"Shifting hypertension management…'indapamide'-based triple comb"

Target blood pressure adjusted to 130/80…has expanded the importance of early intervention with combination therapies

Highlighted the use of SPC…the guidelines recommend the alternative option of using S-amlodipine in patients experiencing swelling

The standard of care in hypertension treatment is shifting.

The recently announced 2026 Guidelines for Hypertension have strengthened target blood pressure goals to below 130/80 mmHg for high-risk cardiovascular patient populations while actively recommending the implementation of upfront combination therapies. As achieving these blood pressure targets relies heavily on dual and triple regimens alongside Single-Pill Combinations (SPCs), changes to treatment strategies are anticipated.

Professor Kwang-il Kim of the Department of Geriatric Medicine at Seoul National University Bundang Hospital

This revision expands beyond a simple numeric adjustment of blood pressure targets. Its significance lies in integrating proactive blood pressure-lowering strategies validated by recent landmark clinical trials, including STEP, ESPRIT, and BPROAD. These studies confirmed that intensive blood pressure control directly correlates with a reduced risk of major cardiovascular and cerebrovascular events and mortality.

According to the revision, the target blood pressure for hypertensive patients with concomitant diabetes has been systematically lowered to below 130/80 mmHg. Similarly, for patients with chronic kidney disease (CKD), a strict target below 130/80 mmHg is now recommended regardless of proteinuria status, with instructions to consider a systolic blood pressure (SBP) target below 120 mmHg if tolerated by the patient. Furthermore, the SBP target for patients with a history of stroke has been intensified from the conventional threshold of below 140 mmHg to below 130 mmHg.

In contrast, the target blood pressure for elderly hypertensive patients and general patients presenting with uncomplicated hypertension remains at the previous threshold of below 140/90 mmHg. This differentiation reflects clinical evidence showing clear prognostic benefits from aggressive blood pressure reduction in high-risk cohorts, contrasted against insufficient data supporting additional clinical benefits for intensive lowering in low-to-moderate risk populations.

Professor Kwang-il Kim of the Department of Geriatric Medicine at Seoul National University Bundang Hospital, who also serves as the Chairman of the Korean Society of Hypertension, discussed these shifting paradigms. During a meeting with DailyPharm, Kim said, "
Managing systolic blood pressure down to 130 mmHg is significantly different from managing to 140", and added, "Because target blood pressure metrics have lowered, patients will likely require the addition of one or more therapeutic intervention, requiring active treatment."

Professor Kim emphasized that "Lowering blood pressure targets in high-risk patient populations is not merely shifting metrics, but a foundational clinical approach to reducing overall cardiovascular event risk and improving long-term prognosis."

Early intervention using second-line treatment is highlighted

Hypertension remains a primary risk factor driving critical cardiovascular sequelae, including myocardial infarction, stroke, heart failure, and chronic kidney disease. For patients with preexisting metabolic or structural comorbidities like diabetes, CKD, or a history of cardiovascular events, even marginal elevations in baseline blood pressure can exponentially increase the risk of an acute cardiovascular event, necessitating rigid clinical control. 

Consequently, the updated guidelines indicate the importance of early use of combination therapy alongside tighter blood pressure targets.

Previously, standard clinical practice followed a stepped-care approach, initiating monotherapy and only escalating dosages or adding secondary classes if a patient failed to achieve target ranges. However, real-world clinical environments have long struggled with therapeutic inertia, where physicians fail to intensify treatment regimens despite patients missing their therapeutic targets. This has been criticized as a major barrier to improving blood pressure control rates.

Professor Kim explained, "Clinical tendencies among healthcare providers and patient medication adherence represent are the primary reasons for blood pressure control failure," and added, "To rapidly achieve and sustainably maintain target blood pressure over long-term timelines, initiating appropriate combination therapies early in the treatment algorithm is essential, adding that deploying these regimens as fixed-dose SPCs is highly preferable."

To support the clinical adoption of SPCs, the 2026 guidelines have introduced a modernized classification framework that categorizes these formulations into ultra-low-, low-, standard-, and high-dose combinations. The Korean Society of Hypertension formally positions SPCs as therapeutically superior to loose-dose multi-pill combinations, particularly in terms of blood pressure reduction rates and long-term treatment persistence.

