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.).

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.

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.

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.

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.

Benefits of the Polypill on Medication Adherence in the Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review.

Background: Higher medication adherence reduces the risk of new cardiovascular events. However, there are individual and health system barriers that lead to lower adherence. The polypill has demonstrated benefits in cardiovascular morbidity and mortality mainly driven by an increase in adherence. We aim to evaluate the impact of the polypill on adherence to cardiovascular medication, its efficacy and safety in cardiovascular disease (CVD) prevention. Methods: A systematic review following PRISMA guidelines was conducted. Databases were searched from January 2003 to December 2022. We included randomized, pragmatic, or real-world clinical trials and observational studies. The primary outcome was medication adherence, secondary outcomes were efficacy in cardiovascular disease in primary and secondary prevention and safety. Results: From the 490 publications screened, 13 met the inclusion criteria and were incorporated into a comparative table Of those included, 70% were randomized controlled trials (RCTs) and 53.8% focused on secondary prevention. Most of the studies received a high and moderate quality rating. Self-report, pill counting and, the Morisky scale were the most frequent methods to evaluate adherence (84.6%). Compared with standard medication, the polypill improved overall medication adherence by 13%, with percentages ranging from 7.6% to 34.9%. Moreover, a potential benefit was also observed in reducing Major Adverse Cardiovascular Events (MACE), particularly in secondary prevention studies, with hazard ratios ranged between 0.43 to 0.76. Compared to standard care, the profile of side effects was similar. Conclusion: The polypill is an effective, safe, and practical strategy to improve adherence in people at risk of CVD. Although there is a demonstrated benefit in reducing MACE, predominantly in secondary prevention, there are still gaps in its efficacy in primary prevention and reducing total mortality. Therefore, the importance of obtaining long-term results of the polypill effect and how this strategy can be implemented in real practice.

Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial.

Importance: Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen. Objective: To determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin. Design, Setting, and Participants: This phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands. Interventions: The single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher. Main Outcomes and Measures: Outcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers. Results: Among 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed. Conclusion: Muvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04472676.

A prospective double-blinded randomized study on drug-eluting stent implantation into nitrate-induced maximally dilated vessels in patients with coronary artery disease.

BACKGROUND: Percutaneous coronary intervention (PCI) has been developed using drug-eluting stents (DES); however, stent implantation is associated with concerns of stent thrombosis and target vessel revascularization (TVR). The stent diameter is a critical factor in TVR and clinical events. The nitrate administration in coronary angiography can dilate the reference vessel diameter, enabling accurate vessel size measurement and optimal stent implantation support. This study was designed to evaluate the effect of stent implantation in the maximally dilated coronary artery in patients with coronary artery disease (CAD). METHODS: This prospective double-blinded randomized (1:1) study is designed to compare the efficacy and safety between DES implantation into the nitrate-induced maximally dilated vessels and conventional DES implantation in patients with CAD. A total of 400 patients who underwent PCI with a sirolimus-eluting stent will be enrolled. The primary endpoint is the mean diameter of the deployed stents. Secondary endpoints include cardiac death, myocardial infarction, stent thrombosis, or ischemia-driven TVR 1 year after the procedure. DISCUSSION: This study will be the first randomized controlled trial to evaluate the effect of DES implantation on nitrate-induced maximally dilated vessels in patients with CAD. TRIAL REGISTRATION: The trial was registered on 18 June 2021 as Effect of Ultimaster Stents Treated to the Most Dilated Coronary Vessels (ClinicalTrials.gov Identifier: NCT04931784).

[Study of cardiovascular drugs usage, among elderly subjects admitted to the emergency department for syncopal falls in Rhône-Alpes region]. / Étude de l'exposition médicamenteuse aux cardiotropes des sujets âgés consultant aux urgences pour chute avec malaise en Rhône-Alpes.

