ACC ASIA 2023: Experts’ discussion on interrelated cardiovascular diseases

During the Southeast Asian leg of the American College of Cardiology (ACC) International Conferences held from 29 to 30 September 2023, key figures in the Philippine cardiology landscape were invited by Servier to discuss several interesting topics regarding a change in dyslipidemia management and the art of decision making in heart failure. Acting as the scientific chair for the symposium was Dr Rody G. Sy, the past president of the Asian Pacific Society of Atherosclerosis and Vascular Diseases, Philippine Lipid Society, and Philippine Heart Association, with Dr Lourdes Ella Santos, the current president of the Philippine Lipid Atherosclerosis Society, and Dr Glenn Rose Advincula, the head of the Heart Failure Clinical Care Program of The Medical City, as speakers for the said event.

 

Change of Paradigm in Dyslipidemia Management: From Statins to Earlier Combination Use  
Dyslipidemia is the imbalance of lipids such as cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, and high-density lipoprotein (HDL); this condition can lead to cardiovascular disease with severe complications.¹ Low-density lipoprotein cholesterol (LDL-C) not only plays a direct causal role in the development of atherosclerotic cardiovascular disease (ASCVD) but lowering LDL-C is recognized as a key therapeutic option to reduce the risk of CVD, particularly amongst those at highest risk of future events.²

Dr Santos explained that the current guidelines, both internationally and locally, push for attaining the goal of lowering a patient’s LDL-C. The European Society of Cardiology (ESC) guidelines for dyslipidemia (2019) and prevention (2021) have three general recommendations with regard to the current dyslipidemia management paradigm: decide to treat and determine the therapeutic target according to the patient’s risk, use a hierarchical order: lifestyle, statins (start with high-intensity statins only in ACS patients), ezetimibe and PCSK9i, and use a strategy of stepwise intensification to reach the LDL-C target and wait 4-6 weeks before checking if the target is reached.

According to Dr Santos, the limitation of the current paradigm is that it takes time to check if patients are hitting their goal in lowering LDL-C since the paradigm suggests that physicians start their patients first with high-intensity statins, check if the LDL-C goal is reached after six weeks, add non-statin therapy if the goal is not reached, and check the patients’ LDL-C again after six weeks. Three large-scale studies involving the Asian population, namely the Dyslipidemia International Study II (DYSIS II), the Pan-Asian CEPHEUS study, and the Return on Expenditure Achieved for Lipid Therapy in Asia (REALITY-Asia) study all conclude that LDL-C goal attainment is low in Asians, with many patients at very high risk of recurrent CV events despite common usage of lipid-lowering therapy (LLT) since it was not used to its full potential.^3-5

Considering these developments in optimal lipid management based on recent clinical trials, a change in paradigm is in order to address the gaps in the current one. The recommendation is to move from a high-intensity statin approach towards a high-intensity statin plus ezetimibe approach to increase the proportion of patients attaining goals, reduce residual risk, and personalize target cholesterol levels. A study done utilizing the SWEDEHEART registry found that patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70–0.84); all-cause mortality 0.71 (0.63–0.80); CV mortality 0.68 (0.57–0.81); MI 0.81 (0.73–0.91); ischaemic stroke 0.76 (0.62–0.93); heart failure hospitalization 0.73 (0.63–0.85), and coronary artery revascularization 0.86 (0.79–0.94).) This supports the paradigm shift that lower is better; and earlier and larger percent LDL-C reduction is more beneficial to patients.⁶



A journal article published in the European Heart Journal introduced an algorithm for the combination lipid-lowering therapy as a first-line strategy in very high-risk patients, solidifying the advances in the armamentarium of LDL cholesterol-lowering therapy that can enable physicians to achieve LDL cholesterol goals in very-high-risk patients without restriction to a specific drug class.⁷

To conclude, Dr Santos imparted three take-home messages to the audience. She said that physicians should (1) investigate CV risk and use this risk level to determine lipid-lowering therapy in combination with lifestyle modification. Another is to (2) initiate appropriate therapies; physicians should strongly consider a change in paradigm aiming for lower LDL-C and attaining a larger percentage reduction of LDL-C earlier for effective and evidence-based CV prevention. Lastly, Dr Santos urged the audience to (3) intensify treatment strategies from a high-intensity statin approach towards a high-intensity statin plus ezetimibe approach to increase the proportion of patients attaining goals, reduce residual risk, and personalize target cholesterol levels.

