Lower Risk Of Primary Outcome Research Articles

Impact of post-percutaneous mitral balloon valvuloplasty mitral valve area indexed for the body size on long-term outcomes in rheumatic mitral stenosis: a 20-year retrospective analysis

Abstract Introduction Percutaneous mitral balloon valvuloplasty (PBMV) remains one of the standard treatments for symptomatic rheumatic mitral stenosis (MS)(1). The procedural success criteria are generally defined as a post-procedural mitral valve area (MVA) of more than 1.5 cm2 without significant mitral regurgitation or in-hospital complications(2, 3). However, the effect of body size on the post-procedural MVA is not well examined. Purpose This study intended to investigate the association between the different methods of indexing post-PBMV MVA for the body size parameters and event-free survival compared to the absolute MVA in rheumatic MS patients treated with PBMV. Methods We retrospectively enrolled clinically significant rheumatic MS patients (MVA ≤1.5 cm2) who underwent PBMV with Inoue balloon between June 2002 and February 2021. The patients who experienced in-hospital complications (stroke, emergency surgery, or death) were excluded. A final number of 584 out of 618 patients were included in the analysis. Post-procedural MVA was assessed using echocardiographic 2D planimetry or pressure half-time if planimetry was not available. Post-PBMV MVA was indexed by body surface area (BSA), body mass index (BMI), body weight or height. The median value of absolute MVA and indexed MVA was used to stratify patients into two groups. The primary outcome was the composite of death, repeat PBMV, and mitral valve surgery. We performed Cox regression analyses to assess the association between groups and outcomes. C-index was calculated to assess the discriminative ability of each index. Results The mean age was 41.5 (±11.9) years, and 490 patients (82.8%) were female. The prevalence of atrial fibrillation was 39.5%. The median Wilkin score was 8 (interquartile range of 7-9). The mean pre-procedural and post-procedural MVA was 0.92 (±0.24) and 1.57 (±0.28) cm2, respectively. The average pre-procedural and post-procedural mean pressure gradient was 13.1 (±6.3) and 5.7 (±3.0) mmHg, respectively. The prevalence of post-procedural MR in a moderately severe to a severe degree was 3.8%. Over a median follow-up of 3.9 years, 194 composite events occurred. Patients with post-procedural indexed MVA of any type greater than a median were not associated with a significantly lower risk of primary outcome compared to those with indexed MVA less than the median (Picture 1). Moreover, absolute MVA greater than a median (1.55 cm2) was independently associated with a lower risk of primary outcome after adjusting with age and gender (Hazard ratio [95% CI] = 0.658 [0.493-0.879], p = 0.005). The discriminative ability of the absolute MVA was highest than the indexed MVA (Picture 2). Conclusion Indexing post-procedural MVA did not provide additional benefit on long-term risk stratification after PBMV compared with the absolute MVA.

Chlorthalidone vs Hydrochlorothiazide for Hypertension-CV Events: Did the Design Influence the Outcome?

The Diuretic Comparison Project (DCP)1 was a real world study planned to evaluate in a pragmatic manner whether Chlorthalidone (CTD), as compared with Hydrochlorothiazide (HCTZ), would reduce the risk of major nonfatal cardiovascular disease outcomes in elderly hypertensive participants (≥65 years) who were receiving HCTZ (25 or 50 mg) at baseline. This study being a real world study lacks the robustness of a randomized controlled trial. The principle limitation being unequal exposure of the two diuretics, prolonged unknown duration of exposure to HCTZ vs a short exposure to CTD (Median 2.4 years). In the high risk population with history of MI/Stroke, CTD conferred a lower risk of primary outcome as compared to low risk population where no significant difference in outcome was seen in both diuretics. Other factors included, lack of established dose equivalency of the two diuretics and absence of use of 12.5 mg HCTZ in older hypertensives. How to cite this article: Pareek A, Messerli FH, Ram CVS. Chlorthalidone vs Hydrochlorothiazide for Hypertension-CV Events: Did the Design Influence the Outcome? J Assoc Physicians India 2023;71(10):93-93.

