Differences in provider approach to initiating and titrating guideline directed medical therapy in heart failure with reduced ejection fraction.

BACKGROUND: Despite the strong evidence supporting guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), prescription rates in clinical practice are still lacking. METHODS: A survey containing 20 clinical vignettes of patients with HFrEF was answered by a national sample of 127 cardiologists and 68 internal/family medicine physicians. Each vignette had 4-5 options for adjusting GDMT and the option to make no medication changes. Survey respondents could only select one option. For analysis, responses were dichotomized to the answer of interest. RESULTS: Cardiologists were more likely to make GDMT changes than general medicine physicians (91.8% vs. 82.0%; OR 1.84 [1.07-3.19]; p = 0.020). Cardiologists were more likely to initiate beta-blockers (46.3% vs. 32.0%; OR 2.38 [1.18-4.81], p = 0.016), angiotensin receptor blocker/neprilysin inhibitor (ARNI) (63.8% vs. 48.1%; OR 1.76 [1.01-3.09], p = 0.047), and hydralazine and isosorbide dinitrate (HYD/ISDN) (38.2% vs. 23.7%; OR 2.47 [1.48-4.12], p < 0.001) compared to general medicine physicians. No differences were found in initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARBs), initiating mineralocorticoid receptor antagonist (MRA), sodium-glucose transporter protein 2 (SGLT2) inhibitors, digoxin, or ivabradine. CONCLUSIONS: Our results demonstrate cardiologists were more likely to adjust GDMT than general medicine physicians. Future focus on improving GDMT prescribing should target providers other than cardiologists to improve care in patients with HFrEF.

Randomized comparison of the effects of tailored text messaging versus pillbox organizers on medication adherence of heart failure patients.

BACKGROUND: Heart failure (HF) is a major public health issue worldwide, affecting approximately 64.3 million people in 2017. Non-adherence to medication is a common and serious issue in the management of HF. However, new reminder systems utilizing mobile technology, such as text messaging, have shown promise in improving medication adherence. The purpose of this study was to compare the impact of tailored text messaging (TTM) and pillbox organizers on medication adherence in individuals with HF. METHODS: A randomized controlled trial was conducted, involving 189 eligible patients with HF who were randomly assigned to either the TTM, pillbox organizer, or control group. Medication adherence was evaluated using pill counting and the Medication Adherence Rating Scale (MARS) over a period of three months and compared across the groups. The data were analyzed using Kruskal-Wallis, Analysis of Variance (ANOVA), and Repeated Measures ANOVA tests. RESULTS: The results indicate that both the TTM and pillbox organizers groups had significantly higher medication adherence compared to the control group, as measured by pill counting (MD = 0.05, 95%CI = 0.03-0.06; p < 0.001 for TTM group, MD = 0.04, 95%CI = 0.03-0.06; p < 0.001 for pillbox organizers group) and the MARS (MD = 1.32, 95%CI = 0.93 to 1.72; p < 0.001 for TTM group, MD = 1.33, 95%CI = 0.95 to 1.72; p < 0.001 for pillbox organizers group). However, there was no statistically significant difference in medication adherence between the two intervention groups using either measurement method. The TTM group exhibited a lower hospitalization rate than the other groups in the first follow up (p = 0.016). CONCLUSIONS: Both the TTM and pillbox organizers were shown to be effective in enhancing medication adherence among patients with HF. Therefore, healthcare providers should take into account the patient's condition and preferences when selecting one of these methods to promote medication adherence. Future research should aim to address the limitations of this study, such as controlling for confounding variables, considering long-term effects, and comparing the effectiveness of different interventions.

Drug-Coated Balloons in the Management of Coronary Artery Disease.

