Double Risk, Double Trouble: Hypertension and Dyslipidemia
28 Apr 2025
Dr Magno leads the first topic on evidence-based management of hypertensionCardiovascular diseases (CVD) are the leading cause of death globally, with hypertension and dyslipidemia as major modifiable risk factors. The coexistence of hypertension and dyslipidemia contributes to an increased risk of CVD, warranting efficient management strategies.1
On February 27, 2025, at the 30th joint convention of the Philippine Society of Hypertension and Philippine Lipid and Atherosclerosis Society, Servier Philippines hosted a lunch symposium led by Dr Jose Donato Magno and Dr Ma. Cecille Cruz. They presented current evidence and evolving approaches in managing clinical scenarios in patients with both hypertension and dyslipidemia.
Evidence-based management of hypertension
Hypertension remains a major public health concern, particularly in Asia, where control rates among treated patients ranged between 35 and 40%, and are as low as 10% in the general population. Asians experience significantly higher systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure compared to Europeans, alongside increased rates of severe hypertension.2 Dr Magno noted that these numbers are an urgent call to review management strategies, taking into consideration evidence-based approaches.
In BP reduction, how low do we go?
The primary goal of hypertension pharmacotherapy is to lower the BP. A meta-analysis of 48 randomized controlled trials (RCT) involving 344,716 participants demonstrated that a 5mmHg reduction in SBP correlates with a 10% decrease in major cardiovascular (CV) events.3 Further evidence supports lowering SBP beyond currently recommended targets likewise decreases CVD.4
Efficacy of ACEis and ARBs
A side-by-side analysis of Cochrane reviews, covering 92 trials on angiotensin converting enzyme inhibitors (ACEis) with 12,954 participants and 46 trials on angiotensin receptor blockers (ARBs) with 13,451 participants, found comparable BP-lowering effects. Baseline levels average at 157/101 mmHg for ACEis and 156/101 mmHg for ARBs.5,6 In addition, a meta-analysis demonstrated that ACEis significantly reduced CV mortality, myocardial infarction, and stroke, not seen in ARBs. (Figure 1).7 Dr Magno stressed that treatment must always be individualized, as multiple factors influence efficacy.
Figure 1. Clinical endpoints of ACEis and ARBs. (7)
*Significant reduction compared to placebo; composite outcome: CV
mortality, MI, and stroke. CV, cardiovascular; MI, myocardial infarction; OR, odds ratio.
European Society of Hypertension (ESH) 2023 guidelines
The latest ESH guidelines advocate an aggressive BP-lowering strategy using single-pill combinations (SPCs) to enhance adherence and therapeutic efficacy, specifically first-line therapy with ACEi or ARB, combined with a calcium channel blocker or thiazide/thiazide-like diuretic.8
Perindopril’s efficient BP control and beyond
An RCT comparing four renin-angiotensin-aldosterone system inhibitors in overweight or obese hypertensive patients demonstrated that perindopril 10 mg achieved the greatest BP reduction.9 Perindopril-based combination therapy was also associated with less BP variability than ARB-based therapy, suggesting a more predictable and consistent BP control and reduced major adverse CV event.10,11
Aside from efficient BP control, other clinical trials demonstrate the effectiveness of perindopril, alone or in combination with indapamide or amlodipine, in reducing CV events, stroke, and mortality across diverse patient populations.12-18
Figure 2. Clinical trials involving perindopril and its combinations (12-18)
Given the evidence presented, Dr Magno raised a critical concern: “Why does there seem to be a disconnect between what we know and what we do?” He urged colleagues to revisit both science and practice and be accountable in ensuring both pharmacologic and non-pharmacologic interventions are applied. He concluded by reminding the audience to critically align their clinical decisions with scientific evidence, tailored to each patient.
