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.
Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI).
Patients =30 years of age who were admitted with first-time MI during 1997 to 2006 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment was analyzed by multivariable time-stratified Cox proportional-hazard models and by incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID treatment was significantly associated with an increased risk of death/recurrent MI (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95% confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio, 3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment).
Even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.
Comment In: Circulation. 2011 Nov 22;124(21):e552; author reply e55522105203
Comment In: Circulation. 2011 Nov 22;124(21):e553; author reply e55522105204
Comment In: Evid Based Med. 2012 Apr;17(2):61-221937502
Comment In: Circulation. 2011 Nov 22;124(21):e554; author reply e55522105205
Comment In: Ann Intern Med. 2011 Oct 18;155(8):JC4-1122007070
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.
Cites: Dan Med Bull. 1997 Sep;44(4):445-89377907
Cites: Int J Cardiol. 2011 Nov 3;152(3):327-3120797803
The objective of this study was to examine the clinical efficacy of clopidogrel treatment on death and recurrent myocardial infarction (MI) among MI patients revascularized by coronary artery bypass graft surgery (CABG).
The benefit from post-operative clopidogrel in CABG-treated MI patients is largely unknown.
All patients admitted with first-time MI between 2002 and 2006, treated with CABG within 180 days after admission, were identified by nationwide administrative registers. Clopidogrel treatment was determined by claimed prescriptions after discharge from surgery. Risk of death or recurrent MI, and of a combined end point of the 2, were assessed by cumulative incidence and Cox proportional hazards model. A propensity score-matched subgroup analysis was done.
We included 3,545 patients, and of these, 957 (27.0%) were treated with clopidogrel after CABG. Mean follow-up was 466 ± 144 days. Among patients treated with clopidogrel, 39 (4.1%) died or experienced a recurrent MI, whereas that occurred in 203 (7.8%) patients without clopidogrel (log-rank p = 0.0003). Hazard ratio was 0.59 (95% confidence interval [CI]: 0.42 to 0.85) for patients treated with clopidogrel, with no-clopidogrel as reference. By propensity score, of 945 patients with or without clopidogrel treatment who were matched, death or recurrent MI occurred in 38 (4.0%) patients with clopidogrel and 57 (6.0%) without clopidogrel (log-rank p = 0.05). Corresponding hazard ratio was 0.67 (95% CI: 0.44 to 1.00) for clopidogrel users, with no-clopidogrel as reference.
Among MI patients revascularized by CABG, only 27% received clopidogrel after discharge. Clopidogrel-treated patients had a lower risk of the combined end point of death or recurrent MI. Focus on discharge clopidogrel treatment of these patients should be made.
Comment In: J Am Coll Cardiol. 2011 Aug 30;58(10):1085; author reply 1085-621867852
Comment In: J Am Coll Cardiol. 2011 Aug 30;58(10):1084-5; author reply 1085-621867851
The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI.
We identified patients aged 30 years or older admitted with first-time MI in 1997 to 2009 and subsequent NSAID use by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. We calculated the incidence rates of death and a composite end point of coronary death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion and analyzed risk by using multivariable adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36 747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5 years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any NSAID in the years following MI was persistently associated with an increased risk of death (hazard ratio 1.59 [95% confidence interval, 1.49-1.69]) after 1 year and hazard ratio 1.63 [95% confidence interval, 1.52-1.74] after 5 years) and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence interval,l 1.22-1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28-1.55]).
The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI.
Comment In: Ann Intern Med. 2013 Jun 18;158(12):903-623580081
Comment In: Ann Intern Med. 2013 Jan 15;158(2):JC1023318332
Undertreatment with evidence-based pharmacotherapy for heart failure (HF) is an important problem, and it has been suggested that specialized HF clinics (HFCs) can improve treatment initiation and correct dosing. The objective of this study was to examine long-term adherence to and dosages of evidence-based pharmacotherapy during and after participation in specialized HFCs.
Initiation, dosages, and adherence were studied in patients with systolic HF attending HFCs in Denmark from 2002 to 2009. Information was obtained from an electronic patient file and research database used in the HFCs combined with prescription data from the Danish Registry of Medicinal Product Statistics. A total of 8792 patients were included in the study. The mean age was 68 years; with a mean LVEF of 30%, and 72% were males. Long-term adherence to treatment was high for the patients who initiated renin-angiotensin system (RAS) inhibitors and beta-blockers. Adherence after 1 year was 93% for RAS inhibitors, 92% for beta-blockers, and 86% for spironolactone. After 3 years, it was 90% for RAS inhibitors, 88% for beta-blockers, and 74% for spironolactone. For patients referred back to their general practitioner (GP), adherence 1 year after they left the HFC was 89% for RAS inhibitors, 89% for beta-blockers, and 72% for spironolactone.