Drug-coated balloons (DCBs) are specialized coronary devices comprised of a semicompliant balloon catheter with an engineered coating that allows the delivery of antiproliferative agents locally to the vessel wall during percutaneous coronary intervention. Although DCBs were initially developed more than a decade ago, their potential in coronary interventions has recently sparked renewed interest, especially in the United States. Originally designed to overcome the limitations of conventional balloon angioplasty and stenting, they aim to match or even improve upon the outcomes of drug-eluting stents without leaving a permanent implant. Presently, in-stent restenosis is the condition with the most robust evidence supporting the use of DCBs. DCBs provide improved long-term vessel patency compared with conventional balloon angioplasty and may be comparable to drug-eluting stents without the need for an additional stent layer, supporting their use as a first-line therapy for in-stent restenosis. Beyond the treatment of in-stent restenosis, DCBs provide an additional tool for de novo lesions for a strategy that avoids a permanent metal scaffold, which may be especially useful for the management of technically challenging anatomies such as small vessels and bifurcations. DCBs might also be advantageous for patients with high bleeding risk due to the decreased necessity for extended antiplatelet therapy, and in patients with diabetes and patients with diffuse disease to minimize long-stented segments. Further studies are crucial to confirm these broader applications for DCBs and to further validate safety and efficacy.

Randomized Trial Comparing a Stent-Avoiding With a Stent-Preferred Strategy in Complex Femoropopliteal Lesions.

BACKGROUND: Limited comparative data exist on different interventional strategies for endovascular revascularization of complex femoropopliteal interventions. OBJECTIVES: In this study, the authors aimed to compare a stent-avoiding (SA) vs a stent-preferred (SP) strategy, promoting optimal lesion preparation and the use of drug-eluting technologies in both arms. METHODS: Within a prospective, multicenter, pilot study, 120 patients with symptomatic complex femoropopliteal lesions (Rutherford classification 2-4, mean lesion length 187.7 ± 78.3 mm, 79.2% total occlusions) were randomly assigned in a 1:1 fashion to endovascular treatment with either paclitaxel-coated balloons or polymer-coated, paclitaxel-eluting stents. Lesion preparation including the use of devices for plaque modification and/or removal was at the operators' discretion in both treatment arms. RESULTS: In the SA group, lesion preparation was more frequently performed (71.7% SA [43/60] vs 51.7% [31/60] SP; P = 0.038) with a high provisional stenting rate (48.3% [29/60]). At the 12-month follow-up, primary patency was 78.2% (43/55) in the SA group and 78.6% (44/56) in the SP group (P = 1.0; relative risk: 0.995; 95% CI: 0.818-1.210). Freedom from major adverse events was determined in 93.1% (54/58) in the SA group and in 94.9% (56/59) in the SP group (P = 0.717; relative risk: 0.981; 95% CI: 0.895-1.075), with all adverse events attributable to clinically driven target lesion revascularization. CONCLUSIONS: Both endovascular strategies promoting lesion preparation before the use of drug-eluting devices suggest promising efficacy and safety results in complex femoropopliteal procedures with a high proportion of total occlusions through 12 months. Ongoing follow-up will show whether different results emerge over time. (Best Endovascular Strategy for Complex Lesions of the Superficial Femoral Artery [BEST-SFA]; NCT03776799).

The Use and Impact of Cilostazol on Patients Undergoing Endovascular Peripheral Interventions.

BACKGROUND: Cilostazol is used for the treatment of intermittent claudication. The impact of cilostazol on the outcomes of peripheral vascular interventions (PVIs) remains controversial. This study assesses the use and impact of cilostazol on patients undergoing PVI for peripheral arterial disease (PAD). METHODS: The Vascular Quality Initiative (VQI) database files for PVI were reviewed. Patients with PAD who underwent PVI for chronic limb threatening-ischemia or claudication were included and divided based on the use of cilostazol preoperatively. After propensity matching for patient demographics and comorbidities, the short-term and long-term outcomes of the 2 groups (preoperative cilostazol use versus no preoperative cilostazol use) were compared. The Kaplan-Meier method was used to determine outcomes. RESULTS: A total of 245,309 patients underwent PVI procedures and 6.6% (N = 16,366) were on cilostazol prior to intervention. Patients that received cilostazol were more likely to be male (62% vs 60%; P < 0.001), White (77% vs. 75%; P < 0.001), and smokers (83% vs. 77%; P < 0.001). They were less likely to have diabetes mellitus (50% vs. 56%; P < 0.001) and congestive heart failure (14% vs. 23%; P < 0.001). Patient on cilostazol were more likely to be treated for claudication (63% vs. 40%, P < 0.001), undergo prior lower extremity revascularization (55% vs. 51%, P < 0.001) and less likely to have undergone prior minor and major amputation (10% vs. 19%; P < 0.001) compared with patients who did not receive cilostazol. After 3:1 propensity matching, there were 50,265 patients included in the analysis with no differences in baseline characteristics. Patients on cilostazol were less likely to develop renal complications and more likely to be discharged home. Patients on cilostazol had significantly lower rates of long-term mortality (11.5% vs. 13.4%, P < 0.001 and major amputation (4.0% vs. 4.7%, P = 0.022). However, there were no significant differences in rates of reintervention, major adverse limb events, or patency after PVI. Amputation-free survival rates were significantly higher for patients on cilostazol, after 4 years of follow up (89% vs. 87%, P = 0.03). CONCLUSIONS: Cilostazol is underutilized in the VQI database and seems to be associated with improved amputation-free survival. Cilostazol therapy should be considered in all patients with PAD who can tolerate it prior to PVI.

Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo. METHODS: In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level. RESULTS: A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients. CONCLUSIONS: In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.).

The efficacy and safety of ivabradine hydrochloride in hemodialysis patients with chronic heart failure.

INTRODUCTION: There is little evidence for ivabradine hydrochloride in patients undergoing hemodialysis. METHODS: In this open-label prospective interventional trial of hemodialysis patients with chronic heart failure, during 12 weeks of treatment, changes in Heart rate (HR), frequency of dialysis-related hypotension were examined, and we investigated health-related quality of life (HR-QOL) and adverse effects. RESULTS: 18 patients from 6 facilities were enrolled in the study. HR significantly decreased over time, from 87 ± 12.61/min at baseline to 75.85 ± 8.91/min (p = 0.0003), and systolic blood pressure also increased significantly (p < 0.0001). The frequency of dialysis-related hypotension was markedly reduced (p = 0.0001). The HR-QOL survey showed significant improvements in Social Functioning among others (p = 0.0178). No specific adverse events occurred. CONCLUSION: Ivabradine hydrochloride improved dialysis-related hypotension. Furthermore, the HR-QOL improvement effect were suggested. These results demonstrated the safety and effectiveness of ivabradine hydrochloride.

Improving medication adherence in cardiovascular disease.

Non-adherence to medication is a global health problem with far-reaching individual-level and population-level consequences but remains unappreciated and under-addressed in the clinical setting. With increasing comorbidity and polypharmacy as well as an ageing population, cardiovascular disease and medication non-adherence are likely to become increasingly prevalent. Multiple methods for detecting non-adherence exist but are imperfect, and, despite emerging technology, a gold standard remains elusive. Non-adherence to medication is dynamic and often has multiple causes, particularly in the context of cardiovascular disease, which tends to require lifelong medication to control symptoms and risk factors in order to prevent disease progression. In this Review, we identify the causes of medication non-adherence and summarize interventions that have been proven in randomized clinical trials to be effective in improving adherence. Practical solutions and areas for future research are also proposed.

Long-term outcomes after coronary intervention with biodegradable polymer stents in patients with acute coronary syndromes.

