Temporal trend of first-line drug choice and treatment continuity for hypertension among citizens 75 years or over - a register-based, cohort study.

BACKGROUND: Limited knowledge of antihypertensive treatment of the elderly potentially impedes effective strategies for hypertension management in this growing patient group. We aimed to investigate temporal trends for first-line drug choice for antihypertensive treatment and treatment continuity among patients ≥75 years from 2000 to 2021. METHODS: Using nationwide Danish registers, patients ≥75 years initiated for the first time on antihypertensive drugs: Angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), thiazides, or combinations, were identified. Patients with other indications than hypertension were excluded. Treatment continuity was described using claimed prescriptions the first 180 days following study entry. RESULTS: From 2000 to 2021, 170,769 patients (median age 80 years [interquartile range:77-84], 60.3% female) were included. From 2000 to 2003 to 2015-2021 the proportion of first-line drug choice increased for ACEi (8.7% to 14.9%), ARB (4.1% to 23.9%), and CCB (10.7% to 27.6%), decreased for thiazides (60.6% to 15.9%) and remained stable for BB (12.9% to 14.1%) and combinations (2.9% to 3.6%). For 157,457 patients alive after 180 days, discontinuation was highest among patients initiated on thiazides (28.3%) whereas most patients continued the same single drug regimen if they started on ACEi (55.2%), ARB (65.0%), BB (57.2%) or CCB (59.3%). CONCLUSIONS: From 2000 to 2021 thiazides have been replaced by ACEi, ARB and CCB. Thiazides had the lowest treatment continuity while ARB appeared preferred slightly over ACEi. Differences in adherence in relation to first-line drug choice may warrant scrutiny regarding recommendations for the elderly.

Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

BACKGROUND: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety. OBJECTIVES: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes. METHODS: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above. RESULTS: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%]). CONCLUSIONS: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.

Impact of breast-, gastrointestinal-, and lung cancer on prognosis in patients with first-time pulmonary embolism: A Danish nationwide cohort study.

BACKGROUND: Pulmonary embolism (PE) is described as a prognostic factor in patients with cancer however, the prognostic impact of PE remains unknown. This study investigated, the 1-year prognosis following PE in patients with breast-, gastrointestinal-, or lung cancer stratified by cancer status. METHODS: All Danish patients with first-time PE from 2008 to 2018 were included. Cancer status was categorized as no cancer, history of cancer, non-active cancer and active cancer. Unadjusted and age-stratified 1-year risk of death was estimated using the Kaplan-Meier estimator. Cause of death was reported using the Aalen-Johansen method. RESULTS: Of 35,679 patients with PE, 18% had a breast-, gastrointestinal-, or lung cancer. Patients with cancer were older compared with no cancer (69.8 years [IQR: 56.2-79.8]). One-year risk of death (95% confidence interval) for active breast-, gastrointestinal-, and lung cancer was 49.5% (44.0%-54.9%), 75.0% (72.5%-77.4%) and 80.1% (78.0%-82.3%) respectively, compared with 18.9% (18.4%-19.3%) for no cancer. Age-stratified analysis revealed no association with increasing age in non-active lung cancer and all active cancers. Further, non-cardiovascular death accounted for an increasing proportion by cancer status (no cancer < history of cancer < non-active cancer < active cancer). CONCLUSIONS: One-year risk of death was dependent on both cancer type and status; no association with age was found for patients with active cancers. Non-cardiovascular death was leading in non-active and active cancers. Thus, the occurrence of first-time PE could be regarded as a marker of cancer severity for patients with breast-, gastrointestinal-, and lung cancer.

Trends in percutaneous left atrial appendage occlusion and 1-year mortality 2013-2021: A nationwide observational study.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) is increasingly used for stroke prevention in patients with atrial fibrillation and anticoagulant-related complications. Yet, real-life studies evaluating changes in patient characteristics and indications for LAAO remain scarce. METHODS: To evaluate changes in patient characteristics and indications for LAAO defined as 2-year history of intracerebral bleeding, any ischemic stroke/systemic embolism (SE), any non-intracerebral bleeding, other indication, and 1-year mortality. All patients undergoing percutaneous LAAO in Denmark from 2013 to 2021 were stratified into the following year groups: 2013-2015, 2016-2018, and 2019-2021. RESULTS: In total, 1465 patients underwent LAAO. Age remained stable (2013-2015: 74 years versus 2019-2021: 75 years). Patients' comorbidity burden declined, exemplified by CHA2DS2-VASc ≥4 and HAS-BLED ≥3 decreased from 56.7% and 63.7% in 2013-2015 to 40.3% and 45.8% in 2019-2021. Indications for LAAO changed over time with other indication comprising 44.7% in 2019-2021; up from 26.9% in 2013-2015. Conversely, fewer patients had an indication of any ischemic stroke/SE (2013-2015: 30.8% vs 2019-2021: 20.3%) or any non-intracerebral bleeding (2013-2015: 29.4% vs 2019-2021: 23.4%). 1-year mortality was 11.3% for any non-intracerebral bleeding and 6.2% for other indication. CONCLUSION: The LAAO patient-profile has changed considerably. Age remained stable, while comorbidity burden decreased during the period 2013-2021. LAAO is increasingly used in patients with no clinical event history and mortality differs according to indication. Selection of patients to LAAO should be done carefully, and contemporary real-life studies investigating clinical practice could add important insights.