Milrinone vs Dobutamine for the Management of Cardiogenic Shock: Implications of Renal Function and Injury

BackgroundCardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction. ObjectivesThis study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function. MethodsIn this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. ResultsBaseline eGFR <60 ml/min/1.73 m2 and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m2 did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome (P interaction = 0.02) and death (P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI. ConclusionsIn patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

Integrated Care for Atrial Fibrillation Using the ABC Pathway in the Prospective APHRS-AF Registry

BackgroundThe Atrial Fibrillation Better Care (ABC) has been proposed as an integrated approach to improve management in patients with atrial fibrillation (AF), based on 3 pillars: “A” Avoid stroke with Anticoagulation; “B” Better symptoms control; “C” Cardiovascular risk-factor and comorbidities management. ObjectivesThis study sought to investigate the association with outcomes of ABC adherence in the prospective multinational Asia-Pacific Heart Rhythm Society (APHRS) Atrial Fibrillation registry. MethodCox-regression analyses adjusted for age, sex, CHA2DS2-VASc score, paroxysmal AF, chronic obstructive pulmonary disease, chronic kidney disease, cancer, dyslipidemia, and dementia were performed to investigate the association with outcomes. Primary outcome was a composite of all-cause death, any thromboembolic events, acute coronary syndrome or percutaneous interventional procedures, and advancing heart failure. ResultsOf the 4,013 included patients with AF (mean age 68 ± 12 years; 34.4% female); 38.6% were adherent to all 3 main ABC pillars. After 1 year of follow-up, adherence to the ABC pathway was associated with a low incidence of composite outcome (4.0% vs 8.5%, P < 0.001), all-cause and cardiovascular death, and advancing heart failure. On Cox regression analysis, ABC adherence was associated with a lower risk of primary outcome (HR: 0.72; 95% CI: 0.53-0.97), with risk reduction progressively higher with a higher number of ABC criteria attained. No significant interaction in the association was seen according to the different geographic areas (Pint = 0.217). ConclusionsIn a large contemporary cohort of Asian patients with AF, adherence to ABC pathway was associated with a reduction of the risk for adverse outcomes. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia (AF-Registry; NCT04807049)

Sodium-Glucose Cotransporter 2 Inhibitor Use in Early-Phase Acute Coronary Syndrome with Severe Heart Failure.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) improves clinical outcomes in patients with heart failure (HF), but has limited evidence of SGLT2i use on early-phase acute coronary syndrome (ACS). We determined association of early SGLT2i use compared with either non-SGLT2i or dipeptidyl peptidase 4 inhibitor (DPP4i) in hospitalized patients with ACS. This retrospective cohort study that used the Japanese nationwide administrative claims database included patients hospitalized with ACS aged≥20 years between April 2014 and March 2021. The primary outcome was a composite of all-cause mortality or HF/ACS rehospitalization. Using 1:1 propensity score matching, the association with outcomes of the early SGLT2i use (≤14 days after admission) compared with non-SGLT2i or DPP4i was determined according to the HF treatment. Among 388185 patients included, 115612 and 272573 with and without severe HF, respectively. Compared to non-SGLT2i users, the SGLT2i users had a lower hazard ratio (HR) with the primary outcome (HR: 0.83, 95% confidence interval [CI]: 0.76-0.91, p<0.001) in the severe HF group; however, there was no significant difference in the non-severe HF group (HR: 0.92, 95% CI: 0.82-1.03, p=0.16). SGLT2i use showed a lower risk of the outcome in patients with severe HF and diabetes compared with DPP4i (HR: 0.83, 95% CI: 0.69-1.00, p=0.049). SGLT2i use in patients with early-phase ACS showed a lower risk of primary outcome in patients with severe HF but the effect was not apparent in patients without severe HF.

Impact of ABC pathway adherence in high-risk patients with atrial fibrillation: an analysis from the ESC-EHRA EORP-AF long-term general registry

Abstract Background The impact of Atrial Fibrillation Better Care (ABC) pathway adherence among high-risk subgroups of patients with atrial fibrillation (AF), ie. those with chronic kidney disease (CKD), advanced age and/or prior thromboembolism remains unknown. We evaluated the impact of ABC pathway adherence on clinical outcomes in these high-risk AF patients. Methods The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. High-risk patients were defined as those with either CKD (eGFR &amp;lt;60 mL/min/1.73 m2), older age (≥75 years) and/or prior thromboembolism. The primary outcome was a composite event of all-cause death, any thromboembolism and acute coronary syndrome, evaluated according to ABC pathway adherence. Results A total of 6646 patients with AF were included (median age was 70 [IQR 61–77] years; 40.2% females). There were 3304 (54.2%) `high risk' patients with either CKD (n=1750), older age (n=2236) or prior thromboembolism (n=728). Among these there were 924 (28.0%) managed as adherent to ABC. At 2-year follow-up, a total of 966 (14.5%) patients reported the primary outcome. The incidence of the primary outcome was significantly lower in high-risk patients managed as adherent to ABC pathway (IRR 0.53 [95% CI, 0.43–0.64]). Consistent results were obtained in the individual subgroups [Table]. Using multivariable Cox proportional hazards analysis, ABC adherence in the high-risk cohort was independently associated with a lower risk of primary outcome (aHR 0.64 [95% CI, 0.51–0.80]), as well as in the CKD (aHR 0.51 [95% CI, 0.37–0.70]) and elderly subgroups (aHR 0.69 [95% CI, 0.53–0.90]). Overall, there was greater reduction in the risk of primary outcome as more ABC criteria were fulfilled, both in the overall high-risk patients, as well as in the individual subgroups [Figure]. Conclusion In a large, contemporary European AF cohort there was a significant proportion of high-risk patients. Among these, a low prevalence of integrated care, as assessed by adherence to ABC pathway, was found. Nonetheless, a clinical management adherent to the ABC pathway was associated with a significant reduction in the risk of adverse outcomes, the benefits of which were more significant with increasing number of ABC criteria adherent. Funding Acknowledgement Type of funding sources: None.

