Venlafaxine is a commonly prescribed antidepressant, but whether its noradrenergic effects impart increased cardiovascular risk is unknown. We sought to examine the cardiac safety of venlafaxine relative to sertraline in older patients.
We conducted a population-based retrospective cohort study using administrative health care databases in Ontario, Canada. We included all patients aged 66 years or older who commenced treatment with either venlafaxine or sertraline between April 1, 2000, and March 31, 2009. We used inverse probability of treatment weighting with the propensity score to account for observed systematic differences in baseline characteristics between the 2 treatment groups. The primary outcome was a composite of death or hospitalization for acute myocardial infarction or congestive heart failure (as defined by codes from the International Classification of Diseases, Ninth and Tenth Revisions) within the first year of therapy. In secondary analyses, each outcome was examined separately.
We studied 48,876 patients initiated on venlafaxine and 41,238 patients initiated on sertraline. Of these, 3,966 (8.1%) and 3,707 (9.0%) experienced the primary outcome, respectively. We found no significant difference in the risk of adverse cardiac events with venlafaxine relative to sertraline (hazard ratio = 0.97; 95% CI, 0.93-1.02). Secondary analyses revealed no differences in the risk of death or acute myocardial infarction between the 2 drugs, but the risk of heart failure was unexpectedly lower among patients treated with venlafaxine (hazard ratio = 0.87; 95% CI, 0.80-0.95). We found consistent results after stratification according to preexisting cardiovascular disease.
As compared with sertraline, low to moderate dose venlafaxine is not associated with an increased risk of adverse cardiac events in older patients. The lower risk of heart failure among venlafaxine patients warrants further study.
Case reports suggest that some selective serotonin reuptake inhibitors can interact with warfarin to increase the likelihood of bleeding. We speculated that, among patients receiving warfarin, initiation of selective serotonin reuptake inhibitor treatment would be associated with an increased risk of hospitalization for upper gastrointestinal tract bleeding (UGIB).
We conducted a population-based, nested, case-control study involving Ontario residents 66 years or older continuously treated with warfarin for at least 1 year. Cases admitted with UGIB were compared with matched controls (1:10) to explore the odds ratio for initiation of various antidepressants within 42, 90, and 180 days before the index admission.
From January 1994 to December 2002, we identified 98,784 elderly patients continuously receiving warfarin for at least 1 year; of whom 1538 (0.6%) were admitted to hospital for UGIB. The adjusted odds ratio for fluoxetine/fluvoxamine exposure in 90 days before UGIB hospitalization is 1.2 (95% confidence interval, 0.8-1.7), and the adjusted odds ratio for other selective serotonin reuptake inhibitors in the same period was 1.1 (95% confidence interval, 0.9-1.4). The odds ratios for exposure to antidepressants in 180 days before UGIB hospitalization were similar.
The initiation of selective serotonin reuptake inhibitor treatment in patients receiving warfarin was not associated with a significant increase in the risk of hospitalization for UGIB.
Beta-blockers may be cardioprotective in patients receiving chronic dialysis. We examined cardiovascular outcomes among incident dialysis patients receiving beta-blocker therapy.
We conducted a retrospective cohort study employing linked healthcare databases in Ontario, Canada. We studied all consecutive chronic dialysis patients aged=66 years who initiated dialysis between 1 July 1991 and 31 July 2007. Patients were divided into three groups according to new medication use after the initiation of chronic dialysis. The three groups were patients initiated on beta-blockers, calcium channel blockers and statins only. Patients in the beta-blocker and calcium channel blocker groups could also be concurrently receiving a statin. The primary outcome was time to a composite endpoint of death, myocardial infarction, stroke or coronary revascularization.
There were a total of 1836 patients (504 beta-blocker, 570 calcium channel blocker and 762 statin-only users). Compared to statin-only use, beta-blocker use was not associated with improved cardiovascular outcomes [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.92-1.23]. As expected, calcium channel blocker use was also not associated with improved cardiovascular outcomes (aHR 0.91, 95% CI 0.79-1.06). Among all subgroup analyses by beta-blocker attributes, only high-dose beta-blocker therapy was associated with better cardiovascular outcomes as compared to low-dose beta-blockers (aHR 0.50, 95% CI 0.29-0.88).
We observed no beneficial effect of beta-blocker use among patients receiving chronic dialysis relative to our comparator groups. Given current uncertainty around the cardioprotective benefits of beta-blockers in patients receiving dialysis, a large randomized clinical trial is warranted.
