Quadpill lowers blood pressure
Small randomized, placebo-controlled crossover trial shows that pill containing four drugs at quarter-dose achieved blood pressure-lowering without additional side effects.
Multiple large-scale population studies show poor blood pressure control in many patients receiving blood pressure-lowering therapy . Monotherapy has, even at high doses, low potency . Moreover, it has been shown that benefit is obtained after intensification of blood pressure-lowering [3,4]. These two observations highlight the importance of new treatment strategies that are more efficacious and still tolerable. In this regard, low-dose combination therapy is promising, however effects at ultra-low doses are uncertain.
To elucidate this, a small randomized trial evaluating a quadpill containing four common blood pressure-lowering medications was performed, as well as a systematic review of 36 quarter-dose blood pressure-lowering trials. In this study, efficacy and tolerability of ultra-low (quarter) dose combination therapy were assessed. The randomized trial (1:1) was double-blind placebo-controlled and crossover, including 18 untreated hypertensive Australian patients that completed the study and received either placebo or irbesartan, amlodipine, hydrochlorothiazide and atenolol, each at quarter dose. A 2-week washout period was in between two times 4-weeks of treatment.
- Mean 24-h systolic and diastolic blood pressure differences between quadpill and placebo were 18.7 mmHg (95% CI 14.3-23.0) and 14.2 mmHg (95% CI 11.5-16.9), respectively (both P<0.0001).
- Mean systolic and diastolic office blood pressure differences were 22.4 mmHg (95% CI 16.5-28.3) and 13.1 mmHg (95% CI 8.9-17.3), respectively (both P<0.0001).
- All participants achieved systolic and diastolic office blood pressure less than 140/90 mmHg when using the quadpill, compared with only 33% on placebo (RR 3.01, 95% CI 1.54-5.89, P=0.0013). 83% of participants taking the quadpill achieved ambulatory blood pressure less than 135/85 mmHg, which was 39% of participants on placebo (RR 2.14, 95% CI 1.25-3.65, P=0.0053).
- A mean of 0.2 (SD 0.4) quadpill capsules were missed in the last week, which was 0.3 (SD 0.6) for placebo. Participants reported that the study medication was either very easy (n=13) or easy (n=5) to swallow.
- No serious adverse events were reported.
- Difference in mean heart rate between quadpill treatment and placebo was 6.5 beats per minute (95% CI 2.3-10.6).
- Creatinine levels (4.4 mmol/L, 95% CI 0.9-7.8, P=0.02), urate levels (0.03 mmol/L, 0.01-0.04, P=0.003) and glucose levels (0.2 mmol/L, 0.02-0.4, P=0.04) were also significantly different between treatment groups.
- In contrast, levels of alanine aminotransferase, aspartate aminotransferase, sodium potassium, total cholesterol or LDL-c did not differ between groups.
- The systematic review analysis showed reduced systolic blood pressure (4.7 mmHg, 95% CI 3.9-5.4) and diastolic blood pressure (2.4 mmHg, 95% CI 1.9-2.8) with quarter-dose blood pressure-lowering drugs, with no drug-related adverse events (RR vs placebo 1.0, 95% CI 0.88-1.10).
- Six studies that tested two drugs at quarter-dose reported pooled reduction in systolic and diastolic blood pressure of 6.7 mmHg (95% CI 4.8-8.6) and 4.4 mmHg (3.3-5.5), respectively. Also no increase in side effects was noted compared to placebo (RR 0.93, 95% CI 0.29-2.9).
This small, randomized, placebo-controlled crossover trial showed blood pressure-lowering when using a capsule containing four blood pressure-lowering drugs each at quarter-dose. Systematic reviewing of trials that used one or two drugs at quarter-dose, revealed similar findings of a large benefit without additional side effects. This novel approach need further study to assess the contributions of different components and the long-term efficacy and safety in a broader population.