BACKGROUND: Patients with acute coronary syndromes (ACS) may have worse outcomes after percutaneous coronary intervention compared to patients without ACS. AIMS: To compare 5-year efficacy and safety outcomes in patients with and without ACS treated with biodegradable polymers, the ultrathin strut sirolimus-eluting Orsiro stent (O-SES) or the biolimus-eluting Nobori stent (N-BES). METHODS: The Scandinavian Organisation for Randomized Trials with Clinical Outcome VII is a randomized trial comparing O-SES and N-BES in an all-comer setting. Of 2525 patients, 1329 (53%) patients had ACS and 1196 (47%) patients were without ACS. Endpoints were target lesion failure (TLF) (a composite of cardiac death, target lesion myocardial infarction, or target lesion revascularization) and definite stent thrombosis within 5 years. RESULTS: At 5-year follow-up, TLF did not differ significantly between patients with and without ACS (12.3% vs. 13.2%; rate ratio (RR) 1.00; 95% confidence interval (CI): 0.70-1.44), whereas the risk of definite stent thrombosis was increased in patients with ACS (2.3% vs. 1.3; RR: 2.01 [95% CI: 1.01-3.98]). In patients with ACS, the rate of TLF was similar between O-SES and N-BES (12.4% vs. 12.3%; RR: 1.02; 95% CI: 0.74-1.40). The reduced risk of definite stent thrombosis in O-SES treated ACS patients within the first year (0.2% vs. 1.6%; RR: 0.12; 95% CI: 0.02-0.93) was not maintained after 5 years (1.8% vs. 2.7%; RR: 0.77; 95% CI: 0.37-1.63). CONCLUSION: Patients with ACS had an increased risk of stent thrombosis regardless of the stent type used. Long-term outcomes were similar for ACS patients treated with O-SES or N-BES at 5 years.

Antianginal effects of empagliflozin in patients with type 2 diabetes and refractory angina; a randomized, double-blind placebo-controlled trial (EMPT-ANGINA Trial).

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are emerging antidiabetic agents with various potential cardiovascular benefits. The EMPT-ANGINA trial examined the effect of empagliflozin on the angina burden in those with concurrent type 2 diabetes mellitus (T2DM) and refractory angina (RA). METHOD: In this 8-week, double-blind, randomized, placebo-controlled trial, 75 patients with T2DM and RA were randomly assigned to one of two groups: empagliflozin (n = 37) and placebo (n = 38). The primary outcome was an improvement in angina, which was assessed by the Seattle Angina Questionnaire (SAQ). The secondary outcomes of this study included alterations in the SAQ domains and exercise test components. RESULTS: The mean age of individuals in the empagliflozin and placebo groups was 67.46 ± 9.4 and 65.47 ± 7.0 years, respectively (p = .304). Patients who received empagliflozin showed a significant improvement in both the primary endpoint, which was the SAQ Summary Score (192.73 ± 20.70 vs. 224 ± 25.36, p < .001) and the secondary endpoints. Exercise test components, including treadmill exercise duration, time till angina, 1 mm ST-segment depression onset, and heart rate (HR) recovery, were all significantly improved in the empagliflozin group. This positive impact was reached with no clinically significant changes in resting and exertion HR or blood pressure. There were no significant side effects in the empagliflozin group (p = .125). CONCLUSION: Empagliflozin can be safely added as a metabolic modulator agent to existing antianginal medications in individuals with concurrent T2DM and RA to reduce angina symptoms and enhance exercise capacity with minimal side effects.

Validation of the Usefulness of the Diameter Reduction, Spiral Shape, Flow Impairment, or Adverse Morphology Classification System in Real-World Clinical Practice.

AIM: The accuracy of the DISFORM (diameter reduction, spiral shape, flow impairment, or adverse morphology) classification system has not been validated. METHODS: This retrospective multicenter observational study enrolled 288 consecutive patients with lower extremity artery disease who underwent endovascular therapy with drug-coated balloons for femoropopliteal lesions between January 2018 and December 2021. Patients were classified into DISFORM I-IV groups. Primary patency (PP) and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months, and recurrence predictors at 12 months were investigated. RESULTS: In total, 183, 66, 11, and 28 patients were classified into DISFORM I, II, III, and IV groups, respectively. In the DISFORM I, II, III, and IV groups, the PP rates were 75.3%, 91.1%, 87.5%, and 50.0%, respectively, and freedom from CD-TLR rates were 86.0%, 91.6%, 88.9%, and 76.7%, respectively, at 12 months. In the DISFORM I-III and IV groups, the PP rates were 79.4% and 50.0%, respectively, and freedom from CD-TLR rates were 87.5% and 76.7%, respectively, at 12 months. Multivariate analysis showed that chronic limb-threatening ischemia, DISFORM IV, and Lutonix™ use were independent predictors of PP loss at 12 months. CONCLUSION: DISFORM IV had a lower PP rate than DISFORM I-III in midterm phase.

