A Randomized Trial to Investigate the Effects of Low-Dose Colchicine in Patients with Hypertension: Rationale and Design of the COlchicine and HypERtENsion Trial (COHERENT).

Hypertension is a prevalent and significant risk factor for cardiovascular disease (CVD). The immune system and inflammatory response are involved in the pathophysiology of hypertension. We hypothesize that treating hypertension with colchicine on top of standard therapy, will decrease pulse wave velocity (PWV), left ventricular mass, cardiac/inflammatory biomarkers. COHERENT was an investigator-initiated, single-center, prospective, randomized, double-blind, placebo-controlled study of the effects of colchicine in patients with hypertension. Potential participants were identified through nationwide health registries. Eligible patients were randomized 1:1 to colchicine 0.5 mg daily or placebo and treated for 6 months. Assessment of vascular function, echocardiography, and measurement of biomarkers were performed at baseline and at 6 months. The primary endpoint of the trial was change from baseline in carotid-femoral PWV at 6 months. Secondary endpoints included blood pressure, echocardiographic measurements, and cardiac/inflammatory biomarkers. We screened 183 potential participants, of whom 150 were randomized from August 2021 to July 2025. A total of 75 (50%) were assigned to receive colchicine. Participants had a mean age of 64.5 years (SD 8.0) and 53 (35%) were female, 82 (55%) were active or former smokers, mean systolic blood pressure was 140 mmHg (SD 16.5), mean diastolic pressure was 86 mmHg (10.5), and median high sensitivity C-reactive protein was 0.97 mg/L (IQR: 0.52-2.05). COHERENT is the first trial to investigate the effects of colchicine in patients with hypertension without other known CVD. The trial will provide important data on whether anti-inflammatory therapy should be considered for patients with hypertension. Clinical Trial registration: Clinicaltrials.gov: NCT04916522, registered June 3, 2021, https://clinicaltrials.gov/study/NCT04916522 Practical Applications COHERENT has the potential to determine whether colchicine can modulate pathological processes in hypertension, such as increased arterial stiffness and blood pressure. If the trial outcome is positive, it could impact therapy for millions of hypertensive patients. Since the socio-economic costs of therapy and care related to hypertension and heart disease are enormous, the results from the study may also be important at a broader societal level, given that colchicine is relatively inexpensive, already approved for treatment in patients following myocardial infarction, and widely considered safe to use with an acceptable low level of side effects when used in low doses. Furthermore, this study can help elucidate the pathophysiological pathways from early-stage cardiovascular disease - where only hypertension is present - and determine whether anti-inflammatory therapy such as colchicine can help prevent deleterious vascular function changes and potentially prevent progression to overt cardiovascular disease.