PACUPod: Cardiology

A concise episode summarizing a post hoc analysis of the STEP trial that investigates how baseline cardiovascular risk modifies the balance of benefits and harms of intensive blood pressure control in older hypertensive adults. We cover study design, key findings (overall reduction in cardiovascular events with intensive targets, modest non-significant rise in adverse events), risk-stratified results, practical targets (110–130 mm Hg vs 130–150 mm Hg), and implications for practice in acute, critical, and chronic care—with emphasis on individualized therapy and vigilant monitoring.

In this episode, hosts Britany and Seth unpack the prospective Murcia AF Project III (MAFP-III) cohort study, which investigates remnant cholesterol (RC) and LDL-C discordance as predictors of thromboembolic events in patients with atrial fibrillation on oral anticoagulation. They explain how RC reflects triglyceride-rich lipoproteins (VLDL/IDL), how RC is calculated from standard lipid panels (total cholesterol minus LDL-C minus HDL-C), and the main finding: elevated RC predicts higher thromboembolic risk particularly when LDL-C is low. Over an average follow-up of about 1.86 years, the study reports an adjusted hazard ratio of 1.82 (95% CI 1.03–3.23, p=0.039) for thromboembolic events in the low-LDL-C group, with a linear RC–risk relationship in this subgroup and no similar association for high LDL-C. The episode discusses clinical implications for risk stratification, measurement practicality, and study limitations (observational design, single-center cohort, adherence not fully addressed) and considers future directions for research and potential RC-targeted therapies.

This PACULit update summarizes a single-center, prospective observational study (ChangZhou Registry) evaluating whether initiating dapagliflozin during hospitalization for acute myocardial infarction reduces malignant ventricular arrhythmias in elderly patients and affects all-cause mortality over about seven months. In 2,607 patients aged 60 and older with confirmed AMI, those treated with dapagliflozin were compared to standard care using propensity score matching. The primary outcome was malignant ventricular arrhythmias during hospitalization; the secondary outcome was all-cause mortality (median ~211 days). Results showed malignant ventricular arrhythmias occurred in 2.2% of the dapagliflozin group versus 5.1% in controls, with odds ratios around 0.34 after matching (roughly 60–65% risk reduction). All-cause mortality was also significantly lower in the dapagliflozin group (p = 0.033). The discussion highlights potential mechanisms for antiarrhythmic effects, including improved myocardial metabolism, reduced fibrosis, ion-channel modulation, and attenuated sympathetic activity. Limitations include its single-center, observational design and potential residual confounding, limiting generalizability. The findings suggest potential benefits of early post-AMI dapagliflozin initiation in elderly patients at high arrhythmia risk and align with broader SGLT2 inhibitor cardiovascular effects, while underscoring the need for multicenter randomized trials focused on malignant ventricular arrhythmias.

This PACUPod episode summarizes Barry et al.'s population-based cohort study on the impact of post-CABG P2Y12 inhibitors (primarily clopidogrel) on major adverse cardiovascular events. Using data from British Columbia (2002–2020) involving over 15,000 adults undergoing isolated CABG, exposure was defined as filling a P2Y12 inhibitor prescription within 30 days after surgery, compared with aspirin alone or no antiplatelet therapy. The primary outcome was time to first MACE (all-cause death, nonfatal MI, or nonfatal ischemic stroke) with up to five years of follow-up, and secondary outcomes included individual MACE components and an extended MACE definition. Inverse probability treatment weighting was employed to adjust for confounders. Results showed a 61% relative reduction in MACE risk at one year (hazard ratio 0.39; 95% CI 0.27–0.55) and a sustained ~35% reduction at five years, along with lower hazards for all-cause and cardiovascular death and the extended MACE outcome. Adherence, as measured by proportion of days covered, did not significantly modify outcomes, suggesting early initiation post-CABG is key. The episode discusses clinical implications for routine early initiation of P2Y12 inhibitors (mainly clopidogrel) in combination with aspirin, the need for multidisciplinary coordination to balance ischemic protection with bleeding risk, and remaining knowledge gaps about optimal duration and comparisons with other P2Y12 inhibitors. Limitations include the observational design, residual confounding, and exposure based on prescription fills rather than confirmed ingestion.

