Mortality associated with cardiovascular drugs in patients with chronic obstructive pulmonary disease and right-sided heart failure - A danish nationwide registry-based study.

BACKGROUND: The optimal medical treatment in patients with chronic obstructive pulmonary disease (COPD) and right-sided heart failure (RHF) is unknown. We aimed to estimate the risks of all-cause mortality associated with the current clinical use of various cardiovascular drugs in this patient-group. METHODS: We followed all patients with registered COPD and RHF (defined as a diagnosis of pulmonary hypertension plus use of loop-diuretics) for the risk of all-cause mortality (Jan 1, 1995 to Dec 31, 2015) using the Danish nationwide administrative registries. The association between mortality and claimed prescriptions for cardiovascular drugs was assessed by multivariable Cox regression models. RESULTS: 5991 patients (mean age 74 ±â€¯standard deviation 10 years, 51% women) were included. Of these, 1440 (24%) used beta-blockers, 2149 (36%) renin-angiotensin system inhibitors [RASi], 1340 (22%) oral anticoagulants, 1376 (23%) calcium channel blockers, 1194 (20%) statins, 1824 (30%) spironolactone, and 2099 (35%) low-dose aspirin. During an average follow-up of 2.2 years (±standard deviation 2.8, min-max 0-19.6 years), 5071 (85%) died, corresponding to a mortality rate of 38 per 100 person-years (95% confidence interval 37-39). Compared to no use, beta-blockers were associated with adjusted hazards ratio 0.90 (95% confidence interval 0.84-0.98), RASi 0.92 (0.86-0.98), calcium channel blockers 0.86 (0.80-0.92), spironolactone 1.17 (1.10-1.24), statins 0.85 (0.78-0.92), oral anticoagulants 0.87 (0.79-0.95), and aspirin 0.99 (0.93-1.05). Propensity-score matched analyses and inverse-probability-weighted models yielded similar results. CONCLUSION: Several cardiovascular drugs may be associated with lowered mortality in COPD and RHF. Given the grave prognosis, randomized clinical trials are warranted to test this hypothesis.

Trends in warfarin use and its associations with thromboembolic and bleeding rates in a population with atrial fibrillation between 1996 and 2011.

AIM: Warfarin is a cornerstone for the prevention of thromboembolism in atrial fibrillation (AF), and several efforts have been taken to increase its usage and safety, including risk stratification schemes. Our aim was to investigate the temporal trends in initiation of warfarin and its effects on incidence of bleeding and thromboembolism in patients with new-onset atrial fibrillation 1996-2011. METHODS: All patients with a first-time diagnosis of non-valvular atrial fibrillation were identified from nationwide administrative registries. Trends were determined by linear regression. RESULTS: In total 153,682 patients were included. Initiation of warfarin increased from 14% to 41% (p<0.0001). Events of thromboembolism decreased from 3.9% to 2.6% annually (p<0.0001). The greatest decline in thromboembolic events was observed for patients with a CHA2DS2VASc score >1, where the annual decline was -0.12% (95%CI: -0.161; -0.084)) for those treated with warfarin and -0.073% (95%CI: -0.116;-0.030)) for those not treated with warfarin. Bleeding increased from 3.3% to 3.9% (p = 0.043). For those with a CHA2DS2VASc score >1 annual bleeding rates increased by 0.095% (95%CI: -0.025; -0.165) in warfarin treated and by 0.056% (95%CI: -0.013; -0.100) in patients not treated with warfarin. CONCLUSION: Warfarin use increased by nearly a 3-fold between 1996 and 2011. During the same period, thromboembolic events declined by a third and bleeding increased by a fifth, suggesting a beneficial effect associated with higher warfarin use. Notably, a small decline in thromboembolic events and increase in bleeding events was observed for the untreated population, suggesting a changing risk profile of AF patients.

Influence of age on perioperative major adverse cardiovascular events and mortality risks in elective non-cardiac surgery.

