BACKGROUND: Blood pressure (BP) control among treated patients in Africa is very suboptimal, with low levels of combination therapy use and therapeutic inertia being among the major barriers to effective control of hypertension. The VERONICA-Nigeria study aims to evaluate, among Black African adults with hypertension, the effectiveness and safety of a triple pill-based treatment protocol compared to Nigeria hypertension treatment protocol (standard care protocol) for the treatment of hypertension.
METHODS: This study involves a randomized, parallel-group and open-label trial. Adults with uncontrolled hypertension (n = 300), untreated or receiving monotherapy, with no contraindication to study treatments will be randomly assigned 1:1 to treatment with a triple pill based-treatment protocol or standard care protocol. Follow-up is for 6 months, with interim follow up visits at month 1, 2, and 3. In a noncomparative extension treatment period, participants completing the 6 months randomized period and on ≤3 BP-lowering drugs will receive treatment with the triple pill-based treatment protocol for 12 months. The primary outcome is change in home mean SBP from baseline to month 6, and key secondary efficacy outcome is percentage of participants with clinic BP <140/90 mmHg at month 6. The primary safety outcome is discontinuation of trial treatment due to adverse events from randomization to month 6. Economic evaluation will be conducted to assess the cost-effectiveness of the triple pill-based treatment protocol, and process evaluation will be conducted to understand the context in which the trial was conducted, implementation of the trial and interventions and mechanisms of effect, and potential barriers and facilitators to implementing the intervention in clinical practice.
CONCLUSIONS: The VERONICA-Nigeria trial will provide evidence of effectiveness and safety of the triple-based treatment protocol for the pharmacological management of hypertension, in Black African adults.
BACKGROUND: PACTR202107579572114.

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socio-economic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence.

Elevated blood pressure (BP) is the largest contributor to the incident cardiovascular disease worldwide. Despite explicit guideline recommendations for the diagnosis and management of hypertension, a large proportion of patients remain undiagnosed, untreated, or treated but uncontrolled. Inadequate BP control is associated with many complex factors including patient preference, physician\'s inertia, health systems disparities, and poor adherence to prescribed antihypertensive drug treatment. The primary driver for reduced cardiovascular morbidity and mortality is lowering of BP \'\'per se\'\' and not class effects of specific pharmacotherapies. The recent ESH guidelines recommend the use of four major classes of drugs including renin-angiotensin-aldosterone system (RAS) blockers (angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEi)), calcium channel blockers (CCB), thiazide and thiazide-like diuretics, and betablockers. Initiation of treatment for hypertension with a two-drug regimen, preferably in a single pill combination (SPC), is recommended for most patients. Preferred combinations should comprise a RAS blocker (either an ACEi or an ARB) with a CCB or thiazide/thiazide-like diuretic. These strategies are supported by robust evidence that combination therapy produces greater BP reductions than monotherapy, reduces side effects of the individual components, improves therapeutic adherence and long-term persistence on treatment, and permits achievement of earlier BP control.

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these \'hypertension polypills\' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

To provide clinical characteristics and to quantify the number of patients receiving the extemporaneous combination of the calcium channel blocker amlodipine and the angiotensin converting enzyme inhibitor zofenopril in a real-world setting. This evidence can provide a snapshot of the potential users of the two molecules in a single pill combination (SPC).
Retrospective observational study using data from the IQVIA Italian Longitudinal Patient Database. Adult patients firstly prescribed with amlodipine and zofenopril between 1 July 2011 and 30 June 2020 were identified and demographic and clinical characteristics were extracted. Treatment adherence was evaluated as proportion of days covered (PDC). The potential number of patients eligible for a SPC was calculated.
A population of 2394 hypertensive patients, mean age of 68.6 years ±12.7, 52.6% male were treated with amlodipine and zofenopril. The majority of patients (54.5%) were low adherent (PDC <40%), 25.9% were intermediate adherent and only 19.6% were high adherent (>80%) to therapy. Around 42,500 adult hypertensive patients were estimated to be prescribed the extemporaneous combination in 2019 in Italy, being potentially eligible for treatment with amlodipine and zofenopril SPC.
The administration of the extemporaneous combination of zofenopril and amlodipine in hypertensive patients is a common practice in Italy. The development of a SPC can be a viable treatment option to simplify therapy and to increase adherence in hypertensive patients who are already on the two monotherapies in combination.