This PACULit episode reviews the PRAGUE-25 randomized multicenter noninferiority trial comparing catheter ablation with lifestyle modification plus guideline-directed antiarrhythmic drugs in adults with obesity (BMI 30–40) and paroxysmal or persistent atrial fibrillation. The ablation strategy focused on pulmonary vein isolation, while the lifestyle arm emphasized weight loss and physical activity paired with antiarrhythmic therapy. The primary endpoint—freedom from AF at 12 months (no episodes >30 seconds on a 7-day Holter)—favored ablation (73% vs 34.6%, p<0.001). Although the lifestyle-plus-drug approach achieved meaningful metabolic gains (average weight loss ~6.4 kg and HbA1c improvement), it did not translate into superior rhythm control. Follow-up averaged ~23.5 months with quarterly rhythm monitoring. The study supports catheter ablation as the preferred rhythm-control strategy in obese AF patients when rhythm suppression is the goal, while lifestyle modification remains important for metabolic risk reduction. Strengths include randomized multicenter design and objective rhythm monitoring; limitations include the 12-month primary endpoint and applicability to patients with more severe comorbidities.

This PACULit episode reviews a large observational cohort study by Aebi et al. using UK CPRD data (2000–2021) to compare new monotherapy users of amlodipine, ramipril, and bendroflūmethylthiazide (bendroflumethiazide) and to assess risk of acute outpatient infections (respiratory, genitourinary, gastrointestinal, sepsis) and SARS-CoV-2 infection during 2020–2021. The primary comparisons were amlodipine versus ramipril and amlodipine versus bendroflumethiazide, with follow-up from prescription start to infection, censoring, or study end. Propensity score weighting balanced baseline covariates, and the study excluded individuals with prior cardiovascular disease to reduce confounding. Findings showed lower infection incidence among amlodipine users (IRR 0.77 vs ramipril; 0.78 vs bendroflumethiazide; infections per 1,000 person-years: 38.9 vs 51.6). During the COVID-19 period, amlodipine was associated with a 43% reduced risk of diagnosed SARS-CoV-2 infection (IRR 0.57). The discussion notes potential immunomodulatory and anti-inflammatory mechanisms, cites in vitro and endothelial studies, and acknowledges limitations inherent to observational designs (residual confounding, potential misclassification, and lack of randomized causality). Implications suggest considering possible infection-related benefits when initiating antihypertensive therapy, while emphasizing the need for randomized trials to confirm causality and assess broader outcomes.

Myocardial bridge (MB) is a common congenital coronary anomaly where a coronary artery tunnels through the myocardium, causing systolic compression. This PACUPod overview examines whether single antiplatelet therapy (APT), such as aspirin, provides ischemic protection for MB patients without other indications, and how the RIALTO registry informs clinical practice. The ambispective study analyzed 221 MB patients after excluding those with established APT or anticoagulation indications, comparing mostly aspirin at discharge versus no APT over a median follow-up of 4.5 years. The primary outcome, net adverse clinical events (NACE), combined cardiovascular death, nonfatal MI, need for coronary imaging, ischemic stroke, and bleeding events. After adjustment for confounders and propensity-matching, single APT was associated with a higher NACE rate (adjusted HR 6.2, p=0.03), chiefly driven by increased minor bleeding (adjusted HR 10.58, p=0.02), with no significant reduction in ischemic events. The findings align with 2019 ACC/AHA primary prevention guidance that cautions aspirin use in the absence of established disease and challenge routine APT in MB patients. The episode discusses MB pathophysiology—ischemia largely results from mechanical compression rather than plaque rupture—and explores management implications, including prioritizing personalized risk assessment, shared decision-making, and careful medication review. Alternatives such as beta-blockers and calcium channel blockers, as well as selective surgical or stenting options for refractory cases, are considered. The role of diagnostic and functional testing (IVUS, OCT, stress imaging) in guiding therapy and avoiding unnecessary APT is highlighted, along with study limitations (observational design, residual confounding) and the need for randomized trials. Related research (e.g., ADAPTT 2023) and the broader context of coronary anomalies are discussed to emphasize individualized care rather than reflexive antiplatelet use.