients (19.1%) in the secondary prevention cohort were prescribed statins. In patients aged 66-74, the adjusted probabilities of statin prescription were 37.7%, 26.7%, and 23.4% for low, intermediate, and high baseline risk, respectively. The likelihood of statin use was 6.4% lower for each year of increase in age and each 1% increase in predicted 3-year mortality risk. The influence of age also interacted synergistically with baseline risk on the prescription of statins. The authors determined that statin prescription progressively decreased as baseline cardiovascular risk and future probability of death increased. Because the benefits of a therapy are dependent on the baseline risk, the maximum benefits of statins may not be fully recognized until therapy is implemented that includes patients at highest risk.

Ko DT, Mamdani M, Alter DA. Lipid-lowering therapy with statins in high-risk elderly patients: The treatment-risk paradox. JAMA 2004;291(15):1864-1870.

USE OF ASPIRIN AND IBUPROFEN COMPARED WITH ASPIRIN ALONE AND THE RISK OF MYOCARDIAL INFARCTION

The therapeutic use of aspirin has consistently increased during the past decade after several large studies were published showing its benefits for the primary and secondary prevention of myocardial infarction. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, has also become common. The importance of aspirin and the prevalence of NSAID use have led to laboratory investigations on the effects of concurrent use of aspirin and ibuprofen. Studies suggest that simultaneous use may attenuate the antiplatelet effect of aspirin, making it less useful for cardioprotection. This article investigates whether there is clinical evidence of this potentially harmful interaction. A retrospective matched case-control study was conducted, examining all patients who were issued outpatient prescriptions for aspirin or ibuprofen from January 1, 1990, to December 31, 2000, at the Durham Veterans Affairs Medical Center pharmacy in Durham, NC. Patients who used aspirin and ibuprofen concurrently were matched against those who used aspirin only by race, sex, age within 10 years, and cholesterol levels (either low-density lipoprotein or total cholesterol) to within 30 mg/dL. Researchers determined the rate ratio of experiencing a myocardial infarction per patient-month of drug exposure. Some 3859 patients received both aspirin and ibuprofen, for a total of 52,139 patient-months of medication use. This group experienced 138 myocardial infarctions. The 10,239 patients who received aspirin only (for a total of 156,417 patient-months of use) experienced 684 infarctions. The rate ratio of having an infarction was 0.61 (95% CI, 0.50-0.73; P < 0.001), favoring the group that took aspirin and ibuprofen simultaneously. An analysis of patients with diabetes showed a rate ratio of 0.48 (95% CI, 0.34-0.66; P < 0.001). Patients who spent time in both groups at different times were also examined, and a rate ratio of infarction during combined use was 0.70 (95% CI, 0.59-0.83; P < 0.001). It was determined that there does not seem to be an increased risk of myocardial infarction among patients who are administered simultaneous aspirin and ibuprofen, as compared with aspirin alone.

Patel TN, Goldberg KC. Use of aspirin and ibuprofen compared with aspirin alone and the risk of myocardial infarction. Arch Intern Med 2004;164(8):852-856.

EVALUATION OF PRIMARY CARE PATIENTS WITH CHRONIC STABLE ANGINA: GUIDELINES FROM THE AMERICAN COLLEGE OF PHYSICIANS

The American College of Physicians (ACP) (formerly the American College of Physicians– American Society of Internal Medicine) and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina in 1999. An updated guideline was then published in 2002, which the ACP recognized as a scientifically valid review of the evidence and background paper. This 2004 updated ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations that will most likely be important to physicians seeing patients in the primary care setting. This guideline is the first of two that will provide guidance on the management of patients with chronic stable angina. It discusses diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. The article also addresses asymptomatic patients, defined as patients with known or suspected coronary disease based on history or on electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. The guidelines target all clinicians who manage patients with chronic stable angina, as well as a patient population without known coronary disease whose symptoms suggest chronic stable angina and asymptomatic patients with evidence of coronary disease on previous testing. A future guideline will cover pharmacologic therapy and follow-up.

Snow V, Barry P, Fihn SD, Gibbons RJ, Owens DK, Williams SV, Weiss KB, Mottur-Pilson C; ACP/ACC Chronic Stable Angina Panel. Evaluation of primary care patients with chronic stable angina: Guidelines from the American College of Physicians. Ann Intern Med 2004; 141:57-64.

EFFECT OF VITAMIN D ON FALLS

Falls have been reported to occur annually in 30% of individuals aged 65 or older and in 40-50% of those aged 80 or older. The risk of falls increases with age and can lead to substantial morbidity and mortality. The moderate protective effect of vitamin D on fracture risk has previously been attributed primarily to bone mineral density changes. It appears that vitamin D may also directly improve muscle strength, thus reducing fracture risk through fall prevention. Despite trial results that show reduced fractures with the use of vitamin D, its role in preventing falls among elderly people has not been well-established. Therefore, the authors’ goal was to assess the effectiveness of vitamin D in preventing an older person from falling. They conducted literature searches from MEDLINE and the Cochrane Controlled Trials Register from January 1960 to February 2004, EMBASE from January 1991 to February 2004, clinical experts, bibliographies, and abstracts. They included only double-blind, randomized, controlled trials of vitamin D in elderly populations (mean age, 60 years) that examined falls resulting from low trauma, for which the method of fall ascertainment and the definition of falls were clearly defined. Studies that included patients in unstable health states were excluded from the data selection. Five of 38 identified studies were included in the primary analysis and five other studies were included in a sensitivity analysis. Data were extracted independently by three authors using predefined data fields including study quality indicators. Based on five randomized, controlled trials involving 1237 participants, vitamin D was found to reduce the corrected odds ratio of falling by 22%, as compared with patients receiving calcium or placebo. From the pooled risk difference, 15 patients would need to be treated with vitamin D to prevent one person from falling. Five additional studies were included, involving 10,001 participants in a sensitivity analysis, which resulted in a smaller but still significant effect size. Subgroup analyses suggested that the effect size was independent of calcium supplementation, type of vitamin D, duration of therapy, and sex, but reduced sample sizes made the results statistically nonsignificant for calcium supplementation, cholecalciferol, and among men. The authors concluded that vitamin D supplementation appears to reduce the risk of falls among ambulatory or institutionalized older individuals with stable health by more than 20%. Further studies should be considered that examine the effect of alternative types of vitamin D and their doses, the role of calcium supplementation, and the effects in men.

Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB. Effect of vitamin D on falls: A meta-analysis. JAMA 2004;291 (16):1999-2006.