10 practice-changing cardiology trials
M3 India Newsdesk Jan 11, 2021
2020 was a difficult year with COVID-19, but it was also a successful year for cardiology clinical trials. Highlighted below are the summaries and key findings of studies that impacted cardiology practice last year.
SGLT2 inhibitors, antithrombotics, and atrial fibrillation were major elements for the most successful trials among our audience. Indeed, the advent of SGLT2 inhibitors as medications for heart failure is a cause for optimism.
The challenge of managing anti-thrombotic choices never fails to amaze, while clinical trials really help to strengthen our knowledge of which patients gain the most from which regimen. It appears that rhythm regulation for atrial fibrillation has made a return.
TICO: Ticagrelor with or without aspirin in acute coronary syndrome after PCI
Ticagrelor monotherapy following 3 months of DAPT was superior to regular DAPT therapy for 12 months in ACS patients who received PCI with ultra-thin biodegradable-polymer sirolimus-eluting stents. Monotherapy with ticagrelor was successful in avoiding net ischaemic composite and bleeding events. Bleeding incidents are specified by the TIMI guidelines, which require fatal bleeding by means of a reminder.
This experiment is identical to the placebo-controlled but similarly structured TWILIGHT trial. Neither of these studies discussed whether aspirin monotherapy would be similarly successful in place of ticagrelor monotherapy in the 3- to 12-month timeframe. Monotherapy with ticagrelor appears to be an evolving technique, especially for patients with an elevated risk of bleeding after a short period of DAPT.
EMPEROR-Reduced: Empagliflozin outcome trial in patients with chronic heart failure and a reduced ejection fraction
The findings of this study show that empagliflozin is better than placebo in enhancing HF outcomes among patients with symptomatic healthy HFrEF (EF ≤40 percent) on excellent guideline medical therapy (GDMT) regardless of diabetes condition. Gain is largely driven by a decrease in HF hospitalisations, not by mortality. There was an early and sustained advantage to the KCCQ-CSS. There was also a boost of renal results.
This is a very significant study and represents related results from the DAPA-HF dapagliflozin trial. Also, patients with serious LV disorder tended to benefit from this. Of note, the DAPA-HF trial was larger and had a gain in cardiovascular and all-cause mortality for dapagliflozin application.
While sodium-glucose cotransporter 2 (SGLT2) inhibitors have been introduced as type 2 diabetes control drugs, the findings of the EMPA-REG OUTCOME and other trials have shown a significant advantage in the treatment of HF. This study recruited a specific HF population and is conclusively advantageous to this patient population, regardless of the status of diabetes. In future HF management rules, these medications will possibly have a prominent role.
VICTORIA: Vericiguat global study in subjects with heart failure with reduced ejection fraction
A novel technique of increasing soluble guanylate cyclase activity with vericiguat was successful in CHF patients with recent decompensation.
Vericiguat was successful in minimising premature mortality or hospitalisation for heart disease, relative to placebo. Among patients <75 years of age, there was a potential increased advantage. In contrast with placebo, there was no apparent decrease in all-cause mortality with vericiguat. Vericiguat was healthy and well accepted and did not need renal function or electrolyte testing. Among patients with recent heart failure exacerbations, vericiguat may represent a novel therapy.
RIVER: Rivaroxaban for valvular heart disease and atrial fibrillation
The findings of this analysis demonstrate that rivaroxaban in patients with AF/AFL and a bioprosthetic mitral valve is non-inferior to warfarin for the prevention of thromboembolic events. With rivaroxaban, all the strokes were lower.
This is one of the first studies in patients with mitral valve disease and atrial arrhythmias to specifically examine the function of direct OAC (DOAC). These patients have traditionally been treated with warfarin. While there are drawbacks to this trial (open-label architecture, etc.), these results are likely to affect practice. The only concern is that it is uncertain if mitral valve surgery was meant for rheumatic heart disease, particularly mitral stenosis, where warfarin is still prescribed as the preferred OAC.
EAST-AFNET 4: Early treatment of atrial fibrillation for stroke prevention trial
The findings of this significant study suggest that a rhythm management approach is superior to normal treatment (rate control in most cases) in improving 5-year CV results among patients with recent AF diagnosis and concomitant CV conditions. For the primary composite endpoint, as well as for CV death and stroke, major decreases were reported for.
The findings of this research vary from other related tests, such as CABANA-AF, AFFIRM, and RACE. The population enrolled-recent onset (within 12 months) in EAST-AFNET 4 vs. more prolonged AF in the other trials-is one distinction. In the present trial, there was also a relatively high incidence of AF ablation (8 percent at registration, 20 percent at 5 years).
