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  INSTITUTE FOR CLINICAL EVALUATIVE SCIENCES

SEPTEMBER 2013

 
At a Glance
  MONTHLY HIGHLIGHTS OF ICES RESEARCH FINDINGS FOR STAKEHOLDERS  
 

Metformin may lower risk of prostate cancer death in men with diabetes

Margel D, Urbach DR, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner N. Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes. J Clin Oncol. 2013;  31(25):3069–75.

ISSUE

Emerging evidence has linked metformin, a drug widely used to treat diabetes, to decreased cancer risk and improved cancer-related outcomes. Is increasing exposure to metformin after a diagnosis of prostate cancer associated with lower mortality in men with diabetes?

STUDY

Identified 3,837 Ontario men older than 66 years who were diagnosed with diabetes between March 1997 and March 2008 and subsequently developed prostate cancer. Determined the cumulative duration of their exposure to 4 antidiabetic medications (metformin, sulfonylurea, thiazolidnedione and insulin) from the date of diabetes diagnosis to death, a last health services contact or March 31, 2009, whichever came first, and measured prostate cancer-specific mortality and all-cause mortality.

KEY FINDINGS

Median age at diagnosis of prostate cancer was 75 years. Prostate cancer-specific mortality decreased by 24% for each additional 6 months of metformin use. The association with decreased all-cause mortality was also significant but declined over time, from 24% in the first 6 months to 7% between 24 and 30 months. Use of other antidiabetic medications did not significantly decrease prostate cancer-specific or all-cause mortality. 

IMPLICATIONS

While these findings are insufficient to institute metformin treatment in men with prostate cancer, they provide a compelling argument for conducting a large-scale, long-term randomized trial as a research priority.
 
 

Fertility therapy not linked to subsequent risk of cardiovascular disease in women

Udell JA, Lu H, Redelmeier DA. Long-term cardiovascular risk in women prescribed fertility therapy. J Am Coll Cardiol. 2013 Jul 19 [Epub ahead of print].

ISSUE

Fertility drugs are known to increase the risk of high blood pressure and gestational diabetes during pregnancy. Does fertility therapy contribute to the risk of cardiovascular disease in women following the birth of their children?

STUDY

Analyzed 1,186,753 million women aged 15 to 55 who gave birth in Ontario between July 1993 and March 2010, and identified those who did and did not receive fertility therapy in the two years prior to delivery. The women were followed until death or hospitalization for a major cardiovascular event (stroke, heart attack or heart failure) or March 31, 2011, whichever came first. 

KEY FINDINGS

During the study period, the proportion of pregnancies conceived after fertility therapy rose five-fold, from 1 in 400 to 1 in 80. After 9.7 years of median follow-up, the 6,979 women who delivered following fertility therapy had about half the risk of subsequent death or a major cardiovascular event than women not receiving the therapy. The decreased risk of long-term adverse events was consistent across age and socioeconomic groups.

IMPLICATIONS

Although there may be differences in other important characteristics of  women who received fertility treatment that may explain the findings, such as smoking or other lifestyle factors, the study provides some reassurance to women who had a live birth following fertility therapy. Outcomes among women whose fertility treatment was unsuccessful should be investigated. 
 
 

Flu carries higher risk for Guillain-Barré syndrome than flu shot

Kwong JC, Vasa PP, Campitelli MA, Hawken S, Wilson K, Rosella LC, Stukel TA, Crowcroft NS, McGeer AJ, Zinman L, Deeks SL. Risk of Guillain-Barré syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study. Lancet Infect Dis. 2013; 13(9):769–76.

ISSUE

Immunization is the best defence against seasonal influenza, but the risk of contracting Guillain-Barré syndrome (GBS), a rare paralytic illness which may result in long-term disability and death, is a concern for large-scale immunization programs. What is the risk of developing GBS after influenza vaccination compared to after influenza infection?

STUDY

Analyzed medical records of all Ontario residents eligible for Ontario Health Insurance Program (OHIP) coverage between April 1999 and March 2011. Linked hospitalizations for GBS to the OHIP database to assess admissions in the 42 weeks after exposure to influenza or the influenza vaccination.