Dr Cruz leads the second topic on dyslipidemia management
Paradigm shift in dyslipidemia management
Dyslipidemia has a 34% prevalence among cardiovascular (CV) risk factors, and Dr Cruz noted that this may be due to its often-asymptomatic nature, leading to underdiagnosis or delayed detection and subsequent undermanagement.19
Throughout the years, dyslipidemia risk stratification and management have evolved with concomitant CV risk factors guiding treatment approaches. For high and very high-risk patients, ESC-EAS guidelines recommend> 50% LDL-C reduction from baseline (Figure 3).20 Dr Cruz commented that such a goal may be difficult to achieve with statin monotherapy. The SANTORINI study revealed that a substantial proportion of patients failed to achieve LDL-C targets despite treatment, emphasizing the need fora new treatment approach.21
Figure 3. Risk stratification and treatment goals based on LDL-C level. (20)
New treatment paradigm: first-line combination therapy
Traditional stepwise intensification of lipid-lowering therapy is time-consuming and leads to higher dosing of statin. However, higher statin dosage can result to severe side effects. To avoid unnecessary steps and save time in achieving LDL-C goals, first-line combination therapy, such as statin plus ezetimibe, may be initiated. This approach significantly improves LDL-C reduction and clinical outcomes.22,23
When it comes to LDL-C reduction, larger reductions (1.85 mmol/L, 75th percentile) within 6 weeks were associated with lower CV mortality.24 Dr Cruz emphasized that cholesterol has a linear relationship, and lower LDL-C levels are safe and linked to continuous CV benefits, with no threshold effect. Earlier and more aggressive LDL-C reduction improves outcomes without safety concerns.25
Upfront use of combination high-intensity statin and ezetimibe
Patients with acute coronary syndrome (ACS) or CV risk, especially those needing significant LDL-C reduction, may benefit from upfront high-intensity statin and ezetimibe combination therapy. The IMPROVE-IT trial showed simvastatin plus ezetimibe lowered LDL-C to 54 mg/dL versus 69 mg/dL with simvastatin alone, reducing CV events.26 Similarly, the HIJ-PROPER trial found pitavastatin plus ezetimibe achieved greater LDL-C reduction compared to pitavastatin alone in post-ACS patients.27
Another study, comparing rosuvastatin 10 mg + ezetimibe 10 mg versus rosuvastatin 20 mg alone, demonstrated that the combination achieved greater LDL-C reduction and superior CV outcomes, supporting first-line combination therapy without strict LDL-C thresholds.28
Dr Cruz concluded by emphasizing the importance of assessing CV risk in patients with dyslipidemia to determine LDL-C goals and guide therapy. For patients requiring greater LDL-C reduction, SPCs like rosuvastatin + ezetimibe offer effective and safe pharmacotherapy, particularly for those with high to very high CV risk.
Conclusion
Effective management of hypertension and dyslipidemia, key modifiable CVD risk factors, requires aggressive, evidence-based strategies. For hypertension, lowering BP beyond current targets and utilizing SPCs, such as perindopril-based regimens, can significantly reduce CV events. For dyslipidemia, early and intensive LDL-C reduction through first-line combination therapy (e.g., high-intensity statins with ezetimibe) improves outcomes, especially in high-risk patients. By adopting these integrated approaches, healthcare providers can better address the dual burden of lipitension (hypertension and dyslipidemia), offering patients safer, more effective therapies to improve CV and holistic health outcomes.
On February 27, 2025, at the 30th joint convention of the Philippine Society of Hypertension and Philippine Lipid and Atherosclerosis Society, Servier Philippines hosted a lunch symposium led by Dr Jose Donato Magno and Dr Ma. Cecille Cruz. They presented current evidence and evolving approaches in managing clinical scenarios in patients with both hypertension and dyslipidemia.
Evidence-based management of hypertension
Hypertension remains a major public health concern, particularly in Asia, where control rates among treated patients ranged between 35 and 40%, and are as low as 10% in the general population. Asians experience significantly higher systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure compared to Europeans, alongside increased rates of severe hypertension.2 Dr Magno noted that these numbers are an urgent call to review management strategies, taking into consideration evidence-based approaches.
In BP reduction, how low do we go?
The primary goal of hypertension pharmacotherapy is to lower the BP. A meta-analysis of 48 randomized controlled trials (RCT) involving 344,716 participants demonstrated that a 5mmHg reduction in SBP correlates with a 10% decrease in major cardiovascular (CV) events.3 Further evidence supports lowering SBP beyond currently recommended targets likewise decreases CVD.4
Efficacy of ACEis and ARBs
A side-by-side analysis of Cochrane reviews, covering 92 trials on angiotensin converting enzyme inhibitors (ACEis) with 12,954 participants and 46 trials on angiotensin receptor blockers (ARBs) with 13,451 participants, found comparable BP-lowering effects. Baseline levels average at 157/101 mmHg for ACEis and 156/101 mmHg for ARBs.5,6 In addition, a meta-analysis demonstrated that ACEis significantly reduced CV mortality, myocardial infarction, and stroke, not seen in ARBs. (Figure 1).7 Dr Magno stressed that treatment must always be individualized, as multiple factors influence efficacy.