In specialized outpatient HFCs, long-term adherence to RAS inhibitors and beta-blockers is close to optimal. Importantly, adherence was maintained after patients were referred back to their GP for continued management. This is likely to provide long-term benefits for the patients.
Psoriasis is an inflammatory disease associated with increased risk of coronary artery disease. However, the potential impact of psoriasis on the prognosis following percutaneous coronary revascularization (PCI) is unknown.
The study comprised the entire Danish population undergoing first-time PCI in the period 2002-09. Cox regression models, controlling for age, gender, socioeconomic status, pharmacological treatment, and comorbidity were used to assess the risk of 1) all-cause mortality and 2) a composite endpoint of death, myocardial infarction, and stroke.
A total of 53,141 patients with first-time PCI in the study period were identified. Of these, 1074 had mild psoriasis and 315 had severe psoriasis. Patients with severe psoriasis, but not those with mild disease had increased risk of both endpoints compared to patients without psoriasis. The incidence rates for all-cause mortality were 30.5 (CI 29.7-31.3), 29.9 (CI 24.7-36.1), and 47.2 (CI 35.0-63.6) per 1000 patient years for patients without psoriasis, with mild psoriasis, and with severe psoriasis, respectively. Hazard ratios were 1.10 (CI 0.91-1.33) and 1.67 (CI 1.24-2.26) for mild and severe psoriasis, respectively. Patients with severe psoriasis were less likely to receive secondary prevention pharmacotherapy with betablockers, statins and platelet inhibitors.
This first study of the prognosis following PCI in patients with psoriasis demonstrated an increased risk of all-cause mortality and of a composite of death, myocardial infarction and stroke, respectively, in patients with severe psoriasis compared to patients without psoriasis. Further studies of this novel association are needed.
To examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction.
Retrospective nationwide propensity score matched study based on administrative data. Setting All hospitals in Denmark.
All aspirin treated patients surviving 30 days after a first myocardial infarction from 1997 to 2006, with follow-up for one year. Patients treated with clopidogrel were excluded.
The risk of the combined end point of cardiovascular death, myocardial infarction, or stroke associated with use of proton pump inhibitors was analysed using Kaplan-Meier analysis, Cox proportional hazard models, and propensity score matched Cox proportional hazard models. Results 3366 of 19,925 (16.9%) aspirin treated patients experienced recurrent myocardial infarction, stroke, or cardiovascular death. The hazard ratio for the combined end point in patients receiving proton pump inhibitors based on the time dependent Cox proportional hazard model was 1.46 (1.33 to 1.61; P
Psoriasis is a chronic inflammatory disease and inflammation contributes to the pathogenesis of atrial fibrillation (AF) and ischaemic stroke. We therefore investigated the risk of these endpoints in patients with psoriasis.
Cohort study of the entire Danish population followed from 1997 to 2006 by individual-level-linkage of nationwide prospectively recorded registers. Multivariable Poisson's regression and sensitivity analyses were used to assess the psoriasis-related risk of AF and ischaemic stroke. A total of 36 765 patients with mild psoriasis and 2793 with severe psoriasis were compared with 4 478 926 individuals, i.e., the reference population. In patients with mild psoriasis, the adjusted rate ratios (RRs) for AF were 1.50 (1.21-1.86) and 1.16 (1.08-1.24) in patients aged
Comment In: Eur Heart J. 2012 Aug;33(16):1989-9122108835
The Stroke burden is increasing in many populations where health institutions may experience more patients. We wanted to examine whether incidence rates and absolute number of hospitalized stroke patients remained stable in Denmark during a 13 years period where exposure to major stroke risk factors decreased, changes in stroke treatment was implemented, and the age of the population increased.
The Danish National Patient Register was used to identify all subjects 25 years of age or above admitted with a first time stroke in Denmark from 1997-2009. Incidence rates (IRs) and age-adjusted Poisson regression analyses were used to examine trends in age-, gender- and stroke subtype (ischaemic or unspecified).
During the 13-year observation period there were 53.5 million person-years at risk (PY) and a total of 84,626 male and 84,705 female stroke patients were admitted to Danish hospitals. The IRs of hospitalized strokes per 1000 PY was 3.21 (95% confidence interval [CI] 3.16-3.27) in 1997, 3.85 (95% CI 3.79-3.91) in 2003 and 3.22 (95% CI 3.16-3.28) in 2009, respectively.Incidence rate ratios of hospitalized stroke events adjusted for age in the period 2007-2009 compared to 1997-2000 were 0.89 (95% CI 0.87- 0.91) for men and 0.92 (95% CI 0.90-0.94) for women.The incidence of hospitalized unspecified strokes decreased from 1997 to 2009 whereas there was a steep rise in incidence for hospitalization with specified ischemic stroke during this period.
This study found a constant rate of stroke hospitalization in Denmark from 1997-2009. The overall rate of hospitalized strokes adjusted for age decreased during this period.
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