Primecuts – This Week In The Journals

March 26, 2012

By Vincent M. Santillo, MD

Faculty Peer Reviewed

The Wonder Drug that Works Wonders!

On March 21st, readers of the New York Times woke up to the headline “Studies Link Daily Doses of Aspirin to Reduced Risk of Cancer.”[1] The author Roni Rabin stated that daily aspirin “may significantly reduce the risk of many cancers and prevent tumors from spreading.”[1] Exciting news for those looking for some way to avoid a dreaded diagnosis, as well as those with cancer looking to prevent metastasis. The author relied on two recent Lancet articles by lead author Peter Rothwell, who is on the executive committee of the ARRIVE trial (sponsored by Bayer), that look at the impact of aspirin on first cardiac events.

The first article is a subgroup meta-analysis of 51 randomized controlled trials of daily aspirin therapy for the prevention of vascular events.[2] The authors analyzed the data for deaths due to cancer, vascular and nonvascular death, and all-cause mortality. Building on data that have shown an association between aspirin and reduced long-term incidence of colon cancer, the authors found that in trials of aspirin for the primary prevention of cardiac events, 91% of the deaths prevented were from reduction in nonvascular deaths. In 6 trials covering 35,535 participants, daily aspirin therapy was found to reduce cancer incidence from 3 years on with an odds ratio (OR) of 0.76 (p=0.0003). In the first 3 years of therapy the reduced risk of major vascular events was offset by an increased risk of major bleeding, but after 3 years there was an absolute reduction in incidence of cancer, and cancer deaths were shown to decline after 5 years of therapy (OR 0.63, p=0.004). The meta-analysis was underpowered in terms of establishing aspirin’s effects on specific cancer types. Of note, in these studies warfarin was not shown to have the same anticancer effects as aspirin.

The second Lancet article looked at the effect of aspirin on cancer metastasis. The authors performed a subgroup meta-analysis of 5 randomized trials with a total of 17,285 participants that studied daily aspirin for the prevention of vascular events.[3] The mean in-trial follow-up was 6.5 years. The authors found that aspirin therapy reduced the risk of cancer with distant metastasis for all cancers (hazard ratio [HR] 0.64, p=0.001) and specifically adenocarcinoma (HR 0.54, p=0.0007). Aspirin therapy reduced the risk of adenocarcinoma with metastasis at initial diagnosis (HR 0.69, p=0.02) and the risk of metastasis on subsequent follow-up in patients with local disease at time of diagnosis (HR 0.45, p=0.0009). The effect was most pronounced in patients with colorectal cancer (HR 0.26, p=0.0008). Aspirin reduced the risk of fatal adenocarcinoma (HR 0.65, p=0.0002) but not the risk of other fatal cancers.

While aspirin therapy has bleeding risks, the data on the anti-inflammatory benefits of long-term therapy continue to accumulate. At a minimum, physicians should ensure that those patients who should be on aspirin therapy for cardiovascular benefit understand that a benefit may also accrue vis-à-vis cancer. It remains to the individual provider and patient to determine if therapy for cancer prevention alone makes sense.

The Lancet this week also published an article on the management of localized prostate cancer, a particularly controversial topic. Fleshner and colleagues performed a 3-year, randomized, double-blind, placebo-controlled study of 302 participants at 65 US academic centers that looked at the safety and efficacy of the 5-alpha-reductase inhibitor dutasteride (Avodart; GlaxoSmithKline, Philadelphia, PA), on prostate cancer progression in men with low-risk disease.[4] The study included men aged 48-82 with low-volume, Gleason score 5-6 prostate cancer who had chosen active surveillance for managing their disease. Participants were given once-daily dutasteride 0.5 mg or placebo. The patients were followed with biopsies performed at 18 months and 3 years after initiating therapy. In this study population, the dutasteride group showed a reduced incidence of prostate cancer progression: 38% of treatment arm versus 48% of placebo arm patients (HR 0.62, p=0.009). A larger number of men experienced (non-statistically significant) breast disorders and problems with sexual function, known side effects of this medication class. These results come after the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study and the Prostate Cancer Prevention Trial (PCPT) raised questions about high-grade tumors seen in men treated with 5-alpha-reductase inhibitors. Dutasteride seems to reduce low-grade cancer but does not reduce the risk of high-grade cancer.

Another Times article entitled “Hospitals Aren’t Hotels”[5] questioned whether patient satisfaction is the best way to rate a hospital when painful, uncomfortable procedures may be necessary for the patient’s long-term recovery. As patient empowerment increases, some physicians may feel pressure to avoid upsetting their difficult patients even when medically necessary. A recent article in the Archives of Internal Medicine showed that increasing patient satisfaction may lead to increased health care expenditures and increased mortality.[6] Researchers found that respondents with the highest patient satisfaction had lower odds of emergency department visits (OR 0.92), higher odds of admission (OR 1.12), 8.8% greater total expenditures, 9.1% greater prescription expenditures, and higher mortality (HR 1.26). All of which demonstrates that “The customer is always right” may be a great slogan for a fast-food restaurant chain but is a terrible one for medicine that leads to increased usage of resources along with an increase in mortality.

Dr. Vincent M. Santillo is a 2nd year resident  at NYU Langone Medical Center

Peer reviewed by Michael Tanner, MD, FACP, executive editor, Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1. Rabin RC. Studies link daily doses of aspirin to reduced risk of cancer. The New York Times. March 21, 2012:A10. http://www.nytimes.com/2012/03/21/health/research/studies-link-aspirin-daily-use-to-reduced-cancer-risk.html

2. Rothwell PM, Price JF, Fowkes GR, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course and risks and benefits in 51 randomised controlled trials. Lancet. 2012; March 21. [Epub ahead of print]  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61720-0/fulltext

3. Rothwell PM, Wilson M, Price JF, Belch JFF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012; March 21. [Epub ahead of print] http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60209-8/fulltext

4. Fleshner NE, Lucia MS, Egerdie B, et al. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012;379:1103-1111.

5. Brown T. Hospitals aren’t hotels. The New York Times. March 15, 2012:A35.  http://www.nytimes.com/2012/03/15/opinion/hospitals-must-first-hurt-to-heal.html

6. Fenton JJ. The cost of satisfaction: a national study of patient satisfaction, health care utilization, expenditures, and mortality. Arch Intern Med. 2012;172:405-411. http://134.147.247.42/han/JAMA/pubs.ama-assn.org/cgi/search?sortspec=date&andorexactfulltext=phrase&fulltext=chronic%20disease&hits=10&journalcode=all

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