KEY FINDINGS

Of 2,831 patients hospitalized for GBS, 330 had an influenza vaccine and 109 had an influenza infection within 42 weeks before admission. The risk of developing GBS within 6 weeks of a flu shot was 52% higher than the usual risk (or one additional case of GBS per one million flu shots). The chance of developing GBS within 6 weeks of an influenza illness was nearly 16 times higher than the usual risk (or one additional case per 60,000 cases of influenza illness requiring medical attention). 

IMPLICATIONS

Patients considering immunization should be fully informed of the risks of GBS from both influenza and the influenza vaccine, as well as the more substantial benefits of preventing morbidity and mortality with immunization. Further investigation is needed to determine whether influenza vaccination is associated with a net increase or decrease in GBS after accounting for the anticipated reductions in the risk of infection in vaccinated people and the possible indirect benefits of mass immunization (e.g., herd immunity).
 
 

Chinese and South Asians have 40% lower mortality risk after diabetes than Europeans

Shah BR, Victor JC, Chiu M, Tu JV, Anand SS, Austin PC, Manuel DG, Hux JE. Cardiovascular complications and mortality after diabetes diagnosis for South Asian and Chinese patients: a population-based cohort study. Diabetes Care. 2013; 36(9):2670–6.

ISSUE

The medical literature demonstrates considerable uncertainty about diabetes complication rates among minority populations. What is the risk of cardiovascular complications and mortality following diabetes diagnosis for South Asian and Chinese Canadians compared to those of European descent?

STUDY

Identified 491,243 Ontario adults aged 18 and older who were diagnosed with diabetes between April 2002 and March 2009 and followed them until March 2011 for the first occurrence of any cardiovascular complication of diabetes and for all-cause mortality. Assignment of ethnicity was based on surname. 

KEY FINDINGS

Cardiovascular complications developed after diabetes at a similar rate in European and South Asian patients (17.9 and 16.8 events per 1,000 person-years, respectively) but at a much lower rate among Chinese patients (8.1 events per 1,000 person-years). The risk of cardiovascular complications in Chinese men was similar to that of European men two decades younger, while Chinese women had a risk similar to European women one decade younger. Compared to European patients, the risk of mortality after diabetes diagnosis was 42% lower for South Asian patients and 44% lower for Chinese patients over a median of 4.7 years of follow-up.

IMPLICATIONS

Developing an understanding of the mechanisms that protect persons of South Asian and Chinese descent from death once diagnosed with diabetes may lead to new strategies to reduce the risk of diabetes complications and mortality in the general population. 
 
 

Cardiac patients given longer prescriptions at discharge more likely to continue medication

Ivers NM, Schwalm JD, Jackevicius CA, Guo H, Tu JV, Natarajan M. Length of initial prescription at hospital discharge and long-term medication adherence for elderly patients with coronary artery disease: a population-level study. Can J Cardiol. 2013 Jun 27 [Epub ahead of print].

ISSUE

Cardiac patients’ adherence to secondary prevention medications declines over time, a development that is associated with increased mortality. Is the length of the initial prescription at hospital discharge associated with long-term adherence? 

STUDY

Identified 18,101 patients aged 65 and older who had coronary angiography performed in Ontario between October 2008 and September 2009, and investigated their adherence to three common classes of cardiac medications: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE-I/ARB), beta-blockers and statins. Over an 18-month period, compared the adherence of those prescribed the medications for less than 31 days, 31 to 60 days, and more than 60 days.  

KEY FINDINGS

The majority of prescriptions at discharge covered less than 31 days. Of all initial prescriptions, 19.5% of ACE-I/ARBs, 11.0% of beta-blockers and 20.6% of statins were for more than 60 days. Patients with prescriptions for more than 60 days were 4 times more likely to adhere to the medication in the long term than those prescribed the medication for 30 days or less. More than 80% of patients had a follow-up appointment with a primary care provider within 30 days of the angiography, regardless of prescription length.  

IMPLICATIONS

Forcing elderly patients to frequently visit outpatient providers to renew prescriptions may exacerbate the problem of medication discontinuation. This study identifies an easily modifiable factor, longer prescription coverage, that is within the control of health care providers to improve adherence.  
 
 
ICES is an independent, non-profit organization that conducts research on a broad range of topical issues to enhance the effectiveness of health care for Ontarians.
 
 
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