NEW INSIGHTS IN THE PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE

At the recent joint convention of the Philippine Lipid and Atherosclerosis Society and the Philippine Society of Hypertension, held last February 21st and 22nd, 2024, Dr Deborah Ona and Dr Federick Cheng shared new insights on primary and secondary prevention of cardiovascular diseases. 

Dyslipidemia andhypertension: Major drivers of ASCVD

Lipitension, which means the coexistence of hypertension and dyslipidemia, accelerates atherosclerosis, thereby increasing the risk of atherosclerotic cardiovascular disease (ASCVD).^1,2 Dr Ona emphasized that preventing the outcomes of this phenomenon involves efficient control of blood pressure, risk identification and stratification to properly direct treatment and dyslipidemia management.

Dr Ona presented a case of a 45-year-old female smoker with elevated blood pressure, a BMI of 31.25 kg/m2, LDLC-C of 141mg/dl and a family history of ASCVD. With this scenario, she guided the audience on new perspectives in primary prevention of cardiovascular disease.

Primary Prevention of Cardiovascular Disease

Prolonged exposure to elevated blood pressure is a significant indicator of potential cardiovascular disease, with studies showing that reducing systolic blood pressure by just 5mmHg can lower the risk of major adverse cardiovascular events by 10%.^3,4 Therefore, the European Society of Cardiology (ESC) advises initiating therapy with a single-pill combination (SPC) comprising an ACE inhibitor or ARB along with a CCB or diuretic for uncomplicated hypertension.⁵

However, it is crucial to recognize that solely focusing on blood pressure management might not suffice. Categorizing patients based on their overall cardiovascular risk yields more substantial benefits. In addition to blood pressure control, the ESC recommends statins for individuals at high or very high risk of cardiovascular events. Furthermore, even patients at low to moderate risk may benefit from statin therapy.⁵

When addressing dyslipidemia, Dr Ona emphasizes the importance of a swift, lower, and sustained reduction in LDL-C levels. Initiating treatment with an LDL-C-lowering agent such as a statin early on can significantly reduce the risk of cardiovascular events.

According to the ESC guidelines (Figure 1), the patient above is classified moderate risk, requiring an LDL-C goal of <100 mg/dl.⁶ The Philippine guideline recommends initiating statins if the patient has diabetes mellitus, an LDL-C > 130 mg/dl, fulfills criteria for Familial Hypercholesterolemia, has ASCVD, CKD-ND, or is > 45 years with two or more risk factors.⁷ Given the patients’ profile and history, statin initiation is warranted along with intensive control of blood pressure through combination therapy.

The benefits of adding a statin in a dual antihypertensive therapy is evidenced by the ASCOT trial which revealed a reduced risk of stroke, total cardiovascular events and procedures, and total coronary events.⁸ Lifetime exposure to a lower level of LDL-C (1mmol/L lower) and lower systolic blood pressure (lower by 10 mmHg results) constitutes an 80% lower CVD risk and 68% lower CV mortality risk.⁹ In addition, the ASCOT legacy trial which followed up patients more than 10 years after the ASCOT trial revealed a 15% lower risk of CV death for patients who were given atorvastatin.¹⁰

Furthermore, a pooled analysis of the effects of perindopril-based regimen showed a 91.2% cumulative event-free survival in the statin/perindopril group.¹¹ The WHO also recognized a fixed dose combination of atorvastatin + perindopril + amlodipine as a cost-effective medication for the prevention ASCVD.¹²

To end her lecture, Dr Ona shared key takeaways. First, a combined approach in treating lipitension with single-pill combination (SPC) is now recommended by international guidelines for optimal CV risk reduction. Second, initial combination therapy allows earlier goal attainment, translating into lesser exposure to risk factors. And last, atorvastatin + perindopril + amlodipine SPC has proven its benefits in addressing lipitension and in the primary prevention of cardiovascular disease.