Figure 1. Clinical endpoints of ACEis and ARBs. (7)
*Significant reduction compared to placebo; composite outcome: CV
mortality, MI, and stroke. CV, cardiovascular; MI, myocardial infarction; OR, odds ratio.European Society of Hypertension (ESH) 2023 guidelines
The latest ESH guidelines advocate an aggressive BP-lowering strategy using single-pill combinations (SPCs) to enhance adherence and therapeutic efficacy, specifically first-line therapy with ACEi or ARB, combined with a calcium channel blocker or thiazide/thiazide-like diuretic.8
Perindopril’s efficient BP control and beyond
An RCT comparing four renin-angiotensin-aldosterone system inhibitors in overweight or obese hypertensive patients demonstrated that perindopril 10 mg achieved the greatest BP reduction.9 Perindopril-based combination therapy was also associated with less BP variability than ARB-based therapy, suggesting a more predictable and consistent BP control and reduced major adverse CV event.10,11
Aside from efficient BP control, other clinical trials demonstrate the effectiveness of perindopril, alone or in combination with indapamide or amlodipine, in reducing CV events, stroke, and mortality across diverse patient populations.12-18
Figure 2. Clinical trials involving perindopril and its combinations (12-18)Given the evidence presented, Dr Magno raised a critical concern: “Why does there seem to be a disconnect between what we know and what we do?” He urged colleagues to revisit both science and practice and be accountable in ensuring both pharmacologic and non-pharmacologic interventions are applied. He concluded by reminding the audience to critically align their clinical decisions with scientific evidence, tailored to each patient.
Dr Cruz leads the second topic on dyslipidemia managementParadigm shift in dyslipidemia management
Dyslipidemia has a 34% prevalence among cardiovascular (CV) risk factors, and Dr Cruz noted that this may be due to its often-asymptomatic nature, leading to underdiagnosis or delayed detection and subsequent undermanagement.19
Throughout the years, dyslipidemia risk stratification and management have evolved with concomitant CV risk factors guiding treatment approaches. For high and very high-risk patients, ESC-EAS guidelines recommend> 50% LDL-C reduction from baseline (Figure 3).20 Dr Cruz commented that such a goal may be difficult to achieve with statin monotherapy. The SANTORINI study revealed that a substantial proportion of patients failed to achieve LDL-C targets despite treatment, emphasizing the need fora new treatment approach.21
Figure 3. Risk stratification and treatment goals based on LDL-C level. (20)New treatment paradigm: first-line combination therapy
Traditional stepwise intensification of lipid-lowering therapy is time-consuming and leads to higher dosing of statin. However, higher statin dosage can result to severe side effects. To avoid unnecessary steps and save time in achieving LDL-C goals, first-line combination therapy, such as statin plus ezetimibe, may be initiated. This approach significantly improves LDL-C reduction and clinical outcomes.22,23
When it comes to LDL-C reduction, larger reductions (1.85 mmol/L, 75th percentile) within 6 weeks were associated with lower CV mortality.24 Dr Cruz emphasized that cholesterol has a linear relationship, and lower LDL-C levels are safe and linked to continuous CV benefits, with no threshold effect. Earlier and more aggressive LDL-C reduction improves outcomes without safety concerns.25
Upfront use of combination high-intensity statin and ezetimibe
Patients with acute coronary syndrome (ACS) or CV risk, especially those needing significant LDL-C reduction, may benefit from upfront high-intensity statin and ezetimibe combination therapy. The IMPROVE-IT trial showed simvastatin plus ezetimibe lowered LDL-C to 54 mg/dL versus 69 mg/dL with simvastatin alone, reducing CV events.26 Similarly, the HIJ-PROPER trial found pitavastatin plus ezetimibe achieved greater LDL-C reduction compared to pitavastatin alone in post-ACS patients.27
Another study, comparing rosuvastatin 10 mg + ezetimibe 10 mg versus rosuvastatin 20 mg alone, demonstrated that the combination achieved greater LDL-C reduction and superior CV outcomes, supporting first-line combination therapy without strict LDL-C thresholds.28
Dr Cruz concluded by emphasizing the importance of assessing CV risk in patients with dyslipidemia to determine LDL-C goals and guide therapy. For patients requiring greater LDL-C reduction, SPCs like rosuvastatin + ezetimibe offer effective and safe pharmacotherapy, particularly for those with high to very high CV risk.
Conclusion
Effective management of hypertension and dyslipidemia, key modifiable CVD risk factors, requires aggressive, evidence-based strategies. For hypertension, lowering BP beyond current targets and utilizing SPCs, such as perindopril-based regimens, can significantly reduce CV events. For dyslipidemia, early and intensive LDL-C reduction through first-line combination therapy (e.g., high-intensity statins with ezetimibe) improves outcomes, especially in high-risk patients. By adopting these integrated approaches, healthcare providers can better address the dual burden of lipitension (hypertension and dyslipidemia), offering patients safer, more effective therapies to improve CV and holistic health outcomes.