Professor Kim highlighted that South Korea possesses a distinct competitive advantage given its highly developed pipeline of diverse SPC formulations and dosage configurations, noting that this wide selection significantly enhances prescribing flexibility for clinicians.

Guidelines introduced the category of intractable hypertension…has expanded the importance of triple combination therapy

The updated guidelines have also newly introduced the diagnostic and therapeutic approach for patients presenting with difficult-to-treat hypertension.

Most notably, the guidelines have officially introduced the clinical definition of 'intractable hypertension,' expanding upon the traditional concept of resistant hypertension. Intractable hypertension classifies cases where patients fail to reach their target blood pressure goals despite the concurrent utilization of two or more antihypertensive drug classes, including a mandatory diuretic component. This expanded categorization integrates both resistant and refractory hypertension, thereby establishing more systematic diagnostic and therapeutic algorithms in real-world clinical practice.

When intractable hypertension is suspected, the guidelines advise clinicians against blindly escalating pill burdens. Instead, providers are directed to first verify patient medication compliance and validate the accuracy of blood pressure measurements. Clinicians must rule out white-coat hypertension by using home blood pressure monitoring (HBPM) or ambulatory blood pressure monitoring (ABPM), while thoroughly evaluating secondary hypertension etiologies, lifestyle factors, and concomitant medications that may inadvertently elevate blood pressure.

Professor Kim emphasized that "Unadjusted high blood pressure readings do not automatically indicate absolute drug resistance," and added, "Poor compliance, measurement errors, or white-coat effects frequently skew clinical metrics." 

"Once these confounding variables are resolved, a more intensive pharmacotherapeutic strategy must be applied to patients who remain uncontrolled."

Specifically, the guidelines highlight the therapeutic importance of a triple combination regimen anchored by an ACE inhibitor or Angiotensin Receptor Blocker (ARB), a Calcium Channel Blocker (CCB), and a diuretic.

Because the pathogenesis of hypertension involves multifaceted, overlapping systems, such as renin-angiotensin system activation, peripheral vasoconstriction, and volume expansion, a triple combination addressing these separate pathways simultaneously is recognized as a highly effective clinical strategy.

Professor Kim stated, "Targeting a single physiological pathway rarely yields sufficient blood pressure lowering," and added, "Transitioning to triple combination therapy may be a highly efficient approach when dual combination therapies fail." 

"The clinical importance of triple combination therapy will expand significantly as high-risk patients require additional agents to meet tighter blood pressure targets," Professor Kim added.

Industry focuses on indapamide-based triple combination therapies

In line with these shifting treatment environments, diverse triple combination therapies are being introduced to the domestic market. 

Indapamide-based triple combination therapies, such as Ankook Pharmaceutical’s 'Levosartan Plus' (a fixed-dose combination of valsartan, S-amlodipine, and indapamide), are attracting significant industry attention amid the clinical push for tighter blood pressure goals and expanded SPC utility.

Indapamide is recognized not only for its diuretic effect, which reduces fluid volume, but also for its direct vasodilatory properties. As a representative thiazide-like diuretic, it has a long-established clinical history, demonstrating blood pressure-lowering efficacy and a favorable metabolic safety profile.

Professor Kim said, "Long-term cardiovascular prognostic benefits have been firmly established for thiazide-like diuretics like indapamide and chlorthalidone across landmark clinical trials, including the HYVET study," and added, "Indapamide offers a distinct clinical advantage due to its minimized risk of metabolic adverse events."

Global guidelines similarly recommend prioritizing thiazide-like diuretics over conventional thiazide diuretics. 

S-amlodipine is attracting clinical interest in light of the updated guidelines. Professor Kim suggested that switching to S-amlodipine represents a viable therapeutic strategy for patients experiencing CCB-induced side effects, such as peripheral edema.

Professor Kim suggested that "S-amlodipine maintains robust blood pressure lowering efficacy while significantly reducing the incidence of peripheral edema compared to conventional amlodipine," and added, "It could be a major alternative for patients whose medication adherence drops due to swelling."

Professor Kim concluded by stating, "Valsartan is an ARB with extensive prognostic evidence, and indapamide is a clinically proven thiazide-like diuretic," and added, "This combination represents a highly effective, optimized therapeutic option for high-risk patients requiring intensive blood pressure reduction."