Key Points:

• Early high-intensity statin therapy is standard of practice in acute STEMI patients, but this is often insufficient to achieve LDL targets. PCSK-9 therapy has never been tested as routine therapy in STEMI.
• In the EPIC STEMI trial, routine PCSK-9 initiation in addition to high-intensity statin prior to primary PCI resulted in a 22% LDL reduction at 6 weeks relative to sham, with a higher proportion of patients achieving therapeutic LDL targets.

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A recent trial by Dr. Salim Yusuf, published in The New England Journal of Medicine, indicated that combination therapy with aspirin plus a polypill (consisting of a statin plus three blood-pressure-lowering drugs) can reduce the incidence of cardiovascular events compared with placebo among participants without established cardiovascular disease, but at moderate cardiovascular risk.

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A recent trial by Dr. Jordana B Cohen, published in The LANCET, indicated that consistent with international society recommendations, patients admitted to the hospital with COVID-19 can safely continue treatment with renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB)) unless there is a distinct medical contraindication to ongoing therapy.

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A recent study by Dr. Bernard R. Chaitman, published in Circulation investigated the impact on clinical interpretation of using different definitions for myocardial infarctions in the ISCHEMIA trial.

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Results of the DAPA trial, published in Circulation: Arrhythmia and Electrophysiology, demonstrated that the use of early prophylactic implantable cardioverter defibrillator (ICD) in high-risk post-primary percutaneous coronary intervention (PCI) patients was associated with lower all-cause and cardiac mortality rates. However, the results of this trial should be interpreted with caution, since the trial was stopped prematurely.

The optimal timing of ICD implantation in STEMI patients treated with primary angioplasty is not identified yet. Previous clinical trials have failed to show the benefit of early ICD implantation (4-60 days) in post-MI patients with a low left ventricular ejection fraction (≤35-40%). The risk of sudden cardiac death (SCD) is high within the post STEMI period.  However, ICD implantation after 40 days may not be indicated due to left ventricular remodeling and a potential increase in LVEF post-primary PCI. The Defibrillator After Primary Angioplasty (DAPA) trial evaluated all-cause and cardiac mortality of patients undergoing early prophylactic ICD implantation after PCI for STEMI. Following a recommendation from the data safety board, the trial was terminated early after just 38% of the planned sample size was enrolled due to slow enrollment.

This multicenter, randomized, controlled trial included patients with STEMI who had undergone primary PCI and met at least one of the following criteria: LVEF<30% within 4 days after admission, primary ventricular fibrillation (VF) within 24 hours (during PCI excluded), signs of heart failure on admission (Killip class ≥ 2), and/or thrombolysis in myocardial infarction (TIMI) flow post PCI < 3. The participants were randomized in a 1:1 ratio to receive either ICD implantation or conventional therapy within 30 to 60 days of the STEMI event. The primary endpoint was all-cause mortality at 3 and 9-years. The secondary endpoints of the study included the incidence of sudden cardiac death (SCD) and hospital admission for sustained ventricular tachyarrhythmias or appropriate ICD therapy.

A total of 266 patients with primary PCI for STEMI were included in the study with 131 patients allocated to the ICD arm and 135 patients assigned to the conventional therapy arm. After 3-years of follow-up, the primary outcome of interest was significantly lower among patients who received ICD implantation (5%) compared to the conventional therapy group (13%) (Hazard ratio (HR):0.37; [95% CI: 0.15-0.95]; p=0.04). This result remained similar at a median of 9-years follow-up (HR: 0.58; [95% CI: 0.37-0.91]; p=0.02). In terms of cardiac mortality, ICD implantation was associated with fewer deaths (11%) compared to the control group (22%) (HR: 0.52; [95% CI: 0.28-0.99]; p=0.04). Although not statistically significant, the incidence of SCD was also lower in the ICD group (3.1%) compared to the control group (5.9%) (HR 0.45; [95% CI 0.14–1.50]; p=0.19).

The results of this study should be interpreted with consideration of the following limitations. First, the premature termination of the study makes it underpowered for analysis. Second, the study used more than one inclusion criteria, so results should be interpreted with consideration of the patient characteristics. The high treatment crossovers (10.2%) within the first 3 years of the study and the lack of information on treatment crossovers between 3 and 9 years are additional limitations of the trial.  Furthermore, while pharmacotherapy of the participants was similar at baseline, there is a lack of data regarding the follow-up medical therapy which may have impacted the mortality rates.

In conclusion, this prematurely terminated trial suggests that early prophylactic ICD implantation may be associated with a better survival rate in patients at high risk of death after primary PCI for STEMI. The results of this trial should be confirmed in future studies.