Hypertension is the leading cause of morbidity and mortality in sub-Saharan Africa (SSA). Current guidelines recommend using two or more antihypertensive agents in single pill combinations (SPCs) to treat hypertension, but data from African patients that support these recommendations are lacking. We assessed the effectiveness and tolerance of three SPCs in lowering blood pressure (BP) amongst hypertensive patients in Douala.
All patients included in the hypertension registry of the Douala General Hospital and the Douala Cardiovascular Center between January 2010 and May 2020, and receiving a two-drug SPCs (renin-angiotensin system inhibitors (RAASi) + diuretics (DIU), calcium channel blockers (CCB) + RAASi, or DIU + CCB) were tracked from baseline through 16 weeks. Our primary outcome was a decrease in systolic BP (SBP) from baseline up to 16 weeks after initiation of treatment. A mixed linear repeated model was used to evaluate the change of SBP from baseline to week 16, while controlling for age, gender, and baseline SBP. Statistical significance was set at p < 0.05.
Of 377 participants on two-drug SPCs, 123 were on CCB + DIU, 96 on RAASi + CCB, and 158 on RAASi + DIU. The mean age was 54.6 (± 11.2) years. At baseline, participants on RAASi + CCB presented with slightly higher SBP compared to the other two groups. Overall, the SBP decreased by 34.3 (± 14.2) mmHg from baseline values and this was comparable across the three groups of SPCs (p = 0.118). The control rate after 16 weeks of follow-up was 62.3% with no significant difference between groups. The occurrence of adverse events was 3.4% and was comparable among the three groups.
The three two-drug SPCs were highly effective in reducing and controlling BP with low and similar rates of adverse effects. Long-term data documenting safety and whether these agents exert a differential cardiovascular effect in addition to and independent of their BP-lowering effect are needed for SSA populations.

Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require combination and double or triple therapies. International guidelines recommend the association of drugs with complementary mechanisms of action and, in particular, the combination of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics. Among the various angiotensin receptor blockers, olmesartan (OM) is available as a monotherapy and in dual and triple single-pill combinations (SPCs) with amlodipine (AML) and/or hydrochlorothiazide (HCTZ). Several phase III and IV studies, together with real-world studies, have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements both in the general population and in special subgroups of hypertensive patients, such as the elderly, diabetic, chronic kidney disease or obese patients. Ambulatory BP monitoring studies assessing 24h BP have also demonstrated that dual, as well as triple, OM-based SPCs induce a more sustained and smoother BP reduction than placebo and monotherapy. Furthermore, triple OM-based SPC has been shown to improve therapeutic adherence in hypertensive patients compared to free combinations. The availability of OM combined with HCTZ, AML or both at different dosages makes it a valuable option to customize therapy based on the levels of BP and the clinical characteristics of hypertensive patients.

UNASSIGNED: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low-income countries. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low- income countries. Overall, 43% to 66% of patients fail to adhere to their prescribed antihypertensive medications, and after 1 year, ≈40% of patients with hypertension may stop their initial drug treatment.
UNASSIGNED: The aim of the study was to evaluate the effects of single pill combination antihypertensive drugs on the adherence to treatment, blood pressure control and cardiovascular events vs. free-combination therapy.
UNASSIGNED: We enrolled 192 adult hypertensive patients not older than 79 years, with untreated or uncontrolled hypertension despite previously receiving free combination antihypertensive therapy, between November 2020 and March 2022. Patients treated with single pill combination (SPC) were compared with an arm of the same size (n = 96) and matched by age and gender who received a standard free combination (FC) antihypertensive therapy.
UNASSIGNED: There were significant reductions from baseline to month 6 of follow-up in office SBP in the SPC group vs. reduction in FC group (21.9 vs. 13.1 mmHg; p < 0.0001). There were significant reductions from baseline to month 6 of follow-up in office DBP in the SPC group vs. group with free-combination therapy (13.7 vs. 8.0 mmHg; p < 0.0001). At 6 months, 94 participants (98%) were still prescribed the SPC therapy. At the final 6-month study visit, 84.2% of patients in the SPC therapy group were adherent to the prescribed antihypertensive therapy vs. 52% of patients in the FC group. Target BP values (mean 24h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of SPC than free-combination therapy (78.2% vs. 46.3%, p < 0.05) at month 6 of follow-up.
UNASSIGNED: Treatment with single pill combinations (SPC), is the emerging best practice for safe, effective, rapid, and convenient hypertension control. It improves the affordability, adherence and control of arterial hypertension.

Clinical guidelines recommend using single pill combinations (SPC) when initiating and intensifying the treatment of arterial hypertension (AH), which is not reflected in the Summaries of Product Characteristics (SMPC) for individual preparations. The drug reimbursement system in Poland (with a few exceptions) does not provide for reimbursement outside the indications specified in the SMPC. Therefore, it excludes the use of SPC under reimbursement. In 2020 the share of SPC in the treatment of AH amounted to 12.8% of unit volume and was lower than the 80% based on the guidelines of the Polish Society of Hypertension.
Using the data from a sample of pharmacies in Poland over the period November-December 2020, the potential was assessed of switching from existing AH therapy with monocomponent drugs containing selected combinations of active ingredients to the equivalent SPC.
The potential of switching from AH treatment in the analyzed period using monocomponent drugs with the equivalent SPC amounted to 19% of unit volume (a reduction of 212M units), with the highest switch potential (43.9%) for drugs containing amlodipine. The public payer\'s savings would be EUR 12.3 million and patient savings would amount to EUR 5.0 million.
Enabling reimbursement of SPC in Poland in line with the clinical guidelines can significantly increase the share of SPC in the treatment of AH, which will result in better health outcomes and a significant reduction in the payer\'s drug reimbursement spending and will lower the financial barrier for patients to access this type of treatment.