The purpose of this study was to determine the risk of adverse cardiovascular events associated with concomitant use of clopidogrel and calcium-channel blockers (CCBs) in patients with myocardial infarction (MI).
CCBs inhibit a variety of cytochrome P-450 enzymes, some of which contribute to clopidogrel metabolic activation. This interaction may diminish the efficacy of clopidogrel.
All patients surviving 30 days after a first-time MI in the period 2000 to 2006 in Denmark were identified by individual-level linkage of nationwide administrative registers. The cohort was divided into patients treated with and without clopidogrel and followed for 1 year after discharge. The risk of a composite of cardiovascular death, MI, or stroke and the risk of the individual components of the composite end point and all-cause death associated with CCBs were analyzed with multivariable Cox proportional hazard models and in univariate propensity score-matched models.
A total of 56,800 patients were included, of whom 24,923 were treated with clopidogrel and 13,380 with CCBs. In the Cox analyses, the risk of the composite end point associated with CCBs was increased in both patients treated and not treated with clopidogrel, with a hazard ratio of 1.15 (95% confidence interval [CI]: 1.07 to 1.24) and 1.05 (95% CI: 1.01 to 1.11), respectively. The increased risk was independent of clopidogrel use; the hazard rate ratio was 1.08 (95% CI: 0.99 to 1.18). Analyses of all additional adverse end points and propensity score-matched models provided similar results.
The clinical efficacy of clopidogrel in patients with a recent MI is not modified by concomitant CCB treatment. This potential drug interaction is unlikely to have clinical significance.
The benefit of extending clopidogrel treatment beyond the 12-month period recommended in current guidelines after myocardial infarction (MI) is debated. We analysed the risk of adverse cardiovascular outcomes after discontinuation of 12 months of clopidogrel treatment.
This Danish retrospective nationwide study included all patients treated with clopidogrel after discharge from a first-time MI during 2004-09. The risk of death or recurrent MI after the discontinuation of clopidogrel was studied by multivariable Poisson regression models. Patients treated with and without percutaneous coronary intervention (PCI) were analysed separately. The follow-up was 18 months. Of the 29,268 patients included, 3214 (11.0%) experienced death or recurrent MI. There were 9819 (33.6%) patients treated only medically and 19,449 (66.4%) patients treated with PCI. Twelve months after the index MI, for patients treated only medically, the risk of death or recurrent MI in the first 90-day period of clopidogrel discontinuation was 1.07 (0.65-1.76; P= 0.79) [adjusted incidence rate ratio (IRR) and 95% confidence interval] compared with the next 90-day period of discontinuation. For patients treated with PCI, the corresponding IRR was 1.59 (1.11-2.30; P= 0.013). The risk of recurrent MI yielded an IRR of 0.77 (0.36-1.67; P= 0.51) for patients treated only medically and 1.87 (1.11-3.15; P= 0.019) for PCI-treated patients.
Discontinuation of clopidogrel 12 months after MI is associated with an increased risk of death or recurrent MI in the first 90 days of discontinuation compared with the next 90-day period of discontinuation for patients treated with PCI, but not for patients not treated with PCI.
Interventional cardiology in Denmark has been carried out since the mid 1980s. Interventional cardiology is only performed at a few high-volume centres. Healthcare coverage is universal and is essentially free of charge. Hospitals are mostly publicly owned and financed by fixed budgets and, in part, an activity-based funding system. Approximately 30,000 coronary angiographies (CAG), 10,000 percutaneous coronary interventions (PCIs) of which approximately 25% are primary PCIs, and 500 transcatheter aortic valve implantations (TAVIs) are carried out each year. The numbers of CAG and PCI have reached a plateau in recent years, whereas structural heart interventions, in particular TAVI, are increasing. Around 90% of all patients treated with PCI have a stent implanted, with more than 95% of these being drug-eluting stents. There is a low but increasing use of bioabsorbable scaffolds and drug-eluting balloons.
To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue.
Nationwide register based cohort study.
All hospitals in Denmark.
All 3322 women aged 40 years or over who survived 30 days after a myocardial infarction and were prescribed hormone replacement therapy at the time of myocardial infarction in the period 1997 to 2008.
Reinfarction, cardiovascular mortality, and all cause mortality 30 to 360 days after discharge.:
A total of 282 (8.5%) women had a reinfarction, 218 (6.6%) died of cardiovascular causes, and 357 (10.7%) died of any cause during follow-up. Women who discontinued overall hormone replacement therapy in the first year after myocardial infarction did not have a significantly different risk of reinfarction (hazard ratio 0.90, 95% confidence interval 0.68 to 1.19), cardiovascular mortality (1.21, 0.90 to 1.62), or all cause mortality (1.22, 0.97 to 1.53) than women who continued use. However, discontinuation of vaginal oestrogen was associated with a lower risk of reinfarction (hazard ratio 0.54, 0.34 to 0.86).
