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Evolution of Hypertension management from monotherapy to combination

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eMediNexus    09 June 2020

Dr k k AggarwalPoor BP control in real life originates more from factors that prevent anti hypertensives (AHTs) from expressing their therapeutic potential, rather than lack of suitable AHTs

Monotherapy at Increasing Doses advocated in the late seventies and the eighties was later discontinued due to increased drug-related side effects that resulted in drug discontinuation and subsequently increased CV risk

Sequential Monotherapy involved switching from one monotherapy to another. Since the magnitude of BP reduction may vary from one drug class to another in the same patient, this approach had some therapeutic rationale. It was beneficial only in select patient groups like ISH. Being a time consuming  strategy, it often lead to treatment discontinuation, leading to poor BP control.

Step care treatment, the strategy recommended by guidelines in the last 2 to 3 decades, involved initial monotherapy followed by addition of 2nd, 3rd or 4th drug. This strategy was supported by evidence suggesting that adding a 2nd drug can increase the chances of BP control by 5 fold vs increasing the dose of the initial AHT. However, in real life situation, the advantage of this strategy would depend on adherence. Studies have shown adherence to be as low as only 1 in every 4 patients.

Combination therapy, till recently recommended as first line therapy in select patient population in the guidelines, has now emerged as the treatment of choice in almost all hypertensive patients according to the recent ACC/ ESC guidelines. Single pill combinations (SPCs) exhibit prompt and better BP control with lower discontinuation subsequently resulting in lower risk of hospitalization for IHD, cerebrovascular disease, and heart failure. The HOPE-3 trial showed that initial combination reduced the risk of CV outcomes by 24% vs placebo. Many studies directly or indirectly conclude that initial combination treatment may be associated with a lower incidence and risk of CV morbid and fatal events. Similarly early BP control was more protective than late BP control as evidenced by the VALUE, ALLHAT and ASCOT-BPLA studies. Initial combination therapy resulted in better BP control with lower risk of CV events (↓38%), HF (↓36%) and stroke (↓21%). Real life medical practice of 2 million patients reinforced the fact that starting and continuing treatment with drug combinations exhibited the lowest risk of CV events. Combination with 2 drugs is also associated with better tolerability. The exceptions could be elderly / frail patients where the guidelines recommend starting with monotherapy to prevent excessive BP fall.

Source: Mancia G, Rea F, Corrao G, Grassi G. Two-Drug Combinations as First-Step Antihypertensive Treatment. Circ Res. 2019;124(7):1113-23.

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