 

Secondary Prevention of Cardiovascular Disease

Dr Cheng presented valuable insights into the management of patients with pre-existing cardiovascular disease. He began his presentation with a case study involving a 52-year-old male who is currently on a regimen of Rosuvastatin 10 mg and has a history of 8 pack-years of smoking. The patient reports occasional leg cramps and presents with chest pain and elevated troponin levels. Upon examination, his blood pressure is found to be elevated, while his laboratory results indicate an LDL-C level of 73 mg/dL, with other lipid profile parameters within normal ranges.

According to the guidelines outlined by the European Society of Cardiology (ESC), the patient falls into the category of very high risk, with the recommended target LDL-C level being <55 mg/dL (refer to Figure 1). Considering the presence of atherosclerotic cardiovascular disease (ASCVD), statin therapy is mandated by the Philippine guideline, which aligns with the current treatment regimen of the patient.⁷ For patients with very high risk of cardiovascular disease, ESC guidelines (refer to Figure 2) recommend upfront use of a high-potency statin plus ezetimibe as initial therapy.⁶

 

 

A change in paradigm of cardiovascular disease management

Despite being classified as high or very high risk, many patients, particularly in Asia, fail to achieve their target LDL-C levels. A cross-sectional study revealed that 20.8% of coronary artery disease patients de-escalated their lipid-lowering therapy upon hospital discharge, while only 11.7% commenced intensified lipid-lowering therapy.¹³ Additionally, another study indicated a decrease in the portion of patients on high-intensity statins from 50% to 30% over five years, with only 45% of initially adherent patients maintaining their lipid-lowering regimen.¹⁴ These findings suggest a need for a paradigm shift in ASCVD management.

Dr Cheng emphasized the significance of achieving lower, earlier, and larger LDL-C reduction in the secondary prevention of ASCVD. Findings from a nationwide cohort study demonstrated that a greater reduction in LDL-C levels and more aggressive statin therapy following myocardial infarction (MI) were linked to a decreased risk of cardiovascular events and all cause-mortality.¹⁵

Several clinical trials support the use of moderate to high intensity statin plus ezetimibe in patients with ASCVD. ^16,17 Concurrently, ESC recommends starting high and very high-risk patients on a high intensity statin such as rosuvastatin plus ezetimibe (Figure 2) for a more efficient reduction of LDL-C.¹⁸ Hence for the case presented, a combination of a statin and ezetimibe can thereby help achieve LDL-C levels fast and right.

Dr Cheng concluded that: (1) investigating CV risk helps determine the appropriate lipid lowering therapy; (2) strongly considering a paradigm change and aiming for a lower LDL-C attains a larger reduction of LDL-C earlier with effective and evidence-based CV prevention strategies; (3) intensifying treatment by considering high intensity lipid -lowering therapy like Rosuvastatin + Ezetimibe SPC as an effective and safe treatment for patients with high to very high risk of CV events.

 

Conclusion

To conclude the session, Dr Gonzales led a discussion with the speakers covering three key points: Firstly, they addressed the inclusion of combination therapy in local guidelines, considering recommendations from international societies like the ESC and ACC, while also noting the influence of current evidence and local demographics. Dr Gonzalez emphasized the importance of individualized therapy, especially for patients with very high-risk cardiovascular disease. Secondly, the panel discussed aggressive therapy for secondary prevention, advocating high-intensity statins combined with non-statin therapy such as ezetimibe for very high-risk patients and highlighting the trend towards early initiation of combination therapies both for dyslipidemia and hypertension. Thirdly, adherence plays a key role in improving patient outcomes, ideally with long-acting agents. Single-pill combinations were highlighted for enhancing medication adherence.

The conversation underscored the importance of proactive measures in primary prevention of cardiovascular disease, stressing the need for meticulous blood pressure management and thorough risk assessment to guide the initiation of combination antihypertensive therapies with statins. In the realm of secondary prevention, lifestyle modifications are coupled with aggressive lipid reduction strategies, often employing upfront use of “high-intensity lipid lowering therapy” such as the combination of a statin + ezetimibe.

Single-pill combination therapies such as statin plus antihypertensive medications, and statins plus ezetimibe, play a pivotal role in enhancing medication adherence. This approach facilitates swifter, earlier, and more sustained attainment of target blood pressure and LDC-C levels, ultimately leading to improved cardiovascular outcomes.