This study is only single-blinded, of course (not to intervention received). That may confuse evaluation of the different endpoints. These results should be promptly considered for a sham-controlled trial to test the true effectiveness of catheter ablation in modulating CV outcomes among patients with AFF, based on recent experiences from substantial sham-controlled trials (SYMPLICITY, ORBITA).
VERTIS CV: Evaluation of ertugliflozin efficacy and safety cardiovascular outcomes trial
The findings of this trial suggest that ertugliflozin in patients with T2DM and developed CVD is non-inferior to placebo for decreasing CV events. While this was not statistically important, patterns were observed to have a positive impact on renal outcomes. An advantage of HHF and HHF/CV mortality with ertugliflozin vs. placebo in patients with higher risk was indicated by subgroup research (presence of albuminuria, higher KDIGO class).
This is the fourth medication to record CV findings on sodium-glucose cotransporter-2 (SGLT2) (after empagliflozin, canagliflozin, and dapagliflozin). In terms of reductions in HF hospitalisations, there seemed to be a consistent class trend, but substantial adverse cardiac injury reductions were statistically significant only for canagliflozin and empagliflozin.
Compared to canagliflozin and empagliflozin, the salutary effects of ertugliflozin tend to be somewhat diminished; it is unknown if this reflects a disparity between studies in patient groups or a real biological difference in medication efficacy (or other issues). As a whole, these are important results, even though SGLT2 inhibitors are first-line agents for T2DM patients, as well as for HF, DM or non-DM patients. These studies contribute to the body of proof that confirms the use of this class in the guidelines.
RATE-AF: Rate control therapy evaluation in permanent atrial fibrillation
Among patients with chronic atrial fibrillation, digoxin struggled to increase quality of life metrics at 6 months compared with beta-blocker.
Given the absence of gain for digoxin on the primary endpoint, digoxin enhanced certain indicators of quality of life at 12 months and was correlated with greater reductions in NYHA class and NT-proBNP.
REALITY: Randomized trial of transfusion strategies in patients with myocardial infarction and anaemia
A conservative PRBC transfusion strategy (transfusion for Hgb <8 g/dl, target 8-10 g/dl) is not inferior to a more liberal strategy (transfusion for Hgb <10 g/dl, target Hgb >11 g/dl). The findings of this analysis suggest that in a more liberal approach, infections and acute lung injuries were higher.
This is a significant trial and speaks against the 10/30 law that post-ACS was once widely practised. One small argument is that in clinical practise in the United States, transfusions are commonly performed for Hgb <7; the threshold examined in this trial was marginally higher (8 g/dl), likely due to the lack of tolerance for Hgb levels <7 g/dl.
POPular TAVI: Antiplatelet therapy for patients undergoing transcatheter aortic-valve implantation
Aspirin alone was associated with a decrease in both bleeding and non-procedural bleeding relative to aspirin plus clopidogrel among patients who underwent TAVR and had no sign of anticoagulation. This benefit was primarily attributed to a dramatic decline in serious bleeding cases. Within 12 months, the function of the valve continued to remain consistent.
The conclusions of this research are close to the ARTE study. Open-label design is a drawback of the experiment. This trial throws some uncertainty on the dual antiplatelet therapy subjective practise after TAVR.
LoDoCo2: Low dose colchicine for secondary prevention of cardiovascular disease 2
The findings of this trial suggest that colchicine increases CV outcomes relative to placebo in patients with chronic coronary artery disease. In MI and ischaemia-driven revascularisation, reductions were reported. There was, however, a signal for greater non-CV colchicine mortality. The aetiology was unknown, but the hospitalisations between the two arms for infections and pneumonia were comparable.
These are fascinating outcomes. The COLCOT trial demonstrated a benefit among a comparable high-risk group in ischaemic outcomes. There was a neutral impact on mortality in that trial (1.8 percent vs. 1.8 percent) and the gain was mostly driven by a decrease in urgent revascularisations. If this is a real indication or a discovery of an opening is uncertain, it will continue to be closely analysed in the future. Colchicine is often stopped due to side effects; 15 percent did not undergo randomisation in this study following enrollment in the run-in process due to side effects.
Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.
The author, Dr. Monish S Raut is a Consultant in Cardiothoracic Vascular Anaesthesiology. His area of expertise is perioperative management and echocardiography with numerous publications in various national and international indexed journals.
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