Recent evidence suggests that, despite widespread use, self-monitoring of blood glucose levels has little clinical benefit in many patients with diabetes. The impact of more focused public-payer policies for the use of blood glucose test strips may be substantial.
We conducted a cross-sectional analysis of annual prescription claims for test strips between 1997 and 2008 for patients in Ontario aged 65 and older with diabetes. Patients were stratified into 1 of 4 hierarchical groups according to the most intensive glucose-lowering treatment received during each calendar year. Test strip use was calculated annually for each group over the study period, and the effects of 5 hypothetical policy scenarios of more selective test strip use were assessed.
Test strip use increased by almost 250% from 1997 to 2008, with 52.6% (n = 263,513) of included patients receiving a prescription during 2008. Almost half of these patients were at low risk for drug-induced hypoglycemia. In 2008, over 117 million test strips were dispensed in Ontario; however, more focused policy scenarios could have reduced this number by between 9.5 million and 74.5 million test strips.
Many people who self-monitor their blood glucose are at relatively low risk for drug-induced hypoglycemia. The economic benefits associated with more selective testing could be redirected to more effective interventions for patients with diabetes.
Cholinesterase inhibitors are commonly used to treat dementia. These drugs enhance the effects of acetylcholine, and reports suggest they may precipitate bradycardia in some patients. We aimed to examine the association between use of cholinesterase inhibitors and hospitalization for bradycardia.
We examined the health care records of more than 1.4 million older adults using a case-time-control design, allowing each individual to serve as his or her own control. Case patients were residents of Ontario, Canada, aged 67 y or older hospitalized for bradycardia between January 1, 2003 and March 31, 2008. Control patients (3:1) were not hospitalized for bradycardia, and were matched to the corresponding case on age, sex, and a disease risk index. All patients had received cholinesterase inhibitor therapy in the 9 mo preceding the index hospitalization. We identified 1,009 community-dwelling older persons hospitalized for bradycardia within 9 mo of using a cholinesterase inhibitor. Of these, 161 cases informed the matched analysis of discordant pairs. Of these, 17 (11%) required a pacemaker during hospitalization, and six (4%) died prior to discharge. After adjusting for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor (adjusted odds ratio [OR] 2.13, 95% confidence interval [CI] 1.29-3.51). The risk was similar among individuals with pre-existing cardiac disease (adjusted OR 2.25, 95% CI 1.18-4.28) and those receiving negative chronotropic drugs (adjusted OR 2.34, 95% CI 1.16-4.71). We found no such association when we replicated the analysis using proton pump inhibitors as a neutral exposure. Despite hospitalization for bradycardia, more than half of the patients (78 of 138 cases [57%]) who survived to discharge subsequently resumed cholinesterase inhibitor therapy.
Among older patients, initiation of cholinesterase inhibitor therapy was associated with a more than doubling of the risk of hospitalization for bradycardia. Resumption of therapy following discharge was common, suggesting that the cardiovascular toxicity of cholinesterase inhibitors is underappreciated by clinicians.
Cites: CMAJ. 2000 May 16;162(10):1421-410834045
Cites: Drug Saf. 2007;30(11):1063-7117973542
Cites: Annu Rev Public Health. 2000;21:193-22110884952
Cites: Arch Intern Med. 2001 Jun 11;161(11):1405-1011386889
Cites: Pharmacoepidemiol Drug Saf. 2001 May;10(3):259-6211501340
Cites: JAMA. 2007 Dec 12;298(22):2634-4318073359
Cites: Epidemiology. 2008 Jan;19(1):30-718091000
Cites: Ann Intern Med. 2008 Mar 4;148(5):370-818316755
Cites: Ann Intern Med. 2008 Mar 4;148(5):379-9718316756
Cites: Neurology. 2008 May 27;70(22):2024-3518322263
Cites: Stat Methods Med Res. 2009 Feb;18(1):67-8018562398
Cites: Arch Intern Med. 2009 May 11;169(9):867-7319433698
Ciprofloxacin can inhibit the cytochrome P450-mediated metabolism of theophylline, but the clinical relevance of this drug interaction is uncertain. We studied the risk of theophylline toxicity associated with the co-prescription of ciprofloxacin and theophylline.
