Background Cardiovascular disease (CVD) is a major cause of disability and mortality globally. Premature fatal and non-fatal CVD is considered to be largely preventable through the control of risk factors by lifestyle modifications and preventive medication. Lipid-lowering and antihypertensive drug therapies for primary prevention are cost-eHective in reducing CVD morbidity and mortality among high-risk people and are recommended by international guidelines. However, adherence to medication prescribed for the prevention of CVD can be poor. Approximately 9% of CVD cases in the EU are attributed to poor adherence to vascular medications. Low-cost, scalable interventions to improve adherence to medications for the primary prevention of CVD have potential to reduce morbidity, mortality and healthcare costs associated with CVD. Objectives To establish the eHectiveness of interventions delivered by mobile phone to improve adherence to medication prescribed for the primary prevention of CVD in adults. Search methods We searched CENTRAL, MEDLINE, Embase, and two other databases on 7 January 2020. We also searched two clinical trials registers on 5 February 2020. We searched reference lists of relevant papers. We applied no language or date restrictions. Selection criteria We included randomised controlled trials investigating interventions delivered wholly or partly by mobile phones to improve adherence to cardiovascular medications prescribed for the primary prevention of CVD. We only included trials with a minimum of one-year follow-up in order that the outcome measures related to longer-term, sustained medication adherence behaviours and outcomes. Eligible comparators were usual care or control groups receiving no mobile phone-delivered component of the intervention. Data collection and analysis We used standard methodological procedures recommended by Cochrane. The main outcomes of interest were objective measures of medication adherence (blood pressure (BP) and cholesterol), CVD events, and adverse events. We contacted study authors for further information when this was not reported. Main results We included 14 trials with 25,633 randomised participants. Participants were recruited from community-based primary and tertiary care or outpatient clinics. The interventions varied widely from those delivered solely through short messaging service (SMS) to those involving a combination of modes of delivery, such as SMS in addition to healthcare worker training, face-to-face counselling, electronic pillboxes, written materials, and home blood pressure monitors. Some interventions only targeted medication adherence, while others additionally targeted lifestyle changes such as diet and exercise. Due to heterogeneity in the nature and delivery of the interventions and study populations, we reported most results narratively, with the exception of two trials which were similar enough to meaningfully pool in metaanalyses. The body of evidence for the eHect of mobile phone-based interventions on objective outcomes of adherence (BP and cholesterol) was of low certainty, due to most trials being at high risk of bias, and inconsistency in outcome eHects. Two trials were at low risk of bias. Among five trials (total study enrolment: 5441 participants) recording low-density lipoprotein cholesterol (LDL-C), two studies found evidence for a small beneficial intervention eHect on reducing LDL-C (-5.30 mg/dL, 95% confidence interval (CI) -8.30 to -2.30; and -9.20 mg/dL, 95% CI -17.70 to -0.70). The other three studies found results varying from a small reduction (-7.7 mg/dL) to a small increase in LDL-C (0.77 mg/dL). All of which had wide confidence intervals that included no eHect. Across 13 studies (25,166 participants) measuring systolic blood pressure, eHect estimates ranged from a large reduction (MD -12.45 mmHg, 95% CI-15.02 to -9.88) to a small increase (MD 2.80 mmHg, 95% CI0.30 to 5.30). We found a similar range of eHect estimates for diastolic BP, ranging from -12.23 mmHg (95% CI-14.03 to -10.43) to 1.64 mmHg (95% CI-0.55 to 3.83) (11 trials, 19,716 participants). Four trials showed intervention benefits for systolic and diastolic BP with confidence intervals excluding no eHect, and among these were all three of the trials evaluating self-monitoring of blood pressure with mobile phone-based telemedicine. The fourth trial included SMS and provider support (with additional varied features). Seven studies (19,185 participants) reported 'controlled' BP as an outcome, and intervention eHect estimates varied from negligible eHects (odds ratio (OR) 1.01, 95% CI 0.76 to 1.34) to large improvements in BP control (OR 2.41, 95% CI: 1.57 to 3.68). The three trials of clinician training or decision support combined with SMS (with additional varied features) had confidence intervals encompassing benefits and harms, with point estimates close to zero. Pooled analyses of the two trials of interventions solely delivered through SMS were indicative of little or no beneficial intervention eHect on systolic BP (MD -1.55 mmHg, 95% CI -3.36 to 0.25; I2= 0%) and small increases in controlled BP (OR 1.32, 95% CI1.06 to 1.65; I2= 0%). Based on four studies (12,439 participants), there was very low-certainty evidence (downgraded twice for imprecision and once for risk of bias) relating to the intervention eHect on combined (fatal and non-fatal) CVD events. Two studies (2535 participants) provided low-certainty evidence for the eHect of the intervention on cognitive outcomes, with little or no diHerence between trial arms for perceived quality of care and satisfaction with treatment. There was moderate-certainty evidence (downgraded due to risk of bias) that the interventions did not cause harm, based on six studies (8285 participants). Three studies reported no adverse events attributable to the intervention. One study reported no diHerence between groups in experience of adverse eHects of statins, and that no participants reported intervention-related adverse events. One study stated that potential side eHects were similar between groups. One study reported a similar number of deaths in each arm, but did not provide further information relating to potential adverse events. Authors' conclusions There is low-certainty evidence on the eHects of mobile phone-delivered interventions to increase adherence to medication prescribed for the primary prevention of CVD. Trials of BP self-monitoring with mobile-phone telemedicine support reported modest benefits. One trial at low risk of bias reported modest reductions in LDL cholesterol but no benefits for BP. There is moderate-certainty evidence that these interventions do not result in harm. Further trials of these interventions are warranted.