One year outcomes of atrial fibrillation ablation: Contemporary analysis of the United States Nationwide Readmission Database.

Data on long-term outcomes of catheter ablation (CA) for atrial fibrillation (AF) in outside of clinical trials settings are sparse. We aimed to assess outcomes and readmissions at 1year following admission for CA for AF. Utilizing the Nationwide Readmissions Database (2016-2018), we identified patients with CA among all patients with a primary admission diagnosis of AF, and a control group by propensity score match adjusted for age, sex, comorbidities, CHA₂DS₂-VASc scores, and the hospital characteristics. The primary outcome was a composite of unplanned heart failure (HF), AF and stroke-related readmissions, and death at 1 year, and secondary outcomes were hospital outcomes and all-cause readmission rates. The study cohort consisted of 29,771 patients undergoing CA and 63,988 controls. Patients undergoing CA were younger with lower CHA₂DS₂-VASc scores and less comorbidities. Over a follow-up of 170 ±1.1 days, the primary outcome occurred in 5.2% in CA group and 6.0% of controls (hazard ratio [HR] and 95% confidence interval [CI]: 0.86 [0.76-0.94], p=.002). CA affected AF and stroke related readmission, but showed no effect on HF and mortality outcome. Male sex (HR: 0.83 [0.74-0.94], p=.03), younger age (HR: 0.71 [0.61-0.83], p<.001], and lower CHA₂DS₂-VASc scores (HR: 0.68 [0.55-0.84], p<.001) were associated with lower risk of primary outcome with CA. In this study, CA for AF was associated with significantly lower AF and stroke-related admissions, but not to HF or all-cause readmission. Better outcomes were seen among males, younger patients, and in patients with less comorbidities and low CHA₂DS₂-VASc scores.

Comparative effectiveness of early rhythm control versus rate control for cardiovascular outcomes according to sex in patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health &amp; Welfare, Republic of Korea Background Rhythm control is associated with better cardiovascular outcomes than usual care among patients recently diagnosed with atrial fibrillation (AF). However, there are limited data on the outcomes of AF ablation according to sex. The purpose of this study was to evaluate gender differences in the effects of early rhythm control compared to rate control on the primary composite outcome of cardiovascular death, ischaemic stroke, hospitalisation for heart failure (HF), or myocardial infarction. Methods We conducted a retrospective population-based cohort study including 22635 patients with AF newly treated with rhythm control (antiarrhythmic drugs or ablation) or rate control in 2011-2015 from the Korean National Health Insurance Service database. Propensity overlap weighting was used. Results Among patients with early AF treatment (initiated within 1 year since diagnosis), compared with rate control, rhythm control was associated with a similar lower risk of the primary composite outcome both women (weighted incidence rate per 100 person-years: 8.68 in rhythm control vs. 10.3 in rate control; hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.69 to 0.90; P&amp;lt;0.001) and men (weighted incidence rate per 100 person-years: 6.33 in rhythm control vs. 8.32 in rate control; HR 0.77, 95% CI 0.67 to 0.88; P&amp;lt;0.001). However, the effective initiation time for rhythm control therapy was within 6 and 11 months after AF diagnosis in female and male patients, respectively. Moreover, the effective times for other outcomes were different between genders (hospitalization for HF; female within 2 months, male within 9 months/ ischemic stroke; female within 11 months, male immediately). Conclusions Early initiation of rhythm control was associated with a lower risk of primary outcome in both genders. However, the effective rhythm control treatment initiation time for primary outcome, stroke and HF-related admission was different in both genders. For rhythm control treatment to be effective, women should start treatment earlier than men.

