The use of antidepressants and the risk of chronic atrial fibrillation.

Serotonin stimulation of the 5HT4 receptor might be responsible for an increased risk of atrial fibrillation (AF). Thus, we assessed whether the use of antidepressants (ADs) is associated with an increased risk of chronic AF (cAF). Using the UK Clinical Practice Research Datalink, a nested case-control analysis was conducted within a cohort of new AD users having a diagnosis of depression and/or anxiety. Cases of cAF occurring during follow-up were individually matched with up to 10 controls on age, sex, year of cohort entry, and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) of cAF associated with current and recent use of ADs, when compared to past use. The cohort included 116,125 new AD users, of whom 1,271 were diagnosed with cAF during follow-up (incidence rate: 1.6 per 1,000 person-years). The adjusted RR of cAF associated with current and recent use of ADs was 0.98 (95%CI: 0.86-1.12) and 1.02 (95%CI: 0.86-1.30), respectively. No association was observed when ADs were classified according to their potency in reducing serotonin reuptake. These findings suggest that exposure to ADs is not associated with an increased risk of cAF.

The use of antidepressants and the risk of idiopathic pulmonary arterial hypertension.

BACKGROUND: Serotonin has been implicated in the development of idiopathic pulmonary arterial hypertension (IPAH). Drugs modulating serotonin pathways, including antidepressants, have been associated with the incidence of IPAH, with conflicting reports as to the direction of the effect. We aimed to determine whether antidepressant exposure is associated with the incidence of IPAH. METHODS: A nested case-control study was conducted using the United Kingdom Clinical Practice Research Datalink and the Hospital Episodes Statistics repository between January 1, 1988 and September 30, 2011. Incident cases of IPAH were identified and matched to all controls in the case's risk set on age, sex, general practice, and date of registration with the practice. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated for the use of antidepressants on the risk of IPAH, with an 18-month lag period before the diagnosis. RESULTS: One hundred ninety-five IPAH cases were identified (incidence 3.84/million per year). Use of any antidepressant was associated with a 67% increased risk of IPAH (RR, 1.67; 95% CI, 1.17-2.37). The rate of IPAH was similar across antidepressant classes, whether with selective serotonin reuptake inhibitors (SSRIs) (RR, 1.67; 95% CI, 1.09-2.57) or non-SSRI antidepressants (RR, 1.66; 95% CI, 1.07-2.59). In sensitivity and exploratory analyses, no change in risk was observed with different lag times, serotonin transporter affinities, or durations of exposure. CONCLUSIONS: The use of antidepressants was associated with a significantly increased risk of IPAH. However, the consistency of this risk across all antidepressants and absence of a dose-response relationship suggests a noncausal association.

Antihypertensive agents acting on the renin-angiotensin system and the risk of sepsis.

AIMS: In response to safety concerns from two large randomized controlled trials, we investigated whether the use of telmisartan, an angiotensin receptor blocker (ARB), ARBs as a class and angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of sepsis, sepsis-associated mortality and renal failure in hypertensive patients. METHODS: We performed a nested case-control study from a retrospective cohort of adults with hypertension from the UK General Practice Research Database diagnosed between 1 January 2000 and 30 June 2009. All subjects hospitalized with sepsis during follow-up were matched for age, sex, practice and duration of follow-up with 10 control subjects. Exposure was defined as current use of antihypertensive drugs. RESULTS: From the cohort of 550 436 hypertensive patients, 1965 were hospitalized with sepsis during follow-up (rate 6.9 per 10 000 per year), of whom 824 died and 346 developed acute renal failure within 30 days. Compared with use of ß-blockers, calcium-channel blockers or diuretics, use of ARBs, including telmisartan, was not associated with an elevated risk of sepsis (relative risk 1.09; 95% confidence interval 0.83-1.43); but use ACEIs was (relative risk 1.65; 95% confidence interval 1.42-1.93). Users of ARBs, ß-blockers, calcium-channel blockers or diuretics, but not users of ACEIs, had lower rates of hospitalization for sepsis compared with untreated hypertensive patients. Findings were similar for sepsis-related 30 day mortality and renal failure. CONCLUSIONS: Hypertensive patients treated with ARBs, including telmisartan, do not appear to be at increased risk of sepsis or sepsis-related 30 day mortality or renal failure. On the contrary, users of ACEIs may have an increased risk.

Fluoroquinolones and the risk of serious arrhythmia: a population-based study.

BACKGROUND: Fluoroquinolones have been suspected to cause cardiac arrhythmia but data are lacking, particularly for the individual fluoroquinolones. We assessed the risk of serious arrhythmia, defined as ventricular arrhythmia or sudden/unattended death identified in hospital discharge diagnoses, related to fluoroquinolones as a class as well as for each individual molecule. METHODS: We used a cohort of patients treated for respiratory conditions from 1 January 1990 to 31 December 2005, identified using the healthcare databases from the province of Quebec (Canada), with follow-up until 31 March 2007. A nested case-control analysis was performed within this cohort, with all cases of serious arrhythmia occurring during follow-up identified from hospitalization records. These cases were matched with up to 20 controls. Conditional logistic regression was used to compute adjusted rate ratios (RRs) of serious arrhythmia associated with fluoroquinolone use. RESULTS: Within the cohort of 605127 subjects, 1838 cases were identified (incidence rate=4.7/10000 person-years). The rate of serious arrhythmia was elevated with current fluoroquinolone use (RR=1.76; 95% confidence interval [CI], 1.19-2.59), in particular with new current use (RR=2.23; 95% CI, 1.31-3.80). Gatifloxacin use was associated with the highest rate (RR=7.38; 95% CI, 2.30-23.70); moxifloxacin and ciprofloxacin were also associated with elevated rates of serious arrhythmia (RR=3.30; 95% CI, 1.47-7.37 and RR=2.15; 95% CI, 1.34-3.46, respectively). CONCLUSIONS: The use fluoroquinolones is associated with an elevated risk of serious arrhythmia, with some differences among molecules. Given that the individual fluoroquinolones share various indications, the relative risks of serious arrhythmia could inform the choice of different molecules in high-risk patients.

Elevated basic fibroblast growth factor levels in patients with pulmonary arterial hypertension.

STUDY OBJECTIVES: Cellular growth in the vascular wall, including endothelial and smooth-muscle cell proliferation, is recognized as a component of the obstructive vasculopathy observed in the small vessels of the lungs in pulmonary arterial hypertension (PAH). We hypothesized that angiogenic growth factors may have a role in the molecular mechanisms underlying this cellular proliferation. DESIGN: Case-control study. SETTING: Multicenter, tertiary care hospitals. PARTICIPANTS: We studied 117 patients with PAH and 60 control subjects. MEASUREMENTS: We measured levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in the blood and urine of these subjects using an enzyme-linked immunoassay. RESULTS: Median levels of urinary and plasma bFGF were significantly higher in patients with PAH compared to normal control subjects. There was a difference in levels of urine and plasma bFGF according to etiology of pulmonary hypertension, with the highest levels seen in patients with primary pulmonary hypertension. Levels of urine or plasma VEGF were not significantly different between patients and control subjects. CONCLUSION: Patients with PAH have substantial alterations in urine and plasma levels of bFGF. This molecule may have a role as a mitogenic factor in the endothelial and smooth-muscle cell proliferation seen in PAH.