A recent study by Dr. Banerjee, published in Circulation: Cardiovascular Interventions, demonstrated the efficacy and safety of low-density lipoprotein (LDL) lowering therapy via a single LDL apheresis treatment plus ongoing statin therapy in nonfamilial hyperlipidemia acute coronary syndrome patients treated with the percutaneous coronary intervention (PCI).
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The post hoc analyses of GLOBAL LEADERS study by Dr. Hara, published in Circulation: Cardiovascular Quality and Outcomes reported that in multiple statistical analyses considering the total number and severity of bleeding and ischemic events, ticagrelor monotherapy consistently decreased the risk of these events by 5% to 8% compared to 1-year conventional dual antiplatelet therapy. This analysis supported the beneficial effects of ticagrelor monotherapy after percutaneous coronary intervention. Continue reading →

A recent meta-analysis of clinical trials with more than 100,000 patients has shown that the carotid intima-media thickness (cIMT) progression can be used as a surrogate marker for cardiovascular risk in the clinical trials. The results of this study published in Circulation. According to Dr. Willeit, the assessment of cIMT progression can provide a link for the development and license of new therapies for cardiovascular disease. Continue reading →

A recent study by Dr. O’Donoghue, published in Circulation, shows that early aspirin discontinuation with continued P2Y12 inhibitor monotherapy, after the percutaneous coronary intervention (PCI),  was associated with a significant reduction in major bleeding compared to dual antiplatelet therapy. This study did not show a significant increase in major adverse cardiovascular events (MACE) after aspirin discontinuation in the participants.
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A recent study by Dr. Julinda Mehilli, M.D., published in Circulation journal, has shown that in patients undergoing elective percutaneous coronary intervention (PCI), pretreatment strategy with the intensified prasugrel loading does not differ from standard clopidogrel loading dose in terms of Safety and Efficacy. According to the trial, both strategies can be safely applied among patients undergoing elective PCI.
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The post hoc analysis of the SCOT-HEART trial by Dr. Adamson MBChB, Ph.D. published in JAMA Cardiology showed that abnormal results of exercise electrocardiography (ECG) were strongly associated with coronary revascularization and increased risk of mortality from coronary heart disease. However, coronary computed tomography (CT) angiography was a more accurate predictor of 5-year coronary events compared with exercise ECG alone. Continue reading →

A recent study by Dr. Mehra, published in the New England Journal of Medicine, disapproved of the previously concerning idea regarding the potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in the clinical context of Coronavirus disease 2019 (Covid-19). This study also demonstrated that Covid-19 may disproportionately affect individuals with cardiovascular disorders.
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In an original investigation done by Dr. Alexander C. Fanaroff et al and recently published in JAMA Cardiology, it was found that there was discordance in medication persistence as measured by patient-reported and the pharmacy fill data. The patient self-reports overestimated and pharmacy fill data underestimated medication persistence. Those who had non-persistence by both measures had the highest rate of major adverse cardiovascular events (MACE). The authors also noted the need for giving preference to interventions that will promote medication-taking behavior. Continue reading →

A recent study by Dr. van der Hoeven, published in the Journal of American Heart Association, has shown the superiority of ticagrelor over prasugrel in patients presenting with ST-segment-elevation myocardial infarction (STEMI). According to the author, ticagrelor has a higher efficacy in platelet inhibition as well as in improving endothelial function when compared with prasugrel. Continue reading →

A recent study by Dr. Knott, published in Circulation, have shown the prognostic value of measuring myocardial blood flow (MBF) using artificial intelligence quantification of cardiovascular magnetic resonance (CMR) perfusion mapping in cardiovascular outcomes. According to this study, both MBF and myocardial perfusion reserve (MPR) were associated with death and major adverse cardiovascular events (MACE) independently of other clinical risk markers. Using this technique, quantitative analysis of myocardial perfusion for clinical use is now available. Continue reading →

A recent study by Dr. Chapman, published in Circulation, showed that implementation of high sensitivity cardiac troponin (hs-cTn) and the fourth universal definition of myocardial infarction (MI) increased the identification of patients at risk for cardiovascular and non-cardiovascular events, but failed to improve the outcomes. This study warrants the importance of seeking new strategies to improve outcomes in patients with type 2 MI and myocardial injury. Continue reading →

Raphael et al. showed in a prospective cohort study, published in Circulation, that type 2 myocardial infarction (T2MI), defined as an acute imbalance between oxygen delivery to the myocardium and the demand of the myocardium in the absence of athero-thrombosis, is associated with higher all-cause mortality compared to type 1 myocardial infarction (T1MI) caused by athero-thrombotic events, with no difference between these 2 groups regarding cardiovascular death.

Raphael et al. retrospectively included 5,460 patients with high troponin levels (more than 0.01) and divided them into 2 groups of T1MI and T2MI. They followed up the patients for 5.5 years. Cases with prior MI were excluded from the analysis.

After including the cases, they retrospectively classified MI types by 2 cardiologists based on clinical signs and laboratory results. MI was defined by a rise and/or fall in cardiac troponin T (cTnT) associated with either ischemic symptoms, new/presumed new ECG changes, new imaging evidence of ischemia, or direct identification of intracoronary thrombus on angiogram or autopsy. The cardiologists defined T2MI based on elevated cardiac troponin without other necessary factors. Other different types of MI including procedure-related MI were categorized as T1MI. They encountered the first MI event as the main event in cases with multiple MI events. They further subclassified T2MI based on its cause to the following subclasses: Arrhythmia, hypotension, anemia, post-surgical status  (in the absence of other causes e.g., T1MI and arrhythmia), hypoxia, and other (including spontaneous coronary artery dissection, coronary embolism, coronary spasm, structural heart disease e.g., severe aortic stenosis and malignant hypertension). They prospectively gathered the information regarding the mortality cause in the patients from the available documents, and divided the cause of mortality into either cardiovascular or non-cardiovascular.

