Fixed-Dose Combination Therapies and Cardiovascular Mortality and Events

A major challenge in improving global cardiovascular health is the poor implementation of proven, simple interventions, like antihypertensives, statins, and antiplatelets, especially in low-resource settings. Despite their benefits, usage rates remain low. For instance, in 2019, only 1 in 5 people with hypertension had controlled blood pressure, and 1 in 10 high-risk individuals used statins. This highlights the failure of the current, fragmented model of CVD prevention.

Single-pill combination (SPC) therapies have long been recognised as a promising strategy to increase uptake of multidrug regimens for both primary and secondary prevention of CVD. Although SPCs were endorsed by experts and the WHO as early as the 2000s, their adoption has been limited due to regulatory and institutional barriers and scepticism about efficacy and safety.

However, recent evidence, including a 2021 meta-analysis and the SECURE trial, supports the effectiveness and safety of SPCs, showing up to a 32–50% reduction in CVD events with very low adverse events. In response, the WHO included SPCs in its 2023 essential medicines list. Building on this, a recent modelling study quantifies the potential global impact of SPC therapy adoption through 2050, examining two implementation scenarios within health systems and public health programs.

Researchers used state-transition and demographic modelling to project ischaemic heart disease and stroke-related deaths and nonfatal events across 182 countries. They compared two SPC rollout strategies against current (non-SPC) care: targeted strategies aimed at improving adherence and reducing therapeutic inertia in individuals already receiving care, and population-based strategies to provide SPC therapies to most people at intermediate-to-high cardiovascular risk.

Between 2023 and 2050, SPC therapies could prevent up to 29 million deaths and 51 million cases in the targeted scenario, and up to 72 million deaths and 130 million cases in the population-based scenario. The largest impact would occur in South and East Asia and the Pacific, due to their large populations. SPC use could also lower all-cause premature mortality by 2.0% to 3.2%, helping advance global health goals.

This modelling study demonstrates that integrating SPC therapies into cardiovascular disease prevention strategies could substantially improve global heart health. Using high-quality data, the authors project that widespread SPC adoption, especially among high-risk individuals not currently in care, could prevent up to 100 million deaths and 250 million CVD events by 2050, with the largest benefits seen in countries with the highest disease burden and weakest primary care systems.

Current prevention methods, which rely on treating one risk factor at a time, are complex and ineffective at scale. In contrast, a simplified, population-based approach, offering a combination of two antihypertensive drugs and a statin to all intermediate- to high-risk individuals, could be easier to implement with similar or better outcomes. While concerns about overmedicalisation and adverse effects exist, evidence from meta-analyses and trials supports SPC safety and effectiveness, showing low rates of serious side effects and a net reduction in strokes, including haemorrhagic strokes.

The study advocates for tailored implementation strategies across countries, such as pharmacist-led risk assessments or age-based eligibility. It emphasises the need for decision support tools, educational materials, and integration with existing frameworks like WHO’s HEARTS programme. Rebranding SPCs and addressing institutional resistance will be key to improving uptake.

Since the 1990s, cardiovascular disease has been the leading cause of death globally. Without urgent intervention, rising population, ageing, and worsening risk factors will further increase CVD rates and strain already burdened health systems. SPC strategies, especially population-based programmes, offer a simplified, scalable approach to prevention that could significantly expand access to proven therapies and save millions of lives.

Source: JACC
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