The prognostic significance of single-lead ST-segment resolution in ST-segment elevation myocardial infarction patients treated with primary PCI - A substudy of the randomized TOTAL trial.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality worldwide. Simple electrocardiogram (ECG) tools, including ST-segment resolution (STR) have been developed to identify high-risk STEMI patients after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We evaluated the prognostic impact of STR in the ECG lead with maximal baseline ST-segment elevation (STE) 30-60 minutes after primary PCI in 7,654 STEMI patients included in the TOTAL trial. Incomplete or no STR was defined as < 70% STR and complete STR as ≥ 70% STR. The primary outcome was the composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or new or worsening New York Heart Association (NYHA) class IV heart failure at 1-year follow-up. RESULTS: Of 7,654 patients, 42.9% had incomplete or no STR and 57.1% had complete STR. The primary outcome occurred in 341 patients (10.4%) in the incomplete or no STR group and in 234 patients (5.4%) in the complete STR group. In Cox regression analysis, adjusted hazard ratio for STR < 70% to predict the primary outcome was 1.56 (95% confidence interval 1.32-1.89; P < .001) (model adjusted for all baseline comorbidities, clinical status during hospitalization, angiographic findings, and procedural techniques). CONCLUSION: In a large international study of STEMI patients, STR < 70% 30-60 minutes post primary PCI in the ECG lead with the greatest STE at admission was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 1-year follow-up. Clinicians should pay attention to this simple ECG finding.

Effects of complete revascularization according to age in patients with ST-segment elevation myocardial infarction and multivessel disease (COMPLETE-AGE).

BACKGROUND: In ST-segment elevation myocardial infarction (STEMI), complete revascularization with percutaneous coronary intervention (PCI) reduces major cardiovascular events compared with culprit-lesion-only PCI. Whether age influences these results remains unknown. METHODS: COMPLETE was a multinational, randomized trial evaluating a strategy of staged complete revascularization, consisting of angiography-guided PCI of all suitable nonculprit lesions, versus a strategy of culprit-lesion-only PCI. In this prespecified subgroup analysis, treatment effect according to age (≥65 years vs <65 years) was determined for the first coprimary outcome of cardiovascular (CV) death or new myocardial infarction (MI) and the second coprimary outcome of CV death, new MI, or ischemia-driven revascularization (IDR). Median follow-up was 35.8 months (interquartile range [IQR]: 27.6-44.3 months). RESULTS: Of 4,041 patients randomized in COMPLETE, 1,613 were aged ≥ 65 years (39.9%). Higher event rates were observed for both coprimary outcomes in patients aged ≥ 65 years comparted with those aged < 65 years (11.2% vs 7.9%, HR 1.49, 95% CI 1.22-1.83; 14.4% vs 11.8%, HR 1.28, 95% CI 1.07-1.52, respectively). Complete revascularization reduced the first coprimary outcome in patients ≥ 65 years (9.7% vs 12.5%, HR 0.77; 95% CI, 0.58-1.04) and < 65 years (6.7% vs 9.1%, HR 0.72; 95% CI, 0.54-0.96)(interaction P = .74). The second coprimary outcome was reduced in those ≥ 65 years (HR 0.56, 95% CI, 0.43-0.74) and < 65 years (HR 0.48, 95% CI, 0.37-0.61 (interaction P = .37). A sensitivity analysis was performed with consistent results demonstrated using a 75-year threshold (albeit attenuated). CONCLUSIONS: In patients with STEMI and multivessel CAD, complete revascularization compared with culprit-lesion-only PCI reduced major cardiovascular events regardless of patient age and could be considered as a revascularization strategy in older adults.

Design and rationale of the CLEAR SYNERGY (OASIS 9) trial: A 2x2 factorial randomized controlled trial of colchicine versus placebo and spironolactone vs placebo in patients with myocardial infarction.

BACKGROUND: Patients experiencing myocardial infarction (MI) remain at high risk of future major adverse cardiovascular events (MACE). While low-dose colchicine and spironolactone have been shown to decrease post-MI MACE, more data are required to confirm their safety and efficacy in an unselected post-MI population. Therefore, we initiated the CLEAR SYNERGY (OASIS 9) trial to address these uncertainties. METHODS: The CLEAR SYNERGY trial is a 2 × 2 factorial randomized controlled trial of low-dose colchicine 0.5 mg daily versus placebo and spironolactone 25 mg daily versus placebo in 7,062 post-MI participants who were within 72 hours of the index percutaneous coronary intervention (PCI). We blinded participants, healthcare providers, research personnel, and outcome adjudicators to treatment allocation. The primary outcome for colchicine is the first occurrence of the composite of cardiovascular death, recurrent MI, stroke, or unplanned ischemia-driven revascularization. The coprimary outcomes for spironolactone are (1) the composite of the total numbers of cardiovascular death or new or worsening heart failure and (2) the first occurrence of the composite of cardiovascular death, new or worsening heart failure, recurrent MI or stroke. We finished recruitment with 7,062 participants from 104 centers in 14 countries on November 8, 2022, and plan to present the results in the fall of 2024. CONCLUSIONS: CLEAR SYNERGY is a large international randomized controlled trial that will inform the effects of low-dose colchicine and spironolactone in largely unselected post-MI patients who undergo PCI. (ClinicalTrials.gov Identifier: NCT03048825).

Evidence Quality and Health Technology Assessment Outcomes in Reappraisals of Drugs for Rare Diseases in Germany.

OBJECTIVES: Evidence on reappraisals of health technologies in Germany is limited, and for rare disease treatments (RDTs), the Federal Joint Committee follows different processes (limited or regular), depending on whether an annual revenue threshold has been exceeded. Our objective is to better understand (re)appraisal processes and their outcomes for RDTs in Germany. METHODS: We analyzed appraisal documents of 55 RDT indications for which an initial appraisal and a reappraisal were conducted between 2011 and 2023. We extracted information for the type of evidence, the risk of bias, the availability of additional evidence, and the change in the maturity of survival data as proxies for evidence quality. Specifically, we reviewed the reasons for conducting reappraisals, examined how evidence quality and the clinical benefit rating (CBR) differed between initial appraisals and reappraisals, and explored the association between evidence quality and (1) the CBR and (2) the change in the CBR after reappraisal. RESULTS: Most reappraisals were conducted because the annual revenue threshold was exceeded or the initial appraisal resolution was time limited. Almost all initial appraisals used the limited process, whereas the majority of reappraisals used the regular process. The CBR increased in only 9 and decreased in 21 of 55 reappraisals. There was some evidence that reappraisals with an accepted randomized controlled trial were significantly more likely to achieve a higher CBR. CONCLUSIONS: Findings confirmed that reasons and processes for conducting reappraisals of RDTs in Germany differ. Further, high CBRs in reappraisals were not common and evidence quality in initial appraisals and reappraisals was limited.