Physicians should consider high-intensity lipid-lowering therapy like rosuvastatin + ezetimibe single pill combination as an effective and safe treatment for patients at high to very high risk of CV events.



Heart Failure, Heart Rate, and The Art of Decision Making  
Beta-blockers are one of the cornerstones in the treatment of patients with chronic heart failure (HF) and the relationship between an elevated heart rate (HR) and mortality in patients with chronic HF is well recognized.⁸ Dr Advincula focused on this as she expounded on a study tackling the results from the National Norwegian Heart Failure Registry. Through this study, it was found that in patients with HFrEF and sinus rhythm, an HR of > 70 bpm was associated with worse clinical variables and outcomes.⁸ The 1-year mortality rates after stable follow-up for the 2,689 patients were 3.1, 3.7, 5.8, and 9.1%, respectively, among the patients with an HR <70, 70–79, 80–89, and >89 bpm. A small proportion (4.5%) of the patients who did not use a β-blocker had a 1-year mortality rate of 7.3%. Only 2 of the patients without β-blockade and an HR <70 bpm died (2.7%) in this period.⁸





Another study discussed by Dr Advincula was the Systolic Heart Failure Treatment with the IF Inhibitor Ivabradine (SHIFT) Trial and the effect of combining ivabradine and beta-blockers. In the trial, it was found that whatever beta-blocker was co-prescribed with ivabradine, there were improvements in CV outcomes in patients with systolic heart failure.⁹



In conclusion, while beta-blockers are an essential pillar in the management of chronic heart failure, HF patients whose heart rate is > 70 bpm are found to have worse clinical variables and outcomes. Ivabradine, in conjunction with any beta blocker, can improve CV outcomes in patients with heart failure. Furthermore, the availability of a single pill combination of a beta-blocker (carvedilol) and ivabradine in the Philippines will improve adherence to treatment considering that pill burden is an identified management gap in heart failure.



Open Forum 
After the scientific sessions on dyslipidemia and heart failure, the open forum was led by Dr Rody Sy, the session’s scientific chair. He directed the first question to Dr Santos, asking for the role of deceleration or a cut-off that physicians should look for in lieu of her recommendation for a very strong combination of high-intensity lipid-lowering therapy with ezetimibe. She addressed the question, stating that guidelines are trying to target maximally tolerated statin therapy, and if the patients can tolerate a particular statin, the recommendation is to keep these patients on that statin forever for secondary prevention. Dr Santos also addressed the fact that statin-induced myopathy is fairly high among the Asian population and, using this combination therapy enables physicians to achieve target goals in lipid-lowering while using moderate-strength statin for a lesser risk of myopathy.

One more question asked by Dr Sy was in patients with LDL-C of 40 mmol/L but had an episode of MI, would other possibilities be considered? Dr Santos answers this affirmatively, stating that here in the Philippines, it is recommended to consider genetic dyslipidemia in patients with this kind of clinical picture. In managing patients with genetic dyslipidemia, Dr Santos explained, physicians should go beyond LDL-C and target other molecules such as lipoprotein (a). Since there are limitations in targeting lipoprotein (a) with statin therapy alone, this gives combination therapy another role in patient management.

One important query by Dr Sy regarding heart rate lowering was how would Dr Advincula manage patients whose heart rate is lower than the target (70 bpm) while taking ivabradine with any beta-blocker. Dr Advincula answered that she does not advise down titrating the medications unless patients present with symptomatic bradycardia.