This was a population-based, nested case-control study of a cohort of Ontario residents aged 66 years of age or older treated with theophylline between April 1, 1992 and March 31, 2009. Within this group, case patients were those hospitalized with theophylline toxicity. For each case, 50 age- and sex-matched control patients were identified from the same cohort. The odds ratio (OR) for the association between hospitalization for theophylline toxicity and receipt of ciprofloxacin in the 14 days preceding hospitalization was determined.
Among the 77,251 elderly patients receiving therapy with theophylline, 180 eligible case patients hospitalized for theophylline toxicity and 9000 matched controls were identified. Following multivariable adjustment, a nearly twofold increase in the risk of theophylline toxicity following the receipt of ciprofloxacin was observed [adjusted OR 1.86, 95% confidence interval (CI) 1.18-2.93]. In contrast, there was no increased risk of theophylline toxicity within a group of patients receiving neutral comparator antibiotics (levofloxacin, trimethoprim-sulfamethoxazole or cefuroxime) (adjusted OR 0.78; 95% CI 0.38-1.62).
Treatment with ciprofloxacin is associated with a significant increase in the risk of theophylline toxicity. When clinically appropriate, alternate antibiotics should be considered for elderly patients receiving theophylline.
To characterize the demographic and clinical profiles of older persons with diabetes treated with a thiazolidinedione (TZD) in comparison to other groups of patients, including all patients with diabetes and those taking other oral hypoglycemic agents (OHAs).
We studied Ontario residents aged 66 and older and alive on 31 March 2008. Five groups were created based on diabetes status and history of treatment with OHAs, including patients prescribed rosiglitazone, patients prescribed pioglitazone, and a sample of three other groups: patients prescribed any other OHA in the preceding year, all patients with diabetes, and elderly Ontarians regardless of diabetes status. We excluded patients receiving insulin or multiple TZDs from the three OHA groups. Study groups were compared based on demographic information, measures of comorbidity, history of cardiovascular diseases, and concomitant use of drugs for cardiovascular disease.
People treated with pioglitazone (n = 16 206) were highly similar to those treated with rosiglitazone (n = 16 066). Individuals treated with either TZD tended to be younger, less likely to reside in a long-term care facility, and had similar cardiovascular profiles to samples of patients with diabetes (n = 50 000) and those taking other OHAs (n = 50 000).
Older patients started on TZDs have cardiovascular risk profiles comparable to other individuals with diabetes, including those taking other OHAs, suggesting that observational studies of TZD safety are not likely confounded by selection bias.
To examine whether variation in prescribing at the level of the individual physician is associated with opioid-related mortality.
A population-based cross-sectional analysis linking prescription data with records from the Office of the Chief Coroner.
The province of Ontario. Participants Family physicians in Ontario and Ontarians aged 15 to 64 who were eligible for prescription drug coverage under the Ontario Public Drug Program.
Variation in family physicians' opioid prescribing and opioid-related mortality among their patients.
The 20% of family physicians (n = 1978) who prescribed opioids most frequently issued opioid prescriptions 55 times more often than the 20% who prescribed opioids least frequently. Family physicians in the uppermost quintile also wrote the final opioid prescription before death for 62.7% of public drug plan beneficiaries whose deaths were related to opioids. Physician characteristics associated with greater opioid prescribing were male sex (P = .003), older age (P
Cites: Ann Intern Med. 2010 Jan 19;152(2):85-9220083827
Cites: CMAJ. 2009 Dec 8;181(12):891-619969578
Cites: J Pain. 2010 Sep;11(9):807-2920430701
Cites: Open Med. 2011;5(1):e13-2222046214
Cites: CMAJ. 2010 Jun 15;182(9):923-3020439443
Cites: Am J Prev Med. 2006 Dec;31(6):506-1117169712
Cites: JAMA. 1990 Jan 26;263(4):549-562104640
Cites: N Engl J Med. 2003 Nov 13;349(20):1943-5314614170
To compare persistence of oxybutynin or tolterodine therapy among older patients newly prescribed one of these drugs.
We conducted a retrospective cohort study of Ontarians aged 66 years and older who were newly prescribed either drug between January 1, 2000 and December 31, 2007. Persistence with treatment was defined on the basis of refills for the drug within a grace period equal to 50% of the prescription duration.
We identified 31,996 patients newly treated with oxybutynin and 24,855 newly treated with tolterodine. After 2 years of follow-up, persistence on oxybutynin (9.4%) was significantly lower than that on tolterodine (13.6%, p?