Des essais cliniques aux recommandations cardiovasculaires

Single Pill Combination vs Free Equivalent Combination

Meta-Analysis

Does an SPC-based regimen lead to improved adherence, persistence, and better BP control compared with FEC therapy in patients with hypertension?

• 44 studies
• 2 pills vs 1, or 3 pills vs 1 (free equivalent vs SPC)

SPC vs FEC on Adherence, Persistence, and Outcomes

Meta-Analysis

Single Pill Combination vs Free Equivalent Combination

Comparing the equivalent doses of two drugs in a single pill with equivalent doses with two pills, the better reduction of blood pressure may only be due to better adherence;

There is no other reason than better adherence.

Initial SPC Reduces CV Events in Hypertension

Meta-Analysis 

SBP and DBP Normalization Ratios

Three studies including 653 patients

Single Pill Combination vs Free Equivalent Combination The Evidence

• Better adherence
• Better persistence with therapy
• Better BP control
• Better target achievement
• Patients' preference

Initial SPC Reduces CV Events in Hypertension Matched Cohorts in US Registry Data

Initial SPC Reduces CV Events in Hypertension Real World Data from Lombardy in Italy

Healthcare utilization database

• 44,534 residents of the region (aged 40-80 y) who started treatment with 1 antihypertensive drug
  (n = 37,078) or a 2-drug FDC (n = 7456) in 2010
• Followed for 1 year after treatment initiation to compare the risk for hospitalization for CVD associated with the 2 treatment strategies

Initial SPC Reduces CV Events in Hypertension

Real World Data

Database of the Lombardy Region (Italy)

• 44,534 residents
• Started on monotherapy (n = 37,078) or an FDC (n = 7456)
• Evaluation of the risk for CV events
• FDCs were associated with more effective CV protection

What Have We Learned From These Studies?

Efficacy of pharmacological therapies is not the major limitation to achieving blood pressure control

Combination Therapy Superiority to Sequential Monotherapy

Initial Treatment of Hypertension

Means of Home SBP in the Monotherapy and Combination Therapy Arms

• This randomized double-blind trial showed that initial combination therapy was associated with a better earlier response rate

Therapeutic Inertia in Hypertension in Primary Care

A Dutch Cohort Study

Julius General Practitioners' Network (n = 530,564)

• Patients with a diagnosis of hypertension, SBP ≥ 140 mm Hg, and/or DBP ≥ 90 mm Hg, and 1 or 2 BP-lowering drugs)
• Therapeutic inertia was defined as not undertaking therapeutic action in follow-up despite uncontrolled BP
• 10% of all patients with hypertension had uncontrolled BP on 1 or 2 BP-lowering drugs
• Therapeutic inertia was 87%
• Older age, closer to target BP, and concurrent diabetes were associated with therapeutic inertia

Why SPCs?

Long-Term Event Rates, Risk Factors, and Treatment Patters in Patients Qualifying for Dual BP-Lowering Therapy

Presented at ESH 2023

Database Study

• CPRD, HES, and ONS databases in England 2005 to 2019
• 1,426,079 individuals aged ≥ 18 y with hypertension, qualifying for dual BP-lowering therapy per the ESC/ESH guidelines
• At variance with guidelines, BP-lowering monotherapy was the most common treatment pattern (42.6%-56.7% of patient-time) over a 5-y follow-up period

Clinicians' Worries About Starting 2 or More Antihypertensive

Medications at Once

Clinicians' Worries About Starting 2 Antihypertensives at Once

• Initiating therapy with 2 drugs in a single pill does not lead to high frequency of hypotension, symptomatic hypotension, or falls
• Most patients tolerate the treatment very well and have better BP control

Studies Reporting Rates of Nonadherence in Patients With Treatment-Resistant Hypertension

Number of Antihypertensives and Adherence

Increased number of antihypertensive drugs prescribed associated with poor adherence

What Have We Learned From These Studies?

There's no reason to start monotherapy knowing that the SPC is effective, is safe, and in the long term improves adherence and persistence

SPC Leads to Improved BP Control and Improved Persistence

• Starting with a single drug leads to lower BP control rate vs combination therapies
• Starting with a single drug leads to clinical inertia lasting for years after treatment initiation
• Rate of treatment discontinuations is lower in patients starting treatment with combination therapy than in patients starting a single-class antihypertensive regimen

Complex Treatment Strategies in Previous Guidelines

Combination Approach Simplifies Treatment Decisions

• Combination approach combining a RAS blocker with a CCB or a diuretic, for most patients, makes it much simpler to follow the guidelines
• Clear, simple algorithms in the latest guidelines

• Start with a single pill in most patients

  Monotherapy for just a few patients

Summary