The results showed that 56% were adjudicated as T1MI and 43% as T2MI. Patients with T2MI were older, female gender predominant, with a higher prevalence of chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) while patients with T1MI were more likely to present with other well known MI risk factors. They also showed a lower level of sufficient MI related medical treatment in the T2MI group compared to T1MI. The rate of MI in both types has shown a decrease in incidence in the population. The rate of all-cause mortality was calculated after sex and age adjustment, and results implicated that the all-cause mortality rate was significantly higher in T2MI compared to T1MI even after adjustments. They showed that the risk of cardiovascular death is the same in both T1MI and T2MI, which may indicate the necessity of better diagnosis and treatment of T2MI after an encounter.

There is a lack of information regarding the T2MI incidence and effect on mortality in the general population. Raphael et al. tried to add to our current knowledge regarding this common type of MI by addressing the effect of this condition on all-cause and cardiovascular mortality.

One of the major factors encountered as a limitation for this study may be the difficulty faced in the diagnosis of T2MI in the clinical setting. A question has still remained that if treatment of T2MI with the same treatment protocol as T1MI will help to decrease cardiovascular and all-cause mortality in the patient’s population.

A cross-sectional observational study enrolling 223 patients with 3-vessel coronary artery disease, has shown that compared to conventional invasive coronary angiography, a noninvasive physiology assessment using fractional flow reserve CT scanning (FFRCT or multi-slice CT scanning) changed heart team’s treatment decision-making and procedural planning in 1/5th of the patients.

The SYNTAX III REVOLUTION Trial was a randomized, multi-center study which randomized two heart teams to make a treatment decision between percutaneous coronary interventions (PCI) and coronary artery bypass grafting (CABG) using either coronary computed tomography angiography (CTA) or conventional invasive angiography while blinded to the other imaging modality. The study included patients with complex coronary artery disease, defined as, left main (isolated, or associated with 1, 2 or 3 vessel disease) or de novo 3-vessel coronary artery disease (DS ≥50%), who were able to receive cardiac CT with a multi-slice CT scanner. Coronary CTA was performed with the GE Revolution CT scanner that has a nominal spatial resolution of 230 microns along the X–Y planes, a rotational speed of 0.28 s, and a Z-plane coverage of 16 cm enabling to image the heart in one heartbeat. Patients with concomitant atrial fibrillation, cardiac valve disease and prior history of PCI or CABG were excluded from the study. The primary outcome was the inter-rater agreement (assessed by Cohen’s Kappa Kappa; a value of 0.82) on revascularization strategy of two heart teams by employing the use of either an “Angio-first” algorithm or a “CT First” algorithm 1 to 2 weeks after patient enrollment. The addition of FFRCT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as a reference, FFRCT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile.

The American and European guidelines recommend a heart team based approach for the decision-making process regarding the revascularization strategy and recommend the evaluation of the anatomical complexity using the SYNTAX score. Patients with SYNTAX scores >34 have been found to do much better with bypass surgery than those with lower SYNTAX scores. The SYNTAX scores can be divided into three tertiles. Higher scores signify complex conditions and indicate greatest risks to patients undergoing PCI. Calculation of the SYNTAX score takes into account complex lesions including bifurcations, chronic total occlusions, thrombus, calcification, and small diffuse disease with a total of 11 measures of lesion complexity. The score ranges from 0 to greater than 60 in very complex coronary anatomy.

Previously validated SYNTAX II score utilizes SYNTAX I score and then combines it with clinical prognostic variables such as age, creatinine clearance, gender, left main vessel involvement, left ventricular ejection fraction, chronic obstructive pulmonary disease (COPD) and peripheral vascular disease (PVD) in order to guide selection between PCI and CABG for patients with multivessel coronary disease. The results of the SYNTAX III Trial suggest the potential feasibility of a treatment decision-making and planning that stems from a non-invasive imaging modality and clinical information.

A randomized, double blind, placebo-controlled, phase II clinical trial studying the effect of a novel protein proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis inhibitor (inclisiran) on serum low density lipoprotein cholesterol (LDL-C) levels has shown that twice a year subcutaneous injections of inclisiran leads to a sustained dose-dependent reduction in serum LDL-C levels over a period of 1 year.

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A randomized, double-blinded, placebo-controlled trial which enrolled 7119 high risk  patients with coronary artery disease who had undergone recent percutaneous coronary intervention (PCI) has shown that, after 3 months of dual anti-platelet therapy (DAPT) using a P2Y12 receptor blocker (ticagrelor) and aspirin, continuing secondary prevention with a single anti-platelet therapy (SAPT) with ticagrelor alone reduces bleeding as compared to extended DAPT.

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