Study of cardiovascular drugs usage, among elderly subjects admitted to the emergency department for syncopal falls in Rhône-Alpes region. Polypharmacy and cardiovascular medication usage are risk factors for falls in the elderly. This study included subjects aged 75 and over, admitted in the emergency department for falls, based on evaluation data of professional practices carried out in the Nord Alpine region by the French Network of North-Alps Emergency Departments (Réseau Nord Alpin des Urgences, RENAU). The patients included were divided into 4 groups: "syncope", "accidental falls", "repeated falls" and "other types of fall". From the emergency room admission prescriptions, we studied the consumption of cardiovascular drugs in number and quality in the "syncope" group compared to other types of falls. The main objective in this study was to highlight higher cardiovascular drug usage among the elderly patients admitted to the emergency department for syncopal falls, in comparison with other types of falls. We included 1,476 patients among whom 262 patients came for "syncopal falls". We found superior usage of cardiovascular medication among syncopal falls compared to other type of falls (p < 0,01). However, there is no statistically significant association between inappropriate cardiovascular drug prescriptions, and the type of falls. The "standardized" fall assessment whose orthostatic hypotension investigation, is not always exhaustive in the emergency room. Orthostatic hypotension diagnostic is insufficiently sought in the emergency room. This study highlights a significantly higher usage of diuretic medication within the syncope group, in comparison to the other groups, and especially loop diuretic. Antihypertensive drugs (angiotensin-converting enzyme inhibitor, angiotensin II receptor blockers, calcium inhibitor) are also recurrent within the syncope group compared to the others. A careful supervising of these prescriptions among elderly patients seems required. These data prompt to revise prescriptions during fall related hospitalizations, and then with the primary-care physician, or with the cardiologist.

Drug-Coated Balloon for the Treatment of Long-Segment Femoropopliteal Artery Disease: Pooled Analysis from the BIOLUX P-III SPAIN and BIOLUX P-III All-Comers Registry Long Lesion Subgroup.

PURPOSE: To investigate the clinical performance and safety of the Passeo-18 Lux drug-coated balloon (DCB) in complex femoropopliteal Trans-Atlantic Inter-Society Consensus (TASC) C and D lesions in an all-comers patient population. MATERIAL AND METHODS: Data from BIOLUX P-III SPAIN, a prospective, national, multicenter, postmarket all-comers registry conducted from 2017 to 2019, and a matching long lesion subgroup from the BIOLUX P-III All-Comers global registry conducted from 2014 to 2018 were pooled for analysis. The primary safety end point was freedom from major adverse events (MAEs) at 6 months, and the primary performance end point was freedom from clinically driven target lesion revascularization (fCD-TLR) at 12 months, both adjudicated by an independent clinical events committee. RESULTS: A total of 159 patients, of whom 32.7% had critical limb ischemia, were included in the Passeo-18 Lux long lesion cohort. The mean lesion length was 248.5 mm ± 71.6, and the majority were occluded (54.1%), calcified (87.4%), and of type TASC C (49.1%) or TASC D (50.9%). Freedom from MAEs was 90.6% (95% CI, 84.6-94.3) at 6 months and 83.9% (95% CI, 76.7-89.0) at 12 months. fCD-TLR was 84.4% (95% CI, 77.3-89.5) at 12 months. Freedom from target limb major amputation was 98.6% (95% CI, 94.6-99.7), and all-cause mortality was 5.3% (95% CI, 2.7-10.4) at 12 months. There were no device- or procedure-related deaths or amputations up to the 12-month follow-up. CONCLUSION: Passeo-18 Lux DCB is safe and effective for the treatment of long femoropopliteal lesions in a real-word setting.

An Introductory Tutorial on Cardiovascular Pharmacogenetics for Healthcare Providers.

Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.

Design and rationale of a prospective, randomized, non-inferiority trial to determine the safety and efficacy of the Biolimus A9™ drug coated balloon for the treatment of in-stent restenosis: First-in-man trial (REFORM).