BACKGROUND AND AIMS: Advanced age increases the risk of perioperative cardiovascular complications and may pose reluctance to subject elderly patients to surgery. We examined the impact of high age on perioperative major adverse cardiovascular events (MACE) and mortality in a nationwide cohort of patients undergoing elective surgery. METHODS: All Danish patients aged ≥20years undergoing non-cardiac, elective surgery in 2005-2011 were identified from nationwide administrative registers. Risks of 30-day MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, or cardiovascular death) and all-cause mortality were analyzed by multivariable logistic regression models (adjusted for comorbidities, revised cardiac risk index, cardiovascular pharmacotherapy, body mass index, and surgery type). RESULTS: A total of 386,818 procedures on 302,459 patients were included; mean age was 54.8years (min-max 20-104), and 44% were men. A total of 1297 (0.34%) had perioperative MACE and 1449 (0.37%) died. Advanced age was associated with increased risks of MACE (odds ratio [OR], 1.87; 95% CI, 1.78-1.98 per 10-year high) and mortality (OR, 1.87; 95% CI, 1.78-1.96 per 10-year high). A total of 21,511 procedures were performed on patients >80-90years old, and 1662 on patients >90years. The numbers of MACE and crude mortality rates were 331 (1.7%) and 388 (2.0%) among >80-90years old, and 50 (3.0%) and 67 (4.0%) for those aged >90years. CONCLUSION: The risk of mortality and major adverse cardiovascular events within 30days after surgery increased with advanced age. However, despite advanced age, the absolute event rates appeared to be relatively modest and around 4% for people aged above 90years.

Identifying Drug-Drug Interactions by Data Mining: A Pilot Study of Warfarin-Associated Drug Interactions.

BACKGROUND: Knowledge about drug-drug interactions commonly arises from preclinical trials, from adverse drug reports, or based on knowledge of mechanisms of action. Our aim was to investigate whether drug-drug interactions were discoverable without prior hypotheses using data mining. We focused on warfarin-drug interactions as the prototype. METHODS AND RESULTS: We analyzed altered prothrombin time (measured as international normalized ratio [INR]) after initiation of a novel prescription in previously INR-stable warfarin-treated patients with nonvalvular atrial fibrillation. Data sets were retrieved from clinical work. Random forest (a machine-learning method) was set up to predict altered INR levels after novel prescriptions. The most important drug groups from the analysis were further investigated using logistic regression in a new data set. Two hundred and twenty drug groups were analyzed in 61 190 novel prescriptions. We rediscovered 2 drug groups having known interactions (ß-lactamase-resistant penicillins [dicloxacillin] and carboxamide derivatives) and 3 antithrombotic/anticoagulant agents (platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors [dabigatran etexilate], and heparins) causing decreasing INR. Six drug groups with known interactions were rediscovered causing increasing INR (antiarrhythmics class III [amiodarone], other opioids [tramadol], glucocorticoids, triazole derivatives, and combinations of penicillins, including ß-lactamase inhibitors) and two had a known interaction in a closely related drug group (oripavine derivatives [buprenorphine] and natural opium alkaloids). Antipropulsives had an unknown signal of increasing INR. CONCLUSIONS: We were able to identify known warfarin-drug interactions without a prior hypothesis using clinical registries. Additionally, we discovered a few potentially novel interactions. This opens up for the use of data mining to discover unknown drug-drug interactions in cardiovascular medicine.

Noncardiac surgery in patients with aortic stenosis: a contemporary study on outcomes in a matched sample from the Danish health care system.

BACKGROUND: Past research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30-day major adverse cardiovascular event (MACE) and all-cause mortality were investigated in a contemporary Danish cohort. HYPOTHESIS: AS is not an independent risk factor for adverse outcomes in noncardiac surgery. METHODS: All patients with and without diagnosed AS who underwent noncardiac surgery in 2005 to 2011 were identified through nationwide administrative registers. AS patients (n = 2823; mean age, 75.5 years, 53% female) were matched with patients without AS (n = 2823) on propensity score for AS and surgery type. RESULTS: In elective surgery, MACE (ie, nonfatal myocardial infarction, ischemic stroke, or cardiovascular death) occurred in 66/1772 (3.7%) of patients with AS and 52/1772 (2.9%) of controls (P = 0.19), whereas mortality occurred in 67/1772 (3.8%) AS patients and 51/1772 (2.9%) controls (P = 0.13). In emergency surgery, 163/1051 (15.5%) AS patients and 120/1051 (11.4%) controls had a MACE (P = 0.006), whereas 225/1051 (21.4%) vs 179/1051 (17.0%) AS patients and controls died, respectively (P = 0.01). Event rates were higher for those with symptoms (defined as use of nitrates, congestive heart failure, or use of loop diuretics), compared with those without symptoms (P < 0.0001). CONCLUSIONS: AS is associated with high perioperative rates of MACE and mortality, but perhaps prognosis is, in practice, not much worse for patients with AS than for matched controls. Symptomatic patients and patients undergoing emergency surgery are at considerable risks of a MACE and mortality.