A New Drug-Coated Balloon for the Treatment of Superficial Femoropopliteal Artery Disease: 12-Month Results from the IN-DEPT SFA Trial.

PURPOSE: To report the outcomes of the IN-DEPT trial assessing the feasibility, preliminary safety data, and 12-month outcomes of a new drug-coated balloon (DCB) product for peripheral artery disease (PAD) in Chinese patients. MATERIALS AND METHODS: This is a prospective, multicenter, single-arm clinical trial. A total of 160 patients with superficial femoral artery (SFA) and/or proximal popliteal artery lesions were treated with a new paclitaxel-coated DCB. The preliminary effectiveness end point was 12-month primary patency. The primary safety end point was freedom from device- and procedure-related mortality over 30 days and freedom from major target limb amputation and clinically driven target lesion revascularization (CD-TLR) within 12 months after the index procedure. RESULTS: In total, 160 patients presented with 162 target lesions. A total of 139 lesions (85.8%) were treated with 1 DCB, whereas the other 23 lesions (14.2%) were treated with 2 devices. The device success rate was 100%. A total of 135 subjects reached the preliminary effectiveness end point, with a 12-month primary patency rate of 84.4%. There was no 30-day device- or procedure-related death or unplanned major target limb amputation at 12 months. Five CD-TLRs (3.1%) occurred during the 12-month follow-up period. CONCLUSIONS: Results from the IN-DEPT SFA trial showed satisfactory feasibility and safety of the new DCB over 12 months in Chinese patients with PAD and femoropopliteal de novo lesions, including both stenoses and total occlusions.

Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. Safety was also assessed. RESULTS: A total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo. The mean (±SD) duration of exposure to semaglutide or placebo was 34.2±13.7 months, and the mean duration of follow-up was 39.8±9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001). CONCLUSIONS: In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 months. (Funded by Novo Nordisk; SELECT ClinicalTrials.gov number, NCT03574597.).

Low-Dose vs High-Dose Drug-Coated Balloon for Symptomatic Femoropopliteal Artery Disease: The PROSPECT MONSTER Study Outcomes.

BACKGROUND: Randomized trials have shown comparable outcomes between second-generation low-dose drug-coated balloons (LD-DCBs) and first-generation high-dose drug-coated balloons (HD-DCBs); but the trial patients had low clinical complexity, and there were no comparisons in medically complex populations. OBJECTIVES: The aim of this study was to compare outcomes between an LD-DCB (Ranger; 2.0 µg/mm2) and an HD-DCB (IN.PACT; 3.5 µg/mm2) in patients with symptomatic femoropopliteal artery disease. METHODS: PROSPECT MONSTER (Prospective Comparison of Second-Generation Low-Dose Drug-Coated Balloon With High-Dose Drug-Coated Balloon) was a prospective, multicenter, nonrandomized trial that prospectively collected data from 581 patients who underwent endovascular therapy with the LD-DCB (n = 370) or the HD-DCB (n = 211) for symptomatic femoropopliteal artery disease (Rutherford classes 2-5). The primary outcome was the 1-year primary patency of the LD-DCB in comparison with that of the HD-DCB, as evaluated using propensity score matching. The incidence of impaired flow after drug-coated balloon application was also evaluated. RESULTS: Propensity score matching extracted 163 pairs (358 and 163 patients in the LD-DCB and HD-DCB groups, respectively), with no significant intergroup difference in baseline characteristics. The 1-year primary patency rates in the matched population were similar between the LD-DCB and HD-DCB groups (87.0% [95% CI: 82.5%-91.7%] vs 81.3% [95% CI: 74.8%-88.5%]; HR: 0.93; 95% CI: 0.55-1.59; P = 0.79), as was the incidence of impaired flow (13.6% vs 9.8%; OR: 1.46; 95% CI: 0.78-2.73; P = 0.24). No baseline characteristics had any significant interaction effects on the association of the LD-DCB vs the HD-DCB and 1-year restenosis risk. CONCLUSIONS: LD-DCBs demonstrate efficacy and safety comparable with HD-DCBs in patients with complex clinical backgrounds, suggesting that drug-coated balloon treatment using a lower dose may be possible.