No certain conclusions can be drawn regarding increased or decreased risk of adverse cardiovascular events with continuing hormone replacement therapy after myocardial infarction. The results rule out neither a modest benefit nor a worrisome increase in risk. These figures may be valuable when a possible cardiovascular risk of hormone replacement therapy needs to be balanced with menopausal symptoms for the individual patient.
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Chronic inflammatory diseases have been linked to increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is unclear. We therefore examined the risk of myocardial infarction (MI), stroke, and cardiovascular death in patients with IBD.
In a nationwide Danish population-based setting, a cohort of patients with incident IBD between 1996 and 2009 were identified in national registers. Hospitalizations with IBD as primary diagnosis, initiation of biological treatment and dispensed prescriptions of corticosteroids were all used as surrogate markers for disease activity, with flares classified as the first 120 days after diagnosis of IBD, and 120 days after a new corticosteroid prescription, biological treatment or IBD hospitalization, respectively. Continued corticosteroid prescriptions or IBD hospitalizations were defined as persistent activity, and periods free of such events were defined as remissions. Poisson regression was used to examine risk of MI, stroke, and cardiovascular death using a matched population-based comparison cohort as reference.
We identified 20,795 IBD patients with a mean age of 40.3 years that were matched according to age and sex with 199,978 controls. During the study period, there were 365 patients with MI, 454 with stroke, and 778 with cardiovascular death. Patients with IBD had an overall increased risk of MI (rate ratio [RR] 1.17 [95% confidence interval 1.05-1.31]), stroke (RR 1.15 [1.04-1.27], and cardiovascular death (RR 1.35 [1.25-1.45]). During flares and persistent IBD activity the RRs of MI increased to 1.49 (1.16-1.93) and 2.05 (1.58-2.65), the RRs of stroke to 1.53 (1.22-1.92) and 1.55 (1.18-2.04) and for cardiovascular death 2.32 (2.01-2.68) and 2.50 (2.14-2.92). In remission periods, the risk of MI, stroke and cardiovascular death was similar to controls.
Inflammatory bowel disease is associated with increased risk of MI, stroke, and cardiovascular death during periods with active disease.
Cites: Am J Gastroenterol. 2009 Jun;104(6):1445-5119491858
Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention--a retrospective nationwide cohort study.
The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention.
All patients aged 30 years or older receiving glucose-lowering drugs (GLDs) and admitted with myocardial infarction (MI) not treated with emergent percutaneous coronary intervention in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations and drug dispensing from pharmacies. Multivariable Cox regression models adjusted for age, sex, calendar year, comorbidity, and concomitant pharmacotherapy were used to assess differences in the composite endpoint of non-fatal MI and cardiovascular mortality between individual GLDs, using metformin monotherapy as reference.
The study comprised 9876 users of GLDs admitted with MI. The mean age was 72.3 years and 56.5% of patients were men. A total of 3649 received sulfonylureas and 711 received metformin at admission. The average length of follow-up was 2.2 (SD 2.6) years. A total of 6,171 patients experienced the composite study endpoint. The sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide were associated with increased risk of cardiovascular mortality and/or nonfatal MI with hazard ratios [HRs] of 1.31 (95% confidence interval [CI] 1.17-1.46), 1.19 (1.06-1.32), 1.25 (1.11-1.42), and 1.18 (1.03-1.34), respectively, compared with metformin. Gliclazide was the only sulfonylurea not associated with increased risk compared with metformin (HR 1.03 [0.88-1.22]).
In patients with diabetes mellitus admitted with MI not treated with emergent percutaneous coronary intervention, monotherapy treatment with the sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide was associated with increased cardiovascular risk compared with metformin monotherapy.
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Our aim was to assess the association between use of hormone replacement therapy (HRT) and risk of new-onset atrial fibrillation (AF) after myocardial infarction.
We used Danish nationwide registers of hospitalizations and prescriptions to identify all women admitted with myocardial infarction in the period 1997 to 2009 and with no known diagnosis of AF. Their use of overall HRT and HRT categories was assessed. Multivariable Cox proportional hazards analysis was used to calculate the risk of new-onset AF first year after discharge, comparing use of HRT to no use.
New-onset atrial fibrillation.
In the period 1997 to 2009, 32 925 women were discharged alive after MI. In the first year after MI, new-onset AF was diagnosed in 1381 women (4.2%). Unadjusted incidence rates of AF decreased with use of HRT (incidence rate 37.4 for use of overall HRT and 53.7 for no use). Overall HRT was associated with a decreased risk of AF (HR 0.82, 95% confidence interval [CI] 0.68-1.00). The lowest risk of AF was found in women =80 years old for use of overall HRT and vaginal estrogen (HR 0.63, CI 0.42-0.94, and HR 0.58, CI 0.34-0.99, respectively). Decreased risk of AF with use of overall HRT and HRT categories was also found in other age groups.
Use of HRT is associated with a decreased risk of new-onset AF in women with myocardial infarction first year after discharge. The underlying mechanisms remain to be determined. Unmeasured confounding might be one of them.
Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular disease including atherosclerosis. The pathogenesis of aortic valve stenosis (AS) also includes an inflammatory component. We therefore investigated the risk of AS in patients with psoriasis compared with the general population in a nationwide cohort.
The study comprised the entire Danish population aged =18 years followed from 1 January 1997 until diagnosis of AS, 31 December 2011, or death. Information on comorbidity, concomitant medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Incidence rates for AS were calculated and incidence rate ratios (IRRs) adjusted for age, gender, calendar year, comorbidity, medications, and socioeconomic status, were estimated in Poisson regression models.
A total of 5 107 624 subjects were eligible for analysis. During the study period, we identified 58 747 patients with mild psoriasis and 11 918 patients with severe psoriasis. The overall incidence rates for AS were 8.09, 16.07, and 20.08 per 10 000 person-years for the reference population (48 539 cases [mean follow-up 12.3 years]), mild psoriasis (509 cases [mean follow-up 6.2 years]), and severe psoriasis (99 cases [mean follow-up 5.4 years]), respectively. Correspondingly, the fully adjusted IRRs for AS were markedly increased in patients with psoriasis with IRR 1.22 (95% confidence interval [CI] 1.12-1.33) and IRR 1.61 (CI 1.32-1.96) for subjects with mild and severe disease, respectively.
In a nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of AS. The mechanisms underlying this novel finding require further study.
Inflammation is considered to play a role in the development of atrial fibrillation (AF). Hence inflammatory bowel disease (IBD) may be associated with AF. We therefore examined the incidence of AF and stroke in patients with IBD.
From Danish nationwide registries 1996-2011, we identified 24 499 patients with new-onset IBD and 236 275 age- and sex-matched controls. Poisson regression analyses with continuously updated covariates were used to estimate incidence rate ratios (IRRs) of AF and stroke. Disease activity stages of flare (new disease activity), persistent activity, and remission were defined by corticosteroid prescriptions, IBD hospital admissions, and biological treatment. Inflammatory bowel disease patients had a mean age of 43.9 years, 53.9% were women, and mean follow-up was 6.8 years. Among IBD patients, 685 had AF and 549 had a stroke, corresponding to incidence rates per 1000 person-years of 4.16 vs. 2.70 for AF and 3.33 vs. 2.44 for stroke, compared with matched controls. Overall IBD-associated risk of AF corresponded to IRR 1.26 (1.16-1.36), but was driven by increased AF incidence during IBD flares [IRR 2.63 (2.26-3.06)] and persistent activity [IRR 2.06 (1.67-2.55)], whereas no increased AF risk was observed in remission periods [IRR 0.97 (0.88-1.08)]. Likewise increased stroke risk was exclusively found during active IBD [IRRs: 1.57 (1.27-1.93), 1.71 (1.32-2.21), and 1.04 (0.93-1.15) for flares, persistent activity, and remission, respectively].
Active IBD is associated with increased risk of AF and stroke. These findings may be relevant to clinical practice.
From the Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark (S.L.K., O.A., J.L., M.L., U.K., G.H.G., P.R.H.); Department of Cardiology, Copenhagen University Hospital Roskilde, Roskilde, Denmark (O.A.); Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark (R.E.); Department of Gastroenterology, Copenhagen University Hospital Herlev, Herlev, Denmark (O.H.N.); Department of Health, Science, and Technology, Aalborg University, Aalborg, Denmark (C.T.-P.); and National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark (G.H.G.). email@example.com.
Inflammatory bowel disease (IBD) has been linked to adverse cardiovascular events, but a relation to heart failure (HF) is uncertain. We investigated the IBD-associated risk of HF in a nationwide setting.
A total of 5 436 647 Danish citizens, with no history of IBD or HF, were included on January 1, 1997, and followed up until first hospitalization for HF, death, or December 31, 2011. Of these subjects, 23 681 developed IBD for which disease activity was determined continuously throughout the study. The risk of hospitalization for HF was estimated with a Poisson regression model adjusting for comorbidity and cardiovascular pharmacotherapy as time-dependent covariates. During a mean follow-up of 11.8 years in the reference population and 6.4 years in the IBD group, hospitalization for HF occurred in 553 subjects with IBD and 171 405 in the reference population. Patients with IBD had a 37% increased risk of hospitalization for HF (incidence rate ratio, 1.37; 95% confidence interval, 1.26-1.49) compared with the reference population. IBD activity-specific analyses showed markedly increased risk of HF hospitalization during flares (incidence rate ratio, 2.54; 95% confidence interval, 2.13-3.04) and persistent activity (incidence rate ratio, 2.73; 95% confidence interval, 2.25-3.33) but not in IBD remission (incidence rate ratio, 1.04; 95% confidence interval, 0.94-1.16).
In a nationwide cohort, IBD was associated with an increased risk of hospitalization for HF, and this risk was strongly correlated to periods of active disease. The mechanisms underlying this finding warrant further studies.