Prognostic Value of Time in Blood Pressure Target Range Among Patients With Heart Failure

BackgroundBlood pressure (BP) is a continuous and dynamic measure. However, standard BP control metrics may not reflect the variability in BP over time. ObjectivesThis study assessed the prognostic value of time in BP target range among hypertensive patients with heart failure (HF). MethodsThe authors performed a post hoc analysis of data from the TOPCAT (Treatment of Preserved Cardiac Function HF with an Aldosterone Antagonist) trial and the BEST (Beta-Blocker Evaluation of Survival Trial). Time in target range (TTR) for each patient was calculated using linear interpolation across the study period with the target range of systolic BP between 120 and 130 mm Hg. ResultsA total of 4,789 hypertensive patients (n = 1,654 from BEST and n = 3,135 from TOPCAT) were included. The cumulative incidences of primary endpoint (ie, cardiovascular death or HF hospitalization) were highest among the top quartile of TTR with a dose-dependent manner across quartiles (Ptrend <0.005). The top quartile of TTR was significantly associated with a lower risk of primary outcome using adjusted Cox regression model (HR: 0.71; 95% CI: 0.60-0.82), cardiovascular mortality (HR: 0.68; 95% CI: 0.55-0.84), HF hospitalization (HR: 0.70; 95% CI: 0.58-0.85), all-cause mortality (HR: 0.69; 95% CI: 0.58-0.83), and any hospitalization (HR: 0.76; 95% CI: 0.67-0.85). Further analyses using restricted cubic spline indicated a linear relationship between TTR and primary outcome. Similar patterns were observed in the individual trial. Sensitivity analyses generated consistent results while redefining target range as 110 to 130 mm Hg for systolic BP or 70 to 80 mm Hg for diastolic BP. ConclusionsTTR could independently predict major adverse cardiovascular events in hypertensive patients with HF.

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

BackgroundST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. MethodsThis prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. ResultsSTEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). ConclusionA genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.

Association Between the Risk for Cardiovascular Events and Antiviral Treatment for Herpes Zoster.

Cardiovascular risk increases following herpes zoster. We investigated whether treatment with antiviral agents, steroids, and common cardiovascular medications was associated with the risk of postherpetic cardiovascular events. This was a nationwide population-based, retrospective, cohort study using the National Health Insurance Service health claims data in Korea. We included patients with a first-ever diagnosis of herpes zoster in 2003-2014 and no prior cardiovascular event. The primary outcome was the occurrence of composites of myocardial infarction (International Statistical Classification of Diseases, Tenth Revision, code I21) and stroke (codes I60-I63) since the herpes zoster. We analyzed the exposure (intravenous or oral administration) to antiviral agents, steroids, antithrombotics, and statins within ±7 days from the index date of herpes zoster diagnosis. Follow-up was performed until occurrence of the primary outcome, death, or 31 December 2015, whichever came first. Of 84 993 patients with herpes zoster, the proportions of patients who received the treatment with antiviral agents, steroids, antithrombotics, and statins were 90.5%, 48.0%, 9.1%, and 7.9%, respectively. During the mean (standard deviation) follow-up period of 5.4 (3.1) years, 1523 patients experienced the primary outcome. Multivariate Cox regression analysis demonstrated that treatment with antiviral agents (adjusted hazard ratio, 0.82; 95% confidence interval, .71-.95) and statins (0.71; .59-.85) were significantly associated with the lower risk of primary outcome. Use of antithrombotics and steroids were not associated with the risk. After herpes zoster, treatment with antiviral agents was significantly associated with lower risk of cardiovascular events. We need more information on the cardiovascular protective role of herpes zoster treatments.

Duration of Clopidogrel-Based Dual Antiplatelet Therapy and Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention - A Real-World Observation in Taiwan From 2012 to 2015.

Little information is available in Asia about the real-world practice of dual antiplatelet therapy (DAPT) duration for acute coronary syndrome (ACS) and its influence on clinical outcomes.Methods and Results:The Taiwan ACS STENT Registry was a prospective, multicenter study to observe ACS patients using clopidogrel-based DAPT after percutaneous coronary intervention (PCI). The primary outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Overall, 2,221 ACS patients (62 years, 83% men) were included. DAPT duration was ≤9 months in 935 (42.1%). The incidence of primary outcome was higher in patients receiving DAPT ≤9 months compared with those receiving DAPT >9 months at 1 year (3.5% vs. 1.6%, P=0.0026). The incidence of stent thrombosis (overall 0.5%) was similar between groups. Multivariable analysis showed that DAPT >9 months was associated with a significantly lower risk of primary outcome (odds ratio 0.725, 95% confidence interval 0.545-0.965). Our data showed that short duration of DAPT (≤9 months) was common (42.1%) in Taiwan for ACS patients undergoing PCI. DAPT ≤9 months increased the risk of the primary outcome.