BACKGROUND: Drug-coated balloon (DCB) angioplasty with paclitaxel-eluting devices is an established treatment for coronary in-stent restenosis (ISR). Biolimus A9™ (BA9), a sirolimus analogue with enhanced lipophilicity, may facilitate enhanced local drug delivery into vascular tissue. A novel DCB coated with Biolimus A9™ represents an alternative to traditional paclitaxel- and sirolimus-coated devices. Hence, we sought to investigate the safety and efficacy of this novel DCB in the treatment of coronary ISR. METHODS AND DESIGN: REFORM (NCT04079192) is a prospective, multicenter, single blind, randomized controlled trial comparing the BA9-DCB (Biosensors Europe SA, Morges, Switzerland) to the paclitaxel-coated SeQuent® Please DCB (Braun Melsungen AG, Germany) in the treatment of coronary ISR. A total of 201 patients with coronary artery disease and an indication for interventional treatment of ISR in a bare-metal stent (BMS) or drug-eluting stent (DES) have been randomized 2:1 to receive treatment with the BA9- or the paclitaxel-DCB comparator. Patients were enrolled across 24 investigational centers in Europe and Asia. The primary endpoint is percent diameter stenosis (%DS) of the target segment as assessed by quantitative coronary angiography (QCA) at 6 months. Key secondary endpoints are in-stent late lumen loss, binary restenosis, target lesion failure, target vessel failure, myocardial infarction and death at 6 months. Subjects will be followed for 24 months from enrolment. IMPLICATIONS: The REFORM trial will seek to prove that the BA9-DCB is non-inferior to the standard paclitaxel-DCB comparator in the treatment of coronary ISR with respect to %DS at 6 months and has similar safety characteristics.

[The polypill in cardiovascular prevention: successful through simplification? : New study results on the benefit of the polypill strategy in primary and secondary prevention]. / "Polypill" in der kardiovaskulären Prävention ­ erfolgreich durch Vereinfachung? : Neue Studienergebnisse zum Nutzen der Polypill-Strategie in der Primär- und Sekundärprävention.

BACKGROUND: Cardiovascular disease is still the major cause of death worldwide. Beside the elevated blood pressure, a major modifiable risk factor is the elevated low-density lipoprotein (LDL) cholesterol. Although both risk factors are well manageable, therapeutic control remains poor with low adherence to medication being a major cause of insufficient treatment success. One solution to overcome this issue is the polypill concept, i.e. a combination of different drugs in one tablet. This not only increases adherence but also significantly improves patients' prognosis by reducing cardiovascular events. OBJECTIVE: This review focuses on current evidence published in randomized control trials in primary and secondary prevention. A major focus is on the recently published SECURE trial dealing with the polypill in secondary prevention. CURRENT DATA: Most trials dealing with the polypill concept focus on the control of risk factors such as blood pressure and LDL cholesterol while lacking a prognostic benefit in the form of a reduction in cardiovascular events. Recent trials such as the HOPE­3, PolyIran and TIPS­3 trials have shown a prognostic improvement for the polypill in primary prevention. In secondary prevention there has been a lack of prognostic benefit for the polypill to date. The recently published SECURE trial closed this gap by showing a significant reduction in major adverse cardiovascular events in post-infarct patients and also showing a reduction in cardiovascular death by 33%. CONCLUSION: The concept of the polypill has evolved from a comfort method for patients aimed at facilitating adherence to an innovative therapeutic concept with a proven prognostic advantage compared to current treatment practice by reducing cardiovascular events and mortality. Therefore, it is time to implement the concept of the polypill in primary and secondary prevention to improve patients' prognosis and reduce the burden of cardiovascular disease worldwide.

Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the years to improve both the data quality and the well being of our animal subjects. Of particular interest for us has been the use of telemetry-based data acquisition for conducting studies on cardiovascular (CV) function. This includes the evolving technical aspects of the studies, as well as the development of new applications that take advantage of this technical approach.