Sleep apnea, the risk of out-of-hospital cardiac arrest, and potential benefits of continuous positive airway pressure therapy: A nationwide study.

OBJECTIVE: Patients with sleep apnea (SA) are at increased cardiovascular risk. However, little is known about the risk of out-of-hospital cardiac arrest (OHCA) in patients with SA. Therefore, we studied the relation between SA patients who did and did not receive continuous positive airway pressure (CPAP) therapy with OHCA in the general population. METHODS: Using nationwide databases, we conducted a nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date matched non-OHCA-controls from the general population. Conditional logistic regression models with adjustments for well-known OHCA risk factors were performed to generate odds ratio (OR) of OHCA comparing patients with SA receiving and not receiving CPAP therapy with individuals without SA. RESULTS: We identified 46,578 OHCA-cases and 232,890 matched non-OHCA-controls [mean: 71 years, 68.8% men]. Compared to subjects without SA, having SA without CPAP therapy was associated with increased odds of OHCA after controlling for relevant confounders (OR:1.20, 95%-Cl:1.06-1.36), while having SA with CPAP therapy was not associated with OHCA (OR:1.04, 95%-Cl:0.93-1.36). Regardless of CPAP therapy, age and sex did not significantly influence our findings. Our findings were confirmed in: (I) patients with neither ischemic heart disease nor heart failure (untreated SA, OR:1.24, 95%-CI:1.04-1.47; SA with CPAP, OR:1.08, 95%-CI:0.93-1.25); and (II) in patients without cardiovascular disease (untreated SA, OR:1.33, 95%-CI:1.07-1.65; SA with CPAP, OR:1.14, 95%-CI:0.94-1.39). CONCLUSION: SA not treated with CPAP was associated with OHCA, while no increased risk of OHCA was found for SA patients treated with CPAP.

Infrequent transition to direct oral anticoagulants in patients with cancer.

INTRODUCTION: Pharmacokinetic drug-drug interactions (DDIs) are challenging aspects of direct oral anticoagulant (DOAC) therapy in patients with cancer. We evaluated the prevalence of potential DOAC/antineoplastic agent DDIs and the one-year cumulative incidence of switching from low-molecular-weight heparin (LMWH) to a DOAC in patients with cancer. METHODS: Patients with cancer and an indication of LMWH were included from Herlev and Gentofte Hospital, Denmark, in the 2014-2019 period. Follow-up was initiated when the first dose of LMWH was dispensed. Data were obtained from electronic medical records. One-year cumulative incidence of switching from LMWH to DOAC was estimated using the Aalen-Johansen estimator. Potential DDIs were evaluated using a report from the European Heart Rhythm Association (EHRA) and a review by Hellfritzsch et al. RESULTS. A total of 161 patients were included with a median age of 70.8 (interquartile range: 64.2-76.1) years. The one-year cumulative incidence of switching from LMWH to DOAC was 32% (95% confidence intervals: 21-43%) in patients eligible for DOACs. Using the EHRA report, a total of 24% of antineoplastic agents were not identified. This percentage decreased to 8% using data from Hellfritzsch et al. CONCLUSIONS. In patients with cancer, the one-year cumulative incidence of switching from LMWH to DOAC was less-t 35% in patients eligible for DOAC, revealing a potential for improved anticoagulant treatment. Furthermore, contemporary data elaborated on potential DDIs between DOACs/antineoplastic agents. FUNDING: "Helsefonden" (21-B-0350) and the "Karen Elise Jensens Fonden" (29-4-2021) funded the study. TRIAL REGISTRATION: Not relevant.

Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study.

BACKGROUND AND AIMS: A rising number of countries allow physicians to treat chronic pain with medical cannabis. However, recreational cannabis use has been linked with cardiovascular side effects, necessitating investigations concerning the safety of prescribed medical cannabis. METHODS: Using nationwide Danish registers, patients with chronic pain initiating first-time treatment with medical cannabis during 2018-21 were identified and matched 1:5 to corresponding control patients on age, sex, chronic pain diagnosis, and concomitant use of other pain medication. The absolute risks of first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome were reported comparing medical cannabis use with no use. RESULTS: Among 1.88 million patients with chronic pain (46% musculoskeletal, 11% cancer, 13% neurological, and 30% unspecified pain), 5391 patients claimed a prescription of medical cannabis [63.2% women, median age: 59 (inter-quartile range 48-70) years] and were compared with 26 941 control patients of equal sex- and age composition. Arrhythmia was observed in 42 and 107 individuals, respectively, within 180 days. Medical cannabis use was associated with an elevated risk of new-onset arrhythmia {180-day absolute risk: 0.8% [95% confidence interval (CI) 0.6%-1.1%]} compared with no use [180-day absolute risk: 0.4% (95% CI 0.3%-0.5%)]: a risk ratio of 2.07 (95% CI 1.34-2.80) and a 1-year risk ratio of 1.36 (95% CI 1.00-1.73). No significant association was found for acute coronary syndrome [180-day risk ratio: 1.20 (95% CI 0.35-2.04)]. CONCLUSIONS: In patients with chronic pain, the use of prescribed medical cannabis was associated with an elevated risk of new-onset arrhythmia compared with no use-most pronounced in the 180 days following the initiation of treatment.